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Sample records for human dilated cardiomyopathy

  1. Dilated Cardiomyopathy

    Science.gov (United States)

    ... Family history of dilated cardiomyopathy Inflammation of heart muscle from immune system disorders, such as lupus Neuromuscular disorders, such as muscular dystrophy Complications Complications from dilated cardiomyopathy include: Heart ...

  2. Genetics of Human and Canine Dilated Cardiomyopathy

    OpenAIRE

    Siobhan Simpson; Jennifer Edwards; Thomas F. N. Ferguson-Mignan; Malcolm Cobb; Nigel P. Mongan; Catrin S. Rutland

    2015-01-01

    Cardiovascular disease is a leading cause of death in both humans and dogs. Dilated cardiomyopathy (DCM) accounts for a large number of these cases, reported to be the third most common form of cardiac disease in humans and the second most common in dogs. In human studies of DCM there are more than 50 genetic loci associated with the disease. Despite canine DCM having similar disease progression to human DCM studies into the genetic basis of canine DCM lag far behind those of human DCM. In th...

  3. Genetics of Human and Canine Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Siobhan Simpson

    2015-01-01

    Full Text Available Cardiovascular disease is a leading cause of death in both humans and dogs. Dilated cardiomyopathy (DCM accounts for a large number of these cases, reported to be the third most common form of cardiac disease in humans and the second most common in dogs. In human studies of DCM there are more than 50 genetic loci associated with the disease. Despite canine DCM having similar disease progression to human DCM studies into the genetic basis of canine DCM lag far behind those of human DCM. In this review the aetiology, epidemiology, and clinical characteristics of canine DCM are examined, along with highlighting possible different subtypes of canine DCM and their potential relevance to human DCM. Finally the current position of genetic research into canine and human DCM, including the genetic loci, is identified and the reasons many studies may have failed to find a genetic association with canine DCM are reviewed.

  4. Genetics of Human and Canine Dilated Cardiomyopathy.

    Science.gov (United States)

    Simpson, Siobhan; Edwards, Jennifer; Ferguson-Mignan, Thomas F N; Cobb, Malcolm; Mongan, Nigel P; Rutland, Catrin S

    2015-01-01

    Cardiovascular disease is a leading cause of death in both humans and dogs. Dilated cardiomyopathy (DCM) accounts for a large number of these cases, reported to be the third most common form of cardiac disease in humans and the second most common in dogs. In human studies of DCM there are more than 50 genetic loci associated with the disease. Despite canine DCM having similar disease progression to human DCM studies into the genetic basis of canine DCM lag far behind those of human DCM. In this review the aetiology, epidemiology, and clinical characteristics of canine DCM are examined, along with highlighting possible different subtypes of canine DCM and their potential relevance to human DCM. Finally the current position of genetic research into canine and human DCM, including the genetic loci, is identified and the reasons many studies may have failed to find a genetic association with canine DCM are reviewed.

  5. Dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Salvatore, M.; Cuocolo, A.

    1988-01-01

    Radionuclide techniques are easily obtainable, noninvasive examinations that provide useful information in the evaluation, diagnosis and management of patients with dilated cardiomyopathy. The gated blood pool scan allows the assessment of ventricular size, configuration, and wall and septal thickness. These data allow the functional class of the cardiomyopathy (congestive, restrictive or hypertrophic) to be defined. Often THallium-201 myocardial perfusion imaging adds further information and is particularly useful in distinguishing congestive cardiomyopathy from severe coronary artery disease and in depicting septal abnormalities in hipertrophic cardiomyopathy. Useful as these techniques are, they are not substitutes for conventional approaches to diagnosis. Careful history taking and physical examination, as well as scrutiny of the electrocardiogram, chest X-ray and echocardiogram should be standard practice for the evaluation of patients with suspected cardiomyopathy. Judicious use of noninvasive techniques may obviate the need for cardiac catheterization in many patients

  6. Data of methylome and transcriptome derived from human dilated cardiomyopathy

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    Bong-Seok Jo

    2016-12-01

    Full Text Available Alterations in DNA methylation and gene expression have been implicated in the development of human dilated cardiomyopathy (DCM. Differentially methylated probes (DMPs and differentially expressed genes (DEGs were identified between the left ventricle (LV, a pathological locus for DCM and the right ventricle (RV, a proxy for normal hearts. The data in this DiB are for supporting our report entitled “Methylome analysis reveals alterations in DNA methylation in the regulatory regions of left ventricle development genes in human dilated cardiomyopathy” (Bong-Seok Jo, In-Uk Koh, Jae-Bum Bae, Ho-Yeong Yu, Eun-Seok Jeon, Hae-Young Lee, Jae-Joong Kim, Murim Choi, Sun Shim Choi, 2016 [1].

  7. Genotype-specific pathogenic effects in human dilated cardiomyopathy.

    Science.gov (United States)

    Bollen, Ilse A E; Schuldt, Maike; Harakalova, Magdalena; Vink, Aryan; Asselbergs, Folkert W; Pinto, Jose R; Krüger, Martina; Kuster, Diederik W D; van der Velden, Jolanda

    2017-07-15

    Mutations in genes encoding cardiac troponin I (TNNI3) and cardiac troponin T (TNNT2) caused altered troponin protein stoichiometry in patients with dilated cardiomyopathy. TNNI3 p.98trunc resulted in haploinsufficiency, increased Ca 2+ -sensitivity and reduced length-dependent activation. TNNT2 p.K217del caused increased passive tension. A mutation in the gene encoding Lamin A/C (LMNA p.R331Q ) led to reduced maximal force development through secondary disease remodelling in patients suffering from dilated cardiomyopathy. Our study shows that different gene mutations induce dilated cardiomyopathy via diverse cellular pathways. Dilated cardiomyopathy (DCM) can be caused by mutations in sarcomeric and non-sarcomeric genes. In this study we defined the pathogenic effects of three DCM-causing mutations: the sarcomeric mutations in genes encoding cardiac troponin I (TNNI3 p.98truncation ) and cardiac troponin T (TNNT2 p.K217deletion ; also known as the p.K210del) and the non-sarcomeric gene mutation encoding lamin A/C (LMNA p.R331Q ). We assessed sarcomeric protein expression and phosphorylation and contractile behaviour in single membrane-permeabilized cardiomyocytes in human left ventricular heart tissue. Exchange with recombinant troponin complex was used to establish the direct pathogenic effects of the mutations in TNNI3 and TNNT2. The TNNI3 p.98trunc and TNNT2 p.K217del mutation showed reduced expression of troponin I to 39% and 51%, troponin T to 64% and 53%, and troponin C to 73% and 97% of controls, respectively, and altered stoichiometry between the three cardiac troponin subunits. The TNNI3 p.98trunc showed pure haploinsufficiency, increased Ca 2+ -sensitivity and impaired length-dependent activation. The TNNT2 p.K217del mutation showed a significant increase in passive tension that was not due to changes in titin isoform composition or phosphorylation. Exchange with wild-type troponin complex corrected troponin protein levels to 83% of controls in the TNNI3

  8. Genotype‐specific pathogenic effects in human dilated cardiomyopathy

    Science.gov (United States)

    Schuldt, Maike; Harakalova, Magdalena; Vink, Aryan; Asselbergs, Folkert W.; Pinto, Jose R.; Krüger, Martina; Kuster, Diederik W. D.; van der Velden, Jolanda

    2017-01-01

    Key points Mutations in genes encoding cardiac troponin I (TNNI3) and cardiac troponin T (TNNT2) caused altered troponin protein stoichiometry in patients with dilated cardiomyopathy. TNNI3p.98trunc resulted in haploinsufficiency, increased Ca2+‐sensitivity and reduced length‐dependent activation. TNNT2p.K217del caused increased passive tension.A mutation in the gene encoding Lamin A/C (LMNA p.R331Q) led to reduced maximal force development through secondary disease remodelling in patients suffering from dilated cardiomyopathy.Our study shows that different gene mutations induce dilated cardiomyopathy via diverse cellular pathways. Abstract Dilated cardiomyopathy (DCM) can be caused by mutations in sarcomeric and non‐sarcomeric genes. In this study we defined the pathogenic effects of three DCM‐causing mutations: the sarcomeric mutations in genes encoding cardiac troponin I (TNNI3p.98truncation) and cardiac troponin T (TNNT2p.K217deletion; also known as the p.K210del) and the non‐sarcomeric gene mutation encoding lamin A/C (LMNAp.R331Q). We assessed sarcomeric protein expression and phosphorylation and contractile behaviour in single membrane‐permeabilized cardiomyocytes in human left ventricular heart tissue. Exchange with recombinant troponin complex was used to establish the direct pathogenic effects of the mutations in TNNI3 and TNNT2. The TNNI3p.98trunc and TNNT2p.K217del mutation showed reduced expression of troponin I to 39% and 51%, troponin T to 64% and 53%, and troponin C to 73% and 97% of controls, respectively, and altered stoichiometry between the three cardiac troponin subunits. The TNNI3p.98trunc showed pure haploinsufficiency, increased Ca2+‐sensitivity and impaired length‐dependent activation. The TNNT2p.K217del mutation showed a significant increase in passive tension that was not due to changes in titin isoform composition or phosphorylation. Exchange with wild‐type troponin complex corrected troponin protein levels to 83% of

  9. Atlas of the clinical genetics of human dilated cardiomyopathy

    DEFF Research Database (Denmark)

    Haas, Jan; Frese, Karen S; Peil, Barbara

    2015-01-01

    AIM: Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome...... these limitations and screened all DCM disease genes in a large cohort. METHODS AND RESULTS: In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes...... disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations...

  10. Genetics Home Reference: familial dilated cardiomyopathy

    Science.gov (United States)

    ... Dilated cardiomyopathy: the complexity of a diverse genetic architecture. Nat Rev Cardiol. 2013 Sep;10(9):531- ... Health & Human Services National Institutes of Health National Library of Medicine Lister Hill National Center for Biomedical ...

  11. New Altered Non-Fibrillar Collagens in Human Dilated Cardiomyopathy: Role in the Remodeling Process.

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    Carolina Gil-Cayuela

    Full Text Available In dilated cardiomyopathy (DCM, cardiac failure is accompanied by profound alterations of extracellular matrix associated with the progression of cardiac dilation and left ventricular (LV dysfunction. Recently, we reported alterations of non-fibrillar collagen expression in ischemic cardiomyopathy linked to fibrosis and cardiac remodeling. We suspect that expression changes in genes coding for non-fibrillar collagens may have a potential role in DCM development.This study sought to analyze changes in the expression profile of non-fibrillar collagen genes in patients with DCM and to examine relationships between cardiac remodeling parameters and the expression levels of these genes.Twenty-three human left ventricle tissue samples were obtained from DCM patients (n = 13 undergoing heart transplantation and control donors (n = 10 for RNA sequencing analysis. We found increased mRNA levels of six non-fibrillar collagen genes, such as COL4A5, COL9A1, COL21A1, and COL23A1 (P < 0.05 for all, not previously described in DCM. Protein levels of COL8A1 and COL16A1 (P < 0.05 for both, were correspondingly increased. We also identified TGF-β1 significantly upregulated and related to both COL8A1 and COL16A1. Interestingly, we found a significant relationship between LV mass index and the gene expression level of COL8A1 (r = 0.653, P < 0.05.In our research, we identified new non-fibrillar collagens with altered expression in DCM, being COL8A1 overexpression directly related to LV mass index, suggesting that they may be involved in the progression of cardiac dilation and remodeling.

  12. Differential gene expression of cardiac ion channels in human dilated cardiomyopathy.

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    Maria Micaela Molina-Navarro

    Full Text Available BACKGROUND: Dilated cardiomyopathy (DCM is characterized by idiopathic dilation and systolic contractile dysfunction of the cardiac chambers. The present work aimed to study the alterations in gene expression of ion channels involved in cardiomyocyte function. METHODS AND RESULTS: Microarray profiling using the Affymetrix Human Gene® 1.0 ST array was performed using 17 RNA samples, 12 from DCM patients undergoing cardiac transplantation and 5 control donors (CNT. The analysis focused on 7 cardiac ion channel genes, since this category has not been previously studied in human DCM. SCN2B was upregulated, while KCNJ5, KCNJ8, CLIC2, CLCN3, CACNB2, and CACNA1C were downregulated. The RT-qPCR (21 DCM and 8 CNT samples validated the gene expression of SCN2B (p < 0.0001, KCNJ5 (p < 0.05, KCNJ8 (p < 0.05, CLIC2 (p < 0.05, and CACNB2 (p < 0.05. Furthermore, we performed an IPA analysis and we found a functional relationship between the different ion channels studied in this work. CONCLUSION: This study shows a differential expression of ion channel genes involved in cardiac contraction in DCM that might partly underlie the changes in left ventricular function observed in these patients. These results could be the basis for new genetic therapeutic approaches.

  13. A predictive model for canine dilated cardiomyopathy-a meta-analysis of Doberman Pinscher data.

    Science.gov (United States)

    Simpson, Siobhan; Edwards, Jennifer; Emes, Richard D; Cobb, Malcolm A; Mongan, Nigel P; Rutland, Catrin S

    2015-01-01

    Dilated cardiomyopathy is a prevalent and often fatal disease in humans and dogs. Indeed dilated cardiomyopathy is the third most common form of cardiac disease in humans, reported to affect approximately 36 individuals per 100,000 individuals. In dogs, dilated cardiomyopathy is the second most common cardiac disease and is most prevalent in the Irish Wolfhound, Doberman Pinscher and Newfoundland breeds. Dilated cardiomyopathy is characterised by ventricular chamber enlargement and systolic dysfunction which often leads to congestive heart failure. Although multiple human loci have been implicated in the pathogenesis of dilated cardiomyopathy, the identified variants are typically associated with rare monogenic forms of dilated cardiomyopathy. The potential for multigenic interactions contributing to human dilated cardiomyopathy remains poorly understood. Consistent with this, several known human dilated cardiomyopathy loci have been excluded as common causes of canine dilated cardiomyopathy, although canine dilated cardiomyopathy resembles the human disease functionally. This suggests additional genetic factors contribute to the dilated cardiomyopathy phenotype.This study represents a meta-analysis of available canine dilated cardiomyopathy genetic datasets with the goal of determining potential multigenic interactions relating the sex chromosome genotype (XX vs. XY) with known dilated cardiomyopathy associated loci on chromosome 5 and the PDK4 gene in the incidence and progression of dilated cardiomyopathy. The results show an interaction between known canine dilated cardiomyopathy loci and an unknown X-linked locus. Our study is the first to test a multigenic contribution to dilated cardiomyopathy and suggest a genetic basis for the known sex-disparity in dilated cardiomyopathy outcomes.

  14. A predictive model for canine dilated cardiomyopathy: a meta-analysis of Doberman Pinscher data

    OpenAIRE

    Simpson, Siobhan; Edwards, Jennifer; Emes, Richard D.; Cobb, Malcolm A.; Mongan, Nigel P.; Rutland, Catrin S.

    2015-01-01

    Dilated cardiomyopathy is a prevalent and often fatal disease in humans and dogs. Indeed dilated cardiomyopathy is the third most common form of cardiac disease in humans, reported to affect approximately 36 individuals per 100,000 individuals. In dogs, dilated cardiomyopathy is the second most common cardiac disease and is most prevalent in the Irish Wolfhound, Doberman Pinscher and Newfoundland breeds. Dilated cardiomyopathy is characterised by ventricular chamber enlargement and systolic d...

  15. Endoplasmic reticulum stress induces different molecular structural alterations in human dilated and ischemic cardiomyopathy.

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    Ana Ortega

    Full Text Available BACKGROUND: The endoplasmic reticulum (ER is a multifunctional organelle responsible for the synthesis and folding of proteins as well as for signalling and calcium storage, that has been linked to the contraction-relaxation process. Perturbations of its homeostasis activate a stress response in diseases such as heart failure (HF. To elucidate the alterations in ER molecular components, we analyze the levels of ER stress and structure proteins in human dilated (DCM and ischemic (ICM cardiomyopathies, and its relationship with patient's functional status. METHODS AND RESULTS: We examined 52 explanted human hearts from DCM (n = 21 and ICM (n = 21 subjects and 10 non-failing hearts as controls. Our results showed specific changes in stress (IRE1, p<0.05; p-IRE1, p<0.05 and structural (Reticulon 1, p<0.01 protein levels. The stress proteins GRP78, XBP1 and ATF6 as well as the structural proteins RRBP1, kinectin, and Nogo A and B, were upregulated in both DCM and ICM patients. Immunofluorescence results were concordant with quantified Western blot levels. Moreover, we show a novel relationship between stress and structural proteins. RRBP1, involved in procollagen synthesis and remodeling, was related with left ventricular function. CONCLUSIONS: In the present study, we report the existence of alterations in ER stress response and shaping proteins. We show a plausible effect of the ER stress on ER structure in a suitable sample of DCM and ICM subjects. Patients with higher values of RRBP1 had worse left ventricular function.

  16. Peripartum cardiomyopathy as a part of familial dilated cardiomyopathy

    NARCIS (Netherlands)

    K.Y. van Spaendonck-Zwarts (Karin); J.P. van Tintelen (Peter); D.J. van Veldhuisen (Dirk); R. van der Werf (Rik); J.D.H. Jongbloed (Jan); W.J. Paulus (Walter); D. Dooijes (Dennis); M.P. van den Berg (Maarten)

    2010-01-01

    textabstractBACKGROUND-: Anecdotal cases of familial clustering of peripartum cardiomyopathy (PPCM) and familial occurrences of PPCM and idiopathic dilated cardiomyopathy (DCM) together have been observed, suggesting that genetic factors play a role in the pathogenesis of PPCM. We hypothesized that

  17. Canine candidate genes for dilated cardiomyopathy: annotation of and polymorphic markers for 14 genes

    OpenAIRE

    Wiersma, Anje C; Leegwater, Peter AJ; van Oost, Bernard A; Ollier, William E; Dukes-McEwan, Joanna

    2007-01-01

    Abstract Background Dilated cardiomyopathy is a myocardial disease occurring in humans and domestic animals and is characterized by dilatation of the left ventricle, reduced systolic function and increased sphericity of the left ventricle. Dilated cardiomyopathy has been observed in several, mostly large and giant, dog breeds, such as the Dobermann and the Great Dane. A number of genes have been identified, which are associated with dilated cardiomyopathy in the human, mouse and hamster. Thes...

  18. ACE I/D polymorphism in Indian patients with hypertrophic cardiomyopathy and dilated cardiomyopathy

    DEFF Research Database (Denmark)

    Rai, Taranjit Singh; Dhandapany, Perundurai Subramaniam; Ahluwalia, Tarun Veer Singh

    2008-01-01

    The study was carried to determine the association of angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism with the risk of hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and restrictive cardiomyopathy (RCM).......The study was carried to determine the association of angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism with the risk of hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and restrictive cardiomyopathy (RCM)....

  19. Gene-Targeted Mice with the Human Troponin T R141W Mutation Develop Dilated Cardiomyopathy with Calcium Desensitization.

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    Mohun Ramratnam

    Full Text Available Most studies of the mechanisms leading to hereditary dilated cardiomyopathy (DCM have been performed in reconstituted in vitro systems. Genetically engineered murine models offer the opportunity to dissect these mechanisms in vivo. We generated a gene-targeted knock-in murine model of the autosomal dominant Arg141Trp (R141W mutation in Tnnt2, which was first described in a human family with DCM. Mice heterozygous for the mutation (Tnnt2R141W/+ recapitulated the human phenotype, developing left ventricular dilation and reduced contractility. There was a gene dosage effect, so that the phenotype in Tnnt2R141W/+mice was attenuated by transgenic overexpression of wildtype Tnnt2 mRNA transcript. Male mice exhibited poorer survival than females. Biomechanical studies on skinned fibers from Tnnt2R141W/+ hearts showed a significant decrease in pCa50 (-log[Ca2+] required for generation of 50% of maximal force relative to wildtype hearts, indicating Ca2+ desensitization. Optical mapping studies of Langendorff-perfused Tnnt2R141W/+ hearts showed marked increases in diastolic and peak systolic intracellular Ca2+ ([Ca2+]i, and prolonged systolic rise and diastolic fall of [Ca2+]i. Perfused Tnnt2R141W/+ hearts had slower intrinsic rates in sinus rhythm and reduced peak heart rates in response to isoproterenol. Tnnt2R141W/+ hearts exhibited a reduction in phosphorylated phospholamban relative to wildtype mice. However, crossing Tnnt2R141W/+ mice with phospholamban knockout (Pln-/- mice, which exhibit increased Ca2+ transients and contractility, had no effect on the DCM phenotype. We conclude that the Tnnt2 R141W mutation causes a Ca2+ desensitization and mice adapt by increasing Ca2+-transient amplitudes, which impairs Ca2+ handling dynamics, metabolism and responses to β-adrenergic activation.

  20. Histologic characterization of canine dilated cardiomyopathy.

    Science.gov (United States)

    Tidholm, A; Jönsson, L

    2005-01-01

    Dilated cardiomyopathy (DCM), characterized by chamber dilatation and myocardial systolic and diastolic dysfunction, is one of the most common heart diseases in dogs. The clinical diagnosis is based on findings on echocardiographic and Doppler examinations, with the active exclusion of other acquired or congenital heart diseases. However, the echocardiographic criteria for the diagnosis of DCM are not wholly specific for the disease, and histologic examination may be necessary for final diagnosis. Review of reports on histologic findings in dogs with clinically diagnosed DCM reveals two histologically distinct forms of DCM: 1) cardiomyopathy of Boxers and Doberman Pinschers, corresponding to the "fatty infiltration-degenerative" type and 2) the form seen in many giant, large-, and medium-sized breeds, including some Boxers and Doberman Pinschers, classified as the "attenuated wavy fiber" type of DCM. The histologic changes of the attenuated wavy fiber type of DCM may precede clinical and echocardiographic signs of heart disease, thus indicating an early stage of DCM.

  1. Frequency and clinical genetics of familial dilated cardiomyopathy in ...

    African Journals Online (AJOL)

    Frequency and clinical genetics of familial dilated cardiomyopathy in Cape Town: Implications for the evaluation of patients with unexplained cardiomyopathy. NBA Ntusi, A Wonkam, G Shaboodien, M Badri, BM Mayosi ...

  2. Multiple Species Comparison of Cardiac Troponin T and Dystrophin: Unravelling the DNA behind Dilated Cardiomyopathy

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    Jennifer England

    2017-07-01

    Full Text Available Animals have frequently been used as models for human disorders and mutations. Following advances in genetic testing and treatment options, and the decreasing cost of these technologies in the clinic, mutations in both companion and commercial animals are now being investigated. A recent review highlighted the genes associated with both human and non-human dilated cardiomyopathy. Cardiac troponin T and dystrophin were observed to be associated with both human and turkey (troponin T and canine (dystrophin dilated cardiomyopathies. This review gives an overview of the work carried out in cardiac troponin T and dystrophin to date in both human and animal dilated cardiomyopathy.

  3. Multiple Species Comparison of Cardiac Troponin T and Dystrophin: Unravelling the DNA behind Dilated Cardiomyopathy.

    Science.gov (United States)

    England, Jennifer; Loughna, Siobhan; Rutland, Catrin Sian

    2017-07-07

    Animals have frequently been used as models for human disorders and mutations. Following advances in genetic testing and treatment options, and the decreasing cost of these technologies in the clinic, mutations in both companion and commercial animals are now being investigated. A recent review highlighted the genes associated with both human and non-human dilated cardiomyopathy. Cardiac troponin T and dystrophin were observed to be associated with both human and turkey (troponin T) and canine (dystrophin) dilated cardiomyopathies. This review gives an overview of the work carried out in cardiac troponin T and dystrophin to date in both human and animal dilated cardiomyopathy.

  4. Intramuscular injection of human umbilical cord-derived mesenchymal stem cells improves cardiac function in dilated cardiomyopathy rats.

    Science.gov (United States)

    Mao, Chenggang; Hou, Xu; Wang, Benzhen; Chi, Jingwei; Jiang, Yanjie; Zhang, Caining; Li, Zipu

    2017-01-28

    Stem cells provide a promising candidate for the treatment of the fatal pediatric dilated cardiomyopathy (DCM). This study aimed to investigate the effects of intramuscular injection of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) on the cardiac function of a DCM rat model. A DCM model was established by intraperitoneal injections of doxorubicin in Sprague-Dawley rats. hUCMSCs at different concentrations or cultured medium were injected via limb skeletal muscles, with blank medium injected as the control. The rats were monitored for 4 weeks, meanwhile BNP, cTNI, VEGF, HGF, GM-CSF, and LIF in the peripheral blood were examined by ELISA, and cardiac function was monitored by echocardiography (Echo-CG). Finally, the expression of IGF-1, HGF, and VEGF in the myocardium was examined by histoimmunochemistry and real-time PCR, and the ultrastructure of the myocardium was examined by electron microscopy. Injection of hUCMSCs markedly improved cardiac function in the DCM rats by significantly elevating left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS). The BNP and cTNI levels in the peripheral blood were reduced by hUCMSCs, while HGF, LIF, GM-CSF, and VEGF were increased by hUCMSCs. Expression of IGF-1, HGF, and VEGF in the myocardium from the DCM rats was significantly increased by hUCMSC injection. Furthermore, hUCMSCs protected the ultrastructure of cardiomyocytes by attenuating mitochondrial swelling and maintaining sarcolemma integrity. Intramuscular injection of UCMSCs can improve DCM-induced cardiac function impairment and protect the myocardium. These effects may be mediated by regulation of relevant cytokines in serum and the myocardium.

  5. Characterization of phosphorus metabolism in dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Auffermann, W.; Chew, W.; Tavares, N.J.; Donnelly, T.; Parmley, W.W.; Chatterjee, K.; Wolfe, C.; Higgins, C.B.

    1988-01-01

    Five patients with dilated cardiomyopathy (ejection fraction, ∼25%) and six normal volunteers were studied with localized, gated P-31 MR spectroscopy at 1.5 T. The typical peaks of adenogine triphosphate (ATP[, phosphocreatine (PCr), phosphodiesters (PD), and peaks attributable to 2,3 diphosphoglycerate, inorganic phosphate, and phosphomonoesters were identified and the areas under each peak numerically integrated after baseline correction. PCr/β-ATP was not significantly lower (1.42 +- 0.06 vs 1.54 +- 0.04), but PD/PCr (1.1 +- 0.02 vs 0.6 +- 0.1) (P ≤ .01) and PD/β-ATP (1.50 +- 0.04 vs 0.97 +- 0.17) (P ≤ .05) were significantly higher in patients with dilated cardiomyopathy compared with normal volunteers. Thus, localized, gated P-31 MR spectroscopy in cardiomyopathic patients identifies abnormal myocardial phosphorus metabolism, which might become useful to monitor noninvasively the response to positive inotropic therapy

  6. Dilated congestive cardiomyopathy in Doberman pinschers

    International Nuclear Information System (INIS)

    Calvert, C.A.

    1986-01-01

    Dilated cardiomyopathy of Doberman Pinschers (DCDP) is a progressive disease often presenting with a history of episodic weakness and syncope, or with clinical signs of predominantly left-sided congestive heart failure. A systematic dissection and histomorphologic evaluation of the heart from 32 Doberman Pinschers with a clinical diagnosis of dilated cardiomyopathy revealed a highly specific location for the characteristic myocardial lesions. The lesions of DCDP were found only in the left ventricular free wall, and in 30 cases, the lesions were characterized by myofiber degeneration and atrophy, and replacement of myocardium by dense bundles of collagen and clusters of adipocytes. In the two remaining hearts, myofiber atrophy and degeneration were accompanied by collagen deposition, but not adipocytes. In stained longitudinal (base to apex) tissue sections of the left ventricle, the lesions of DCDP were usually apparent to the unaided eye; appearing as a central linear pale zone, aligned in the long axis of the ventricular free wall. The lesions did not contain inflammatory cell infiltrates and often involved >50% of ventricular wall

  7. Oxidative Stress in Dilated Cardiomyopathy Caused by MYBPC3 Mutation

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    Thomas L. Lynch

    2015-01-01

    Full Text Available Cardiomyopathies can result from mutations in genes encoding sarcomere proteins including MYBPC3, which encodes cardiac myosin binding protein-C (cMyBP-C. However, whether oxidative stress is augmented due to contractile dysfunction and cardiomyocyte damage in MYBPC3-mutated cardiomyopathies has not been elucidated. To determine whether oxidative stress markers were elevated in MYBPC3-mutated cardiomyopathies, a previously characterized 3-month-old mouse model of dilated cardiomyopathy (DCM expressing a homozygous MYBPC3 mutation (cMyBP-C(t/t was used, compared to wild-type (WT mice. Echocardiography confirmed decreased percentage of fractional shortening in DCM versus WT hearts. Histopathological analysis indicated a significant increase in myocardial disarray and fibrosis while the second harmonic generation imaging revealed disorganized sarcomeric structure and myocyte damage in DCM hearts when compared to WT hearts. Intriguingly, DCM mouse heart homogenates had decreased glutathione (GSH/GSSG ratio and increased protein carbonyl and lipid malondialdehyde content compared to WT heart homogenates, consistent with elevated oxidative stress. Importantly, a similar result was observed in human cardiomyopathy heart homogenate samples. These results were further supported by reduced signals for mitochondrial semiquinone radicals and Fe-S clusters in DCM mouse hearts measured using electron paramagnetic resonance spectroscopy. In conclusion, we demonstrate elevated oxidative stress in MYPBC3-mutated DCM mice, which may exacerbate the development of heart failure.

  8. Significance of thymosin β4 and implication of PINCH-1-ILK-α-parvin (PIP complex in human dilated cardiomyopathy.

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    Nikolai Sopko

    Full Text Available Myocardial remodeling is a major contributor in the development of heart failure (HF after myocardial infarction (MI. Integrin-linked kinase (ILK, LIM-only adaptor PINCH-1, and α-parvin are essential components of focal adhesions (FAs, which are highly expressed in the heart. ILK binds tightly to PINCH-1 and α-parvin, which regulates FA assembly and promotes cell survival via the activation of the kinase Akt. Mice lacking ILK, PINCH or α-parvin have been shown to develop severe defects in the heart, suggesting that these proteins play a critical role in heart function. Utilizing failing human heart tissues (dilated cardiomyopathy, DCM, we found a 2.27-fold (p<0.001 enhanced expression of PINCH, 4 fold for α-parvin, and 10.5 fold (p<0.001 for ILK as compared to non-failing (NF counterparts. No significant enhancements were found for the PINCH isoform PINCH-2 and parvin isoform β-parvin. Using a co-immunoprecipitation method, we also found that the PINCH-1-ILK-α-parvin (PIP complex and Akt activation were significantly up-regulated. These observations were further corroborated with the mouse myocardial infarction (MI and transaortic constriction (TAC model. Thymosin beta4 (Tβ4, an effective cell penetrating peptide for treating MI, was found to further enhance the level of PIP components and Akt activation, while substantially suppressing NF-κB activation and collagen expression--the hallmarks of cardiac fibrosis. In the presence of an Akt inhibitor, wortmannin, we show that Tβ4 had a decreased effect in protecting the heart from MI. These data suggest that the PIP complex and activation of Akt play critical roles in HF development. Tβ4 treatment likely improves cardiac function by enhancing PIP mediated Akt activation and suppressing NF-κB activation and collagen-mediated fibrosis. These data provide significant insight into the role of the PIP-Akt pathway and its regulation by Tβ4 treatment in post-MI.

  9. Cushing’s Disease Presented by Reversible Dilated Cardiomyopathy

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    Berna İmge Aydoğan

    2015-01-01

    Full Text Available Introduction. Dilated cardiomyopathy is rarely reported among CS patients especially without hypertension and left ventricular hypertrophy. Materials and Methods. We hereby report a Cushing’s syndrome case presenting with dilated cardiomyopathy. Results. A 48-year-old female patient was admitted to our clinic with severe proximal myopathy and dilated cardiomyopathy without ventricular hypertrophy. Cushing’s disease was diagnosed and magnetic-resonance imaging of the pituitary gland revealed a microadenoma. Under diuretic and ketoconazole treatments, she underwent a successful transnasal/transsphenoidal adenomectomy procedure. Full recovery of symptoms and echocardiographic features was achieved after six months of surgery. Conclusion. Cushing’s syndrome must be kept in mind as a reversible cause of dilated cardiomyopathy. Recovery of cardiomyopathy is achieved with successful surgery.

  10. Modeling Treatment Response for Lamin A/C Related Dilated Cardiomyopathy in Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Lee, Yee-Ki; Lau, Yee-Man; Cai, Zhu-Jun; Lai, Wing-Hon; Wong, Lai-Yung; Tse, Hung-Fat; Ng, Kwong-Man; Siu, Chung-Wah

    2017-07-28

    Precision medicine is an emerging approach to disease treatment and prevention that takes into account individual variability in the environment, lifestyle, and genetic makeup of patients. Patient-specific human induced pluripotent stem cells hold promise to transform precision medicine into real-life clinical practice. Lamin A/C (LMNA)-related cardiomyopathy is the most common inherited cardiomyopathy in which a substantial proportion of mutations in the LMNA gene are of nonsense mutation. PTC124 induces translational read-through over the premature stop codon and restores production of the full-length proteins from the affected genes. In this study we generated human induced pluripotent stem cells-derived cardiomyocytes from patients who harbored different LMNA mutations (nonsense and frameshift) to evaluate the potential therapeutic effects of PTC124 in LMNA -related cardiomyopathy. We generated human induced pluripotent stem cells lines from 3 patients who carried distinctive mutations (R225X, Q354X, and T518fs) in the LMNA gene. The cardiomyocytes derived from these human induced pluripotent stem cells lines reproduced the pathophysiological hallmarks of LMNA -related cardiomyopathy. Interestingly, PTC124 treatment increased the production of full-length LMNA proteins in only the R225X mutant, not in other mutations. Functional evaluation experiments on the R225X mutant further demonstrated that PTC124 treatment not only reduced nuclear blebbing and electrical stress-induced apoptosis but also improved the excitation-contraction coupling of the affected cardiomyocytes. Using cardiomyocytes derived from human induced pluripotent stem cells carrying different LMNA mutations, we demonstrated that the effect of PTC124 is codon selective. A premature stop codon UGA appeared to be most responsive to PTC124 treatment. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  11. Dilated cardiomyopathy in cats - A case report

    Directory of Open Access Journals (Sweden)

    K. Jeyaraja

    2013-08-01

    Full Text Available Two cats were brought to Madras Veterinary College Teaching Hospital with the history and clinical signs suggestive of congestive heart failure ie, coughing, exercise intolerance, dyspnea, abdominal distension etc. There was history of feeding the cat with home made diet in one case and in other with commercial dog food. Based on electrocardiographic, radiographic and echocardiographic findings, the diagnosis of dilated cardiomyopathy was done in both the cases. The cases were managed with enalapril maleate, furosemide, dietary taurine supplementation and other supportive therapy. Among these two cases, one cat died on 2nd day of treatment and the other showed recovery after 8 days of treatment. [Vet World 2013; 6(4.000: 226-227

  12. A Case Report of Reversible Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Abhishek Singhai

    2014-01-01

    Full Text Available Dilated cardiomyopathy (DCM is mostly an idiopathic disease with a progressive and irreversible course. It carries poor prognosis and outcome. Rarely, a reversible metabolic etiology that is amenable to specific therapy is identified. Alteration in thyroid status can lead to changes in systolic and diastolic function of left ventricle. Heart is sensitive to thyroid hormone changes, and cardiac disorders are commonly associated with both hyper and hypothyroidism. Diastolic dysfunction is the most common abnormality reported in hypothyroidism. In systolic function, prolonged systolic time interval or normal cardiac function has been reported by most workers. DCM is a rare presentation of hypothyroidism. Here, we report a case of 40-year-old female diagnosed with DCM due to hypothyroidism

  13. The Mutations Associated with Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Ruti Parvari

    2012-01-01

    Full Text Available Cardiomyopathy is an important cause of heart failure and a major indication for heart transplantation in children and adults. This paper describes the state of the genetic knowledge of dilated cardiomyopathy (DCM. The identification of the causing mutation is important since presymptomatic interventions of DCM have proven value in preventing morbidity and mortality. Additionally, as in general in genetic studies, the identification of the mutated genes has a direct clinical impact for the families and population involved. Identifying causative mutations immediately amplifies the possibilities for disease prevention through carrier screening and prenatal testing. This often lifts a burden of social isolation from affected families, since healthy family members can be assured of having healthy children. Identification of the mutated genes holds the potential to lead to the understanding of disease etiology, pathophysiology, and therefore potential therapy. This paper presents the genetic variations, or disease-causing mutations, contributing to the pathogenesis of hereditary DCM, and tries to relate these to the functions of the mutated genes.

  14. Genetics Home Reference: X-linked dilated cardiomyopathy

    Science.gov (United States)

    ... The other conditions in the spectrum, Duchenne and Becker muscular dystrophy , are characterized by progressive weakness and wasting of ... linked dilated cardiomyopathy is sometimes classified as subclinical Becker muscular dystrophy. Related Information What does it mean if a ...

  15. Characterization and Long-Term Prognosis of Postmyocarditic Dilated Cardiomyopathy Compared With Idiopathic Dilated Cardiomyopathy.

    Science.gov (United States)

    Merlo, Marco; Anzini, Marco; Bussani, Rossana; Artico, Jessica; Barbati, Giulia; Stolfo, Davide; Gigli, Marta; Muça, Matilda; Naso, Paola; Ramani, Federica; Di Lenarda, Andrea; Pinamonti, Bruno; Sinagra, Gianfranco

    2016-09-15

    Dilated cardiomyopathy (DC) is the final common pathway of different pathogenetic processes and presents a significant prognostic heterogeneity, possibly related to its etiologic variety. The characterization and long-term prognosis of postmyocarditic dilated cardiomyopathy (PM-DC) remain unknown. This study assesses the clinical-instrumental evolution and long-term prognosis of a large cohort of patients with PM-DC. We analyzed 175 patients affected with DC consecutively enrolled from 1993 to 2008 with endomyocardial biopsy (EMB) data available. PM-DC was defined in the presence of borderline myocarditis at EMB or persistent left ventricular dysfunction 1 year after diagnosis of active myocarditis at EMB. Other patients were defined as affected by idiopathic dilated cardiomyopathy (IDC). Analysis of follow-up evaluations was performed at 24, 60, and 120 months. We found 72 PM-DC of 175 enrolled patients (41%). Compared with IDC, patients with PM-DC were more frequently females and less frequently presented a familial history of DC. No other baseline significant differences were found. During the long-term follow-up (median 154, first to third interquartile range 78 to 220 months), patients with PM-DC showed a trend toward slower disease progression. Globally, 18 patients with PM-DC (25%) versus 49 with IDC (48%) experienced death/heart transplantation (p = 0.045). The prognostic advantage for patients with PM-DC became significant beyond 40 months of follow-up. At multivariable time-dependent Cox analysis, PM-DC was confirmed to have a global independent protective role (hazard ratio 0.53, 95% confidence interval 0.28 to 0.97, p = 0.04). In conclusion, PM-DC is characterized by better long-term prognosis compared with IDC. An exhaustive etiologic characterization appears relevant in the prognostic assessment of DC. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Intraventricular vortex properties in nonischemic dilated cardiomyopathy

    Science.gov (United States)

    Benito, Yolanda; Alhama, Marta; Yotti, Raquel; Martínez-Legazpi, Pablo; del Villar, Candelas Pérez; Pérez-David, Esther; González-Mansilla, Ana; Santa-Marta, Cristina; Barrio, Alicia; Fernández-Avilés, Francisco; del Álamo, Juan C.

    2014-01-01

    Vortices may have a role in optimizing the mechanical efficiency and blood mixing of the left ventricle (LV). We aimed to characterize the size, position, circulation, and kinetic energy (KE) of LV main vortex cores in patients with nonischemic dilated cardiomyopathy (NIDCM) and analyze their physiological correlates. We used digital processing of color-Doppler images to study flow evolution in 61 patients with NIDCM and 61 age-matched control subjects. Vortex features showed a characteristic biphasic temporal course during diastole. Because late filling contributed significantly to flow entrainment, vortex KE reached its maximum at the time of the peak A wave, storing 26 ± 20% of total KE delivered by inflow (range: 1–74%). Patients with NIDCM showed larger and stronger vortices than control subjects (circulation: 0.008 ± 0.007 vs. 0.006 ± 0.005 m2/s, respectively, P = 0.02; KE: 7 ± 8 vs. 5 ± 5 mJ/m, P = 0.04), even when corrected for LV size. This helped confining the filling jet in the dilated ventricle. The vortex Reynolds number was also higher in the NIDCM group. By multivariate analysis, vortex KE was related to the KE generated by inflow and to chamber short-axis diameter. In 21 patients studied head to head, Doppler measurements of circulation and KE closely correlated with phase-contract magnetic resonance values (intraclass correlation coefficient = 0.82 and 0.76, respectively). Thus, the biphasic nature of filling determines normal vortex physiology. Vortex formation is exaggerated in patients with NIDCM due to chamber remodeling, and enlarged vortices are helpful for ameliorating convective pressure losses and facilitating transport. These findings can be accurately studied using ultrasound. PMID:24414062

  17. Characteristic adaptations of the extracellular matrix in dilated cardiomyopathy

    NARCIS (Netherlands)

    Louzao-Martinez, Laura; Vink, Aryan; Harakalova, Magdalena; Asselbergs, Folkert W; Verhaar, Marianne C; Cheng, Caroline

    2016-01-01

    Dilated cardiomyopathy (DCM) is a relatively common heart muscle disease characterized by the dilation and thinning of the left ventricle accompanied with left ventricular systolic dysfunction. Myocardial fibrosis is a major feature in DCM and therefore it is inevitable that corresponding

  18. Molecular genetics of dilated cardiomyopathy in the Dobermann dog

    NARCIS (Netherlands)

    Stabej, Polona

    2005-01-01

    Canine dilated cardiomyopathy (DCM) is a disease of the myocardium associated with dilatation and impaired contraction of the ventricles. It primarily affects large and giant breed dogs with Dobermanns being one of the most frequently affected. The high prevalence of DCM in specific breeds suggests

  19. Multiple Genetic Associations with Irish Wolfhound Dilated Cardiomyopathy.

    Science.gov (United States)

    Simpson, Siobhan; Dunning, Mark D; Brownlie, Serena; Patel, Janika; Godden, Megan; Cobb, Malcolm; Mongan, Nigel P; Rutland, Catrin S

    2016-01-01

    Cardiac disease is a leading cause of morbidity and mortality in dogs and humans, with dilated cardiomyopathy being a large contributor to this. The Irish Wolfhound (IWH) is one of the most commonly affected breeds and one of the few breeds with genetic loci associated with the disease. Mutations in more than 50 genes are associated with human dilated cardiomyopathy (DCM), yet very few are also associated with canine DCM. Furthermore, none of the identified canine loci explain many cases of the disease and previous work has indicated that genotypes at multiple loci may act together to influence disease development. In this study, loci previously associated with DCM in IWH were tested for associations in a new cohort both individually and in combination. We have identified loci significantly associated with the disease individually, but no genotypes individually or in pairs conferred a significantly greater risk of developing DCM than the population risk. However combining three loci together did result in the identification of a genotype which conferred a greater risk of disease than the overall population risk. This study suggests multiple rather than individual genetic factors, cooperating to influence DCM risk in IWH.

  20. Multiple Genetic Associations with Irish Wolfhound Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Siobhan Simpson

    2016-01-01

    Full Text Available Cardiac disease is a leading cause of morbidity and mortality in dogs and humans, with dilated cardiomyopathy being a large contributor to this. The Irish Wolfhound (IWH is one of the most commonly affected breeds and one of the few breeds with genetic loci associated with the disease. Mutations in more than 50 genes are associated with human dilated cardiomyopathy (DCM, yet very few are also associated with canine DCM. Furthermore, none of the identified canine loci explain many cases of the disease and previous work has indicated that genotypes at multiple loci may act together to influence disease development. In this study, loci previously associated with DCM in IWH were tested for associations in a new cohort both individually and in combination. We have identified loci significantly associated with the disease individually, but no genotypes individually or in pairs conferred a significantly greater risk of developing DCM than the population risk. However combining three loci together did result in the identification of a genotype which conferred a greater risk of disease than the overall population risk. This study suggests multiple rather than individual genetic factors, cooperating to influence DCM risk in IWH.

  1. Titin gene mutations are common in families with both peripartum cardiomyopathy and dilated cardiomyopathy

    NARCIS (Netherlands)

    van Spaendonck-Zwarts, Karin Y.; Posafalvi, Anna; van den Berg, Maarten P.; Hilfiker-Kleiner, Denise; Bollen, Ilse A. E.; Sliwa, Karen; Alders, Marielle; AlMomani, Rowida; van Langen, Irene M.; van der Meer, Peter; Sinke, Richard J.; van der Velden, Jolanda; Van Veldhuisen, Dirk J.; van Tintelen, J. Peter; Jongbloed, Jan D. H.

    2014-01-01

    Aim Peripartum cardiomyopathy (PPCM) can be an initial manifestation of familial dilated cardiomyopathy (DCM). We aimed to identify mutations in families that could underlie their PPCM and DCM. Methods and results We collected 18 families with PPCM and DCM cases from various countries. We studied

  2. Titin gene mutations are common in families with both peripartum cardiomyopathy and dilated cardiomyopathy

    NARCIS (Netherlands)

    van Spaendonck-Zwarts, Karin Y.; Posafalvi, Anna; van den Berg, Maarten P.; Hilfiker-Kleiner, Denise; Bollen, Ilse A. E.; Sliwa, Karen; Alders, Mariëlle; Almomani, Rowida; van Langen, Irene M.; van der Meer, Peter; Sinke, Richard J.; van der Velden, Jolanda; van Veldhuisen, Dirk J.; van Tintelen, J. Peter; Jongbloed, Jan D. H.

    2014-01-01

    Peripartum cardiomyopathy (PPCM) can be an initial manifestation of familial dilated cardiomyopathy (DCM). We aimed to identify mutations in families that could underlie their PPCM and DCM. We collected 18 families with PPCM and DCM cases from various countries. We studied the clinical

  3. Dilated cardiomyopathy and severe heart failure. An update for pediatricians.

    Science.gov (United States)

    Caviedes Bottner, Paola; Córdova Fernández, Tamara; Larraín Valenzuela, Marcos; Cruces Romero Presentación de Casos Clínicos, Pablo

    2018-06-01

    Dilated cardiomyopathy is the main cause of heart failure leading to heart transplant. Its prognosis is variable and depends on the etiology, the patient's age at onset, and the severity. The management of dilated cardiomyopathy is aimed at minimizing symptoms and preventing disease progression; it requires a comprehensive screening for comorbidities and the prevention of complications to improve the overall status of these children and mitigate their prognosis. Here we present a review oriented at the multidisciplinary management that pediatricians should consider when seeing these patients. Sociedad Argentina de Pediatría.

  4. A Rare Occurance with Epidermolysis Bullosa Disease: Dilated Cardiomyopathy

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    Derya Cimen

    2014-02-01

    Full Text Available Epidermolysis bullosa is a congenital and herediter vesiculobullous disease. Dystrophic form of this disease is characterized by severe malnutrition, failure to thrive, adhesions at fingers, joint contractures related with the formation of scar tissues, carcinoma of the skin, anemia, hipoalbuminemia, wound enfections and sepsis. Rarely, mortal dilated cardiomyopathy may occur in patients. In this report we present a 13 year-old pediatric patient with dilated cardiomyopathy, clinically diagnosed with Epidermolysis bullosa as well as a review of recent related literature.

  5. A negative screen for mutations in calstabin 1 and 2 genes in patients with dilated cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Biagi Diogo G

    2012-01-01

    Full Text Available Abstract Background Calstabins 1 and 2 bind to Ryanodine receptors regulating muscle excitation-contraction coupling. Mutations in Ryanodine receptors affecting their interaction with calstabins lead to different cardiac pathologies. Animal studies suggest the involvement of calstabins with dilated cardiomyopathy. Results We tested the hypothesis that calstabins mutations may cause dilated cardiomyopathy in humans screening 186 patients with idiopathic dilated cardiomyopathy for genetic alterations in calstabins 1 and 2 genes (FKBP12 and FKBP12.6. No missense variant was found. Five no-coding variations were found but not related to the disease. Conclusions These data corroborate other studies suggesting that mutations in FKBP12 and FKBP12.6 genes are not commonly related to cardiac diseases.

  6. Canine candidate genes for dilated cardiomyopathy: annotation of and polymorphic markers for 14 genes

    Directory of Open Access Journals (Sweden)

    van Oost Bernard A

    2007-10-01

    Full Text Available Abstract Background Dilated cardiomyopathy is a myocardial disease occurring in humans and domestic animals and is characterized by dilatation of the left ventricle, reduced systolic function and increased sphericity of the left ventricle. Dilated cardiomyopathy has been observed in several, mostly large and giant, dog breeds, such as the Dobermann and the Great Dane. A number of genes have been identified, which are associated with dilated cardiomyopathy in the human, mouse and hamster. These genes mainly encode structural proteins of the cardiac myocyte. Results We present the annotation of, and marker development for, 14 of these genes of the dog genome, i.e. α-cardiac actin, caveolin 1, cysteine-rich protein 3, desmin, lamin A/C, LIM-domain binding factor 3, myosin heavy polypeptide 7, phospholamban, sarcoglycan δ, titin cap, α-tropomyosin, troponin I, troponin T and vinculin. A total of 33 Single Nucleotide Polymorphisms were identified for these canine genes and 11 polymorphic microsatellite repeats were developed. Conclusion The presented polymorphisms provide a tool to investigate the role of the corresponding genes in canine Dilated Cardiomyopathy by linkage analysis or association studies.

  7. Canine candidate genes for dilated cardiomyopathy: annotation of and polymorphic markers for 14 genes.

    Science.gov (United States)

    Wiersma, Anje C; Leegwater, Peter Aj; van Oost, Bernard A; Ollier, William E; Dukes-McEwan, Joanna

    2007-10-19

    Dilated cardiomyopathy is a myocardial disease occurring in humans and domestic animals and is characterized by dilatation of the left ventricle, reduced systolic function and increased sphericity of the left ventricle. Dilated cardiomyopathy has been observed in several, mostly large and giant, dog breeds, such as the Dobermann and the Great Dane. A number of genes have been identified, which are associated with dilated cardiomyopathy in the human, mouse and hamster. These genes mainly encode structural proteins of the cardiac myocyte. We present the annotation of, and marker development for, 14 of these genes of the dog genome, i.e. alpha-cardiac actin, caveolin 1, cysteine-rich protein 3, desmin, lamin A/C, LIM-domain binding factor 3, myosin heavy polypeptide 7, phospholamban, sarcoglycan delta, titin cap, alpha-tropomyosin, troponin I, troponin T and vinculin. A total of 33 Single Nucleotide Polymorphisms were identified for these canine genes and 11 polymorphic microsatellite repeats were developed. The presented polymorphisms provide a tool to investigate the role of the corresponding genes in canine Dilated Cardiomyopathy by linkage analysis or association studies.

  8. Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice

    DEFF Research Database (Denmark)

    Pinto, Yigal M; Elliott, Perry M; Arbustini, Eloisa

    2016-01-01

    In this paper the Working Group on Myocardial and Pericardial Disease proposes a revised definition of dilated cardiomyopathy (DCM) in an attempt to bridge the gap between our recent understanding of the disease spectrum and its clinical presentation in relatives, which is key for early diagnosis...

  9. Idiopathic dilated cardiomyopathy: computerized anatomic study of relashionship between septal and free left ventricle wall.

    Science.gov (United States)

    Juliani, Paulo Sérgio; Costa, Eder França da; Correia, Aristides Tadeu; Monteiro, Rosangela; Jatene, Fabio Biscegli

    2014-01-01

    A feature of dilated cardiomyopathy is the deformation of ventricular cavity, which contributes to systolic dysfunction. Few studies have evaluated this deformation bearing in mind ventricular regions and segments of the ventricle, which could reveal important details of the remodeling process, supporting a better understanding of its role in functional impairment and the development of new therapeutic strategies. To evaluate if, in basal, equatorial and apical regions, increased internal transverse perimeter of left ventricle in idiopathic dilated cardiomyopathy occurs proportionally between the septal and non-septal segment. We performed an anatomical study with 28 adult hearts from human cadavers. One group consisted of 18 hearts with idiopathic dilated cardiomyopathy and another group with 10 normal hearts. After lamination and left ventricle digital image capture, in three different regions (base, equator and apex), the transversal internal perimeter of left ventricle was divided into two segments: septal and not septal. These segments were measured by proper software. It was established an index of proportionality between these segments, called septal and non-septal segment index. Then we determined whether this index was the same in both groups. Among patients with normal hearts and idiopathic dilated cardiomyopathy, the index of proportionality between the two segments (septal and non-septal) showed no significant difference in the three regions analyzed. The comparison results of the indices NSS/SS among normal and enlarged hearts were respectively: in base 1.99 versus 1.86 (P=0.46), in equator 2.22 versus 2.18 (P=0.79) and in apex 2.96 versus 3.56 (P=0.11). In the idiopathic dilated cardiomyopathy, the transversal dilatation of left ventricular internal perimeter occurs proportionally between the segments corresponding to the septum and free wall at the basal, equatorial and apical regions of this chamber.

  10. Multiple species comparison of cardiac troponin T and dystrophin: unravelling the DNA behind dilated cardiomyopathy

    OpenAIRE

    England, Jennifer; Loughna, Siobhan; Rutland, Catrin S.

    2017-01-01

    Animals have frequently been used as models for human disorders and mutations. Following advances in genetic testing and treatment options, and the decreasing cost of these technologies in the clinic, mutations in both companion and commercial animals are now being investigated. A recent review highlighted the genes associated with both human and non-human dilated cardiomyopathy. Cardiac troponin T and dystrophin were observed to be associated with both human and turkey (troponin T) and canin...

  11. Superior vena thrombosis with peripartum dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Munir, R.; Hussain, S.; Kayani, A.M.

    2014-01-01

    A 30 years multiparous female with history of emergency caesarean section 10 days back was referred to us with cough, severe breathlessness at rest, orthopnea with pain in neck and arms. Clinical examination revealed signs of heart failure. Echocardiography showed ejection fraction of 15%, with no right ventricular strain. A diagnosis of peripartum cardiomyopathy was made. Doppler ultrasound of neck veins showed bilateral internal jugular vein thrombosis. Subsequent multislice CT examination showed thrombosis of superior vena cava and both internal jugular veins (with collateral formation) and pulmonary embolism. There were no mediastinal abnormalities on the CT scan. Her thrombophilia screen and CT scan brain was normal. She was managed in collaboration with cardiologist. Following treatment with subcutaneous enoxaparin therapy and warfarin her symptoms of upper limb pain improved. She responded very well to medical therapy for heart failure with marked improvement of NYHA functional class. (author)

  12. A novel locus for dilated cardiomyopathy maps to canine chromosome 8.

    Science.gov (United States)

    Werner, Petra; Raducha, Michael G; Prociuk, Ulana; Sleeper, Meg M; Van Winkle, Thomas J; Henthorn, Paula S

    2008-06-01

    Dilated cardiomyopathy (DCM), the most common form of cardiomyopathy, often leads to heart failure and sudden death. While a substantial proportion of DCMs are inherited, mutations responsible for the majority of DCMs remain unidentified. A genome-wide linkage study was performed to identify the locus responsible for an autosomal recessive inherited form of juvenile DCM (JDCM) in Portuguese water dogs using 16 families segregating the disease. Results link the JDCM locus to canine chromosome 8 with two-point and multipoint lod scores of 10.8 and 14, respectively. The locus maps to a 3.9-Mb region, with complete syntenic homology to human chromosome 14, that contains no genes or loci known to be involved in the development of any type of cardiomyopathy. This discovery of a DCM locus with a previously unknown etiology will provide a new gene to examine in human DCM patients and a model for testing therapeutic approaches for heart failure.

  13. Dilated cardiomyopathy as part of familial dystrophia myotonica

    DEFF Research Database (Denmark)

    Gadgaard, Tenna; Eiskjær, Hans; Jensen, Peter Kjestrup Axel

    2014-01-01

    Dilated cardiomyopathy (DCM) is a condition characterized by non-ischaemic heart failure and is often hereditary. We present a family in which the proband had DCM in isolation while several relatives presented with myotonia, hypotonia, poly-hydramnion during pregnancy or a mental handicap....... The disease presentation and subsequent genetic investigations were consistent with a diagnosis of dystrophia myotonica. This case presentation illustrate that DCM may be part of a systemic condition and that familial investigations may have important implications for correct diagnosis, treatment...

  14. A Family History of Dilated Cardiomyopathy Induced by Viral Myocarditis

    Directory of Open Access Journals (Sweden)

    Thomas Cognet

    2012-01-01

    Full Text Available Myocarditis can lead to acute heart failure, cardiogenic shock, or sudden death and later, dilated cardiomyopathy (DCM with chronic heart failure. We report the cases of two DCM induced by acute and past myocarditis in the same family and expressed by its two main complications within few weeks: an hemodynamic presentation as a fulminant myocarditis rapidly leading to cardiac tranplantation and a rythmologic presentation as an electrical storm leading to catheter ablation of ventricular tachycardia. These cases ask the question of the family predisposition to viral myocarditis leading to DCM.

  15. FLNC Gene Splice Mutations Cause Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Rene L. Begay, BS

    2016-08-01

    Full Text Available A genetic etiology has been identified in 30% to 40% of dilated cardiomyopathy (DCM patients, yet only 50% of these cases are associated with a known causative gene variant. Thus, in order to understand the pathophysiology of DCM, it is necessary to identify and characterize additional genes. In this study, whole exome sequencing in combination with segregation analysis was used to identify mutations in a novel gene, filamin C (FLNC, resulting in a cardiac-restricted DCM pathology. Here we provide functional data via zebrafish studies and protein analysis to support a model implicating FLNC haploinsufficiency as a mechanism of DCM.

  16. OBSCN Mutations Associated with Dilated Cardiomyopathy and Haploinsufficiency.

    Directory of Open Access Journals (Sweden)

    Steven Marston

    Full Text Available Studies of the functional consequences of DCM-causing mutations have been limited to a few cases where patients with known mutations had heart transplants. To increase the number of potential tissue samples for direct investigation we performed whole exon sequencing of explanted heart muscle samples from 30 patients that had a diagnosis of familial dilated cardiomyopathy and screened for potentially disease-causing mutations in 58 HCM or DCM-related genes.We identified 5 potentially disease-causing OBSCN mutations in 4 samples; one sample had two OBSCN mutations and one mutation was judged to be not disease-related. Also identified were 6 truncating mutations in TTN, 3 mutations in MYH7, 2 in DSP and one each in TNNC1, TNNI3, MYOM1, VCL, GLA, PLB, TCAP, PKP2 and LAMA4. The mean level of obscurin mRNA was significantly greater and more variable in healthy donor samples than the DCM samples but did not correlate with OBSCN mutations. A single obscurin protein band was observed in human heart myofibrils with apparent mass 960 ± 60 kDa. The three samples with OBSCN mutations had significantly lower levels of obscurin immunoreactive material than DCM samples without OBSCN mutations (45±7, 48±3, and 72±6% of control level.Obscurin levels in DCM controls, donor heart and myectomy samples were the same.OBSCN mutations may result in the development of a DCM phenotype via haploinsufficiency. Mutations in the obscurin gene should be considered as a significant causal factor of DCM, alone or in concert with other mutations.

  17. In regard to the question of macroscopic differential diagnosis of alcoholic and dilated cardiomyopathy

    Directory of Open Access Journals (Sweden)

    O. V. Sokolova

    2014-01-01

    Full Text Available The differential diagnosis of alcoholic and dilated cardiomyopathy according to the macroscopic data is represented in the article. The identity of macroscopic changes of heart, related to alcoholic and dilated cardiomyopathy, cannot diagnose these diseases based on the macroscopic characteristics; especially if there are no other visceral manifestations typical for chronic alcoholism.

  18. Frequency and echocardiographic study of dilated cardiomyopathy in children presenting with cardiac failure

    International Nuclear Information System (INIS)

    Khan, M.A.; Mohammad, J.; Hussain, M.

    2004-01-01

    Objective: To evaluate the role of echocardiography in diagnosis of dilated cardiomyopathy as a cause of cardiac failure in children. Design: This was descriptive study. Children presenting with cardiac failure from indoor patients were selected and echocardiography along with chest X- ray, ECG, cardiac enzymes and ASO titre was performed in all patients. Subject: Fifty hospitalized patients with congestive heart failure were selected consecutively from hospitalized patients. Main Outcome: Role of echocardiography in the diagnosis of dilated cardiomyopathy in children presenting with cardiac failure. Results: Out of fifty patients admitted with cardiac failure 27 (54%) cases were found to be dilated cardiomyopathy while congenital heart disease, myocarditis and rheumatic heart disease were found in 12 (24%), 8 (16%) and 3 (6%) cases respectively. Conclusion: Dilated cardiomyopathy is an important cause of cardiac failure in children and echocardiography is an important tool to diagnose and differentiate dilated cardiomyopathy from other causes of cardiac failure. (author)

  19. Magnetic resonance imaging of dilated cardiomyopathy; MRT bei dilatativen Kardiomyopathien

    Energy Technology Data Exchange (ETDEWEB)

    D' Anastasi, M. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer Klinische Radiologie, Muenchen (Germany); Greif, M. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Medizinische Klinik und Poliklinik I, Muenchen (Germany); Reiser, M.F.; Theisen, D. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer Klinische Radiologie, Muenchen (Germany); Deutsches Zentrum fuer Herzkreislaufforschung (DZHK), Muenchen (Germany)

    2013-01-15

    Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy with a prevalence of 1 out of 2,500 in adults. Due to mild clinical symptoms in the early phase of the disease, the true prevalence is probably even much higher. Patients present with variable clinical symptoms ranging from mild systolic impairment of left ventricular function to congestive heart failure. Even sudden cardiac death may be the first clinical symptom of DCM. The severity of the disease is defined by the degree of impairment of global left ventricular function. Arrhythmias, such as ventricular or supraventricular tachycardia, atrioventricular (AV) block, ventricular extrasystole and atrial fibrillation are common cardiac manifestations of DCM. Magnetic resonance imaging (MRI) plays an important role in the exact quantification of functional impairment of both ventricles and in the evaluation of regional wall motion abnormalities. With its excellent ability for the assessment of myocardial structure, it is becoming increasingly more important for risk stratification and therapy guidance. (orig.) [German] Die dilatative Kardiomyopathie (DCM) ist die haeufigste Form der Kardiomyopathie mit einer Praevalenz von 1/2500 Erwachsenen. Aufgrund der zunaechst milden klinischen Symptomatik ist jedoch von einer relativ hohen Dunkelziffer auszugehen. Die klinische Praesentation ist variabel, die Schwere der Erkrankung wird vom Ausmass der systolischen Funktionseinschraenkung bestimmt. Herzrhythmusstoerungen, wie ventrikulaere oder supraventrikulaere Tachykardien, AV-Blockierungen, ventrikulaere Extrasystolen und Vorhofflimmern sind moegliche klinische Manifestationen. Bei manchen Patienten ist der ploetzliche Herztod die erste klinische Manifestation der Erkrankung. Die kardiale MRT spielt eine bedeutende Rolle fuer die Beurteilung des Ausmasses der ventrikulaeren Dilatation, Dysfunktion und fuer die Beurteilung regionaler Wandbewegungsstoerungen. Darueber hinaus kann sie zur Anwendung kommen

  20. Ethanol vapour induced dilated cardiomyopathy in chick embryos

    International Nuclear Information System (INIS)

    Kamran, K.; Khan, M.Y.; Minhas, L.A.

    2013-01-01

    Objective: To study the effects of ethanol vapour inhalation on the heart chambers of chick embryo. Methods: The case-control study was conducted at the College of Physicians and Surgeons Pakistan regional centre in Islamabad from January to October 2007. Both experimental and control groups were divided into three sub-groups each, based on the day of the sacrifice. Each group was dissected on day 7, day 10 and day 22 or hatching whichever was earlier. The experimental sub-groups sacrificed on day 7, day 10 and on hatching, were exposed to ethanol vapours till day 6, 9 and 9 of incubation respectively. The diameter of all 4 chambers was measured in experimental hearts and compared with age-matched controls. SPSS 10 was used for statistical analysis. Results: Ethanol vapour exposure caused widening of all heart chambers in the experimental chick embryos sacrificed on day 7 and day 10 compared to the controls. The chambers of newly hatched chick hearts showed dilatation in all the chambers except the left ventricle. Conclusion: Ethanol vapour exposure during development affects the heart, resulting in the widening of all heart chambers. The exposure is as dangerous as drinking alcohol. Alcohol vapour exposure during development leads to progressive dilatation in different heart chambers, producing dilated cardiomyopathy. (author)

  1. Epidemiology of cardiomyopathy - A clinical and genetic study of dilated cardiomyopathy: The EPOCH-D study

    Directory of Open Access Journals (Sweden)

    Soumi Das

    2015-01-01

    Full Text Available Background: Dilated Cardiomyopathy (DCM is a genetic disorder where a heterogeneous group of cardiac-muscles are involved and is characterized by ventricular dilatation, impaired systolic function, reduced myocardial contractility with left ventricular ejection fraction (LVEF less than 40%. Our study aims to report the Demographic, Clinical and Genetic profile of Indian Dilated Cardiomyopathy patients. Methodology: All patients were recruited with prior written informed consent and are of Indian origin. Results: In a total of 80 DCM patients, the prevalence was higher among males. In males, mean age of onset was comparatively less than females. In this cohort, 40% had familial inheritance. Sixty two percent of DCM patients belong to NYHA functional class II with ejection fraction (EF ranging between 21-30% and, around one third of the patients had atrial fibrillation (AF. Genetic screening revealed a novel splice site mutation LMNA (c.639+ G>C and a rare variant MYH7 (c.2769 C>T in a patient and insilico analysis of both variants suggested functional changes that were considered pathogenic. We report 3% and 4% occurance of variants, each in LMNA and MYH7, where as reported frequencies of these genes are 6% LMNA and 4% MYH7. Conclusions: DCM is often familial and all possible candidate genes should be screened to identify mutations. Such type of exercise may help in the identification of mechanistic pathways. Next generation sequencing platforms may play an important role in this respect in future.

  2. Chronic oral exposure to the aldehyde pollutant acrolein induces dilated cardiomyopathy

    Science.gov (United States)

    Ismahil, Mohamed Ameen; Hamid, Tariq; Haberzettl, Petra; Gu, Yan; Chandrasekar, Bysani; Srivastava, Sanjay; Bhatnagar, Aruni

    2011-01-01

    Environmental triggers of dilated cardiomyopathy are poorly understood. Acute exposure to acrolein, a ubiquitous aldehyde pollutant, impairs cardiac function and cardioprotective responses in mice. Here, we tested the hypothesis that chronic oral exposure to acrolein induces inflammation and cardiomyopathy. C57BL/6 mice were gavage-fed acrolein (1 mg/kg) or water (vehicle) daily for 48 days. The dose was chosen based on estimates of human daily unsaturated aldehyde consumption. Compared with vehicle-fed mice, acrolein-fed mice exhibited significant (P acrolein adduct formation indicative of physical translocation of ingested acrolein to the heart. Acrolein also induced myocyte hypertrophy (∼2.2-fold increased myocyte area, P acrolein-exposed hearts, along with upregulated gene expression of proinflammatory cytokines tumor necrosis factor-α and interleukin-1β. Long-term oral exposure to acrolein, at an amount within the range of human unsaturated aldehyde intake, induces a phenotype of dilated cardiomyopathy in the mouse. Human exposure to acrolein may have analogous effects and raise consideration of an environmental, aldehyde-mediated basis for heart failure. PMID:21908791

  3. Basal wall hypercontraction of Takotsubo cardiomyopathy in a patient who had been diagnosed with dilated cardiomyopathy: a case report.

    Science.gov (United States)

    Ichihara, Noboru; Fujita, Shuichi; Kanzaki, Yumiko; Fujisaka, Tomohiro; Ozeki, Michishige; Ishizaka, Nobukazu

    2017-12-12

    Takotsubo cardiomyopathy is characterized by the basal hypercontractility and apical ballooning of the left ventriculum and T-wave inversion in the electrocardiogram. It has been suggested that Takotsubo cardiomyopathy might underlie the pathogenesis of persistent cardiac dysfunction; however, few reports are present demonstrating the advent of Takotsubo cardiomyopathy in patients with idiopathic cardiomyopathy. A 64-year-old women was admitted due to dyspnea on effort and lower extremity edema. She had been diagnosed with idiopathic dilated cardiomyopathy 2.5 years before owing to the reduced left ventricular ejection fraction (24%), normal coronary artery, and interstitial fibrosis of the myocardial samples. On admission, her electrocardiogram showed giant negative T wave in II, III, aVF, and precordial leads. Echocardiography showed dyskinesis of the left ventricular apex and hypercontraction of the basal wall, which had not been observed in the previous examinations. Coronary angiography showed normal coronary arteries, and apical ballooning and basal hypercontractility was confirmed by left ventriculography. On day 15 of admission, contraction of apical wall was recovered, and basal hypercontraction was disappeared. The present case is the first report demonstrating appearance the transient basal wall hypercontraction along with the advent of Takotsubo cardiomyopathy in a patient diagnosed with dilated cardiomyopathy. Whether such findings are indicative of fair prognosis and have the utility of understanding the pathogenesis of dilated cardiomyopathy needs further investigation.

  4. Pathomorphological Changes of the Myocardium in Canine Dilated Cardiomyopathy (DCM

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    Janus Izabela

    2015-04-01

    Full Text Available The study was conducted on ventricular and atrial wall preparations from 11 dogs with clinically diagnosed dilated cardiomyopathy. After fixation, the specimens were stained with haematoxylin and eosin and Masson-Goldner trichrome technique. Parenchymal changes (fibrosis and fatty infiltration, vascular changes (congestion and coronary vessel wall hypertrophy, degenerative changes (loss of striation, changes in cardiomycyte and nuclei structure, and presence of inflammatory infiltrates (mononuclear and polynuclear were estimated. Complex histological changes in both ventricular and atrial muscles were shown. It was not determined whether the processes occurring in the myocardium have a primary character, or are a consequence of developing heart failure. Such issues will be put under further and more detailed examination.

  5. Analyzing gene expression profiles in dilated cardiomyopathy via bioinformatics methods.

    Science.gov (United States)

    Wang, Liming; Zhu, L; Luan, R; Wang, L; Fu, J; Wang, X; Sui, L

    2016-10-10

    Dilated cardiomyopathy (DCM) is characterized by ventricular dilatation, and it is a common cause of heart failure and cardiac transplantation. This study aimed to explore potential DCM-related genes and their underlying regulatory mechanism using methods of bioinformatics. The gene expression profiles of GSE3586 were downloaded from Gene Expression Omnibus database, including 15 normal samples and 13 DCM samples. The differentially expressed genes (DEGs) were identified between normal and DCM samples using Limma package in R language. Pathway enrichment analysis of DEGs was then performed. Meanwhile, the potential transcription factors (TFs) and microRNAs (miRNAs) of these DEGs were predicted based on their binding sequences. In addition, DEGs were mapped to the cMap database to find the potential small molecule drugs. A total of 4777 genes were identified as DEGs by comparing gene expression profiles between DCM and control samples. DEGs were significantly enriched in 26 pathways, such as lymphocyte TarBase pathway and androgen receptor signaling pathway. Furthermore, potential TFs (SP1, LEF1, and NFAT) were identified, as well as potential miRNAs (miR-9, miR-200 family, and miR-30 family). Additionally, small molecules like isoflupredone and trihexyphenidyl were found to be potential therapeutic drugs for DCM. The identified DEGs (PRSS12 and FOXG1), potential TFs, as well as potential miRNAs, might be involved in DCM.

  6. Analyzing gene expression profiles in dilated cardiomyopathy via bioinformatics methods

    Directory of Open Access Journals (Sweden)

    Liming Wang

    Full Text Available Dilated cardiomyopathy (DCM is characterized by ventricular dilatation, and it is a common cause of heart failure and cardiac transplantation. This study aimed to explore potential DCM-related genes and their underlying regulatory mechanism using methods of bioinformatics. The gene expression profiles of GSE3586 were downloaded from Gene Expression Omnibus database, including 15 normal samples and 13 DCM samples. The differentially expressed genes (DEGs were identified between normal and DCM samples using Limma package in R language. Pathway enrichment analysis of DEGs was then performed. Meanwhile, the potential transcription factors (TFs and microRNAs (miRNAs of these DEGs were predicted based on their binding sequences. In addition, DEGs were mapped to the cMap database to find the potential small molecule drugs. A total of 4777 genes were identified as DEGs by comparing gene expression profiles between DCM and control samples. DEGs were significantly enriched in 26 pathways, such as lymphocyte TarBase pathway and androgen receptor signaling pathway. Furthermore, potential TFs (SP1, LEF1, and NFAT were identified, as well as potential miRNAs (miR-9, miR-200 family, and miR-30 family. Additionally, small molecules like isoflupredone and trihexyphenidyl were found to be potential therapeutic drugs for DCM. The identified DEGs (PRSS12 and FOXG1, potential TFs, as well as potential miRNAs, might be involved in DCM.

  7. Dilated cardiomyopathy with Graves disease in a young child

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    Yu Jung Choi

    2016-06-01

    Full Text Available Graves disease (GD can lead to complications such as cardiac arrhythmia and heart failure. Although dilated cardiomyopathy (DCMP has been occasionally reported in adults with GD, it is rare in children. We present the case of a 32-month-old boy with DCMP due to GD. He presented with irritability, vomiting, and diarrhea. He also had a history of weight loss over the past few months. On physical examination, he had tachycardia without fever, a mild diffuse goiter, and hepatomegaly. The chest radiograph showed cardiomegaly with pulmonary edema, while the echocardiography revealed a dilated left ventricle with an ejection fraction (EF of 28%. The thyroid function test (TFT showed elevated serum T3 and decreased thyroid stimulating hormone (TSH levels. The TSH receptor autoantibody titer was elevated. He was diagnosed with DCMP with GD; treatment with methylprednisolone, diuretics, inotropics, and methimazole was initiated. The EF improved after the TFT normalized. At follow-up several months later, although the TFT results again showed evidence of hyperthyroidism, his EF had not deteriorated. His cardiac function continues to remain normal 1.5 months after treatment was started, although he still has elevated T3 and high TSH receptor antibody titer levels due to poor compliance with drug therapy. To summarize, we report a young child with GD-induced DCMP who recovered completely with medical therapy and, even though the hyperthyroidism recurred several months later, there was no relapse of the DCMP.

  8. Cell therapy in dilated cardiomyopathy: from animal models to clinical trials

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    C. del Corsso

    2011-05-01

    Full Text Available Dilated cardiomyopathy can be the end-stage form and common denominator of several cardiac disorders of known cause, such as hypertensive, ischemic, diabetic and Chagasic diseases. However, some individuals have clinical findings, such as an increase in ventricular chamber size and impaired contractility (classical manifestations of dilated cardiomyopathy even in the absence of a diagnosed primary disease. In these patients, dilated cardiomyopathy is classified as idiopathic since its etiology is obscure. Nevertheless, regardless of all of the advances in medical, pharmacological and surgical procedures, the fate of patients with dilated cardiomyopathy (of idiopathic or of any other known cause is linked to arrhythmic episodes, severe congestive heart failure and an increased risk of sudden cardiac death. In this review, we will summarize present data on the use of cell therapies in animal models of dilated cardiomyopathies and will discuss the few clinical trials that have been published so far involving patients affected by this disease. The animal models discussed here include those in which the cardiomyopathy is produced by genetic manipulation and those in which disease is induced by chemical or infectious agents. The specific model used clearly creates restrictions to translation of the proposed cell therapy to clinical practice, insofar as most of the clinical trials performed to date with cell therapy have used autologous cells. Thus, translation of genetic models of dilated cardiomyopathy may have to wait until the use of allogeneic cells becomes more widespread in clinical trials of cell therapies for cardiac diseases.

  9. Echocaridography, electrocardiography, and radiography of cats with dilatation cardiomyopathy, hypertrophic cardiomyopathy, and hyperyroidism

    International Nuclear Information System (INIS)

    Moise, N.S.; Dietze, A.E.; Mezza, L.E.; Strickland, D.; Erb, H.N.; Edwards, N.J.

    1986-01-01

    The echocardiographic, ECG, and radiographic findings of sequentially examined cats with dilatation cardiomyopathy (DCM, n = 7), hypertrophic cardiomyopathy (HCM, n = 8), and hyperthyroidism (HT, n = 20) were compared with those of healthy control cats (n = 11). Cats with DCM were easily differentiated from healthy cats by echocardiography and from cats with HCM and HT by a dilated left ventricle at end-diastole with a mean +/- SD of 2.20 +/- 0.36 cm, reduced fractional shortening (2.9% +/- 3.7%), reduced aortic amplitude (0.07 +/- 0.05 cm), reduced left ventricular wall amplitude (0.09 +/- 0.09 cm), and increased E-point septal separation (0.83 +/- 0.29 cm). The cats with HCM were most consistently recognized echocardiographically by increased left ventricular wall thickness at end-diastole (0.75 +/- 0.12 cm). Some cats with HT had abnormal echocardiograms with left ventricular wall hypertrophy. These cats could usually be differentiated from the cats with HCM because of normal or increased ventricular wall amplitude, aortic amplitude, or percentage of thickening of the left ventricular wall and interventricular septum. Left atrial enlargement (left atrial diameter greater than 1.57 cm or left atrium/aorta greater than 1.75) was commonly detected by the echocardiogram in cats with DCM, HCM, or HT. The echocardiogram was helpful in differentiating the type of cardiomyopathy (DCM, HCM, or HT) when plain thoracic radiographs indicated that cardiomegaly existed. The ECG may have indicated incorrectly that there was left ventricular enlargement in some cats with HT, and it did not indicate consistently that left ventricular enlargement existed when present in cats with DCM or HCM. The ECG was a poor indicator of left atrial enlargement in all cats

  10. The value of myocardial perfusion imaging in differentiating between idiopathic dilated cardiomyopathy from the ischemic form

    International Nuclear Information System (INIS)

    Fad, A.; Emami, F.; Eftekhari, M.; Saghari, M.; Fallahi, B.; Beiki, D.; Tkavar, A.

    2004-01-01

    Introduction: differentiating between ischemic cardiomyopathy and idiopathic dilated cardiomyopathy is important as coronary revascularization can improve prognosis in the ischemic subgroup. Due to inherent problems of coronary angiography in patients with depressed ejection fraction introducing a noninvasive tool to diagnose those who will benefit from angiography seems to be rewarding. We examined usefulness of myocardial perfusion scan in this group of patients. Materials and methods: study was performed on 64 patients (62 male and 2 female) aged 57.1 ± 6.7 y (mean ± SD) all with dilation of the left ventricular cavity and ejection fraction less than 40 % by echocardiography. Myocardial perfusion scan was performed in stress and rest phases. All the patients had coronary angiography which was used as the gold standard test. On each set of images, heart was arbitrary divided into 17 segments and perfusion abnormality in each segment was scored by a 5 grade scoring system (0-4). Summed stress Score was used as the scan criteria to differentiate dilated ischemic from idiopathic cardiomyopathy. Scores more than 17 were considered ischemic, and less than that, idiopathic. Results were compared with angiography. Results: from total 40 cases of ischemic cardiomyopathy (proved by angiography) 39 were correctly diagnosed by scan and only one case was mis categorized as idiopathic dilated cardiomyopathy . All 24 cases of idiopathic dilated cardiomyopathy were correctly diagnosed by scintigraphy. Sensitivity, specificity, positive predictive value, and negative predictive value of myocardial perfusion imaging for discrimination between ischemic and idiopathic dilated cardiomyopathy were 97.5 %, 100 %, 100 %, and 96 % respectively. Conclusion: Considering excellent accuracy of myocardial perfusion scan with scoring system in discrimination of ischemic dilated cardiomyopathy from idiopathic cardiomyopathy, this noninvasive test could be considered the main diagnostic test

  11. Three-dimensional MR microscopy of a transgenic mouse model of dilated cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Sze, R.W.; Strife, J.L. [Dept. of Radiology, Children' s Hospital Medical Center, Cincinnati, OH (United States); Chan, C.B.; Sanbe, A.; Robbins, J. [Div. of Molecular Cardiovascular Biology, Department of Pediatrics, Children' s Hospital Research Foundation, Cincinnati, OH (United States); Dardzinski, B.J.; Dunn, S.; Schmithorst, V.; Holland, S.K. [Imaging Research Center, Children' s Hospital Medical Center, Cincinnati, OH (United States)

    2001-02-01

    Background. Scientists are now able to alter the genetics of vertebrate embryos routinely to produce animal models of human developmental diseases. However, our understanding of structural changes in these animal models is limited by current methodologies. Histological techniques, although providing great anatomic detail, display only ''static'' data (one time point only) in two dimensions. Ultrasound may be used to generate continuous time course data, but is limited by interobserver variation, limited acoustic windows, and relatively low resolution. Objective. To apply the high resolution, non-destructive, and three-dimensional acquisition capabilities of magnetic resonance (MR) microscopy to compare the hearts of normal mice versus an established transgenic mouse model of dilated cardiomyopathy. Materials and methods. Transgenic mice exhibiting dilated cardiomyopathy were developed via the introduction of a mutated, heart-specific gene (myosin light chain). Post-mortem cardiac imaging was performed on the transgenic mice and normal controls. MR imaging was performed on a Bruker 3T imaging magnet using a custom radiofrequency coil following contrast perfusion of the atrial and ventricular chambers. Image resolution was 156 {mu}m isotropic voxels. MR images were compared to gross pathologic specimens. Imaging data were post-processed using custom software to calculate the volumes of the atria and ventricles and to display the three-dimensional morphology of the chambers and myocardium. Results. Of the seven mice scanned, four exhibited normal right atrial (average = 14.8 {mu}l {+-} 1.4), left atrial (average = 8.5 {mu}l {+-} 0.3), right ventricular (average = 12.9 {mu}l {+-} 2.7), and left ventricular (average 3.3 {mu}l {+-} 0.5) volumes. Three mice exhibited dilatation of the right and left cardiac chambers (RA average = 23.9 {mu}l {+-} 5.6; LA average = 15.9 {mu}l {+-} 4.8; RV average = 32.5 {mu}l {+-} 6.8; LV average 24.0 {mu}l {+-} 1

  12. Subtle abnormalities in contractile function are an early manifestation of sarcomere mutations in dilated cardiomyopathy

    DEFF Research Database (Denmark)

    Lakdawala, Neal K; Thune, Jens J; Colan, Steven D

    2012-01-01

    Sarcomere mutations cause both dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM); however, the steps leading from mutation to disease are not well described. By studying mutation carriers before a clinical diagnosis develops, we characterize the early manifestations of sarcomere...... mutations in DCM and investigate how these manifestations differ from sarcomere mutations associated with HCM....

  13. Clinical predictors of outcome in patients with inflammatory dilated cardiomyopathy.

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    Konstantinos Karatolios

    Full Text Available The study objectives were to identify predictors of outcome in patients with inflammatory dilated cardiomyopathy (DCMi.From 2004 to 2008, 55 patients with biopsy-proven DCMi were identified and followed up for 58.2±19.8 months. Predictors of outcome were identified in a multivariable analysis with a Cox proportional hazards analysis. The primary endpoint was a composite of death, heart transplantation and hospitalization for heart failure or ventricular arrhythmias.For the primary endpoint, a QTc interval >440msec (HR 2.84; 95% CI 1.03-7.87; p = 0.044, a glomerular filtration rate (GFR 440msec, a GFR<60ml/min/1.73m2 and worsening of NYHA classification during follow-up were univariate predictors of adverse prognosis. In contrast, NYHA classification at baseline, left ventricular ejection fraction, atrial fibrillation, treatment with digitalis or viral genome detection were not related to outcome. After multivariable analysis, a GFR <60ml/min/1.73m2 remained independently associated with adverse outcome.

  14. Right ventricular function in patients with dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Kubota, Shuhei; Kubota, Sachio; Iwase, Takashi; Iizuka, Toshio; Imai, Susumu; Murata, Kazuhiko; Inoue, Tomio; Suzuki, Tadashi; Sasaki, Yasuhito.

    1993-01-01

    The characteristics and pathogenesis of right ventricular dysfunction in 14 patients with dilated cardiomyopathy (DCM) were investigated by equilibrium right ventricular blood pool scintigraphy using ultrashort-lifetime 81m Kr. Thirteen patients with severe left ventricular dysfunction due to old anterior myocardial infarction (OMI) and nine normal subjects were used as controls. The right ventricular end-diastolic pressure and volume index, mean pulmonary arterial pressure, and total pulmonary vascular resistance index were almost the same in the DCM and OMI patients. The right ventricular ejection fraction was 44.2±6.0% (mean±SD) in DCM patients and 47.1±7.9% in OMI patients, both significantly lower than those in the normal subjects (54.5±5.3%), but with no difference between the two case groups. The right ventricular peak filling rate was significantly reduced in both case groups as compared with the normal subjects (2.46±0.81 EDV/sec). The reduction was significantly greater (p 81m Kr blood pool scintigraphy is useful in the study of the right ventricular systolic and diastolic function. The diastolic parameters are more sensitive indicators for evaluation of right ventricular function in DCM than the systolic parameters. (author)

  15. Defective Circulating Regulatory B Cells in Patients with Dilated Cardiomyopathy

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    Jiao Jiao

    2018-03-01

    Full Text Available Background/Aims: Newly identified IL-10-producing regulatory B cells (Bregs have been shown to play an important role in the suppression of immune responses. Chronic immune activation participates in the pathogenesis of dilated cardiomyopathy (DCM but whether Bregs are involved in its development remains unclear. We aimed to investigate the circulating frequency and function of Bregs in DCM. Methods: In total, 35 DCM patients (20 men and 15 women and 44 healthy controls (23 men and 21 women were included in the experiment, and the frequency of Bregs was detected using flow cytometry. Results: According to our results, the frequency of circulating IL-10-producing Bregs was significantly lower in DCM patients compared with healthy controls. Furthermore, the CD24hiCD27+ B cell subset in which IL-10-producing Bregs were mainly enriched from DCM patients showed impaired IL-10 expression and a decreased ability to suppress the TNF-α production of CD4+CD25- Tconv cells and to maintain Tregs differentiation. Correlation analysis showed that the frequency of IL-10-producing Bregs and the suppressive function of CD24hiCD27+ B cells were positively correlated with left ventricular ejection fraction and negatively correlated with NT-proBNP in DCM patients. Conclusions: In conclusion, the reduced frequency and impaired functions suggest a potential role of Bregs in the development of DCM.

  16. Genetic Modifiers of Duchenne Muscular Dystrophy and Dilated Cardiomyopathy.

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    Andrea Barp

    Full Text Available Dilated cardiomyopathy (DCM is a major complication and leading cause of death in Duchenne muscular dystrophy (DMD. DCM onset is variable, suggesting modifier effects of genetic or environmental factors. We aimed to determine if polymorphisms previously associated with age at loss of independent ambulation (LoA in DMD (rs28357094 in the SPP1 promoter, rs10880 and the VTTT/IAAM haplotype in LTBP4 also modify DCM onset.A multicentric cohort of 178 DMD patients was genotyped by TaqMan assays. We performed a time-to-event analysis of DCM onset, with age as time variable, and finding of left ventricular ejection fraction 70 mL/m2 as event (confirmed by a previous normal exam < 12 months prior; DCM-free patients were censored at the age of last echocardiographic follow-up.Patients were followed up to an average age of 15.9 ± 6.7 years. Seventy-one/178 patients developed DCM, and median age at onset was 20.0 years. Glucocorticoid corticosteroid treatment (n = 88 untreated; n = 75 treated; n = 15 unknown did not have a significant independent effect on DCM onset. Cardiological medications were not administered before DCM onset in this population. We observed trends towards a protective effect of the dominant G allele at SPP1 rs28357094 and recessive T allele at LTBP4 rs10880, which was statistically significant in steroid-treated patients for LTBP4 rs10880 (< 50% T/T patients developing DCM during follow-up [n = 13]; median DCM onset 17.6 years for C/C-C/T, log-rank p = 0.027.We report a putative protective effect of DMD genetic modifiers on the development of cardiac complications, that might aid in risk stratification if confirmed in independent cohorts.

  17. Serum proteome profiling in canine idiopathic dilated cardiomyopathy using TMT-based quantitative proteomics approach.

    Science.gov (United States)

    Bilić, Petra; Guillemin, Nicolas; Kovačević, Alan; Beer Ljubić, Blanka; Jović, Ines; Galan, Asier; Eckersall, Peter David; Burchmore, Richard; Mrljak, Vladimir

    2018-05-15

    Idiopathic dilated cardiomyopathy (iDCM) is a primary myocardial disorder with an unknown aetiology, characterized by reduced contractility and ventricular dilation of the left or both ventricles. Naturally occurring canine iDCM was used herein to identify serum proteomic signature of the disease compared to the healthy state, providing an insight into underlying mechanisms and revealing proteins with biomarker potential. To achieve this, we used high-throughput label-based quantitative LC-MS/MS proteomics approach and bioinformatics analysis of the in silico inferred interactome protein network created from the initial list of differential proteins. To complement the proteomic analysis, serum biochemical parameters and levels of know biomarkers of cardiac function were measured. Several proteins with biomarker potential were identified, such as inter-alpha-trypsin inhibitor heavy chain H4, microfibril-associated glycoprotein 4 and apolipoprotein A-IV, which were validated using an independent method (Western blotting) and showed high specificity and sensitivity according to the receiver operating characteristic curve analysis. Bioinformatics analysis revealed involvement of different pathways in iDCM, such as complement cascade activation, lipoprotein particles dynamics, elastic fibre formation, GPCR signalling and respiratory electron transport chain. Idiopathic dilated cardiomyopathy is a severe primary myocardial disease of unknown cause, affecting both humans and dogs. This study is a contribution to the canine heart disease research by means of proteomic and bioinformatic state of the art analyses, following similar approach in human iDCM research. Importantly, we used serum as non-invasive and easily accessible biological source of information and contributed to the scarce data on biofluid proteome research on this topic. Bioinformatics analysis revealed biological pathways modulated in canine iDCM with potential of further targeted research. Also, several

  18. Frequency of echocardiographic complications of dilated cardiomyopathy at a tertiary care hospital

    International Nuclear Information System (INIS)

    Rashid, A.; Ahmed, H.N.; Ahmed, N.

    2012-01-01

    Dilated cardiomyopathy can lead to a variety of complications recognisable on clinical, echocardiographic, electrocardiographic and radiographic assessment. Among this, transthoracic echocardiography has the dual advantage of being helpful in making the diagnosis of dilated cardiomyopathy as well as an effective tool in early recognition of certain complications for timely management to improve the quality of life of these patients. Methods: This descriptive (case series) study was undertaken at departments of medicine, cardiology, paediatrics and obs/gyn, Ayub Teaching Hospital, Abbottabad from July to December, 2008. fifty patients of dilated cardiomyopathy without age and gender discrimination were selected by convenience sampling. Those with hypertrophic and restrictive cardiomyopathies, valvular and congenital heart disease, hypertension and ischemic heart disease were excluded. Results: mean age was 47.12 +- 17.9 year with male predominance (males=34, females=16). Mean ejection fraction was 30.6 +- 6.9%. complications revealed on echocardiography were intracardiac thrombi (5, 10%), spontaneous echo contrast (5, 10%), pericardial effusion (6, 12%), mitral regurgitation (46, 92%), tricuspid (25, 50%), aortic (5, 10%), pulmonary (2, 4%) multi-valvular regurgitation (28, 56%), and left atrial dilatation (36, 72%). Conclusion: lv systolic dysfunction, cardiac thrombi, spontaneous echo contrast, mitral and tricuspid regurgitation and left atrial enlargement are important complications of dilated cardiomyopathy. echocardiography is important tool towards identification of these complications. (author)

  19. Application of radionuclide techniques in evaluation of dilated cardiomyopathy and ischemic cardiomyopathy

    International Nuclear Information System (INIS)

    Tian Yueqin; Liu Xiujie; Shi Rongfang

    2000-01-01

    Objective: To assess the clinical significance of radionuclide techniques in differentiating dilated cardiomyopathy (DCM) from ischemic cardiomyopathy (CAD-CM). Methods: 28 patients (pts) with DCM and 55 pts with CAD-CM were studied. All pts underwent 99 Tc m -MIBI myocardial perfusion SPECT and 18 F-FDG myocardial metabolic PET. 73 pts had 99 Tc m -RBC radionuclide ventriculography and 68 pts had coronary angiography. Results: 23 pts (82%) with DCM showed perfusion abnormalities with mild and not segmental distribution. 52 pts (95%) with CAD-CM showed perfusion abnormalities that distributed along the coronary vessel territories. Perfusion defects were found in 4 pts (14%) with DCM and 45 pts (82%) with CAD-CM (P<0.01). The average perfusion score was 4.5 +- 2.6 in DCM and 9.5 +- 2.9 in CAD-CM, the area of perfusion diminished uptake was significantly smaller in DCM than in CAD-CM (P < 0.001). 2 pts with DCM and 18 pts with CAD-CM had metabolic defect. The patterns of perfusion/metabolic imaging showed mismatch in most pts with CAD-CM but match in pts with DCM. The LVEF in pts with DCM and CAD-CM was decreased but no significant difference between DCM and CAD-CM was observed. The RVEF in pts with DCM was significantly lower than that in pts with CAD-CM (32.4% +- 13.9% vs 40.9% +- 15.4%, P < 0.05). Conclusions: The radionuclide techniques showed to be helpful for distinguishing DCM from CAD-CM. The discriminate analysis revealed that segmental perfusion abnormality and RVEF were the most important factors for differentiation of DCM from CAD-CM

  20. Elevated Serum Bisphenol A Level in Patients with Dilated Cardiomyopathy

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    Qinmei Xiong

    2015-05-01

    Full Text Available background: This study aimed to determine serum Bisphenol A (BPA concentrations in patients with dilated cardiomyopathy (DCM as well as the association between serum BPA and several hormonal parameters in DCM patients compared with a healthy control group. Materials and methods: Eighty-eight DCM patients and 88 age- and gender-matched healthy controls were included. Serum BPA levels and several hormonal parameters (including total testosterone (T, sex hormone-binding globulin (SHBG and estradiol (E2 were measured by using corresponding ELISA Kits. The free androgen index (FAI was calculated by the formula: total T in nmol/L × 100/SHBG in nmol/L. Results: BPA levels in the total DCM group were significantly higher compared with that in the controls (6.9 ± 2.7 ng/mL vs. 3.8 ± 1.9 ng/mL, p < 0.001. Significant difference was also observed in SHBG and FAI between DCM patients and controls, (76.9 ± 30.9 nM/L vs. 41.0 ± 15.6 nM/L and 2.9 ± 3.5 vs.5.3 ± 2.6, respectively, both of p < 0.001. Similar trends were observed in the male and female subgroup. Mean T level was lower in DCM group than in control group (540.8 ± 186.0 pg/mL vs. 656.3 ± 112.9 pg/mL, p < 0.001. Linear regression analysis has shown that increasing serum BPA levels were statistically significantly associated with increased SHBG levels. However, no statistical difference was noted for E2. Conclusion: Our findings firstly demonstrated that BPA exposure increased in DCM patients compared with that in healthy controls, while FAI and T levels decreased. SHBG presented a positive association with BPA. It is concluded that hormone disorder induced by BPA exposure might be an environmental factor in the pathology of DCM.

  1. An angiographic study of left- and right-ventricular function in patients with alcoholic heart and dilatation cardiomyopathy

    International Nuclear Information System (INIS)

    Savchenko, A.P.; Samko, A.N.; Smetnev, A.S.; Grudtsyn, G.V.

    1986-01-01

    An angiographic study of left- and right-ventricular function in 57 patients with alcoholic heart and dilatation cardiomyopathy demonstrated preclinical disorders of left-ventricular myocardial contractility and more marked right-ventricular changes in patients with second-stage chronic alcoholism. In cases of dilatation cardiomyopathy, left-ventricular dysfunction was predominant, while right-venricular changes were less pronouced

  2. Status of therapeutic gene transfer to treat canine dilated cardiomyopathy in dogs.

    Science.gov (United States)

    Sleeper, Meg M; Bish, Lawrence T; Sweeney, H Lee

    2010-07-01

    Therapeutic gene transfer holds promise as a way to treat dilated cardiomyopathy from any underlying cause because the approach attempts to address metabolic disturbances that occur at the molecular level of the failing heart. Calcium-handling abnormalities and increased rates of apoptosis are abnormalities that occur in many types of heart disease, and gene therapies that target these metabolic defects have proven to be beneficial in numerous rodent models of heart disease. The authors are currently evaluating this approach to treat canine idiopathic dilated cardiomyopathy.

  3. [Dimenhydrinate overdosage in a 3(1/2) year-old-girl with dilative cardiomyopathy].

    Science.gov (United States)

    Girisch, M; Hofbeck, M; Rauch, R; Apitz, C; Sieverding, L

    2009-01-01

    Dimenhydrinate overdosage in a 3(1/2) year-old-girl with dilative cardiomyopathy. Dimenhydrinate (Vomex(R)) is frequently used in the treatment of sickness and vomiting. The symptoms of overdosage present like an anticholinergic syndrome. We report on the clinical findings of an intoxication with dimenhydrinate in a 3(1/2) year-old-girl with functional dilative cardiomyopathy following a congenital left ventricular diverticle. Especially in small children, with the application of 40 mg suppositories once or twice per day the maximum dose of 3.75 mg/kgBW/d is achieved.

  4. Tc-99m MAA findings in dilated cardiomyopathy with partial anomalous venous connections.

    Science.gov (United States)

    Ishii, Shirou; Shishido, Fumio; Miyajima, Masayuki; Sakuma, Koutarou; Shigihara, Takeshi; Kikuchi, Ken

    2011-07-01

    Tc-99m MAA showed asymmetric uptake in the lung field in a 21-year-old man with dilated cardiomyopathy. CT revealed partial anomalous venous connections in the left upper lobe. Angiogram of the left pulmonary upper lobe showed all the contrast material drained into the left vertical vein. The possible cause of relative increase in the left upper lobe blood flow is that right pulmonary blood flow is slowed by the high pressure in the left atrium due to dilated cardiomyopathy, whereas the flow from the left upper lobe drains into the superior vena cava which has less pressure than left atrium.

  5. Difference in myocardial flow reserve between patients with dilated cardiomyopathy and those with dilated phase of hypertrophic cardiomyopathy. Evaluation by 15O-water PET

    International Nuclear Information System (INIS)

    Ohba, Muneo; Kambara, Naoshige; Hosokawa, Ryohei

    2007-01-01

    The clinical features of patients with the dilated phase of hypertrophic cardiomyopathy (DHCM) may resemble those of patients with dilated cardiomyopathy (DCM); that is, systolic dysfunction and left ventricular dilatation. Myocardial flow reserve (MFR) is impaired in patients with nonischemic cardiomyopathy, and the reduced MFR may be related to poor prognosis. Several studies report that the mortality rate for patients with DHCM is higher than for DCM, but the difference between these 2 cardiomyopathies is still unclear. The purpose of this study was to assess the MFR of these 2 cardiomyopathies, using 15 O-water positron emission tomography (PET) to elucidate their differences. In total 30 patients were investigated: 23 with DCM (Group A) and 7 with DHCM (Group B). All those who were in a stable condition underwent cardiac catheterization. Myocardial blood flow (MBF) at rest and under adenosine 5'-triphosphate (ATP) infusion was measured by 15 O-water PET, and the MFR was calculated. There were no significant differences in the hemodynamics of the 2 groups. The mean MFR in DHCM was significantly lower than that in DCM (1.49±0.31 vs 2.62±1.08; p=0.042), whereas MBF at rest did not differ (DCM vs DHCM: 0.66±0.20 vs 0.49±0.05 ml·min -1 ·g -1 ; no significance (NS)). The MFR in both Group A and B was significantly decreased compared with the normal controls (MFR in normal controls: 5.15±1.64, p=0.00015, 0.00013, respectively). These results suggest that impaired vasodilatation (ie, dysfunction of the microcirculation) is more severe in patients with DHCM than in patients with DCM, even though patients' characteristics and hemodynamics do not differ. (author)

  6. Evaluation of myocardial disorders in patients with dilated cardiomyopathy and left ventricular eccentric hypertrophy

    International Nuclear Information System (INIS)

    Yamazaki, Junichi; Ohsawa, Hidefumi; Uchi, Takashi

    1992-01-01

    201 Tl myocardial SPECT was performed in cases of dilated cardiomyopathy and valvular heart disease with left ventricular eccentric hypertrophy, and the two groups were compared from the standpoint of the mechanism of onset of myocardial disorders. Significant coefficients of correlation were seen between the Tl score and LVDd (r=0.792, r=0.785) and Tl score and LVEF (r=-0.634, r=-0.555) in both dilated cardiomyopathy and valvular heart disease. In cases of valvular heart disease, significant correlation coefficients (r=-0.756, r=-0.720) between LVDd and r-WR (relative-washout rate), and Tl score and r-WR were observed, but no such correlation was seen in dilated cardiomyopathy. In valvular heart disease, a decrease in myocardial perfusion associated with enlargement of the left ventricle appeared, while in dilated cardiomyopathy, there was a marked decrease in LVEF in proportion to the thallium defect. Therefore, it was assumed that left ventricular wall disorders occur due to myocardial metabolic disorders and coronary microcirculation disorders. (author)

  7. A systematic analysis of genetic dilated cardiomyopathy reveals numerous ubiquitously expressed and muscle-specific genes

    NARCIS (Netherlands)

    Harakalova, Magdalena; Kummeling, GJM; Sammani, Arjan; Linschoten, Marijke; Baas, AF; van der Smagt, Jasper; Doevendans, Pieter A.; van Tintelen, J. Peter; Dooijes, Dennis; Mokry, Michal; Asselbergs, Folkert W.

    AimsDespite considerable progress being made in genetic diagnostics for dilated cardiomyopathy (DCM) using panels of the most prevalent genes, the cause remains unsolved in a substantial percentage of patients. We hypothesize that several previously described DCM genes with low or unknown prevalence

  8. Addison's Disease and Dilated Cardiomyopathy: A Case Report and Review of the Literature.

    Science.gov (United States)

    Mozolevska, Viktoriya; Schwartz, Anna; Cheung, David; Shaikh, Bilal; Bhagirath, Kapil M; Jassal, Davinder S

    2016-01-01

    Addison's disease is often accompanied by a number of cardiovascular manifestations. We report the case of a 30-year-old man who presented with a new onset dilated cardiomyopathy due to Addison's disease. The clinical presentation, treatment, and outcomes of this rare hormone mediated cardiac disorder are reviewed.

  9. Dynamic functional modules in co-expressed protein interaction networks of dilated cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Oyang Yen-Jen

    2010-10-01

    Full Text Available Abstract Background Molecular networks represent the backbone of molecular activity within cells and provide opportunities for understanding the mechanism of diseases. While protein-protein interaction data constitute static network maps, integration of condition-specific co-expression information provides clues to the dynamic features of these networks. Dilated cardiomyopathy is a leading cause of heart failure. Although previous studies have identified putative biomarkers or therapeutic targets for heart failure, the underlying molecular mechanism of dilated cardiomyopathy remains unclear. Results We developed a network-based comparative analysis approach that integrates protein-protein interactions with gene expression profiles and biological function annotations to reveal dynamic functional modules under different biological states. We found that hub proteins in condition-specific co-expressed protein interaction networks tended to be differentially expressed between biological states. Applying this method to a cohort of heart failure patients, we identified two functional modules that significantly emerged from the interaction networks. The dynamics of these modules between normal and disease states further suggest a potential molecular model of dilated cardiomyopathy. Conclusions We propose a novel framework to analyze the interaction networks in different biological states. It successfully reveals network modules closely related to heart failure; more importantly, these network dynamics provide new insights into the cause of dilated cardiomyopathy. The revealed molecular modules might be used as potential drug targets and provide new directions for heart failure therapy.

  10. Drugs and dilated cardiomyopathies: A case/noncase study in the French PharmacoVigilance Database.

    Science.gov (United States)

    Montastruc, Guillaume; Favreliere, Sylvie; Sommet, Agnès; Pathak, Atul; Lapeyre-Mestre, Maryse; Perault-Pochat, Marie-Christine; Montastruc, Jean-Louis

    2010-03-01

    To evaluate putative associations between drugs and dilated cardiomyopathy. We used the case/noncase method in the French PharmacoVigilance Database (FPVD). Cases were all the observations with dilated cardiomyopathy registered into the FPVD between 1 January 1990 and 30 June 2007. Noncases were all other reports other than those studied. Anthracyclines were used as positive controls. Data were expressed as reporting odds ratio (ROR) with their 95% confidence intervals. Out of the 258 729 adverse drug reaction (ADR) reports recorded in the FPVD between 1 January 1990 and 30 June 2007, 47 (22 men, mean age 49 years) were defined as dilated cardiomyopathy. In these 47 patients, 67 drugs were 'suspect'. A significant ROR was found with cytotoxic (epirubicin, mitoxantrone, cyclophosphamide, gemcitabine, fluorouracil) and antiretroviral (lamividune, zidovudine, abacavir) but also with isotretinoin, prednisone, appetite suppressant (clobenzorex) and psychotropic [antipsychotic (clozapine, olanzapine), lithium, antidepressant (clomipramine, amitriptyline, fluvoxamine)] drugs. The present study describes an association between some drugs and reports of dilated cardiomyopathies. This relationship involves not only some already suspected drugs (anthracyclines, antiretrovirals), but also other drugs (antipsychotics, lithium, antidepressants, retinoids) less known to induce such an ADR. Despite the mandatory limits of this kind of study (underreporting, confounding factors . . .), these data represent a pharmacovigilance signal and could contribute to establish further prospective studies in order to confirm such signals.

  11. Propionic acidemia as a cause of adult-onset dilated cardiomyopathy

    NARCIS (Netherlands)

    Riemersma, M.; Hazebroek, M.R.; Helderman-van den Enden, A.T.; Salomons, G.S.; Ferdinandusse, S.; Brouwers, M.; Ploeg, L. van der; Heymans, S.; Glatz, J.F.C.; Wijngaard, A. van den; Krapels, I.P.C.; Bierau, J.; Brunner, H.G.

    2017-01-01

    Dilated cardiomyopathy (DCM) is extremely heterogeneous with a large proportion due to dominantly inherited disease-causing variants in sarcomeric genes. Recessive metabolic diseases may cause DCM, usually with onset in childhood, and in the context of systemic disease. Whether metabolic defects can

  12. Disturbed Desmoglein-2 in the intercalated disc of pediatric patients with dilated cardiomyopathy

    NARCIS (Netherlands)

    Kessler, Elise L.; Nikkels, Peter GJ; van Veen, Toon AB

    2017-01-01

    Dilated cardiomyopathy (DCM) leads to disturbed contraction and force transduction, and is associated with substantial mortality in all age groups. Involvement of a disrupted composition of the intercalated disc (ID) has been reported. However, in children, little is established about such

  13. Initial presentation with dilated cardiomyopathy in a patient of tuberous sclerosis: A rare case report

    Directory of Open Access Journals (Sweden)

    Dharmendra Jain

    2013-01-01

    Full Text Available A 35-year-old man presented with dilated cardiomyopathy, an unusual association with tuberous sclerosis. Clinical history and examination were consistent with tuberous sclerosis including major features of tuberous sclerosis complex (TSC like facial angiofibroma, shagreen patch, subependymal nodules, and angiomyolipoma of kidney. The clinical manifestations, pathogenesis and evaluation of tuberous sclerosis are discussed.

  14. A systematic analysis of genetic dilated cardiomyopathy reveals numerous ubiquitously expressed and muscle-specific genes

    NARCIS (Netherlands)

    Harakalova, Magdalena; Kummeling, Gijs; Sammani, Arjan; Linschoten, Marijke; Baas, Annette F.; van der Smagt, Jasper; Doevendans, Pieter A.; van Tintelen, J. Peter; Dooijes, Dennis; Mokry, Michal; Asselbergs, Folkert W.

    2015-01-01

    Despite considerable progress being made in genetic diagnostics for dilated cardiomyopathy (DCM) using panels of the most prevalent genes, the cause remains unsolved in a substantial percentage of patients. We hypothesize that several previously described DCM genes with low or unknown prevalence

  15. Study on microbial persistence in end-stage idiopathic dilated cardiomyopathy.

    NARCIS (Netherlands)

    Leeuw, N. de; Melchers, W.J.G.; Balk, A.H.M.M.; Jonge, N. de; Galama, J.M.D.

    1999-01-01

    Microbial persistence may be involved in the pathogenesis of idiopathic dilated cardiomyopathy (IDC). Therefore, we evaluated the role of various cardiopathogenic microorganisms in patients with end-stage IDC. In a previous study, we did not find evidence for the persistence of enterovirus RNA in

  16. CARDIAC TRANSPLANTATION IN YOUNG PATIENT WITH DILATED CARDIOMYOPATHY AND SECONDARY ANTIPHOSPHOLIPID SYNDROME

    Directory of Open Access Journals (Sweden)

    E. V. Shlyakhto

    2013-01-01

    Full Text Available Patients with congestive heart failure have an increased incidence of thromboembolic events. The choice of me- dical management in patients with antiphospholipid antibodies and generalized thrombosis due to hypercoagula- bility is complex issue. We report heart transplant outcome in 15 years old patient with dilated cardiomyopathy and secondary anti-phospholipid syndrome. 

  17. Canine dilated cardiomyopathy: a retrospective study of signalment, presentation and clinical findings in 369 cases.

    Science.gov (United States)

    Martin, M W S; Stafford Johnson, M J; Celona, B

    2009-01-01

    To review the clinical and diagnostic findings and survival of dilated cardiomyopathy from a large population of dogs in England. A retrospective study of the case records of dogs with dilated cardiomyopathy collected between January 1993 and May 2006. There were 369 dogs with dilated cardiomyopathy of which all were pure-bred dogs except for four. The most commonly affected breeds were dobermanns and boxers. Over 95 per cent of dogs weighed more than 15 kg and 73 per cent were male. The median duration of signs before referral was three weeks with 65 per cent presenting in stage 3 heart failure. The most common signs were breathlessness (67 per cent) and coughing (64 per cent). The majority of dogs (89 per cent) had an arrhythmia at presentation and 74 per cent of dogs had radiographic signs of pulmonary oedema or pleural effusion. The median survival time was 19 weeks. Dilated cardiomyopathy occurs primarily in medium to large breed pure-bred dogs, and males are more frequently affected than females. The duration of clinical signs before referral is often short and the survival times are poor. Greater awareness of affected breeds, clinical signs and diagnostic findings may help in early recognition of this disease which often has a short clinical phase.

  18. Evaluation of pulsatile plasma concentrations of growth hormone in healthy dogs and dogs with dilated cardiomyopathy

    NARCIS (Netherlands)

    Beijerink, N.J.; Lee, W.M.; Stokhof, A.A.; Voorhout, G.; Mol, J.A.; Kooistra, H.S.

    2011-01-01

    Abstract OBJECTIVE: To evaluate plasma concentrations of growth hormone (GH) and insulin-like growth factor I (IGF-I) in healthy dogs and large-breed dogs with dilated cardiomyopathy (DCM). ANIMALS: 8 dogs with DCM and 8 healthy control dogs of comparable age and body weight. PROCEDURES: Blood

  19. Anti-calreticulin antibodies and calreticulin in sera of patients diagnosed with dilated or hypertrophic cardiomyopathy

    Czech Academy of Sciences Publication Activity Database

    Sánchez, Daniel; Gregor, P.; Čurila, K.; Hoffmanová, I.; Hábová, Věra; Tučková, Ludmila; Tlaskalová-Hogenová, Helena

    2016-01-01

    Roč. 49, č. 8 (2016), s. 554-562 ISSN 0891-6934 R&D Projects: GA ČR GA13-14608S; GA TA ČR TA04010762 Institutional support: RVO:61388971 Keywords : Anti-calreticulin antibodies * calreticulin * dilated cardiomyopathy Subject RIV: EC - Immunology Impact factor: 2.629, year: 2016

  20. Human umbilical cord mesenchymal stem cells alleviate interstitial fibrosis and cardiac dysfunction in a dilated cardiomyopathy rat model by inhibiting TNF-α and TGF-β1/ERK1/2 signaling pathways

    Science.gov (United States)

    Zhang, Changyi; Zhou, Guichi; Chen, Yezeng; Liu, Sizheng; Chen, Fen; Xie, Lichun; Wang, Wei; Zhang, Yonggang; Wang, Tianyou; Lai, Xiulan; Ma, Lian

    2018-01-01

    Dilated cardiomyopathy (DCM) is a disease of the heart characterized by pathological remodeling, including patchy interstitial fibrosis and degeneration of cardiomyocytes. In the present study, the beneficial role of human umbilical cord-derived mesenchymal stem cells (HuMSCs) derived from Wharton's jelly was evaluated in the myosin-induced rat model of DCM. Male Lewis rats (aged 8-weeks) were injected with porcine myosin to induce DCM. Cultured HuMSCs (1×106 cells/rat) were intravenously injected 28 days after myosin injection and the effects on myocardial fibrosis and the underlying signaling pathways were investigated and compared with vehicle-injected and negative control rats. Myosin injections in rats (vehicle group and experimental group) for 28 days led to severe fibrosis and significant deterioration of cardiac function indicative of DCM. HuMSC treatment reduced fibrosis as determined by Masson's staining of collagen deposits, as well as quantification of molecular markers of myocardial fibrosis such as collagen I/III, profibrotic factors transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), and connective tissue growth factor (CTGF). HuMSC treatment restored cardiac function as observed using echocardiography. In addition, western blot analysis indicated that HuMSC injections in DCM rats inhibited the expression of TNF-α, extracellular-signal regulated kinase 1/2 (ERK1/2) and TGF-β1, which is a master switch for inducing myocardial fibrosis. These findings suggested that HuMSC injections attenuated myocardial fibrosis and dysfunction in a rat model of DCM, likely by inhibiting TNF-α and the TGF-β1/ERK1/2 fibrosis pathways. Therefore, HuMSC treatment may represent a potential therapeutic method for treatment of DCM. PMID:29115435

  1. Familial Dilated Cardiomyopathy Caused by a Novel Frameshift in the BAG3 Gene.

    Directory of Open Access Journals (Sweden)

    Rocio Toro

    Full Text Available Dilated cardiomyopathy, a major cause of chronic heart failure and cardiac transplantation, is characterized by left ventricular or biventricular heart dilatation. In nearly 50% of cases the pathology is inherited, and more than 60 genes have been reported as disease-causing. However, in 30% of familial cases the mutation remains unidentified even after comprehensive genetic analysis. This study clinically and genetically assessed a large Spanish family affected by dilated cardiomyopathy to search for novel variations.Our study included a total of 100 family members. Clinical assessment was performed in alive, and genetic analysis was also performed in alive and 1 deceased relative. Genetic screening included resequencing of 55 genes associated with sudden cardiac death, and Sanger sequencing of main disease-associated genes. Genetic analysis identified a frame-shift variation in BAG3 (p.H243Tfr*64 in 32 patients. Genotype-phenotype correlation identified substantial heterogeneity in disease expression. Of 32 genetic carriers (one deceased, 21 relatives were clinically affected, and 10 were asymptomatic. Seventeen of the symptomatic genetic carriers exhibited proto-diastolic septal knock by echocardiographic assessment.We report p.H243Tfr*64_BAG3 as a novel pathogenic variation responsible for familial dilated cardiomyopathy. This variation correlates with a more severe phenotype of the disease, mainly in younger individuals. Genetic analysis in families, even asymptomatic individuals, enables early identification of individuals at risk and allows implementation of preventive measures.

  2. Studying Dynamic Myofiber Aggregate Reorientation in Dilated Cardiomyopathy Using In Vivo Magnetic Resonance Diffusion Tensor Imaging.

    Science.gov (United States)

    von Deuster, Constantin; Sammut, Eva; Asner, Liya; Nordsletten, David; Lamata, Pablo; Stoeck, Christian T; Kozerke, Sebastian; Razavi, Reza

    2016-10-01

    The objective of this study is to assess the dynamic alterations of myocardial microstructure and strain between diastole and systole in patients with dilated cardiomyopathy relative to healthy controls using the magnetic resonance diffusion tensor imaging, myocardial tagging, and biomechanical modeling. Dual heart-phase diffusion tensor imaging was successfully performed in 9 patients and 9 controls. Tagging data were acquired for the diffusion tensor strain correction and cardiac motion analysis. Mean diffusivity, fractional anisotropy, and myocyte aggregate orientations were compared between both cohorts. Cardiac function was assessed by left ventricular ejection fraction, torsion, and strain. Computational modeling was used to study the impact of cardiac shape on fiber reorientation and how fiber orientations affect strain. In patients with dilated cardiomyopathy, a more longitudinal orientation of diastolic myofiber aggregates was measured compared with controls. Although a significant steepening of helix angles (HAs) during contraction was found in the controls, consistent change in HAs during contraction was absent in patients. Left ventricular ejection fraction, cardiac torsion, and strain were significantly lower in the patients compared with controls. Computational modeling revealed that the dilated heart results in reduced HA changes compared with a normal heart. Reduced torsion was found to be exacerbated by steeper HAs. Diffusion tensor imaging revealed reduced reorientation of myofiber aggregates during cardiac contraction in patients with dilated cardiomyopathy relative to controls. Left ventricular remodeling seems to be an important factor in the changes to myocyte orientation. Steeper HAs are coupled with a worsening in strain and torsion. Overall, the findings provide new insights into the structural alterations in patients with dilated cardiomyopathy. © 2016 The Authors.

  3. Prevalence of cardiac dyssynchrony and correlation with atrio-ventricular block and QRS width in dilated cardiomyopathy

    DEFF Research Database (Denmark)

    Anzouan-Kacou, J B; Ncho-Mottoh, M P; Konin, C

    2012-01-01

    Cardiac dyssynchrony causes disorganised cardiac contraction, delayed wall contraction and reduced pumping efficiency. We aimed to assess the prevalence of different types of dyssynchrony in patients with dilated cardiomyopathy (DCM), and to establish the correlation between atrio-ventricular block...

  4. Modeling and study of the mechanism of dilated cardiomyopathy using induced pluripotent stem cells derived from individuals with Duchenne muscular dystrophy.

    Science.gov (United States)

    Lin, Bo; Li, Yang; Han, Lu; Kaplan, Aaron D; Ao, Ying; Kalra, Spandan; Bett, Glenna C L; Rasmusson, Randall L; Denning, Chris; Yang, Lei

    2015-05-01

    Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene (DMD), and is characterized by progressive weakness in skeletal and cardiac muscles. Currently, dilated cardiomyopathy due to cardiac muscle loss is one of the major causes of lethality in late-stage DMD patients. To study the molecular mechanisms underlying dilated cardiomyopathy in DMD heart, we generated cardiomyocytes (CMs) from DMD and healthy control induced pluripotent stem cells (iPSCs). DMD iPSC-derived CMs (iPSC-CMs) displayed dystrophin deficiency, as well as the elevated levels of resting Ca(2+), mitochondrial damage and cell apoptosis. Additionally, we found an activated mitochondria-mediated signaling network underlying the enhanced apoptosis in DMD iPSC-CMs. Furthermore, when we treated DMD iPSC-CMs with the membrane sealant Poloxamer 188, it significantly decreased the resting cytosolic Ca(2+) level, repressed caspase-3 (CASP3) activation and consequently suppressed apoptosis in DMD iPSC-CMs. Taken together, using DMD patient-derived iPSC-CMs, we established an in vitro model that manifests the major phenotypes of dilated cardiomyopathy in DMD patients, and uncovered a potential new disease mechanism. Our model could be used for the mechanistic study of human muscular dystrophy, as well as future preclinical testing of novel therapeutic compounds for dilated cardiomyopathy in DMD patients. © 2015. Published by The Company of Biologists Ltd.

  5. Usefulness of sugammadex in a patient with Becker muscular dystrophy and dilated cardiomyopathy.

    Science.gov (United States)

    Shimauchi, Tsukasa; Yamaura, Ken; Sugibe, Sayaka; Hoka, Sumio

    2014-09-01

    A 54-year-old patient with Becker muscular dystrophy and dilated cardiomyopathy underwent laparoscopic cholecystectomy under total intravenous anesthesia. Muscle relaxation was induced by rocuronium (0.4 mg/kg body weight) under train-of-four (TOF) ratio monitoring. The TOF ratio was 0 at intubation, and 0.2 at the end of surgery. Residual muscle relaxant activity was successfully reversed by sugammadex (2 mg/kg body weight) without any hemodynamic adverse effects (TOF ratio 1.0 at extubation). The clinical and hemodynamic findings suggest that sugammadex can be safely used in patients with Becker muscular dystrophy and dilated cardiomyopathy. Copyright © 2014. Published by Elsevier B.V.

  6. Electrical storm in a patient with dilated non-ischaemic cardiomyopathy.

    Science.gov (United States)

    De Meyer, Grim; Van Beeumen, Katarina; Duytschaever, Mattias

    2009-10-01

    Bundle-branch re-entrant ventricular tachycardia (BBRVT) is usually seen in patients with dilated cardiomyopathy. The diagnosis should be suspected in case the QRS morphology during the tachycardia is identical to that in sinus rhythm. Identifying patients with BBRVT is important because they can be easily treated by catheter ablation. This report describes a patient previously implanted with a cardiac resynchronization therapy defibrillator (CRT-D) presenting with an electrical storm due to BBRVT.

  7. Myocardium of patients with dilated cardiomyopathy presents altered expression of genes involved in thyroid hormone biosynthesis.

    Directory of Open Access Journals (Sweden)

    Carolina Gil-Cayuela

    Full Text Available The association between dilated cardiomyopathy (DCM and low thyroid hormone (TH levels has been previously described. In these patients abnormal thyroid function is significantly related to impaired left ventricular (LV function and increased risk of death. Although TH was originally thought to be produced exclusively by the thyroid gland, we recently reported TH biosynthesis in the human ischemic heart.Based on these findings, we evaluated whether the genes required for TH production are also altered in patients with DCM.Twenty-three LV tissue samples were obtained from patients with DCM (n = 13 undergoing heart transplantation and control donors (n = 10, and used for RNA sequencing analysis. The number of LV DCM samples was increased to 23 to determine total T4 and T3 tissue levels by ELISA.We found that all components of TH biosynthesis are expressed in human dilated heart tissue. Expression of genes encoding thyroperoxidase (-2.57-fold, P < 0.05 and dual oxidase 2 (2.64-fold, P < 0.01, the main enzymatic system of TH production, was significantly altered in patients with DCM and significantly associated with LV remodeling parameters. Thyroxine (T4 cardiac tissue levels were significantly increased (P < 0.01, whilst triiodothyronine (T3 levels were significantly diminished (P < 0.05 in the patients.Expression of TH biosynthesis machinery in the heart and total tissue levels of T4 and T3, are altered in patients with DCM. Given the relevance of TH in cardiac pathology, our results provide a basis for new gene-based therapeutic strategies for treating DCM.

  8. Diagnosis and assessment of dilated cardiomyopathy: a guideline protocol from the British Society of Echocardiography

    Directory of Open Access Journals (Sweden)

    Thomas Mathew

    2017-06-01

    Full Text Available Heart failure (HF is a debilitating and life-threatening condition, with 5-year survival rate lower than breast or prostate cancer. It is the leading cause of hospital admission in over 65s, and these admissions are projected to rise by more than 50% over the next 25 years. Transthoracic echocardiography (TTE is the first-line step in diagnosis in acute and chronic HF and provides immediate information on chamber volumes, ventricular systolic and diastolic function, wall thickness, valve function and the presence of pericardial effusion, while contributing to information on aetiology. Dilated cardiomyopathy (DCM is the third most common cause of HF and is the most common cardiomyopathy. It is defined by the presence of left ventricular dilatation and left ventricular systolic dysfunction in the absence of abnormal loading conditions (hypertension and valve disease or coronary artery disease sufficient to cause global systolic impairment. This document provides a practical approach to diagnosis and assessment of dilated cardiomyopathy that is aimed at the practising sonographer.

  9. [Dilated cardiomyopathy (DCM) in dogs--pathological, clinical, diagnosis and genetic aspects].

    Science.gov (United States)

    Broschk, C; Distl, O

    2005-10-01

    Dilated cardiomyopathy (DCM) is a heart disease which is often found in humans and animals. The age of onset of this progressive disease varies between 3 and 7 years of age. A juvenile form of DCM has been found in Portuguese Water Dogs and Doberman Pinscher Dogs. Some breeds such as Doberman pinscher, Newfoundland, Portuguese Water dog, Boxer, Great Dane, Cocker Spaniel and Irish Wolfhound exhibit a higher prevalence to DCM. There also seems to be a sex predisposition as male dogs are affected more often than female dogs and in Great Danes an X-linked recessive inheritance is likely. In Newfoundland and Boxer an autosomal dominant inheritance was found whereas an autosomal recessive inheritance was described in Portuguese Water Dogs. Atrial fibrillation as a cause or consequence of DCM is assumed for certain breeds. The causes of DCM are widely unknown in dogs. A genetic basis for this heart disease seems to exist. Apart from a few exceptions the mode of inheritance and the possible underlying gene mutations are not known for DCM in dogs. In humans mutations in several genes responsible for DCM have been identified. Comparative genetic analyses in dogs using genes causing DCM in men and a genome-wide scan with anonymus markers were not able to detect causative mutations or genomic regions harboring gene loci linked to DCM. The investigation of the genetic basis of canine DCM may lead to new insights into the pathogenesis of DCM and may result in new therapeutic approaches and breeding strategies.

  10. Intracoronary allogeneic cardiosphere-derived stem cells are safe for use in dogs with dilated cardiomyopathy.

    Science.gov (United States)

    Hensley, Michael Taylor; Tang, Junnan; Woodruff, Kathleen; Defrancesco, Teresa; Tou, Sandra; Williams, Christina M; Breen, Mathew; Meurs, Kathryn; Keene, Bruce; Cheng, Ke

    2017-08-01

    Cardiosphere-derived cells (CDCs) have been shown to reduce scar size and increase viable myocardium in human patients with mild/moderate myocardial infarction. Studies in rodent models suggest that CDC therapy may confer therapeutic benefits in patients with non-ischaemic dilated cardiomyopathy (DCM). We sought to determine the safety and efficacy of allogeneic CDC in a large animal (canine) model of spontaneous DCM. Canine CDCs (cCDCs) were grown from a donor dog heart. Similar to human CDCs, cCDCs express CD105 and are slightly positive for c-kit and CD90. Thirty million of allogeneic cCDCs was infused into the coronary vessels of Doberman pinscher dogs with spontaneous DCM. Adverse events were closely monitored, and cardiac functions were measured by echocardiography. No adverse events occurred during and after cell infusion. Histology on dog hearts (after natural death) revealed no sign of immune rejection from the transplanted cells. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  11. Molecular evaluation of five cardiac genes in Doberman Pinschers with dilated cardiomyopathy.

    Science.gov (United States)

    Meurs, Kathryn M; Hendrix, Kristina P; Norgard, Michelle M

    2008-08-01

    To sequence the exonic and splice site regions of 5 cardiac genes associated with the human form of familial dilated cardiomyopathy (DCM) in Doberman Pinschers with DCM and to identify a causative mutation. 5 unrelated Doberman Pinschers with DCM and 2 unaffected Labrador Retrievers (control dogs). Exonic and splice site regions of the 5 genes encoding the cardiac proteins troponin C, lamin A/C, cysteine- and glycine-rich protein 3, cardiac troponin T, and the beta-myosin heavy chain were sequenced. Sequences were compared for nucleotide changes between affected dogs and the published canine sequences and 2 control dogs. Base pair changes were considered to be causative for DCM if they were present in an affected dog but not in the control dogs or published sequences and if they involved a conserved amino acid and changed that amino acid to a different polarity, acid-base status, or structure. A causative mutation for DCM in Doberman Pinschers was not identified, although single nucleotide polymorphisms were detected in some dogs in the cysteine- and glycine-rich protein 3, beta-myosin heavy chain, and troponin T genes. Mutations in 5 of the cardiac genes associated with the development of DCM in humans did not appear to be causative for DCM in Doberman Pinschers. Continued evaluation of additional candidate genes or a focused approach with an association analysis is warranted to elucidate the molecular cause of this important cardiac disease in Doberman Pinschers.

  12. An Upgrade on the Rabbit Model of Anthracycline-Induced Cardiomyopathy: Shorter Protocol, Reduced Mortality, and Higher Incidence of Overt Dilated Cardiomyopathy

    Science.gov (United States)

    Talavera, Jesús; Fernández-Del-Palacio, María Josefa; García-Nicolás, Obdulio; Seva, Juan; Brooks, Gavin; Moraleda, Jose M.

    2015-01-01

    Current protocols of anthracycline-induced cardiomyopathy in rabbits present with high premature mortality and nephrotoxicity, thus rendering them unsuitable for studies requiring long-term functional evaluation of myocardial function (e.g., stem cell therapy). We compared two previously described protocols to an in-house developed protocol in three groups: Group DOX2 received doxorubicin 2 mg/kg/week (8 weeks); Group DAU3 received daunorubicin 3 mg/kg/week (10 weeks); and Group DAU4 received daunorubicin 4 mg/kg/week (6 weeks). A cohort of rabbits received saline (control). Results of blood tests, cardiac troponin I, echocardiography, and histopathology were analysed. Whilst DOX2 and DAU3 rabbits showed high premature mortality (50% and 33%, resp.), DAU4 rabbits showed 7.6% premature mortality. None of DOX2 rabbits developed overt dilated cardiomyopathy; 66% of DAU3 rabbits developed overt dilated cardiomyopathy and quickly progressed to severe congestive heart failure. Interestingly, 92% of DAU4 rabbits showed overt dilated cardiomyopathy and 67% developed congestive heart failure exhibiting stable disease. DOX2 and DAU3 rabbits showed alterations of renal function, with DAU3 also exhibiting hepatic function compromise. Thus, a shortened protocol of anthracycline-induced cardiomyopathy as in DAU4 group results in high incidence of overt dilated cardiomyopathy, which insidiously progressed to congestive heart failure, associated to reduced systemic compromise and very low premature mortality. PMID:26788502

  13. A novel alpha-tropomyosin mutation associates with dilated and non-compaction cardiomyopathy and diminishes actin binding

    NARCIS (Netherlands)

    van de Meerakker, Judith B. A.; Christiaans, Imke; Barnett, Phil; Lekanne Deprez, Ronald H.; Ilgun, Aho; Mook, Olaf R. F.; Mannens, Marcel M. A. M.; Lam, Jan; Wilde, Arthur A. M.; Moorman, Antoon F. M.; Postma, Alex V.

    2013-01-01

    Dilated cardiomyopathy (DCM) is characterized by idiopathic dilatation and systolic contractile dysfunction of the ventricle(s) leading to an impaired systolic function. The origin of DCM is heterogeneous, but genetic transmission of the disease accounts for up to 50% of the cases. Mutations in

  14. Dysregulated IER3 Expression is Associated with Enhanced Apoptosis in Titin-Based Dilated Cardiomyopathy

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    Qifeng Zhou

    2017-03-01

    Full Text Available Apoptosis (type I programmed cell death of cardiomyocytes is a major process that plays a role in the progression of heart failure. The early response gene IER3 regulates apoptosis in a wide variety of cells and organs. However, its role in heart failure is largely unknown. Here, we investigate the role of IER3 in an inducible heart failure mouse model. Heart failure was induced in a mouse model that imitates a human titin truncation mutation we found in a patient with dilated cardiomyopathy (DCM. Transferase dUTP nick end labeling (TUNEL and ssDNA stainings showed induction of apoptosis in titin-deficient cardiomyocytes during heart failure development, while IER3 response was dysregulated. Chromatin immunoprecipitation and knock-down experiments revealed that IER3 proteins target the promotors of anti-apoptotic genes and act as an anti-apoptotic factor in cardiomyocytes. Its expression is blunted during heart failure development in a titin-deficient mouse model. Targeting the IER3 pathway to reduce cardiac apoptosis might be an effective therapeutic strategy to combat heart failure.

  15. A predictive model for canine dilated cardiomyopathy—a meta-analysis of Doberman Pinscher data

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    Siobhan Simpson

    2015-03-01

    Full Text Available Dilated cardiomyopathy is a prevalent and often fatal disease in humans and dogs. Indeed dilated cardiomyopathy is the third most common form of cardiac disease in humans, reported to affect approximately 36 individuals per 100,000 individuals. In dogs, dilated cardiomyopathy is the second most common cardiac disease and is most prevalent in the Irish Wolfhound, Doberman Pinscher and Newfoundland breeds. Dilated cardiomyopathy is characterised by ventricular chamber enlargement and systolic dysfunction which often leads to congestive heart failure. Although multiple human loci have been implicated in the pathogenesis of dilated cardiomyopathy, the identified variants are typically associated with rare monogenic forms of dilated cardiomyopathy. The potential for multigenic interactions contributing to human dilated cardiomyopathy remains poorly understood. Consistent with this, several known human dilated cardiomyopathy loci have been excluded as common causes of canine dilated cardiomyopathy, although canine dilated cardiomyopathy resembles the human disease functionally. This suggests additional genetic factors contribute to the dilated cardiomyopathy phenotype.This study represents a meta-analysis of available canine dilated cardiomyopathy genetic datasets with the goal of determining potential multigenic interactions relating the sex chromosome genotype (XX vs. XY with known dilated cardiomyopathy associated loci on chromosome 5 and the PDK4 gene in the incidence and progression of dilated cardiomyopathy. The results show an interaction between known canine dilated cardiomyopathy loci and an unknown X-linked locus. Our study is the first to test a multigenic contribution to dilated cardiomyopathy and suggest a genetic basis for the known sex-disparity in dilated cardiomyopathy outcomes.

  16. Myofilament Remodeling and Function Is More Impaired in Peripartum Cardiomyopathy Compared with Dilated Cardiomyopathy and Ischemic Heart Disease.

    Science.gov (United States)

    Bollen, Ilse A E; Ehler, Elisabeth; Fleischanderl, Karin; Bouwman, Floor; Kempers, Lanette; Ricke-Hoch, Melanie; Hilfiker-Kleiner, Denise; Dos Remedios, Cristobal G; Krüger, Martina; Vink, Aryan; Asselbergs, Folkert W; van Spaendonck-Zwarts, Karin Y; Pinto, Yigal M; Kuster, Diederik W D; van der Velden, Jolanda

    2017-12-01

    Peripartum cardiomyopathy (PPCM) and dilated cardiomyopathy (DCM) show similarities in clinical presentation. However, although DCM patients do not recover and slowly deteriorate further, PPCM patients show either a fast cardiac deterioration or complete recovery. The aim of this study was to assess if underlying cellular changes can explain the clinical similarities and differences in the two diseases. We, therefore, assessed sarcomeric protein expression, modification, titin isoform shift, and contractile behavior of cardiomyocytes in heart tissue of PPCM and DCM patients and compared these with nonfailing controls. Heart samples from ischemic heart disease (ISHD) patients served as heart failure control samples. Passive force was only increased in PPCM samples compared with controls, whereas PPCM, DCM, and ISHD samples all showed increased myofilament Ca 2+ sensitivity. Length-dependent activation was significantly impaired in PPCM compared with controls, no impairment was observed in ISHD samples, and DCM samples showed an intermediate response. Contractile impairments were caused by impaired protein kinase A (PKA)-mediated phosphorylation because exogenous PKA restored all parameters to control levels. Although DCM samples showed reexpression of EH-myomesin, an isoform usually only expressed in the heart before birth, PPCM and ISHD did not. The lack of EH-myomesin, combined with low PKA-mediated phosphorylation of myofilament proteins and increased compliant titin isoform, may explain the increase in passive force and blunted length-dependent activation of myofilaments in PPCM samples. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  17. Clinical assessment of serum myosin light chain I in patients with dilated cardiomyopathy

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    Tsuda, Takashi; Izumi, Tohru; Shibata, Akira (Niigata Univ. (Japan). School of Medicine)

    1992-08-01

    Serum cardiac myosin light chain I (LCI) levels were quantitated using a radioimmunoassay kit in patients suspected of dilated cardiomyopathy (DCM). In this study, 55 patients were evaluated between 1986 and 1991. They were composed of 40 males and 15 females, and their age was 27-75 years (51[+-]11 years). The patients with renal dysfunction were excluded due to their serum creatinine levels (>2.0 mg/dl). After cardiac catheterization, endomyocardial biopsy and echocardiography, 44 patients were diagnosed as DCM, 2 as ischemic heart disease, 2 as chronic myocarditis, 1 as restrictive cardiomyopathy, 1 as dilated hypertrophic cardiomyopathy, 1 as cardiac amyloidosis, 2 as myopathy, 1 as polymyositis and 1 as hypothyroidism. Only two patients with DCM had elevated LCI. Besides, two patients with myopathy or hypothyroidism had elevated LCI. In the follow-up, one patient died suddenly 6 months later and another showed normal value of LCI four years later. LCI elevation in DCM was not related to either the severity of heart failure or cardiac function and it showed no finding of [sup 201]Tl myocardial defect or elevated CPK. The mechanism for elevated LCI in myopathy is related to a crossreaction with myosin light chain in the skeletal muscle. In hypothyroidism, it may be related to decreased clearance of normal LCI concentration or increased myosin light chain from damaged skeletal muscle. In conclusion, it is evident that the measurement of LCI is not helpful in clinical assessment of patients with DCM, but may be useful in detection of secondary cardiomyopathy. (author).

  18. Clinical assessment of serum myosin light chain I in patients with dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Tsuda, Takashi; Izumi, Tohru; Shibata, Akira

    1992-01-01

    Serum cardiac myosin light chain I (LCI) levels were quantitated using a radioimmunoassay kit in patients suspected of dilated cardiomyopathy (DCM). In this study, 55 patients were evaluated between 1986 and 1991. They were composed of 40 males and 15 females, and their age was 27-75 years (51±11 years). The patients with renal dysfunction were excluded due to their serum creatinine levels (>2.0 mg/dl). After cardiac catheterization, endomyocardial biopsy and echocardiography, 44 patients were diagnosed as DCM, 2 as ischemic heart disease, 2 as chronic myocarditis, 1 as restrictive cardiomyopathy, 1 as dilated hypertrophic cardiomyopathy, 1 as cardiac amyloidosis, 2 as myopathy, 1 as polymyositis and 1 as hypothyroidism. Only two patients with DCM had elevated LCI. Besides, two patients with myopathy or hypothyroidism had elevated LCI. In the follow-up, one patient died suddenly 6 months later and another showed normal value of LCI four years later. LCI elevation in DCM was not related to either the severity of heart failure or cardiac function and it showed no finding of 201 Tl myocardial defect or elevated CPK. The mechanism for elevated LCI in myopathy is related to a crossreaction with myosin light chain in the skeletal muscle. In hypothyroidism, it may be related to decreased clearance of normal LCI concentration or increased myosin light chain from damaged skeletal muscle. In conclusion, it is evident that the measurement of LCI is not helpful in clinical assessment of patients with DCM, but may be useful in detection of secondary cardiomyopathy. (author)

  19. Hypoxia induces dilated cardiomyopathy in the chick embryo: mechanism, intervention, and long-term consequences.

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    Andrei Tintu

    Full Text Available Intrauterine growth restriction is associated with an increased future risk for developing cardiovascular diseases. Hypoxia in utero is a common clinical cause of fetal growth restriction. We have previously shown that chronic hypoxia alters cardiovascular development in chick embryos. The aim of this study was to further characterize cardiac disease in hypoxic chick embryos.Chick embryos were exposed to hypoxia and cardiac structure was examined by histological methods one day prior to hatching (E20 and at adulthood. Cardiac function was assessed in vivo by echocardiography and ex vivo by contractility measurements in isolated heart muscle bundles and isolated cardiomyocytes. Chick embryos were exposed to vascular endothelial growth factor (VEGF and its scavenger soluble VEGF receptor-1 (sFlt-1 to investigate the potential role of this hypoxia-regulated cytokine.Growth restricted hypoxic chick embryos showed cardiomyopathy as evidenced by left ventricular (LV dilatation, reduced ventricular wall mass and increased apoptosis. Hypoxic hearts displayed pump dysfunction with decreased LV ejection fractions, accompanied by signs of diastolic dysfunction. Cardiomyopathy caused by hypoxia persisted into adulthood. Hypoxic embryonic hearts showed increases in VEGF expression. Systemic administration of rhVEGF(165 to normoxic chick embryos resulted in LV dilatation and a dose-dependent loss of LV wall mass. Lowering VEGF levels in hypoxic embryonic chick hearts by systemic administration of sFlt-1 yielded an almost complete normalization of the phenotype.Our data show that hypoxia causes a decreased cardiac performance and cardiomyopathy in chick embryos, involving a significant VEGF-mediated component. This cardiomyopathy persists into adulthood.

  20. Evaluation of 10 genes encoding cardiac proteins in Doberman Pinschers with dilated cardiomyopathy.

    Science.gov (United States)

    O'Sullivan, M Lynne; O'Grady, Michael R; Pyle, W Glen; Dawson, John F

    2011-07-01

    To identify a causative mutation for dilated cardiomyopathy (DCM) in Doberman Pinschers by sequencing the coding regions of 10 cardiac genes known to be associated with familial DCM in humans. 5 Doberman Pinschers with DCM and congestive heart failure and 5 control mixed-breed dogs that were euthanized or died. RNA was extracted from frozen ventricular myocardial samples from each dog, and first-strand cDNA was synthesized via reverse transcription, followed by PCR amplification with gene-specific primers. Ten cardiac genes were analyzed: cardiac actin, α-actinin, α-tropomyosin, β-myosin heavy chain, metavinculin, muscle LIM protein, myosinbinding protein C, tafazzin, titin-cap (telethonin), and troponin T. Sequences for DCM-affected and control dogs and the published canine genome were compared. None of the coding sequences yielded a common causative mutation among all Doberman Pinscher samples. However, 3 variants were identified in the α-actinin gene in the DCM-affected Doberman Pinschers. One of these variants, identified in 2 of the 5 Doberman Pinschers, resulted in an amino acid change in the rod-forming triple coiled-coil domain. Mutations in the coding regions of several genes associated with DCM in humans did not appear to consistently account for DCM in Doberman Pinschers. However, an α-actinin variant was detected in some Doberman Pinschers that may contribute to the development of DCM given its potential effect on the structure of this protein. Investigation of additional candidate gene coding and noncoding regions and further evaluation of the role of α-actinin in development of DCM in Doberman Pinschers are warranted.

  1. Nuclear magnetic resonance imaging in patients with hypertrophic and dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Boisvieux, A.

    1987-01-01

    Patients with hypertrophic and dilated cardiomyopathy and normal subjects were investigated with nuclear magnetic resonance imaging. To evaluate the NMR scanner possibilities, the results were compared with the echocardiographic investigation of the same patients. The capabilities of NMR imaging to provide information about intracardiac anatomy are emphasized. This study is preceded by a description of the physical principles underlying the phenomenon of nuclear magnetic resonance and of the techniques used to obtain NMR images and a review of the clinical use of NMR imaging for cardiac diagnosis [fr

  2. New and emerging biomarkers in left ventricular systolic dysfunction--insight into dilated cardiomyopathy.

    Science.gov (United States)

    Gopal, Deepa M; Sam, Flora

    2013-08-01

    Dilated cardiomyopathy (DCM) is characterized by deteriorating cardiac performance, impaired contraction and dilation of the left ventricle (or both ventricles). Blood markers--known as "biomarkers"--allow insight into underlying pathophysiologic mechanisms and biologic pathways while predicting outcomes and guiding heart failure management and/or therapies. In this review, we provide an alternative approach to conceptualize heart failure biomarkers: the cardiomyocyte, its surrounding microenvironment, and the macroenvironment, integrating these entities which may impact cellular processes involved in the pathogenesis and/or propagation of DCM. Newer biomarkers of left ventricular systolic dysfunction can be categorized under: (a) myocyte stress and stretch, (b) myocyte apoptosis, (c) cardiac interstitium, (d) inflammation, (e) oxidative stress, (f) cardiac energetics, (g) neurohormones, and (h) renal biomarkers. Biomarkers provide insight into the pathogenesis of DCM while predicting and potentially providing prognostic information in these patients with heart failure.

  3. New and Emerging Biomarkers in Left Ventricular Systolic Dysfunction - Insight into Dilated Cardiomyopathy

    Science.gov (United States)

    Gopal, Deepa M.; Sam, Flora

    2013-01-01

    Background Dilated cardiomyopathy (DCM) is characterized by deteriorating cardiac performance and impaired contraction and dilation of the left (or both) ventricles. Blood markers – known as “biomarkers” allow insight into underlying pathophysiologic mechanisms and biologic pathways, while predicting outcomes and guiding heart failure management and/or therapies. Content In this review, we provide an alternative approach to conceptualize heart failure biomarkers: the cardiomyocyte, its surrounding microenvironment, and the macroenvironment with clear interaction between these entities which may impact cellular processes involved in the pathogenesis and/or propagation of DCM. Newer biomarkers of left ventricular systolic dysfunction can be categorized under: (a) myocyte stress and stretch, (b) myocyte apoptosis, (c) cardiac interstitium, (d) inflammation, (e) oxidative stress, (f) cardiac energetics, (g) neurohormones and (h) renal biomarkers. Summary Biomarkers provide insight into the pathogenesis of DCM while predicting and potentially providing prognostic information in these patients with heart failure. PMID:23609585

  4. Heart rate turbulence after ventricular premature beats in healthy Doberman pinschers and those with dilated cardiomyopathy.

    Science.gov (United States)

    Harris, J D; Little, C J L; Dennis, J M; Patteson, M W

    2017-10-01

    To describe the measurement of heart rate turbulence (HRT) after ventricular premature beats and compare HRT in healthy Doberman pinschers and those with dilated cardiomyopathy (DCM), with and without congestive heart failure (CHF). Sixty-five client-owned Dobermans: 20 healthy (NORMAL), 31 with preclinical DCM and 14 with DCM and CHF (DCM + CHF). A retrospective study of data retrieved from clinical records and ambulatory ECG (Holter) archives, including data collected previously for a large-scale prospective study of Dobermans with preclinical DCM. Holter data were reanalysed quantitatively, including conventional time-domain heart rate variability and the HRT parameters turbulence onset and turbulence slope. Heart rate turbulence could be measured in 58/65 dogs. Six Holter recordings had inadequate ventricular premature contractions (VPCs) and one exhibited VPCs too similar to sinus morphology. Heart rate turbulence parameter, turbulence onset, was significantly reduced in DCM dogs, whereas conventional heart rate variability measures were not. Heart rate variability and HRT markers were reduced in DCM + CHF dogs as expected. Heart rate turbulence can be measured from the majority of good quality standard canine 24-hour Holter recordings with >5 VPCs. Turbulence onset is significantly reduced in Dobermans with preclinical DCM which indicates vagal withdrawal early in the course of disease. Heart rate turbulence is a powerful prognostic indicator in human cardiac disease which can be measured from standard 24-hour ambulatory ECG (Holter) recordings using appropriate computer software. Further studies are warranted to assess whether HRT may be of prognostic value in dogs with preclinical DCM and in other canine cardiac disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Dilated cardiomyopathy and left bundle branch block associated with ingestion of colloidal gold and silver is reversed by British antiLewisite and vitamin E: The potential toxicity of metals used as health supplements

    Science.gov (United States)

    Archer, Stephen Lawrence

    2008-01-01

    A case of left bundle branch block and a dilated, nonhypertrophic cardiomyopathy associated with ingestion of colloidal gold and silver as an ‘energy tonic’ is described. The cardiac disease was reversed within two months by a course of dimercaprol (Akorn Inc, USA) (British antiLewisite) and vitamin E. This is the first case of gold and silver cardiomyopathy in humans, and highlights the risks of these colloidal metal ‘health supplements’. PMID:18464946

  6. Infectious agents and inflammation in donated hearts and dilated cardiomyopathies related to cardiovascular diseases, Chagas' heart disease, primary and secondary dilated cardiomyopathies.

    Science.gov (United States)

    Mangini, Sandrigo; Higuchi, Maria de Lourdes; Kawakami, Joyce Tiyeko; Reis, Marcia Martins; Ikegami, Renata Nishiyama; Palomino, Suely Aparecida Pinheiro; Pomerantzeff, Pablo Maria Alberto; Fiorelli, Alfredo Inácio; Marcondes-Braga, Fabiana Goulart; Bacal, Fernando; Ferreira, Sílvia Moreira Ayub; Issa, Victor Sarli; Souza, Germano Emílio Conceição; Chizzola, Paulo Roberto; Bocchi, Edimar Alcides

    2015-01-15

    Clinical and experimental conflicting data have questioned the relationship between infectious agents, inflammation and dilated cardiomyopathy (DCM). The aim of this study was to determine the frequency of infectious agents and inflammation in endomyocardial biopsy (EMB) specimens from patients with idiopathic DCM, explanted hearts from different etiologies, including Chagas' disease, compared to donated hearts. From 2008 to 2011, myocardial samples from 29 heart donors and 55 patients with DCMs from different etiologies were studied (32 idiopathic, 9 chagasic, 6 ischemic and 8 other specific etiologies). Inflammation was investigated by immunohistochemistry and infectious agents by immunohistochemistry, molecular biology, in situ hybridization and electron microscopy. There were no differences regarding the presence of macrophages, expression of HLA class II and ICAM-I in donors and DCM. Inflammation in Chagas' disease was predominant. By immunohistochemistry, in donors, there was a higher expression of antigens of enterovirus and Borrelia, hepatitis B and C in DCMs. By molecular biology, in all groups, the positivity was elevated to microorganisms, including co-infections, with a higher positivity to adenovirus and HHV6 in donors towards DCMs. This study was the first to demonstrate the presence of virus in the heart tissue of chagasic DCM. The presence of inflammation and infectious agents is frequent in donated hearts, in the myocardium of patients with idiopathic DCM, myocardial dysfunction related to cardiovascular diseases, and primary and secondary cardiomyopathies, including Chagas' disease. The role of co-infection in Chagas' heart disease physiopathology deserves to be investigated in future studies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Assessment of cardiac neuronal function with iodine-123 MIBG scintigraphy in children with idiopathic dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Maunoury, Ch.; Sebahoun, St.; Hallaj, I.; Barritault, L.; Acar, Ph.; Sidi, D.; Kachaner, J.; Agostini, D.; Bouvard, G.

    2000-01-01

    The I-123 MIBG cardiac scintigraphy can assess norepinephrine uptake. It has been showed that cardiac adrenergic neuronal function was impaired in adults with dilated cardiomyopathy. The aim of this prospective study was to assess cardiac neuronal function in children with idiopathic dilated cardiomyopathy (DCM) and to compare cardiac uptake of I-123 MIBG with left ventricular ejection fraction (LVEF). We studied 26 consecutive patients with idiopathic DCM, aged 44 ± 50 months, and 12 controls, aged 49 ±65 months. A planar scintigraphy was performed in all children 4 hours after intravenous injection of 20 to 75 MBq of I-123 MIBG. A static anterior view was acquired for 10 minutes. Cardiac uptake of I-123 MIBG was expressed as the heart to mediastinum count ratio (HMR). Equilibrium radionuclide angiography was performed following a standard protocol. Cardiac uptake of I-123 MIBG was significantly decreased in patients with idiopathic DCM when compared with cardiac uptake in controls (172±34% vs 277±14%, P<0.0001. There was a good correlation between RCM and LVEF in patients with idiopathic DCM (y = 2.5 x +113.3, r = 0.80, P < 0.0001). In conclusion, cardiac neuronal function was impaired in children with idiopathic DCM and related to impairment of left ventricular function. (author)

  8. Autosomal recessive dilated cardiomyopathy due to DOLK mutations results from abnormal dystroglycan O-mannosylation.

    Directory of Open Access Journals (Sweden)

    Dirk J Lefeber

    2011-12-01

    Full Text Available Genetic causes for autosomal recessive forms of dilated cardiomyopathy (DCM are only rarely identified, although they are thought to contribute considerably to sudden cardiac death and heart failure, especially in young children. Here, we describe 11 young patients (5-13 years with a predominant presentation of dilated cardiomyopathy (DCM. Metabolic investigations showed deficient protein N-glycosylation, leading to a diagnosis of Congenital Disorders of Glycosylation (CDG. Homozygosity mapping in the consanguineous families showed a locus with two known genes in the N-glycosylation pathway. In all individuals, pathogenic mutations were identified in DOLK, encoding the dolichol kinase responsible for formation of dolichol-phosphate. Enzyme analysis in patients' fibroblasts confirmed a dolichol kinase deficiency in all families. In comparison with the generally multisystem presentation in CDG, the nonsyndromic DCM in several individuals was remarkable. Investigation of other dolichol-phosphate dependent glycosylation pathways in biopsied heart tissue indicated reduced O-mannosylation of alpha-dystroglycan with concomitant functional loss of its laminin-binding capacity, which has been linked to DCM. We thus identified a combined deficiency of protein N-glycosylation and alpha-dystroglycan O-mannosylation in patients with nonsyndromic DCM due to autosomal recessive DOLK mutations.

  9. Imaging and 1-day kinetics of intracoronary stem cell transplantation in patients with idiopathic dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Lezaic, Luka; Socan, Aljaz; Peitl, Petra Kolenc; Poglajen, Gregor; Sever, Matjaz; Cukjati, Marko; Cernelc, Peter; Vrtovec, Bojan

    2016-01-01

    Background: Stem cell transplantation is an emerging method of treatment for patients with cardiovascular disease. There are few studies completed or ongoing on stem cell therapy in patients with idiopathic dilated cardiomyopathy (IDCM). Information on stem cell homing and distribution in the myocardium after transplantation might provide important insight into effectiveness of transplantation procedure. Aim: To assess early engraftment, retention and migration of intracoronarily transplanted stem cells in the myocardium of patients with advanced dilated cardiomyopathy of non-ischaemic origin using stem cell labeling with 99m Tc-exametazime (HMPAO). Materials, methods: Thirty-five patients with IDCM and advanced heart failure were included in the study. Autologous hematopoietic (CD34 +) stem cells were harvested by peripheral blood apheresis after bone marrow stimulation, labeled with 99m Tc-HMPAO, tested for viability and injected into coronary vessel supplying areas of myocardium selected by myocardial perfusion scintigraphy as dysfunctional yet viable. Imaging was performed 1 h and 18 h after transplantation. Results: Myocardial stem cell retention ranged from 0 to 1.44% on early and 0–0.97% on delayed imaging. Significant efflux of stem cells occurred from site of delivery in this time period (p < 0.001). Stem cell viability was not affected by labeling. Conclusion: Stem cell labeling with 99m Tc-HMPAO is a feasible method for stem cell tracking after transplantation in patients with IDCM.

  10. Oral Chinese Herbal Medicine for Treatment of Dilated Cardiomyopathy: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yu-Shuo Zhu

    2016-01-01

    Full Text Available Dilated cardiomyopathy (DCM is one of the main causes of heart failure and could increase death, hospitalization, and rehospitalization rate. The effect of conventional medicine treatment (CMT is limited; meanwhile, the combination of CMT and Oral Chinese Herbal Medicine (OCHM represents exciting adjunctive therapies. In this study, we ascertained the therapeutic effect of OCHM in combination with CMT for dilated cardiomyopathy by using meta-analysis methods for controlled clinical trials. We searched studies from five databases and extracted data from these studies. We also assessed the methodological quality of the included studies. We evaluated the following outcome measures to estimate the prognosis in patients with DCM: left ventricular ejection fraction (LVEF, left ventricular end-diastolic dimension (LVEDD, stroke volume (SV, brain natriuretic peptide (BNP, 6-minute walk test (6MWT, and overall efficacy. The result showed that OCHM combined with CMT for the improvement of therapeutic effect in DCM patients. However, the evidence remains weak due to the small sample size, high clinical heterogeneity, and poor methodological quality of the included trials. Further, large sample size and well-designed trials are needed.

  11. Myocarditis in Paediatric Patients: Unveiling the Progression to Dilated Cardiomyopathy and Heart Failure

    Directory of Open Access Journals (Sweden)

    Inês Teixeira Farinha

    2016-11-01

    Full Text Available Myocarditis is a challenging and potentially life-threatening disease associated with high morbidity in some paediatric patients, due to its ability to present as an acute and fulminant disease and to ultimately progress to dilated cardiomyopathy. It has been described as an inflammatory disease of the myocardium caused by diverse aetiologies. Viral infection is the most frequent cause of myocarditis in developed countries, but bacterial and protozoal infections or drug hypersensitivity may also be causative agents. The prompt diagnosis in paediatric patients is difficult, as the spectrum of clinical manifestation can range from no myocardial dysfunction to sudden cardiac death. Recent studies on myocarditis pathogenesis have revealed a triphasic nature of this disease, which influences the diagnostic and therapeutic strategies to adopt in each patient. Endomyocardial biopsy remains the gold standard for diagnosing myocarditis, and several non-invasive diagnostic tools can be used to support the diagnosis. Intravenous immunoglobulin has become part of routine practice in the treatment of myocarditis in paediatric patients at many centres, but its true effect on the cardiac function has been the target of many studies. The aim of this review is to approach the recently discovered facets of paediatric myocarditis regarding its progression to dilated cardiomyopathy.

  12. With computed tomography confirmed anterolateral left ventricular pseudoaneurysm in patient with dilatative alcoholic cardiomyopathy

    International Nuclear Information System (INIS)

    Letonja, Mitja; Letonja, Marija Santl

    2011-01-01

    Pseudoaneurysms are rare complications of myocardial infarction with propensity for rupture. There is still a challenge with which diagnostic imaging we performed a final diagnosis of pseudoaneurysm and differentiate it from true aneurysm what is clinically important due to the different treatment. We presented the unusual case of a 56-year-old man with signs of decompensated heart failure which had worsened a few months before hospitalization. We believed that during worsening of symptoms the patient suffered a silent myocardial infarction complicated by subacute free wall rupture which resulted into left ventricular pseudoaneurysm formation without tamponade. Echocardiography showed dilatative cardiomyopathy which was already present years before and a very rare location of the left ventricular pseudoaneurysm on the anterolateral part of the left ventricle. Pseudoaneurysm was confirmed with CT scan. Due to the severity of contractile dysfunction and no response in treatment for congestive heart failure the directive for the resection was tempered and the patient died due to the progressive heart failure and embolic phenomena. This report shows the importance of non-invasive imaging diagnostic evaluation of acute decompensated heart failure where echocardiography and chest X-ray are the first diagnostic steps. Based on those findings further imaging diagnostic steps must be performed such as CT scan in our case which finally confirms left ventricular pseudoaneurysm with dilatative cardiomyopathy

  13. Investigation of MMP-2 and MMP-9 activities in canine sera with dilated cardiomyopathy.

    Science.gov (United States)

    Chegeni, S; Khaki, Z; Shirani, D; Vajhi, A; Taheri, M; Tamrchi, Y; Rostami, A

    2015-01-01

    Dilated cardiomyopathy (DCM) is accompanied by myocytes and connective tissue changes. Matrix metalloproteinases (MMPs) play important roles in cardiac remodeling. It seems that the gelatinases (MMP-2 and MMP-9) are effective enzymes in cardiomyopathy. Dilated cardiomyopathy was confirmed in 22 dogs (patient group) including 11 female and 11 male by clinical examination, auscultation, thoracic radiography and echocardiography. 17 healthy dogs (control group) with similar weight and breed to patients were also selected from referred cases to Small Animal Hospital of the Veterinary Faculty of Tehran University and the same diagnostic procedures were performed on them. After that, serum MMP-2 and MMP-9 of control and patient groups were measured by semi-quantitative zymography. Semiquantitative analysis of zymograms from canine serums with DCM showed that total MMP-9 in patients is more than control group, while there was no significant difference in total MMP-2 between the two groups. Pro-MMP-2 was not detected in patient group but its active form was present in both groups, of course MMP-2 activity in patients was significantly more than control. Active form of MMP-9 was detected only in patients. Although pro-MMP-9 was present in both groups, its level in control group was significantly higher than patients. The heart enlargement was observed in the left, right or both parts. Statistically significant differences in active form of MMP-2 and MMP-9 levels were observed between different groups of heart enlargement (right, left and both parts) compared to control but this difference was not significant considering chambers affected and VHS (vertebral heart score) groups. In conclusion, although there are some changes in serum MMP-2 and MMP-9 levels in canine DCM, it seems that increase of MMP-9 is more prominent than MMP-2 and neither of them were affected by heart enlargement or VHS grade.

  14. Analyses of more than 60,000 exomes questions the role of numerous genes previously associated with dilated cardiomyopathy

    DEFF Research Database (Denmark)

    Nouhravesh, Nina; Ahlberg, Gustav; Ghouse, Jonas

    2016-01-01

    BACKGROUND: Hundreds of genetic variants have been described as disease causing in dilated cardiomyopathy (DCM). Some of these associations are now being questioned. We aimed to identify the prevalence of previously DCM associated variants in the Exome Aggregation Consortium (ExAC), in order...... to identify potentially false-positive DCM variants. METHODS: Variants listed as DCM disease-causing variants in the Human Gene Mutation Database were extracted from ExAC. Pathogenicity predictions for these variants were mined from dbNSFP v 2.9 database. RESULTS: Of the 473 DCM variants listed in HGMD, 148...... (31%) were found in ExAC. The expected number of individuals with DCM in ExAC is 25 based on the prevalence in the general population. Yet, 35 variants were found in more than 25 individuals. In 13 genes, we identified all variants previously associated with DCM; four genes contained variants above...

  15. The relationship between the improvement of cardiac function and the myocardial uptake of I-123 metaiodobenzylguanidine in patients with dilated cardiomyopathy treated by beta-blocker

    International Nuclear Information System (INIS)

    Wakita, Tomio; Numata, Yuichi; Ogata, Yasuhiro; Harada, Eisaku; Mizumasa, Yutaka

    1995-01-01

    Chronic β-blocker therapy improves hemodynamics and cardiac function in patients with idiopathic dilated cardiomyopathy. However, the change in myocardial uptake of I-123 metaiodobenzylguanidine ( 123 I-MIBG) before and after treatment has not been determined. Myocardial imaging with 123 I-MIBG was performed before and 2 or 3 months after β-blocker (bisoprolol) therapy in 11 patients with dilated cardiomyopathy. The following parameters were compared before and after the treatment : 1) New York Heart Association functional class, 2) X-ray cardiothoracic ratio, 3) heart rate and blood pressure, 4) echocardiographic data (left ventricular end-diastolic and end-systolic diameters, and left ventricular ejection fraction), 5) plasma concentrations of epinephrine, norepinephrine and human atrial natriuretic peptide (HANP), and 6) exercise tolerance time by treadmill. The heart-to-mediastinum ratio of 123 I-MIBG activities obtained 3 hours after intravenous injection (late H/M) and washout rate improved significantly after β-blocker therapy. Cardiothoracic ratio, heart rate, echocardiographic parameters, HANP and exercise tolerance also improved significantly. Late H/M had no significant relationship with any of the clinical parameters, but washout rate was significantly related to left ventricular ejection fraction. These findings suggest that washout rate may be useful to assess the effect of short-term β-blocker therapy in dilated cardiomyopathy patients. (author)

  16. Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice : a position statement of the ESC working group on myocardial and pericardial diseases

    NARCIS (Netherlands)

    Pinto, Yigal M.; Elliott, Perry M.; Arbustini, Eloisa; Adler, Yehuda; Anastasakis, Aris; Boehm, Michael; Duboc, Denis; Gimeno, Juan; de Groote, Pascal; Imazio, Massimo; Heymans, Stephane; Klingel, Karin; Komajda, Michel; Limongelli, Giuseppe; Linhart, Ales; Mogensen, Jens; Moon, James; Pieper, Petronella G.; Seferovic, Petar M.; Schueler, Stephan; Zamorano, Jose L.; Caforio, Alida L. P.; Charron, Philippe

    2016-01-01

    In this paper the Working Group on Myocardial and Pericardial Disease proposes a revised definition of dilated cardiomyopathy (DCM) in an attempt to bridge the gap between our recent understanding of the disease spectrum and its clinical presentation in relatives, which is key for early diagnosis

  17. Autosomal recessive atrial dilated cardiomyopathy with standstill evolution associated with mutation of Natriuretic Peptide Precursor A.

    Science.gov (United States)

    Disertori, Marcello; Quintarelli, Silvia; Grasso, Maurizia; Pilotto, Andrea; Narula, Nupoor; Favalli, Valentina; Canclini, Camilla; Diegoli, Marta; Mazzola, Silvia; Marini, Massimiliano; Del Greco, Maurizio; Bonmassari, Roberto; Masè, Michela; Ravelli, Flavia; Specchia, Claudia; Arbustini, Eloisa

    2013-02-01

    Atrial dilatation and atrial standstill are etiologically heterogeneous phenotypes with poorly defined nosology. In 1983, we described 8-years follow-up of atrial dilatation with standstill evolution in 8 patients from 3 families. We later identified 5 additional patients with identical phenotypes: 1 member of the largest original family and 4 unrelated to the 3 original families. All families are from the same geographic area in Northeast Italy. We followed up the 13 patients for up to 37 years, extended the clinical investigation and monitoring to living relatives, and investigated the genetic basis of the disease. The disease was characterized by: (1) clinical onset in adulthood; (2) biatrial dilatation up to giant size; (3) early supraventricular arrhythmias with progressive loss of atrial electric activity to atrial standstill; (4) thromboembolic complications; and (5) stable, normal left ventricular function and New York Heart Association functional class during the long-term course of the disease. By linkage analysis, we mapped a locus at 1p36.22 containing the Natriuretic Peptide Precursor A gene. By sequencing Natriuretic Peptide Precursor A, we identified a homozygous missense mutation (p.Arg150Gln) in all living affected individuals of the 6 families. All patients showed low serum levels of atrial natriuretic peptide. Heterozygous mutation carriers were healthy and demonstrated normal levels of atrial natriuretic peptide. Autosomal recessive atrial dilated cardiomyopathy is a rare disease associated with homozygous mutation of the Natriuretic Peptide Precursor A gene and characterized by extreme atrial dilatation with standstill evolution, thromboembolic risk, preserved left ventricular function, and severely decreased levels of atrial natriuretic peptide.

  18. Markers of immune activation and apoptosis in endomyocardial biopsies of individuals with recent-onset dilated cardiomyopathy

    Czech Academy of Sciences Publication Activity Database

    Kubánek, M.; Sramko, M.; Malušková, J.; Chudíčková, Milada; Holáň, Vladimír; Kautzner, J.

    2013-01-01

    Roč. 34, č. 1 (2013), s. 211-211 ISSN 0195-668X. [Congress of the European-Society-of- Cardiology (ESC). 31.08.2013-,04.09.2013, Amsterdam] Institutional support: RVO:68378041 Keywords : dilated cardiomyopathy * immune activation and apoptosis Subject RIV: EC - Immunology

  19. The Importance of the Family History in Caring for Families With Long QT Syndrome and Dilated Cardiomyopathy

    NARCIS (Netherlands)

    Ruiter, J.S.; Berkenbosch-Nieuwhof, K.; van den Berg, M.P.; van Dijk, R.; Middel, B.; van Tintelen, J.P.

    In potentially inherited cardiac diseases, the family history is of great importance. We looked at the way cardiologists take a family history in patients with idiopathic dilated cardiomyopathy (DCM) or long QT syndrome (LQTS) and whether this led to screening of relatives or other follow-up. We

  20. Evaluation of myocardial disorders in patients with dilated cardiomyopathy and left ventricular eccentric hypertrophy; By sup 201 Tl myocardial SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, Junichi; Ohsawa, Hidefumi; Uchi, Takashi (Toho Univ., Tokyo (Japan). School of Medicine) (and others)

    1992-03-01

    {sup 201}Tl myocardial SPECT was performed in cases of dilated cardiomyopathy and valvular heart disease with left ventricular eccentric hypertrophy, and the two groups were compared from the standpoint of the mechanism of onset of myocardial disorders. Significant coefficients of correlation were seen between the Tl score and LVDd (r=0.792, r=0.785) and Tl score and LVEF (r=-0.634, r=-0.555) in both dilated cardiomyopathy and valvular heart disease. In cases of valvular heart disease, significant correlation coefficients (r=-0.756, r=-0.720) between LVDd and r-WR (relative-washout rate), and Tl score and r-WR were observed, but no such correlation was seen in dilated cardiomyopathy. In valvular heart disease, a decrease in myocardial perfusion associated with enlargement of the left ventricle appeared, while in dilated cardiomyopathy, there was a marked decrease in LVEF in proportion to the thallium defect. Therefore, it was assumed that left ventricular wall disorders occur due to myocardial metabolic disorders and coronary microcirculation disorders. (author).

  1. Severe reversible dilated cardiomyopathy associated with a large left ventricular thrombus in a young child with middle aortic syndrome

    OpenAIRE

    Ponniah, U; Overholt, E

    2014-01-01

    this article reports a case of a seven-year girl who presented with severe dilated cardiomyopathy (DCM) associated with a large thrombus in the left ventricle (LV). She had a long segment stenosis of the lower thoracic descending aorta, possibly due to non-specific aortitis and underwent successful stent angioplasty. The LV thrombus resolved after heparin without sequelae.

  2. 2-Deoxyadenosine triphosphate restores the contractile function of cardiac myofibril from adult dogs with naturally occurring dilated cardiomyopathy

    OpenAIRE

    Cheng, Yuanhua; Hogarth, Kaley A.; O'Sullivan, M. Lynne; Regnier, Michael; Pyle, W. Glen

    2015-01-01

    1) First report to characterize and define the contractile kinetics and defects associated with naturally occurring dilated cardiomyopathy (DCM) in dogs. 2) Novel findings that dATP is able to reverse the contractile defects associated with naturally occurring canine DCM.

  3. Characterization of the canine desmin (DES) gene and evaluation as a candidate gene for dilated cardiomyopathy in the Dobermann.

    Science.gov (United States)

    Stabej, Polona; Imholz, Sandra; Versteeg, Serge A; Zijlstra, Carla; Stokhof, Arnold A; Domanjko-Petric, Aleksandra; Leegwater, Peter A J; van Oost, Bernard A

    2004-10-13

    Canine-dilated cardiomyopathy (DCM) in dogs is a disease of the myocardium associated with dilatation and impaired contraction of the ventricles and is suspected to have a genetic cause. A missense mutation in the desmin gene (DES) causes DCM in a human family. Human DCM closely resembles the canine disease. In the present study, we evaluated whether DES gene mutations are responsible for DCM in Dobermann dogs. We have isolated bacterial artificial chromosome clones (BACs) containing the canine DES gene and determined the chromosomal location by fluorescence in situ hybridization (FISH). Using data deposited in the NCBI trace archive and GenBank, the canine DES gene DNA sequence was assembled and seven single nucleotide polymorphisms (SNPs) were identified. From the canine DES gene BAC clones, a polymorphic microsatellite marker was isolated. The microsatellite marker and four informative desmin SNPs were typed in a Dobermann family with frequent DCM occurrence, but the disease phenotype did not associate with a desmin haplotype. We concluded that mutations in the DES gene do not play a role in Dobermann DCM. Availability of the microsatellite marker, SNPs and DNA sequence reported in this study enable fast evaluation of the DES gene as a DCM candidate gene in other dog breeds with DCM occurrence.

  4. Accuracy of 16-detector Multislice Spiral Computed Tomography in the initial evaluation of dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Cornily, Jean-Christophe; Gilard, Martine; Le Gal, Gregoire; Pennec, Pierre-Yves; Vinsonneau, Ulric; Blanc, Jean-Jacques; Mansourati, Jacques; Boschat, Jacques

    2007-01-01

    Background: Multislice Computed Tomography (MSCT) recently proved its accuracy in the detection of coronary artery disease (CAD). It can also give information about left ventricular function and venous network anatomy. We here sought to validate a MSCT-based strategy in the initial evaluation of patients with dilated cardiomyopathy (DCM). Methods: 36 patients with DCM underwent cardiac MSCT before conventional coronary angiography with ventriculography. We analysed arterial calcium score (Agatston score equivalent: ASE), coronary stenosis, left ventricular parameters and venous network. Results: The sensitivity of a MSCT-based strategy in detecting significant CAD was 100% and the specificity 80%. The positive and negative predictive values were respectively 67% and 100%. For ASE 1.000, conventional coronary angiography is mandatory due to MSCT's poor interest in such cases; when ASE <1.000, a contrast-enhanced MSCT may, when normal, replace coronary angiography

  5. Segmented Poincaré plot analysis for risk stratification in patients with dilated cardiomyopathy.

    Science.gov (United States)

    Voss, A; Fischer, C; Schroeder, R; Figulla, H R; Goernig, M

    2010-01-01

    The prognostic value of heart rate variability in patients with dilated cardiomyopathy (DCM) is limited and does not contribute to risk stratification although the dynamics of ventricular repolarization differs considerably between DCM patients and healthy subjects. Neither linear nor nonlinear methods of heart rate variability analysis could discriminate between patients at high and low risk for sudden cardiac death. The aim of this study was to analyze the suitability of the new developed segmented Poincaré plot analysis (SPPA) to enhance risk stratification in DCM. In contrast to the usual applied Poincaré plot analysis the SPPA retains nonlinear features from investigated beat-to-beat interval time series. Main features of SPPA are the rotation of cloud of points and their succeeded variability depended segmentation. Significant row and column probabilities were calculated from the segments and led to discrimination (up to pplot analysis of heart rate variability was able to contribute to risk stratification in patients suffering from DCM.

  6. Radiofrequency catheter ablation for electrical storm in a patient with dilated cardiomyopathy.

    Science.gov (United States)

    Kolettis, Theofilos M; Naka, Katerina K; Katsouras, Christos S

    2005-01-01

    We report a case of successful radiofrequency catheter ablation in a patient with dilated cardiomyopathy, who presented with multiple, haemodynamically poorly tolerated episodes of monomorphic ventricular tachycardia, resistant to antiarrhythmic drug treatment. The ablation procedure consisted of focal ablation of three mapped left ventricular sites, using pace and activation mapping. Additional linear ablation lesions were created across these sites. After the procedure, the patient remained free of tachycardia episodes and seven days post-ablation he underwent implantation of a cardioverter-defibrillator. During a twelve-month follow-up period, the patient has remained free of monomorphic ventricular tachycardia episodes. Radiofrequency catheter ablation is feasible in electrical storm, using conventional mapping techniques, even in haemodynamically unstable tachycardias.

  7. Clinical and pathologic findings of myocarditis in two families with dilated cardiomyopathy

    International Nuclear Information System (INIS)

    O'Connell, J.B.; Fowles, R.E.; Robinson, J.A.; Subramanian, R.; Henkin, R.E.; Gunnar, R.M.

    1984-01-01

    The use of endomyocardial biopsy and gallium-67 scans in patients with dilated cardiomyopathy (DCM) has demonstrated the presence of myocardial inflammation in a subset of patients. A family with DCM was studied with endomyocardial biopsy and gallium-67 scanning; both identified the presence of myocarditis in the proband. Evaluation of histologic sections from deceased family members revealed myocarditis as the principal pathologic finding. This patient identified during life demonstrated a defect in suppressor lymphocytic function and improved with immunosuppressive therapy. A second family with DCM was discovered when postmortem examination of the proband and his father's heart showed myocarditis. A living sibling was identified with asymptomatic myocardial dysfunction. Longitudinal follow-up of surviving members of both families are in progress. This study indicates that thorough diagnostic evaluation of all patients with familial DCM should be pursued to identify subgroups with potentially treatable inflammation

  8. Eosinophilic myocarditis due to Churg-Strauss syndrome mimicking reversible dilated cardiomyopathy.

    Science.gov (United States)

    Chen, Ming-xian; Yu, Bi-lian; Peng, Dao-quan; Zhou, Sheng-hua

    2014-01-01

    A 41-year-old woman with a history of asthma arrived at the emergency room of our hospital with dyspnea. The electrocardiogram showed no specific results. Echocardiography defects revealed an obvious decrease in the left ventricular systolic function and enlargement of the left chamber. We initially considered her condition to be dilated cardiomyopathy. However, she had eosinophilia in the peripheral blood and elevated cardiac enzymes. The coronary angiography showed normal coronary arteries. Single photon emission computed tomography (SPECT) showed infiltrative myocardial disease. She was then diagnosed with eosinophil infiltrations. Combined with peripheral nerve injury and lung involvement, she was diagnosed as having Churg-Strauss syndrome. After initiating prednisone treatment, her eosinophilia and rising cardiac enzymes recovered to normal, and both her echocardiographic abnormalities and symptoms noticeably improved. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Genetic association study identifies HSPB7 as a risk gene for idiopathic dilated cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Klaus Stark

    2010-10-01

    Full Text Available Dilated cardiomyopathy (DCM is a structural heart disease with strong genetic background. Monogenic forms of DCM are observed in families with mutations located mostly in genes encoding structural and sarcomeric proteins. However, strong evidence suggests that genetic factors also affect the susceptibility to idiopathic DCM. To identify risk alleles for non-familial forms of DCM, we carried out a case-control association study, genotyping 664 DCM cases and 1,874 population-based healthy controls from Germany using a 50K human cardiovascular disease bead chip covering more than 2,000 genes pre-selected for cardiovascular relevance. After quality control, 30,920 single nucleotide polymorphisms (SNP were tested for association with the disease by logistic regression adjusted for gender, and results were genomic-control corrected. The analysis revealed a significant association between a SNP in HSPB7 gene (rs1739843, minor allele frequency 39% and idiopathic DCM (p = 1.06 × 10⁻⁶, OR  = 0.67 [95% CI 0.57-0.79] for the minor allele T. Three more SNPs showed p < 2.21 × 10⁻⁵. De novo genotyping of these four SNPs was done in three independent case-control studies of idiopathic DCM. Association between SNP rs1739843 and DCM was significant in all replication samples: Germany (n =564, n = 981 controls, p = 2.07 × 10⁻³, OR = 0.79 [95% CI 0.67-0.92], France 1 (n = 433 cases, n = 395 controls, p =3.73 × 10⁻³, OR  = 0.74 [95% CI 0.60-0.91], and France 2 (n = 249 cases, n = 380 controls, p = 2.26 × 10⁻⁴, OR  = 0.63 [95% CI 0.50-0.81]. The combined analysis of all four studies including a total of n = 1,910 cases and n = 3,630 controls showed highly significant evidence for association between rs1739843 and idiopathic DCM (p = 5.28 × 10⁻¹³, OR= 0.72 [95% CI 0.65-0.78]. None of the other three SNPs showed significant results in the replication stage.This finding of the HSPB7 gene from a genetic search for idiopathic DCM using

  10. E2F6 Impairs Glycolysis and Activates BDH1 Expression Prior to Dilated Cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Jennifer L Major

    Full Text Available The E2F pathway plays a critical role in cardiac growth and development, yet its role in cardiac metabolism remains to be defined. Metabolic changes play important roles in human heart failure and studies imply the ketogenic enzyme β-hydroxybutyrate dehydrogenase I (BDH1 is a potential biomarker.To define the role of the E2F pathway in cardiac metabolism and dilated cardiomyopathy (DCM with a focus on BDH1.We previously developed transgenic (Tg mice expressing the transcriptional repressor, E2F6, to interfere with the E2F/Rb pathway in post-natal myocardium. These Tg mice present with an E2F6 dose dependent DCM and deregulated connexin-43 (CX-43 levels in myocardium. Using the Seahorse platform, a 22% decrease in glycolysis was noted in neonatal cardiomyocytes isolated from E2F6-Tg hearts. This was associated with a 39% reduction in the glucose transporter GLUT4 and 50% less activation of the regulator of glucose metabolism AKT2. The specific reduction of cyclin B1 (70% in Tg myocardium implicates its importance in supporting glycolysis in the postnatal heart. No changes in cyclin D expression (known to regulate mitochondrial activity were noted and lipid metabolism remained unchanged in neonatal cardiomyocytes from Tg hearts. However, E2F6 induced a 40-fold increase of the Bdh1 transcript and 890% increase in its protein levels in hearts from Tg pups implying a potential impact on ketolysis. By contrast, BDH1 expression is not activated until adulthood in normal myocardium. Neonatal cardiomyocytes from Wt hearts incubated with the ketone β-hydroxybutyrate (β-OHB showed a 100% increase in CX-43 protein levels, implying a role for ketone signaling in gap junction biology. Neonatal cardiomyocyte cultures from Tg hearts exhibited enhanced levels of BDH1 and CX-43 and were not responsive to β-OHB.The data reveal a novel role for the E2F pathway in regulating glycolysis in the developing myocardium through a mechanism involving cyclin B1. We

  11. Adverse events in families with hypertrophic or dilated cardiomyopathy and mutations in the MYBPC3 gene

    Directory of Open Access Journals (Sweden)

    Lehrke Stephanie

    2008-10-01

    Full Text Available Abstract Background Mutations in MYBPC3 encoding myosin binding protein C belong to the most frequent causes of hypertrophic cardiomyopathy (HCM and may also lead to dilated cardiomyopathy (DCM. MYBPC3 mutations initially were considered to cause a benign form of HCM. The aim of this study was to examine the clinical outcome of patients and their relatives with 18 different MYBPC3 mutations. Methods 87 patients with HCM and 71 patients with DCM were screened for MYBPC3 mutations by denaturing gradient gel electrophoresis and sequencing. Close relatives of mutation carriers were genotyped for the respective mutation. Relatives with mutation were then evaluated by echocardiography and magnetic resonance imaging. A detailed family history regarding adverse clinical events was recorded. Results In 16 HCM (18.4% and two DCM (2.8% index patients a mutation was detected. Seven mutations were novel. Mutation carriers exhibited no additional mutations in genes MYH7, TNNT2, TNNI3, ACTC and TPM1. Including relatives of twelve families, a total number of 42 mutation carriers was identified of which eleven (26.2% had at least one adverse event. Considering the twelve families and six single patients with mutations, 45 individuals with cardiomyopathy and nine with borderline phenotype were identified. Among the 45 patients, 23 (51.1% suffered from an adverse event. In eleven patients of seven families an unexplained sudden death was reported at the age between 13 and 67 years. Stroke or a transient ischemic attack occurred in six patients of five families. At least one adverse event occurred in eleven of twelve families. Conclusion MYBPC3 mutations can be associated with cardiac events such as progressive heart failure, stroke and sudden death even at younger age. Therefore, patients with MYBPC3 mutations require thorough clinical risk assessment.

  12. Exome-wide association study reveals novel susceptibility genes to sporadic dilated cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Ulrike Esslinger

    Full Text Available Dilated cardiomyopathy (DCM is an important cause of heart failure with a strong familial component. We performed an exome-wide array-based association study (EWAS to assess the contribution of missense variants to sporadic DCM.116,855 single nucleotide variants (SNVs were analyzed in 2796 DCM patients and 6877 control subjects from 6 populations of European ancestry. We confirmed two previously identified associations with SNVs in BAG3 and ZBTB17 and discovered six novel DCM-associated loci (Q-value<0.01. The lead-SNVs at novel loci are common and located in TTN, SLC39A8, MLIP, FLNC, ALPK3 and FHOD3. In silico fine mapping identified HSPB7 as the most likely candidate at the ZBTB17 locus. Rare variant analysis (MAF<0.01 demonstrated significant association for TTN variants only (P = 0.0085. All candidate genes but one (SLC39A8 exhibit preferential expression in striated muscle tissues and mutations in TTN, BAG3, FLNC and FHOD3 are known to cause familial cardiomyopathy. We also investigated a panel of 48 known cardiomyopathy genes. Collectively, rare (n = 228, P = 0.0033 or common (n = 36, P = 0.019 variants with elevated in silico severity scores were associated with DCM, indicating that the spectrum of genes contributing to sporadic DCM extends beyond those identified here.We identified eight loci independently associated with sporadic DCM. The functions of the best candidate genes at these loci suggest that proteostasis regulation might play a role in DCM pathophysiology.

  13. Gallium-67 imaging in patients with dilated cardiomyopathy and biopsy-proven myocarditis

    International Nuclear Information System (INIS)

    O'Connell, J.B.; Henkin, R.E.; Robinson, J.A.; Subramanian, R.; Scanlon, P.J.; Gunnar, R.M.

    1984-01-01

    Current standards for detection of myocarditis in a clinical setting rely on endomyocardial biopsy for accurate diagnosis. With this technique a subset of patients with dilated cardiomyopathy show unsuspected myocarditis histologically. Endomyocardial biopsy, despite its specificity, may lack sensitivity due to sampling error if the inflammation is patchy or focal. Therefore, inflammation-sensitive radioisotopic imaging may be a useful adjunct in the diagnosis of myocarditis. This study was designed to evaluate the applicability of gallium-67 (67Ga) myocardial imaging as an adjunct to endomyocardial biopsy in the diagnosis of myocarditis. Sixty-eight consecutive patients referred for evaluation of dilated cardiomyopathy underwent 71 parallel studies with 67Ga imaging and biopsies that served as the basis of comparison for this study. Histologic myocarditis was identified in 8% of biopsy specimens. Clinical and hemodynamic parameters could not be used to predict the presence of myocarditis. Five of six biopsy samples (87%) with myocarditis showed dense 67Ga uptake, whereas only nine of 65 negative biopsy samples (14%) were paired with equivocally positive 67Ga scans. The single patient with myocarditis and no myocardial 67Ga uptake had dense mediastinal lymph node uptake that may have obscured cardiac uptake. The incidence of myocarditis on biopsy with a positive 67Ga scan was 36% (5/14); however, the incidence of myocarditis with a negative 67Ga scan was only 1.8% (1/57). Follow-up scans for three patients showed close correlation of 67Ga uptake with myocarditis on biopsy. In conclusion 67Ga may be a useful screening test for identifying patients with a high yield of myocarditis on biopsy, and serial scans may eliminate the need for frequent biopsies in patients with proven myocarditis

  14. Epidemiological study of dilated cardiomyopathy from eastern India with special reference to left atrial size

    Directory of Open Access Journals (Sweden)

    Rudrajit Paul, Saumen Nandi, Pradip K Sinha

    2014-07-01

    Full Text Available Dilated cardiomyopathy (DCM is a common cause of emergency visit in our country. The disease is often misdiagnosed and mistreated. There are very few studies on DCM from India. We undertook a small study on DCM patients from Eastern India to find the demographic and echocardiographic characteristics. Patients and methods: We under took this study in a tertiary care Medical College of Eastern India. All patients coming to the emergency with dyspnea were evaluated for cardiac dysfunction. Emergency echocardiography was done to diagnose dilated cardiomyopathy. Patients with DCM were then evaluated as per protocol. After stabilization, echocardiography was repeated to note the study parameters like left atrial diameter. Standard statistical tests were used. Results: we had a total of 70 patients in our study with a male: female ratio of 43:27. Most patients were aged over 40 years. Patients with COPD, history of radiation, malignancy or drug abuse were excluded. Most patients (47% were on NYHA stage 3 at the time of presentation. In our patient cohort, 24% were alcoholic and 46% were smokers. Atrial fibrillation was present in 15.7% of the patients and right and left bundle branch block had been present in 8 and 15 patients respectively. In echocardiography, increased left atrial (LA size (>40 mm was found in 45 patients. Many patients had valvular regurgitation, mitral, aortic or tricuspid. LA size was positively correlated with left ventricular systolic diameter (r=0.403 and negatively correlated with ejection fraction (r= -0.23. Analysis and conclusion: different ECG abnormalities like bundle branch block and arrhythmias like atrial fibrillation are quite common in DCM. In echocardiography, left atrial size is an important prognostic marker and correlates with left ventricular function.

  15. Reverse remodeling and the mechanism of mitral regurgitation improvement in patients with dilated cardiomyopathy.

    Science.gov (United States)

    Kuperstein, Rafael; Blechman, Ido; Ben Zekry, Sagit; Klempfner, Robert; Freimark, Dov; Arad, Michael

    2015-01-01

    Functional mitral regurgitation (MR) is a common finding in dilated cardiomyopathy. Left ventricular (LV) reverse remodeling with LV size reduction and improvement in LV function is a well recognized phenomenon. We aimed to evaluate the impact of LV remodeling on the mechanism leading to functional MR. Among 188 patients with non-ischemic dilated cardiomyopathy, 10 patients significantly improved their LV function, reduced LV size and MR severity during follow-up (RRMR). A comparison was made between their baseline and follow-up echocardiographic examinations and to a matched-control group of patients who did not improve (no RRMR). LV and left atrium (LA) dimensions and volumes, LV mass (LVM), LV ejection fraction (LVEF) (Simpsons), sphericity index (SI), mitral valve tenting area (TA) coaptation distance (CD), effective regurgitant orifice (ERO), and regurgitant volume were calculated. Multivariable analysis was performed in order to evaluate which echocardiographic parameters related to MR improvement in reverse remodeling. LV and LA dimensions and volumes, LVM, SI, TA, CD, ERO and right ventricle, in the RRMR group significantly decreased at follow-up (p < 0.04 for all). When compared to no RRMR, despite a similar ERO (0.2 ± 0.05 vs. 0.2 ± 0.08, p = 0.13) and a larger regurgitant volume (38 ± 9 vs. 29 ± 8 mL, p = 0.05) and despite similar clinical characteristics and medical treatment we found significantly higher LVEF, smaller LV dimensions and volumes, smaller LVM and SI in the RRMR group (p < 0.05 for all). On multivariable analysis the SI was the sole predictor of RRMR (p = 0.04, OR = 0.76, CI 0.58-0.99). Reverse remodeling characterized by improvement in LV function, reduction in LV size and an associated reduction in MR severity is related to LV SI at baseline.

  16. A young man with hemoptysis: Rare association of idiopathic pulmonary hemosiderosis, celiac disease and dilated cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Gopi C Khilnani

    2015-01-01

    Full Text Available Idiopathic pulmonary hemosiderosis (IPH is a rare cause of recurrent diffuse alveolar hemorrhage (DAH with no specific treatment. Herein, we discuss a case of hemoptysis, who had IPH and other rare associations. A 19-year-old man presented with recurrent hemoptysis, generalized weakness and progressive dyspnea for 3 years. Earlier, he was diagnosed with anemia and was treated with blood transfusions and hematinics. On examination he had pallor, tachycardia and was underweight. Investigations revealed low level of hemoglobin (7.8 g/dl and iron deficiency. An electrocardiography (ECG showed sinus tachycardia, interventricular conduction delay and T-wave inversion. Echocardiography revealed dilated cardiomyopathy with left ventricular dysfunction. Computed tomography of the chest demonstrated bilateral diffuse ground glass opacity suggestive of pulmonary hemorrhage. Pulmonary function tests showed restrictive pattern with increased carbon monoxide diffusion. Bronchoalveolar lavage and transbronchial lung biopsy showed hemosiderin-laden macrophages. Patient could recall recurrent episodes of diarrhea in childhood. Serum antitissue transglutamase antibodies were raised (291.66 IU/ml, normal <30 IU/ml. Duodenal biopsy showed subtotal villous atrophy consistent with celiac disease. He was started on gluten-free diet, beta blockers and diuretics. After two years of treatment, he has been showing consistent improvement. Screening for CD is important in patients with IPH. Cardiomyopathy forms rare third association. All three show improvement with gluten-free diet.

  17. Right ventricular bifocal stimulation in the treatment of dilated cardiomyopathy with heart failure

    Directory of Open Access Journals (Sweden)

    José Carlos Pachón Mateos

    1999-12-01

    Full Text Available OBJECTIVE: To describe a new more efficient method of endocardial cardiac stimulation, which produces a narrower QRS without using the coronary sinus or cardiac veins. METHODS: We studied 5 patients with severe dilated cardiomyopathy, chronic atrial fibrillation and AV block, who underwent definitive endocardial pacemaker implantation, with 2 leads, in the RV, one in the apex and the other in the interventricular septum (sub pulmonary, connected, respectively, to ventricular and atrial bicameral pacemaker outputs. Using Doppler echocardiography, we compared, in the same patient, conventional (VVI, high septal ("AAI" and bifocal ("DDT" with AV interval ~ 0 stimulation. RESULTS: The RV bifocal stimulation had the best results with an increase in ejection fraction and cardiac output and reduction in QRS duration, mitral regurgitation and in the left atrium area (p <= 0.01. The conventional method of stimulation showed the worst result. CONCLUSION: These results suggest that, when left ventricular stimulation is not possible, right ventricular bifocal stimulation should be used in patients with severe cardiomyopathy where a pacemaker is indicated.

  18. Histological characterization of dilated cardiomyopathy in the juvenile toy Manchester terrier.

    Science.gov (United States)

    Legge, C H; López, A; Hanna, P; Côté, E; Hare, E; Martinson, S A

    2013-11-01

    Dilated cardiomyopathy (DCM), the most common form of cardiomyopathy in the dog, most often occurs in certain breeds. The objective of this study was to describe a rapidly progressive form of DCM that has been recently recognized in juvenile Toy Manchester Terrier dogs (TMTs). The clinical history and gross findings were reviewed in a group of 14 TMTs, and histologic sections of heart were examined in 12 of those 14 TMTs with DCM. Histochemical and histomorphometric analyses were employed to compare the heart in TMTs affected by DCM with that of control dogs. TMTs ranged in age from 10 to 58.3 weeks, with males and females being equally affected. Affected TMT hearts contained foci of degeneration and loss of myofibers with fibrosis and mild lymphoplasmacytic infiltrates. Less prominent features included foci of acute myofiber degeneration and necrosis with or without intralesional mineralization and mild to moderate suppurative and lymphoplasmacytic infiltrates. Morphometric quantification demonstrated that the right ventricle was more severely affected (P ≤ .05) than the left ventricle with variable involvement of the interventricular septum. Immunohistochemistry for canine parvovirus was negative in all heart samples. However, the absence of parvoviral antigen does not rule out a possible viral or autoimmune cause. The presence of these myocardial lesions among closely related dogs suggests a genetic contribution to this disease process in the TMT.

  19. Clinical usefulness of Tc-99m hexakis 2-methoxybutyl isonitrile gated SPECT in patients with dilated cardiomyopathy: retrospective analysis

    International Nuclear Information System (INIS)

    Khan, Z.R.; Khan, A.Z.

    2010-01-01

    Background: In Dilated cardiomyopathy the heart is enlarged and ventricles are dilated. Gated myocardial perfusion single photon emission computed tomography is considered state of the art for myocardial perfusion imaging. A retrospective analysis was conducted to evaluate patients with dilated cardiomyopathy with Tc-99m sestamibi gated myocardial perfusion single photon emission computed tomography to evaluate its clinical utility. Methods: A 10 year retrospective medical record review was done from 1991 to 2001 at Wake Forest University, North Carolina, USA. Eligibility criteria included a diagnosis of dilated cardiomyopathy and availability of coronary angiography and Tc-99m sestamibi cardiac imaging results. 26 cases were selected for the final review and inclusion in the study. The study was done with standard protocols for cardiac sestamibi imaging. Results: A total of 26 cases were included in the final analysis. Cases were divided into two main groups. Group-A included 16 patients with no correlation between Tc-99m sestamibi and cardiac catheterisation reports. Group-B included 10 patients with good correlation between the above tests. There were no significant differences between the left ventricular ejection fraction, angina history, sex distribution and diabetic status between the two groups. We applied Wilcoxon Signed Rank Test and z-test to quantify the difference between the two groups. Data was tabulated and z-test was performed. The calculated p value was <0.0001. This is significantly less than the tabulated p-value at 5% level of significance, i.e., 1.96. Significant differences exist between Group-A and Group-B. Conclusion: Tc-99m sestamibi is an excellent agent for investigating myocardial perfusion in dilated cardiomyopathy. The reversible and fixed perfusion defects (small to medium sized) seen in dilated cardiomyopathy after performance of Tc-99m sestamibi gated single photon emission computed tomography imaging may not be due to coronary

  20. Brain natriuretic peptide is not predictive of dilated cardiomyopathy in Becker and Duchenne muscular dystrophy patients and carriers.

    Science.gov (United States)

    Schade van Westrum, Steven; Dekker, Lukas; de Haan, Rob; Endert, Erik; Ginjaar, Ieke; de Visser, Marianne; van der Kooi, Anneke

    2013-07-16

    Cardiomyopathy is reported in Duchenne and Becker muscle dystrophy patients and female carriers. Brain Natriuretic peptide (BNP) is a hormone produced mainly by ventricular cardiomyocytes and its production is up regulated in reaction to increased wall stretching. N-terminal-proBNP (NT-proBNP) has been shown to be a robust laboratory parameter to diagnose and monitor cardiac failure, and it may be helpful to screen for asymptomatic left ventricular dysfunction. Therefore we tested whether NT-proBNP can distinguish patients with Duchenne or Becker muscular dystrophy patients and carriers of a dystrophin mutation with a dilated cardiomyopathy from those without. In a cohort of Duchenne and Becker muscle dystrophy patients (n = 143) and carriers (n = 219) NT-proBNP was measured, and echocardiography was performed to diagnose dilated cardiomyopathy (DCM). In total sixty-one patients (17%) fulfilled the criteria for DCM, whereas 283 patients (78%) had an elevated NT-pro BNP. The sensitivity of NT-proBNP for DCM in patients or carriers was 85%, the specificity 23%, area under the ROC-curve = 0.56. In the specified subgroups there was also no association. Measurement of NT-pro BNP in patients suffering from Duchenne or Becker muscular dystrophy and carriers does not distinguish between those with and without dilated cardiomyopathy.

  1. Effects of candesartan on electrical remodeling in the hearts of inherited dilated cardiomyopathy model mice.

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    Fuminori Odagiri

    Full Text Available Inherited dilated cardiomyopathy (DCM is characterized by dilatation and dysfunction of the ventricles, and often results in sudden death or heart failure (HF. Although angiotensin receptor blockers (ARBs have been used for the treatment of HF, little is known about the effects on postulated electrical remodeling that occurs in inherited DCM. The aim of this study was to examine the effects of candesartan, one of the ARBs, on cardiac function and electrical remodeling in the hearts of inherited DCM model mice (TNNT2 ΔK210. DCM mice were treated with candesartan in drinking water for 2 months from 1 month of age. Control, non-treated DCM mice showed an enlargement of the heart with prolongation of QRS and QT intervals, and died at t1/2 of 70 days. Candesartan dramatically extended the lifespan of DCM mice, suppressed cardiac dilatation, and improved the functional parameters of the myocardium. It also greatly suppressed prolongation of QRS and QT intervals and action potential duration (APD in the left ventricular myocardium and occurrence of ventricular arrhythmia. Expression analysis revealed that down-regulation of Kv4.2 (Ito channel protein, KChIP2 (auxiliary subunit of Kv4.2, and Kv1.5 (IKur channel protein in DCM was partially reversed by candesartan administration. Interestingly, non-treated DCM heart had both normal-sized myocytes with moderately decreased Ito and IKur and enlarged cells with greatly reduced K+ currents (Ito, IKur IK1 and Iss. Treatment with candesartan completely abrogated the emergence of the enlarged cells but did not reverse the Ito, and IKur in normal-sized cells in DCM hearts. Our results indicate that candesartan treatment suppresses structural remodeling to prevent severe electrical remodeling in inherited DCM.

  2. Clinical Profile and Prognosis of Patients with Right Ventricular Dilated Cardiomyopathy: Results of a Prospective Study

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    Ya.R. Akhmatov

    2015-12-01

    Full Text Available The aim of our study was to investigate the clinical prevalence of dilated cardiomyopathy (DCM with predominantly failure of the right-side heart (right ventricular DCM, RV-DCM, and features of the clinical course and prognosis of the disease compared to DCM with biventricular heart failure (BV-HF. The study design suggests a prospective observation of 300 patients with idiopathic DCM between 2000 and 2012. Herewith, we followed the criteria of the WHO/ISFC Task Force (1995 on the Definationa and Classification of Cardiomyopathies. All patients underwent a comprehensive examination. Two groups were formed for further comparative analysis. Group 1 included 22 patients (mean age 42.9±14.3 years, male/female 5/17 with RV-DCM. Group 2 included 38 patients (mean age 43.6±13.8, male/female 29/9 with DCM and BV-HF. The groups were matched for age, sex, NYHA class II-III, and disease duration. According to our aim, we studied 5-year survival prognosis and analyzed the incidence and causes of deaths, as well as the occurrence of nonfatal complications of the disease. Medical therapy for DCM patients was performed according to the CHF therapy guidelines (ACC/AHA 2001, 2005. The results of our investigations during many years of research have shown that the clinical incidence of RV-DCM was 7.3% among all forms of DCM. The study of life prognosis in patients with 2 forms of DCM showed that 5-year mortality of patients was about 50%. Herewith, we detected the differences in causes of death depending on the type of heart damage, primarily development of fatal pulmonary embolism.

  3. Skeletal Myoblast Cell Sheet Implantation Ameliorates Both Systolic and Diastolic Cardiac Performance in Canine Dilated Cardiomyopathy Model.

    Science.gov (United States)

    Shirasaka, Tomonori; Miyagawa, Shigeru; Fukushima, Satsuki; Kawaguchi, Naomasa; Nakatani, Satoshi; Daimon, Takashi; Okita, Yutaka; Sawa, Yoshiki

    2016-02-01

    Improving both systolic and diastolic function may be the most important factor in treating heart failure. In this study, we hypothesized that cell-sheet transplantation could improve these function in the damaged heart. We generated a dilated cardiomyopathy model in beagles by continuous ventricle pacing at 240 beats per minute. After 4 weeks, the beagles underwent skeletal myoblast cell sheet transplantation (SMCST) or a sham operation, and rapid ventricle pacing continued for an additional 4 weeks. Six of the e8 beagles treated by SMCST were still alive 4 weeks after the procedure. We evaluated SMCST's cardiotherapeutic effects by comparing beagles treated by SMCST with beagles that underwent a sham operation (control, n = 5). Diastolic function, as well as systolic function improved significantly in the SMCST group as compared with the sham group (control vs SMCST group, median [interquartile range]: E/E', 16 [0.9] vs 11 [1.0]; P dilated cardiomyopathy heart.

  4. Autoantibodies in dilated cardiomyopathy induce vascular endothelial growth factor expression in cardiomyocytes

    Energy Technology Data Exchange (ETDEWEB)

    Saygili, Erol, E-mail: erol.saygili@med.uni-duesseldorf.de [Division of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf (Germany); Noor-Ebad, Fawad; Schröder, Jörg W.; Mischke, Karl [Department of Cardiology, University RWTH Aachen, Pauwelsstr. 30, D-52074 Aachen (Germany); Saygili, Esra [Clinic for Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University, Moorenstrasse 5, D-40225 Düsseldorf (Germany); Rackauskas, Gediminas [Department of Cardiovascular Medicine, Vilnius University Hospital Santariskiu Klinikos, Vilnius University (Lithuania); Marx, Nikolaus [Department of Cardiology, University RWTH Aachen, Pauwelsstr. 30, D-52074 Aachen (Germany); Kelm, Malte; Rana, Obaida R. [Division of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf (Germany)

    2015-09-11

    Background: Autoantibodies have been identified as major predisposing factors for dilated cardiomyopathy (DCM). Patients with DCM show elevated serum levels of vascular endothelial growth factor (VEGF) whose source is unknown. Besides its well-investigated effects on angiogenesis, evidence is present that VEGF signaling is additionally involved in fibroblast proliferation and cardiomyocyte hypertrophy, hence in cardiac remodeling. Whether autoimmune effects in DCM impact cardiac VEGF signaling needs to be elucidated. Methods: Five DCM patients were treated by the immunoadsorption (IA) therapy on five consecutive days. The eluents from the IA columns were collected and prepared for cell culture. Cardiomyocytes from neonatal rats (NRCM) were incubated with increasing DCM-immunoglobulin-G (IgG) concentrations for 48 h. Polyclonal IgG (Venimmun N), which was used to restore IgG plasma levels in DCM patients after the IA therapy was additionally used for control cell culture purposes. Results: Elevated serum levels of VEGF decreased significantly after IA (Serum VEGF (ng/ml); DCM pre-IA: 45 ± 9.1 vs. DCM post–IA: 29 ± 6.7; P < 0.05). In cell culture, pretreatment of NRCM by DCM-IgG induced VEGF expression in a time and dose dependent manner. Biologically active VEGF that was secreted by NRCM significantly increased BNP mRNA levels in control cardiomyocytes and induced cell-proliferation of cultured cardiac fibroblast (Fibroblast proliferation; NRCM medium/HC-IgG: 1 ± 0.0 vs. NRCM medium/DCM-IgG 100 ng/ml: 5.6 ± 0.9; P < 0.05). Conclusion: The present study extends the knowledge about the possible link between autoimmune signaling in DCM and VEGF induction. Whether this observation plays a considerable role in cardiac remodeling during DCM development needs to be further elucidated. - Highlights: • Mechanisms of remodeling in dilated cardiomyopathy (DCM) are not fully understood. • Autoantibodies have been identified as major predisposing factors

  5. Fractalkine in human inflammatory cardiomyopathy.

    Science.gov (United States)

    Escher, F; Vetter, R; Kühl, U; Westermann, D; Schultheiss, H-P; Tschöpe, C

    2011-05-01

    Cardiac inflammation is important for the prognosis of patients with inflammatory cardiomyopathy (CMi), but the mechanisms leading to it are not fully elucidated. To study the role of fractalkine (CX3CL1) in chemotactic and adhesive properties of peripheral blood mononuclear cells (PBMCs) in patients with CMi. Patients with enterovirus (EV)-positive CMi, patients with virus-negative CMi, patients with parvovirus B19 (B19) genomes with low intramyocardial inflammation and patients without cardiac inflammation and viral infection in the endomyocardial biopsy (EMB) were enrolled (n=10/group). The expression of CX3CL1 and monocyte chemoattractant protein (MCP-1) in EMBs was significantly increased in EV-positive and virus-negative patients with CMi in contrast to controls and B19-positive patients (EV+ vs controls: CX3CL1-area fraction (AF) % 0.078±0.012 vs 0.009±0.003 pattenuated positive chronotropic response to β-adrenergic stimulation with isoproterenol. The cardiac and plasma CX3CL1/CX3CR1 system is upregulated in CMi and this affects the functional potential of PBMCs. Moreover, a direct cardiodepressive effect of CX3CL1 in cardiac tissue was demonstrated since neonatal cardiomyocytes exhibited an attenuated positive chronotropic response to β-adrenergic stimulation.

  6. Dilated cardiomyopathy secondary to rickets-related hypocalcaemia: eight case reports and a review of the literature.

    Science.gov (United States)

    Yilmaz, Osman; Olgun, Hasim; Ciftel, Murat; Kilic, Omer; Kartal, Ibrahim; Iskenderoglu, Nebahat Y; Laloglu, Fuat; Ceviz, Naci

    2015-02-01

    Dilated cardiomyopathy is usually idiopathic and may arise secondary to infections or metabolic or genetic causes. Another rare cause is hypocalcaemia. Owing to the fact that calcium plays an essential role in excitation and contraction of myocardial muscle, myocardial contractility may decline in patients with hypocalcaemia. Patients with symptoms of congestive heart failure and rickets-related hypocalcaemia were assessed clinically and by echocardiography in a paediatric cardiology clinic. Echocardiography was performed for all patients. Rickets was diagnosed according to the clinical, laboratory, and radiologic findings. Maternal lifestyle and living conditions were investigated, and the maternal 25-OH vitamin D3 blood level was measured. We evaluated eight patients who developed heart failure as a result of severe hypocalcaemia associated with rickets between August, 1999 and June, 2012. The age distribution of the patients was 3-12 months. Laboratory results were consistent with advanced-stage rickets. Severe hypocalcaemia was detected in all patients. The maternal 25-OH vitamin D3 levels were low. Echocardiography revealed increased pre-treatment left ventricle end-systolic and end-diastolic diameters for age and reduced ejection fraction and fractional shortening. After clinical improvement, the patients were discharged. Severe hypocalcaemia associated with rickets must always be kept in mind among the causes of dilated cardiomyopathy and impaired cardiac function in infants. If diagnosed and treated in time, dilated cardiomyopathy and severe heart failure related to rickets respond well.

  7. Pitavastatin-attenuated cardiac dysfunction in mice with dilated cardiomyopathy via regulation of myocardial calcium handling proteins

    Directory of Open Access Journals (Sweden)

    Hu Wei

    2014-03-01

    Full Text Available C57BL/6 mice with dilated cardiomyopathy (DCM were randomly divided to receive placebo or pitavastatin at a dose of 1 or 3 mg kg-1d-1. After 8 weeks treatment, mice with dilated cardiomyopathy developed serious cardiac dysfunction characterized by significantly enhanced left ventricular end-diastolic diameter (LVIDd, decreased left ventricular ejection fraction (LVEF as well as left ventricular short axis fractional shortening (LVFS, accompanied with enlarged cardiomyocytes, and increased plasma levels of N-terminal pro-B type natriuretic peptide (NT-proBNP and plasma angiotensin II (AngII concentration. Moreover, myocardium sarcoplasmic reticulum Ca2+ pump (SERCA-2 activity was decreased. The ratio of phosphorylated phospholamban (PLB to total PLB decreased significantly with the down-regulation of SERCA- -2a and ryanodine receptor (RyR2 expression. Pitavastatin was found to ameliorate the cardiac dysfunction in mice with dilated cardiomyopathy by reversing the changes in the ratios of phosphorylated PLB to total PLB, SERCA-2a and RyR2 via reducing the plasma AngII concentration and the expressions of myocardium angiotensin II type 1 receptor (AT1R and protein kinase C (PKCb2. The possible underlying mechanism might be the regulation of myocardial AT1R-PKCb2-Ca2+ handling proteins.

  8. Prognostic significance of radionuclide-assessed right ventricular function in dilated cardiomyopathy

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    Ohno, Akira; Nishimura, Tsunehiko; Uehara, Toshiisa; Shimonagata, Tsuyoshi; Kumita, Shinichiro; Ogawa, Youji; Nagata, Seiki; Miyatake, Kunio [National Cardiovascular Center, Suita, Osaka (Japan)

    1991-09-01

    To assess the prognostic significance of right ventricular function in dilated cardiomyopathy (DCM), we studied consecutive 57 DCM patients. There were 41 men and 16 women, whose mean age was 48 years (range 3-68 years). The mean left ventricular ejection fraction (LVEF) in all patients was 29{+-}11%, and the mean interval from the onset of symptom of cardiac failure (CHF history) was 4 years (range 0-33 years). With follow-up of 3.8 years, five patients had died until the first year, and 14 had died until the third year. By using multivariate regression analysis, there were no prognostic significance in clinical parameters such as age, CHF history, sex, atrial fibrillation, except for NYHA class, and medication at the third year. In survival curves according to Kaplan-Meier method, right ventricular ejection fraction (RVEF) and mean pulmonary artery (PA) had predictive value (p<0.05), while LVEF did not. The patients with RVEF<45% had poor survival rate compared to those with RVEF{>=}45%. The patients with RVEF<45% showed lower LVEF and left ventricular end-systolic volume index. RVEF may offer prognostic predictive value through the effect of not only mean PA but also left ventricular parameter. In conclusion, radionuclide assessment of right ventricular function should be valuable for the prognostic evaluation of DCM patients. (author).

  9. Protein Aggregates and Novel Presenilin Gene Variants in Idiopathic Dilated Cardiomyopathy

    Science.gov (United States)

    Gianni, Davide; Li, Airong; Tesco, Giuseppina; McKay, Kenneth M.; Moore, John; Raygor, Kunal; Rota, Marcello; Gwathmey, Judith K; Dec, G William; Aretz, Thomas; Leri, Annarosa; Semigran, Marc J; Anversa, Piero; Macgillivray, Thomas E; Tanzi, Rudolph E.; Monte, Federica del

    2010-01-01

    Background Heart failure (HF) is a debilitating condition resulting in severe disability and death. In a subset of cases, clustered as Idiopathic Dilated Cardiomyopathy (iDCM), the origin of HF is unknown. In the brain of patients with dementia, proteinaceous aggregates and abnormal oligomeric assemblies of β-amyloid impair cell function and lead to cell death. Methods and Results We have similarly characterized fibrillar and oligomeric assemblies in the hearts of iDCM patients pointing to abnormal protein aggregation as a determinant of iDCM. We also showed that oligomers alter myocyte Ca2+ homeostasis. Additionally, we have identified two new sequence variants in the presenilin-1 (PSEN1) gene promoter leading to reduced gene and protein expression. We also show that presenilin-1 co-immunoprecipitates with SERCA2a. Conclusions Based on these findings we propose that two mechanisms may link protein aggregation and cardiac function: oligomer-induced changes on Ca2+ handling and a direct effect of PSEN1 sequence variants on EC-coupling protein function. PMID:20194882

  10. The relationship between potency of oxidative stress and severity of dilated cardiomyopathy.

    Science.gov (United States)

    Demirbag, Recep; Yilmaz, Remzi; Erel, Ozcan; Gultekin, Unal; Asci, Durmus; Elbasan, Zafer

    2005-08-01

    It has been suggested that oxidative stress may have a role in the etiopathogenesis of congestive heart failure. To investigate and compare the oxidative-antioxidative status and oxidative stress index (OSI) of patients with idiopathic dilated cardiomyopathy (IDC) with those of healthy volunteers, and to determine the relationship between total antioxidant capacity (TAC) and ejection fraction (EF). Twenty-eight patients with IDC and 24 control subjects were enrolled in the study. Antioxidative status was evaluated by measuring the TAC and the vitamin C and thiol levels in the plasma. Oxidative status was evaluated by measuring the total peroxide level. The per cent ratio of TAC to total peroxide level was accepted as the OSI. EF was measured using Simpson's method. TAC and vitamin C and thiol levels of plasma were found to be significantly lower in patients with IDC than in control subjects (P total peroxide levels and OSIs were significantly higher in patients with IDC than in control subjects (P = 0.002 and P = 0.002, respectively). An important positive correlation was found between TAC and EF (r = 0.772; P total peroxide levels in patients. Oxidants are increased and antioxidants are decreased in patients with IDC; as a result, the oxidative-antioxidative balance is shifted to the oxidative side. There is a significant correlation between the potency of oxidative stress and the severity of IDC. It is believed that supplementation of antioxidants in the treatment of IDC may be helpful to these patients.

  11. Prognostic significance of radionuclide-assessed right ventricular function in dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Ohno, Akira; Nishimura, Tsunehiko; Uehara, Toshiisa; Shimonagata, Tsuyoshi; Kumita, Shinichiro; Ogawa, Youji; Nagata, Seiki; Miyatake, Kunio

    1991-01-01

    To assess the prognostic significance of right ventricular function in dilated cardiomyopathy (DCM), we studied consecutive 57 DCM patients. There were 41 men and 16 women, whose mean age was 48 years (range 3-68 years). The mean left ventricular ejection fraction (LVEF) in all patients was 29±11%, and the mean interval from the onset of symptom of cardiac failure (CHF history) was 4 years (range 0-33 years). With follow-up of 3.8 years, five patients had died until the first year, and 14 had died until the third year. By using multivariate regression analysis, there were no prognostic significance in clinical parameters such as age, CHF history, sex, atrial fibrillation, except for NYHA class, and medication at the third year. In survival curves according to Kaplan-Meier method, right ventricular ejection fraction (RVEF) and mean pulmonary artery (PA) had predictive value (p<0.05), while LVEF did not. The patients with RVEF<45% had poor survival rate compared to those with RVEF≥45%. The patients with RVEF<45% showed lower LVEF and left ventricular end-systolic volume index. RVEF may offer prognostic predictive value through the effect of not only mean PA but also left ventricular parameter. In conclusion, radionuclide assessment of right ventricular function should be valuable for the prognostic evaluation of DCM patients. (author)

  12. Lagged segmented Poincaré plot analysis for risk stratification in patients with dilated cardiomyopathy.

    Science.gov (United States)

    Voss, Andreas; Fischer, Claudia; Schroeder, Rico; Figulla, Hans R; Goernig, Matthias

    2012-07-01

    The objectives of this study were to introduce a new type of heart-rate variability analysis improving risk stratification in patients with idiopathic dilated cardiomyopathy (DCM) and to provide additional information about impaired heart beat generation in these patients. Beat-to-beat intervals (BBI) of 30-min ECGs recorded from 91 DCM patients and 21 healthy subjects were analyzed applying the lagged segmented Poincaré plot analysis (LSPPA) method. LSPPA includes the Poincaré plot reconstruction with lags of 1-100, rotating the cloud of points, its normalized segmentation adapted to their standard deviations, and finally, a frequency-dependent clustering. The lags were combined into eight different clusters representing specific frequency bands within 0.012-1.153 Hz. Statistical differences between low- and high-risk DCM could be found within the clusters II-VIII (e.g., cluster IV: 0.033-0.038 Hz; p = 0.0002; sensitivity = 85.7 %; specificity = 71.4 %). The multivariate statistics led to a sensitivity of 92.9 %, specificity of 85.7 % and an area under the curve of 92.1 % discriminating these patient groups. We introduced the LSPPA method to investigate time correlations in BBI time series. We found that LSPPA contributes considerably to risk stratification in DCM and yields the highest discriminant power in the low and very low-frequency bands.

  13. Traditional Chinese Medicine Tongxinluo Improves Cardiac Function of Rats with Dilated Cardiomyopathy

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    Fang-Fang Shen

    2014-01-01

    Full Text Available The study aimed at testing the hypothesis that tongxinluo capsule might exert its cardioprotective effect by preventing ventricular remodeling and improving coronary microvascular function in a rat model of doxorubicin-induced dilated cardiomyopathy (DCM. Rats that survived DCM induction were randomly divided into three groups to be given 1.5 g·kg−1·day−1 (TXL-H, n=9 or 0.15 g·kg−1·day−1 (TXL-L, n=10 of tongxinluo, or normal saline at the same volume (DCM-C, n=10 intragastrically. Age matched normal rats treated with normal saline were used as normal controls (NOR-C, n=9. After four weeks of treatment, the DCM-C, TXL-H, and TXL-L groups exhibited significant cardiac dysfunction, left ventricular remodeling, and coronary microvascular dysfunction, compared with the NOR-C rats. However, myocardial functional parameters were significantly improved and microvascular density (MVD increased in the TXL-H group compared with the DCM-C group (all P<0.01. Left ventricular remodeling was prevented. There were close linear relationships between CVF and LVEF (r=-0.683, P<0.05, MVD and LVEF (r=0.895, P<0.05, and MVD and CVF (r=-0.798, P<0.05. It was indicated that high-dose tongxinluo effectively improved cardiac function in rat model of DCM.

  14. Protein aggregates and novel presenilin gene variants in idiopathic dilated cardiomyopathy.

    Science.gov (United States)

    Gianni, Davide; Li, Airong; Tesco, Giuseppina; McKay, Kenneth M; Moore, John; Raygor, Kunal; Rota, Marcello; Gwathmey, Judith K; Dec, G William; Aretz, Thomas; Leri, Annarosa; Semigran, Marc J; Anversa, Piero; Macgillivray, Thomas E; Tanzi, Rudolph E; del Monte, Federica

    2010-03-16

    Heart failure is a debilitating condition resulting in severe disability and death. In a subset of cases, clustered as idiopathic dilated cardiomyopathy (iDCM), the origin of heart failure is unknown. In the brain of patients with dementia, proteinaceous aggregates and abnormal oligomeric assemblies of beta-amyloid impair cell function and lead to cell death. We have similarly characterized fibrillar and oligomeric assemblies in the hearts of iDCM patients, pointing to abnormal protein aggregation as a determinant of iDCM. We also showed that oligomers alter myocyte Ca(2+) homeostasis. Additionally, we have identified 2 new sequence variants in the presenilin-1 (PSEN1) gene promoter leading to reduced gene and protein expression. We also show that presenilin-1 coimmunoprecipitates with SERCA2a. On the basis of these findings, we propose that 2 mechanisms may link protein aggregation and cardiac function: oligomer-induced changes on Ca(2+) handling and a direct effect of PSEN1 sequence variants on excitation-contraction coupling protein function.

  15. Evaluation of second-generation sequencing of 19 dilated cardiomyopathy genes for clinical applications.

    Science.gov (United States)

    Gowrisankar, Sivakumar; Lerner-Ellis, Jordan P; Cox, Stephanie; White, Emily T; Manion, Megan; LeVan, Kevin; Liu, Jonathan; Farwell, Lisa M; Iartchouk, Oleg; Rehm, Heidi L; Funke, Birgit H

    2010-11-01

    Medical sequencing for diseases with locus and allelic heterogeneities has been limited by the high cost and low throughput of traditional sequencing technologies. "Second-generation" sequencing (SGS) technologies allow the parallel processing of a large number of genes and, therefore, offer great promise for medical sequencing; however, their use in clinical laboratories is still in its infancy. Our laboratory offers clinical resequencing for dilated cardiomyopathy (DCM) using an array-based platform that interrogates 19 of more than 30 genes known to cause DCM. We explored both the feasibility and cost effectiveness of using PCR amplification followed by SGS technology for sequencing these 19 genes in a set of five samples enriched for known sequence alterations (109 unique substitutions and 27 insertions and deletions). While the analytical sensitivity for substitutions was comparable to that of the DCM array (98%), SGS technology performed better than the DCM array for insertions and deletions (90.6% versus 58%). Overall, SGS performed substantially better than did the current array-based testing platform; however, the operational cost and projected turnaround time do not meet our current standards. Therefore, efficient capture methods and/or sample pooling strategies that shorten the turnaround time and decrease reagent and labor costs are needed before implementing this platform into routine clinical applications.

  16. Canine dilated cardiomyopathy: a retrospective study of prognostic findings in 367 clinical cases.

    Science.gov (United States)

    Martin, M W S; Stafford Johnson, M J; Strehlau, G; King, J N

    2010-08-01

    To review the association between clinical signs and diagnostic findings and the survival time of dogs with dilated cardiomyopathy (DCM), and any influence of treatment prescribed. A retrospective observational study of 367 dogs with DCM. Survival times until death or euthanasia for cardiac reasons were analysed using the Kaplan-Meier method plus univariate and multivariate Cox proportional hazards models. Two-tailed P values less than 0.05 were considered statistically significant. In the multivariate model, left ventricular diameter (LVDs)-index (P=0.0067), presence of pulmonary oedema on radiography (P=0.043), presence of ventricular premature complexes (VPCs) (P=0.0012), higher plasma creatinine (P=0.0002), lower plasma protein (P=0.029) and great Dane breed (P=0.0003) were negatively associated with survival. Most dogs were treated with angiotensin-converting enzyme inhibitors (93%) or furosemide (86%), and many received digoxin (50%) and/or pimobendan (30%). Thirteen dogs were lost to follow-up. No conclusions could be made in this study on the association between use of drugs and survival. The LVDs-index was the single best variable for assessing the prognosis in this group of dogs with DCM. Other variables that were negatively associated with survival were presence of pulmonary oedema on radiography, presence of VPCs, higher plasma creatinine, lower plasma protein and great Dane breed.

  17. Cardiomiopatia dilatada em cão: relato de caso Canine dilated cardiomyopathy: case report

    Directory of Open Access Journals (Sweden)

    Ruthnéa Aparecida Lázaro Muzzi

    2000-04-01

    Full Text Available Um canino macho, sem raça definida, com três anos, pesando 36kg, foi atendido no Hospital Veterinário da Universidade Federal de Minas Gerais, apresentando tosse noturna, intolerância ao exercício, cansaço freqüente, emagrecimento e episódios de síncope. O exame clínico revelou mucosas discretamente cianóticas, tempo de perfusão capilar aumentado, presença de sopro sistólico no ápice cardíaco esquerdo e sinais de insuficiência cardíaca congestiva. Foram realizados exames radiográficos, eletrocardiográficos e ecocardiográficos, sendo diagnosticada cardiomiopatia dilatada canina.A three year-old male mixed breed dog, weighing 36kg was presented to Universidade Federal de Minas Gerais Veterinary Hospital, Brazil with history of nocturnal coughing, exercise intolerance, weakness, weight loss and syncopal episodes. Physical examination revealed cyanotic mucous membranes, prolonged capillary refill time, systolic regurgitant murmur at left apex and signs of congestive heart failure. Diagnostic techniques for heart disease were performed such as radiography, eletrocardiography and ecocardiography. These tests showed canine dilated cardiomyopathy.

  18. Evaluation of the phospholamban gene in purebred large-breed dogs with dilated cardiomyopathy.

    Science.gov (United States)

    Stabej, Polona; Leegwater, Peter A; Stokhof, Arnold A; Domanjko-Petric, Aleksandra; van Oost, Bernard A

    2005-03-01

    To evaluate the role of the phospholamban gene in purebred large-breed dogs with dilated cardiomyopathy (DCM). 6 dogs with DCM, including 2 Doberman Pinschers, 2 Newfoundlands, and 2 Great Danes. All dogs had clinical signs of congestive heart failure, and a diagnosis of DCM was made on the basis of echocardiographic findings. Blood samples were collected from each dog, and genomic DNA was isolated by a salt extraction method. Specific oligonucleotides were designed to amplify the promoter, exon 1, the 5'-part of exon 2 including the complete coding region, and part of intron 1 of the canine phospholamban gene via polymerase chain reaction procedures. These regions were screened for mutations in DNA obtained from the 6 dogs with DCM. No mutations were identified in the promoter, 5' untranslated region, part of intron 1, part of the 3' untranslated region, and the complete coding region of the phospholamban gene in dogs with DCM. Results indicate that mutations in the phospholamban gene are not a frequent cause of DCM in Doberman Pinschers, Newfoundlands, and Great Danes.

  19. Characterization of canine mitochondrial protein expression in natural and induced forms of idiopathic dilated cardiomyopathy.

    Science.gov (United States)

    Lopes, Rosana; Solter, Philip F; Sisson, D David; Oyama, Mark A; Prosek, Robert

    2006-06-01

    To map canine mitochondrial proteins and identify qualitative and quantitative differences in heart mitochondrial protein expression between healthy dogs and dogs with naturally occurring and induced dilated cardiomyopathy (DCM). Left ventricle samples were obtained from 7 healthy dogs, 7 Doberman Pinschers with naturally occurring DCM, and 7 dogs with induced DCM. Fresh and frozen mitochondrial fractions were isolated from the left ventricular free wall and analyzed by 2-dimensional electrophoresis. Protein spots that increased or decreased in density by >or= 2-fold between groups were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or quadrupole selecting, quadrupole collision cell, time-of-flight mass spectrometry. Within narrow pH gradients of control canine heart mitochondrial samples, a total of 1,528 protein spots were revealed. Forty subunits of heart mitochondrial proteins that differ significantly from control tissues were altered in tissue specimens from dogs with naturally occurring and induced forms of DCM. The most affected heart mitochondrial proteins in both groups were those of oxidative phosphorylation (55%). Upregulation of manganese superoxide dismutase was suggestive of heart oxidative injury in tissue specimens from dogs with both forms of DCM. Evidence of apoptosis was associated with overexpression of the heart mitochondrial voltage-dependent anion channel-2 protein and endonuclease G in tissue specimens from dogs with induced DCM. Alterations of heart mitochondrial proteins related to oxidative phosphorylation dysfunction were more prevalent in tissue specimens from dogs with induced or naturally occurring DCM, compared with those of control dogs.

  20. Genomic expression patterns of cardiac tissues from dogs with dilated cardiomyopathy.

    Science.gov (United States)

    Oyama, Mark A; Chittur, Sridar

    2005-07-01

    To evaluate global genome expression patterns of left ventricular tissues from dogs with dilated cardiomyopathy (DCM). Tissues obtained from the left ventricle of 2 Doberman Pinschers with end-stage DCM and 5 healthy control dogs. Transcriptional activities of 23,851 canine DNA sequences were determined by use of an oligonucleotide microarray. Genome expression patterns of DCM tissue were evaluated by measuring the relative amount of complementary RNA hybridization to the microarray probes and comparing it with gene expression for tissues from 5 healthy control dogs. 478 transcripts were differentially expressed (> or = 2.5-fold change). In DCM tissue, expression of 173 transcripts was upregulated and expression of 305 transcripts was downregulated, compared with expression for control tissues. Of the 478 transcripts, 167 genes could be specifically identified. These genes were grouped into 1 of 8 categories on the basis of their primary physiologic function. Grouping revealed that pathways involving cellular energy production, signaling and communication, and cell structure were generally downregulated, whereas pathways involving cellular defense and stress responses were upregulated. Many previously unreported genes that may contribute to the pathophysiologic aspects of heart disease were identified. Evaluation of global expression patterns provides a molecular portrait of heart failure, yields insights into the pathophysiologic aspects of DCM, and identifies intriguing genes and pathways for further study.

  1. Timing of left heart base descent in dogs with dilated cardiomyopathy and normal dogs.

    Science.gov (United States)

    Simpson, Kerry E; Devine, Bryan C; Woolley, Richard; Corcoran, Brendan M; French, Anne T

    2008-01-01

    The identification and assessment of myocardial failure in canine idiopathic dilated cardiomyopathy (DCM) is achieved using a variety of two-dimensional and Doppler echocardiographic techniques. More recently, the availability of tissue Doppler imaging (TDI) has raised the potential for development of new ways of more accurately identifying a disease phenotype. Nevertheless, TDI has not been universally adapted to veterinary clinical cardiology primarily because of the lack of information on its utility in diagnosis. We assessed the application of timing of left heart base descent using TDI in the identification of differences between DCM and normal dogs. The times from the onset of the QRS complex on a simultaneously recorded electrocardiograph to the onset (Q--S'), peak (Q--peak S'), and end (Q--end S') of the systolic velocity peak were measured in the interventricular septum (IVS) and the left ventricular free wall. The duration of S' was also calculated. The Q--S' (FW), Q--end S' (FW), and duration S' (FW) were correlated with ejection fraction in the diseased group (P canine DCM and identifies new TDI parameters that can be added to the range of Doppler and echocardiographic parameters used for detecting myocardial failure in the dog.

  2. Idiopathic Dilated Cardiomyopathy-proton magnetic resonance spectroscopy ( 1 H MRS ) in evaluation of myocardial metabolism. Preliminary study

    International Nuclear Information System (INIS)

    Michalak, M.; Walecki, J.; Michalak, E.; Bilinska, Z.; Ruzyllo, W.

    2002-01-01

    Primary dilated cardiomyopathy is a disease of unknown etiology and it leads to serious cardiac insufficiency. Abnormalities in cardiac metabolism can play an important role in clinical manifestation and prognosis in this group. The aim of this study was an attempt to assess cardiac metabolism using proton spectroscopy magnetic resonance method (1H MRS) and to find a relationship between cardiac metabolites and functional class NYHA and left ventricular function parameters obtained by echocardiography. Proton spectroscopy magnetic resonance was performed in 15 patients with angiographically documented idiopathic dilated cardiomyopathy and 12 healthy volunteers with voxel localized at interventricular septum area. The contents of total creatine (CR) e.g. creatine+phosphocreatine, lipids (LIP) lactates (LAC) and their ratios (CR1A, CR2A, CR1/H20, CR2/H20, CR2/CR1, LIPA, LIP/H20, LIP/CR1, LACA, LAC/H20, LAC/CR1) were examined. Patents with dilated cardiomyopathy had significantly lower level of creatine CR1A (5.04I0.88 vs. 5.94I1.15, p<0.02) and ratios LIP/H20 (4.34I2.3 vs. 15.46I20.39, p<0.04) and LIP/CR1 (24.49I21.26 vs. 34.08I13.36, p<0.05) compared to healthy volunteers. Significant correlations between NYHA functional class and ratios CR2/CR1, CR2/H20 (r=0.59 p<0.038, r=0.59 p<0.02) and between %EFLV and LIP/CR1 (r=0.64, p<0.036), as well as between the duration of the disease (CTCH) and LIP/CR1 (r=0.67, p<0.046) were found. Preliminary study with proton spectroscopy magnetic resonance (1H MRS) showed impairment cardiac metabolism in patients with idiopathic dilated cardiomyopathy. A tendency to lowered values of creatine, lipids and some ratios of these metabolites were observed in dilated cardiomyopathy group compared to healthy subjects. Our results needs further study. (author)

  3. A mutation in the glutamate-rich region of RNA-binding motif protein 20 causes dilated cardiomyopathy through missplicing of titin and impaired Frank-Starling mechanism

    DEFF Research Database (Denmark)

    Beqqali, Abdelaziz; Bollen, I. A. E.; Rasmussen, T. B.

    2016-01-01

    Mutations in the RS-domain of RNA-binding motif protein 20 (RBM20) have recently been identified to segregate with aggressive forms of familial dilated cardiomyopathy (DCM). Loss of RBM20 in rats results in missplicing of the sarcomeric gene titin (TTN). The functional and physiological consequen......Mutations in the RS-domain of RNA-binding motif protein 20 (RBM20) have recently been identified to segregate with aggressive forms of familial dilated cardiomyopathy (DCM). Loss of RBM20 in rats results in missplicing of the sarcomeric gene titin (TTN). The functional and physiological...... consequences of RBM20 mutations outside the mutational hotspot of RBM20 have not been explored to date. In this study, we investigated the pathomechanism of DCM caused by a novel RBM20 mutation in human cardiomyocytes. We identified a family with DCM carrying a mutation (RBM20(E913K/+)) in a glutamate...... to the early onset, and malignant course of DCM caused by RBM20 mutations. Altogether, our results demonstrate that heterozygous loss of RBM20 suffices to profoundly impair myocyte biomechanics by its disturbance of TTN splicing....

  4. Prognostic value of sympathetic innervation and cardiac asynchrony in dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Manrique, Alain; Hitzel, Anne; Vera, Pierre; Bernard, Mathieu; Bauer, Fabrice; Menard, Jean-Francois; Sabatier, Remi; Jacobson, Arnold; Agostini, Denis

    2008-01-01

    The purpose of the study is to examine prognostic values of cardiac I-123 metaiodobenzylguanidine (MIBG) uptake and cardiac dyssynchrony in patients with dilated cardiomyopathy (DCM). Ninety-four patients with non-ischemic DCM underwent I-123 MIBG imaging for assessing cardiac sympathetic innervation and equilibrium radionuclide angiography. Mean phase angles and SD of the phase histogram were computed for both right ventricular (RV) and left ventricular (LV). Phase measures of interventricular (RV-LV) and intraventricular (SD-RV and SD-LV) asynchrony were computed. Most patients were receiving beta-blockers (89%) and angiotensin-converting enzyme inhibitors (88%). One patient (1%) was lost to follow-up, six had cardiac death (6.4%), eight had heart transplantation (8.6%), and seven had unplanned hospitalization for heart failure (7.5%; mean follow-up: 37 ± 16 months). Patients with poor clinical outcome were older, had higher The New York Heart Association functional class, impaired right ventricular ejection fraction and left ventricular ejection fraction, and impaired cardiac I-123 MIBG uptake. On multivariate analysis, I-123 MIBG heart-to-mediastinum (H/M) uptake ratio <1.6 was the only predictor of both primary (cardiac death or heart transplantation, RR = 7.02, p < 0.01) and secondary (cardiac death, heart transplantation, or recurrent heart failure, RR = 8.10, p = 0.0008) end points. In patients receiving modern medical therapy involving beta-blockers, I-123 MIBG uptake, but not intra-LV asynchrony, was predictive of clinical outcome. The impact of beta-blockers on the prognostic value of ventricular asynchrony remains to be clarified. (orig.)

  5. Beneficial effects of edaravone, a novel antioxidant, in rats with dilated cardiomyopathy

    Science.gov (United States)

    Arumugam, Somasundaram; Thandavarayan, Rajarajan A; Veeraveedu, Punniyakoti T; Nakamura, Takashi; Arozal, Wawaimuli; Sari, Flori R; Giridharan, Vijayasree V; Soetikno, Vivian; Palaniyandi, Suresh S; Harima, Meilei; Suzuki, Kenji; Nagata, Masaki; Kodama, Makoto; Watanabe, Kenichi

    2012-01-01

    Edaravone, a novel antioxidant, acts by trapping hydroxyl radicals, quenching active oxygen and so on. Its cardioprotective activity against experimental autoimmune myocarditis (EAM) was reported. Nevertheless, it remains to be determined whether edaravone protects against cardiac remodelling in dilated cardiomyopathy (DCM). The present study was undertaken to assess whether edaravone attenuates myocardial fibrosis, and examine the effect of edaravone on cardiac function in rats with DCM after EAM. Rat model of EAM was prepared by injection with porcine cardiac myosin 28 days after immunization, we administered edaravone intraperitoneally at 3 and 10 mg/kg/day to rats for 28 days. The results were compared with vehicle-treated rats with DCM. Cardiac function, by haemodynamic and echocardiographic study and histopathology were performed. Left ventricular (LV) expression of NADPH oxidase subunits (p47phox, p67phox, gp91phox and Nox4), fibrosis markers (TGF-β1 and OPN), endoplasmic reticulum (ER) stress markers (GRP78 and GADD 153) and apoptosis markers (cytochrome C and caspase-3) were measured by Western blotting. Edaravone-treated DCM rats showed better cardiac function compared with those of the vehicle-treated rats. In addition, LV expressions of NADPH oxidase subunits levels were significantly down-regulated in edaravone-treated rats. Furthermore, the number of collagen-III positive cells in the myocardium of edaravone-treated rats was lower compared with those of the vehicle-treated rats. Our results suggest that edaravone ameliorated the progression of DCM by modulating oxidative and ER stress-mediated myocardial apoptosis and fibrosis. PMID:22268705

  6. Segmental wall motion abnormalities in dilated cardiomyopathy: hemodynamic characteristics and comparison with thallium-201 myocardial scintigraphy

    International Nuclear Information System (INIS)

    Yamaguchi, S.; Tsuiki, K.; Hayasaka, M.; Yasui, S.

    1987-01-01

    This study assessed the hemodynamic characteristics of segmental wall motion abnormality of the left ventricle in patients with dilated cardiomyopathy (DCM) and its relation to the thallium-201 (TI-201) myocardial scintigraphy (MPI). Left ventriculograms and MPI in 23 patients were analyzed by the use of quantitative indexes of regional wall motion and TI-201 uptake based on a mean and a standard deviation of 13 normal subjects. Relative normokinesis in our definition was more frequently seen in the inferior wall than in the anterior wall (p less than 0.01). In contrast, severe asynergy was more often seen in the anterior wall than in the inferior wall (p less than 0.01). There were 11 patients who had relative normokinesis and asynergy together. By means of the index of wall motion, the DCM patients were divided into two groups, one with segmental wall motion abnormality (SWMA) and another with diffuse wall motion abnormality (DWMA). The DWMA group had higher left ventricular end-diastolic pressures (p less than 0.05) and the tendency of large left ventricular end-diastolic volumes than the SWMA group. There was a rough correlation (r = 0.58) between the quantitative indexes of TI-201 uptake and wall motion at the same region of the left ventricle. Thus, the nonuniformity of the left ventricular wall motion was recognized in the patients with DCM and more increased preload was shown in the patients with DWMA than in the group with SWMA. Further, the regional asynergy may be related to the localized fibrosis within the left ventricle in DCM, considering the result that the worse TI-201 uptake was roughly accompanied by the more severe asynergy

  7. Neopterin and Beta-2 Microglobulin Relations to Immunity and Inflammatory Status in Nonischemic Dilated Cardiomyopathy Patients

    Directory of Open Access Journals (Sweden)

    Celina Wojciechowska

    2014-01-01

    Full Text Available Background. The aim of the study was to assess the relationships among serum neopterin (NPT, β2-microglobulin (β2-M levels, clinical status, and endomyocardial biopsy results of dilated cardiomyopathy patients (DCM. Methods. Serum NPT and β-2 M were determined in 172 nonischaemic DCM patients who underwent right ventricular endomyocardial biopsy and 30 healthy subjects (ELISA test. The cryostat biopsy specimens were assessed using histology, immunohistology, and immunochemistry methods (HLA ABC, HLA DR expression, CD3 + lymphocytes, and macrophages counts. Results. The strong increase of HLA ABC or HLA DR expression was detected in 27.2% patients—group A—being low in 72.8% patients—group B. Neopterin level was increased in patients in group A compared to healthy controls 8.11 (4.50–12.57 versus 4.99 (2.66–8.28 nmol/L (P<0.05. β-2 microglobulin level was higher in DCM groups A (2.60 (1.71–3.58 and B (2.52 (1.51–3.72 than in the control group 1.75 (1.28–1.96 mg/L, P<0.001. Neopterin correlated positively with the number of macrophages in biopsy specimens (P<0.05 acute phase proteins: C-reactive proteins (P<0.05; fibrinogen (P<0.01; and NYHA functional class (P<0.05 and negatively with left ventricular ejection fraction (P<0.05. Conclusions. Neopterin but not β-2 microglobulin concentration reflected immune response in biopsy specimens. Neopterin correlated with acute phase proteins and stage of heart failure and may indicate a general immune and inflammatory activation in heart failure.

  8. Cholesterol metabolism as a prognostic marker in patients with mildly symptomatic nonischemic dilated cardiomyopathy.

    Science.gov (United States)

    Sawamura, Akinori; Okumura, Takahiro; Hiraiwa, Hiroaki; Aoki, Soichiro; Kondo, Toru; Ichii, Takeo; Furusawa, Kenji; Watanabe, Naoki; Kano, Naoaki; Fukaya, Kenji; Morimoto, Ryota; Bando, Yasuko K; Murohara, Toyoaki

    2017-06-01

    Little is known about whether the alteration of cholesterol metabolism reflects abdominal organ impairments due to heart failure. Therefore, we investigated the prognostic value of cholesterol metabolism by evaluating serum campesterol and lathosterol levels in patients with early-stage nonischemic dilated cardiomyopathy (NIDCM). We enrolled 64 patients with NIDCM (median age 57.5 years, 31% female) with New York Heart Association functional class I/II. Serum campesterol and lathosterol levels were measured in all patients. The patients were then divided into four subsets based on the median non-cholesterol sterol levels (campesterol 3.6μg/mL, lathosterol 1.4μg/mL): reference (R-subset), high-campesterol/high-lathosterol; absorption-reduced (A-subset), low-campesterol/high-lathosterol; synthesis-reduced (S-subset), high-campesterol/low-lathosterol; double-reduced (D-subset), low-campesterol/low-lathosterol. Endpoint was a composite of cardiac events, including cardiac-related death, hospitalization for worsening heart failure, and lethal arrhythmia. Median brain natriuretic peptide (BNP) level was 114pg/mL. Mean left ventricular ejection fraction was 31.4%. D-subset had the lowest total cholesterol level and cardiac index and the highest BNP level and pulmonary capillary wedge pressure. D-subset also had the highest cardiac event rate during the mean 3.8 years of follow-up (log-rank p=0.001). Multivariate regression analysis showed that D-subset was an independent determinant of cardiac events. The receiver operating characteristic curve analysis revealed that total cholesterol cholesterol absorption and liver synthesis predicts future cardiac events in patients with mildly symptomatic NIDCM. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  9. European Society of Veterinary Cardiology screening guidelines for dilated cardiomyopathy in Doberman Pinschers.

    Science.gov (United States)

    Wess, G; Domenech, O; Dukes-McEwan, J; Häggström, J; Gordon, S

    2017-10-01

    Dilated cardiomyopathy (DCM) is the most common cardiac disease in large breed dogs and is inherited in Doberman Pinschers with a high prevalence (58%). The European Society for Veterinary Cardiology convened a task force to formulate screening guidelines for DCM in Dobermans. Screening for occult DCM in Dobermans should start at three years of age and use both Holter monitoring and echocardiography. Yearly screening over the life of the dog is recommended, as a one-time screening is not sufficient to rule out future development of DCM. The preferred echocardiographic method is the measurement of the left ventricular volume by Simpson's method of discs (SMOD). Less than 50 single ventricular premature complexes (VPCs) in 24 h are considered to be normal in Dobermans, although detection of any number of VPCs is cause for concern. Greater than 300 VPCs in 24 h or two subsequent recordings within a year showing between 50 and 300 VPCs in 24 h is considered diagnostic of occult DCM in Dobermans regardless of the concurrent echocardiographic findings. The guidelines also provide recommendations concerning ancillary tests, that are not included in the standard screening protocol, but which may have some utility when recommended tests are not available or financially untenable on an annual basis. These tests include assay of cardiac biomarkers (Troponin I and N-Terminal pro-B-type Natriuretic Peptide) as well as a 5-min resting electrocardiogram (ECG). The current guidelines should help to establish an early diagnosis of DCM in Dobermans. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  10. Predictors of Sudden Cardiac Death in Doberman Pinschers with Dilated Cardiomyopathy.

    Science.gov (United States)

    Klüser, L; Holler, P J; Simak, J; Tater, G; Smets, P; Rügamer, D; Küchenhoff, H; Wess, G

    2016-05-01

    Doberman Pinschers with dilated cardiomyopathy (DCM) are at high risk of sudden cardiac death (SCD). Risk factors for SCD are poorly defined. To assess cardiac biomarkers, Holter-ECG, echocardiographic variables and canine characteristics in a group of Doberman Pinschers with DCM dying of SCD and in a DCM control group to identify factors predicting SCD. A longitudinal prospective study was performed in 95 Doberman Pinschers with DCM. Forty-one dogs died within 3 months after the last cardiac examination (SCD-group) and were compared to 54 Doberman Pinschers with DCM surviving 1 year after inclusion. Holter-ECG, echocardiography, measurement of N-terminal prohormone of brain-natriuretic peptide (NT-proBNP), and cardiac Troponin I (cTnI) concentrations were recorded for all dogs. Volume overload of the left ventricle (left ventricular end-diastolic volume (LVEDV/BSA) > 91.3 mL/m²) was the single best variable to predict SCD. The probability of SCD increases 8.5-fold (CI0.95  = 0.8-35.3) for every 50 mL/m²-unit increment in LVEDV/BSA. Ejection fraction (EF), left ventricular end-systolic volume (LVESV/BSA) and NT-proBNP were highly correlated with LVEDV/BSA (r = -0.63, 0.96, 0.86, respectively). Generated conditional inference trees (CTREEs) revealed that the presence of ventricular tachycardia (VT), increased concentration of cTnI, and the fastest rate (FR) of ventricular premature complexes (VPC) ≥260 beats per minute (bpm) are additional important variables to predict SCD. Conditional inference trees provided in this study might be useful for risk assessment of SCD in Doberman Pinschers with DCM. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  11. Decreased triadin and increased calstabin2 expression in Great Danes with dilated cardiomyopathy.

    Science.gov (United States)

    Oyama, M A; Chittur, S V; Reynolds, C A

    2009-01-01

    Dilated cardiomyopathy (DCM) is a common cardiac disease of Great Dane dogs, yet very little is known about the underlying molecular abnormalities that contribute to disease. Discover a set of genes that are differentially expressed in Great Dane dogs with DCM as a way to identify candidate genes for further study as well as to better understand the molecular abnormalities that underlie the disease. Three Great Dane dogs with end-stage DCM and 3 large breed control dogs. Prospective study. Transcriptional activity of 42,869 canine DNA sequences was determined with a canine-specific oligonucleotide microarray. Genome expression patterns of left ventricular tissue samples from affected Great Dane dogs were evaluated by measuring the relative amount of complementary RNA hybridization to the microarray probes and comparing it with expression from large breed dogs with noncardiac disease. Three hundred and twenty-three transcripts were differentially expressed (> or = 2-fold change). The transcript with the greatest degree of upregulation (+61.3-fold) was calstabin2 (FKBP12.6), whereas the transcript with the greatest degree of downregulation (-9.07-fold) was triadin. Calstabin2 and triadin are both regulatory components of the cardiac ryanodine receptor (RyR2) and are critical to normal intracellular Ca2+ release and excitation-contraction coupling. Great Dane dogs with DCM demonstrate abnormal calstabin2 and triadin expression. These changes likely affect Ca2+ flux within cardiac cells and may contribute to the pathophysiology of disease. Microarray-based analysis identifies calstabin2, triadin, and RyR2 function as targets of future study.

  12. The potential role of myocardial serotonin receptor 2B expression in canine dilated cardiomyopathy.

    Science.gov (United States)

    Fonfara, Sonja; Hetzel, Udo; Oyama, Mark A; Kipar, Anja

    2014-03-01

    Serotonin signalling in the heart is mediated by receptor subtype 2B (5-HTR2B). A contribution of serotonin to valvular disease has been reported, but myocardial expression of 5-HTR2B and its role in canine dilated cardiomyopathy (DCM) is not known. The aim of the present study was to investigate myocardial 5-HTR2B mRNA expression in dogs with DCM and to correlate results with expression of markers for inflammation and remodelling. Myocardial samples from eight healthy dogs, four dogs with DCM, five with cardiac diseases other than DCM and six with systemic non-cardiac diseases were investigated for 5-HTR2B mRNA expression using quantitative PCR (qPCR). The results were compared to mRNA expression of selected cytokines, matrix metalloproteinases (MMP) and tissue inhibitors of matrix metalloproteinase (TIMP). Laser microdissection with subsequent qPCR and immunohistochemistry were employed to identify the cells expressing 5-HTR2B. The myocardium of control dogs showed constitutive 5-HTR2B mRNA expression. In dogs with DCM, 5-HTR2B mRNA values were significantly greater than in all other groups, with highest levels of expression in the left ventricle and right atrium. Myocytes were identified as the source of 5-HTR2B mRNA and protein. A significant positive correlation of 5-HTR2B mRNA with expression of several cytokines, MMPs and TIMPs was observed. The findings suggest that serotonin might play a role in normal cardiac structure and function and could contribute to myocardial remodelling and functional impairment in dogs with DCM. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Successive myocardial fatty acid metabolic imaging in patients with dilated cardiomyopathy. Usefulness as a prognostic indicator

    International Nuclear Information System (INIS)

    Narita, Michihiro; Kurihara, Tadashi; Sindoh, Takashi; Sawada, Yoshihiro; Honda, Minoru

    2000-01-01

    To evaluate the prognostic value of fatty acid metabolic imaging in patients with idiopathic dilated cardiomyopathy (DCM), we performed myocardial imaging with 123 I-BMIPP (BMIPP). We studied 23 patients with DCM who were admitted because of congestive heart failure (CHF) and after discharge the stable condition persisted for more than one year. BMIPP imaging was obtained when CHF recovered (first study) and the second study was performed one year after the first study. From BMIPP imaging we calculated % Uptake (percentage of cardiac uptake of isotope to total injected dose) and Defect Score (degree and extent of regional abnormality in BMIPP uptake, DS). In the first study, we performed myocardial imaging with 201 Tl to calculate Uptake Ratio of BMIPP (% Uptake of BMIPP divided by % Uptake of 201 Tl, UR). During the follow up period of 18.2±9.5 months (4.5-39.6 months) after the second study, cardiac event developed in 8 patients (cardiac death; 4, deterioration of CHF; 4). On univariate analysis, the following indices differed significantly between the event and event-free groups; left ventricular end-systolic dimension, graded DS, UR and % Uptake of 201 Tl at the first study, % Uptake of BMIPP and DS at the second study, difference of % Uptake of BMIPP and DS between the first and second study, and newly designed index from graded DS of the first study and its change in the second study (Defect Index, DI). Cox proportional hazard analysis showed that DI (p=0.0026) and age (p=0.0262) were independent predictors of cardiac event. In patients with DI≥3, the relative risk of cardiac event was 25.0 times greater than that in patients with DI≤2. These data suggested that the extent and degree of regional abnormality of BMIPP uptake (DS) and its changes with time were useful for evaluating the prognosis in patients with DCM even though a clinically stable condition is persisting. (author)

  14. Effect of benazepril on heart rate turbulence in patients with dilated cardiomyopathy.

    Science.gov (United States)

    Zhong, Jiang-Hua; Chen, Xiao-Pan; Zeng, Chun-Fang; Yun, Mei-Ling; Yang, Xin-Wei; Chen, Yan-Fang; Yao, Zhen

    2007-07-01

    1. Heart rate (HR) turbulence describes short-term sinus rhythmic fluctuation after a single premature ventricular beat. Turbulence onset (TO) and turbulence slope (TS) are two essential parameters in HR turbulence. Turbulence onset and TS have been used to evaluate cardiac autonomic nerve function. 2. In the present study, we measured the HR turbulence in dilated cardiomyopathy (DCM) and determined the possible role of benazepril, an angiotensin-converting enzyme inhibitor (ACEI), on these parameters. There were three groups: control, DCM and DCM treated with benazepril. The control group consisted of normal subjects with PVB, but no structural heart disease. Ambulatory electrocardiogram, blood pressure and echocardiography were analysed. 3. There was an increase in TO and a decrease in TS in DCM patients. Benazepril treatment (10 mg/day, p.o.) reduced those changes. There were no significant differences in blood pressure and left ventricular ejection fraction (LVEF) between DCM patients and DCM patients treated with benazepril. 4. Linear regression analysis showed that TO was negatively correlated with LVEF, whereas TS was positively correlated with LVEF, in the DCM group. After benazepril treatment, the correlations between TO and TS and LVEF disappeared. 5. It is concluded that the TO and TS of HR turbulence are altered in patients with DCM. These alterations indicate a dysfunction of the autonomic control of cardiac electrophysiology in DCM patients. Although TO and TS are correlated with LVEF in DCM patients, the effect of benazepril in improving HR turbulence parameters is not a result of its action on heart function, which suggests a new beneficial effect of ACEI in the treatment of DCM patients.

  15. Efficacy of benazepril hydrochloride to delay the progression of occult dilated cardiomyopathy in Doberman Pinschers.

    Science.gov (United States)

    O'Grady, M R; O'Sullivan, M L; Minors, S L; Horne, R

    2009-01-01

    Angiotensin converting enzyme inhibitors (ACEIs) are recommended in people to treat asymptomatic (occult) dilated cardiomyopathy (DCM). Efficacy of therapy in occult DCM in dogs is unknown. ACEIs, specifically benazepril hydrochloride (BH), will delay the onset of overt DCM in Doberman Pinschers. Ninety-one Doberman Pinschers were studied, 57 dogs received BH, and 34 dogs no ACEI. Retrospective study of the medical records of all Doberman Pinschers with occult DCM that received BH or no ACEI between April 1989 and February 2003. Two criteria of left ventricular enlargement were used for enrollment: one independent of body weight (BW) (C1) and the other indexed to BW (C2). Cox proportional hazards analyses were used to identify variables associated with the onset of overt DCM. On univariate analysis the median time to onset of overt DCM was significantly longer for the benazepril group (for C1: 425 days for BH, 95% confidence interval [CI] 264-625 days; 339 days for no ACEI, CI 172-453 days, P= .02; for C2: 454 days for BH, CI 264-628 days; 356 days for no ACEI, CI 181-547 days, P= .02). The hazard ratio (HR) (benazepril/no ACEI) was 0.57, CI 0.35-0.94, P= .03 for C1; HR = 0.56, CI 0.34-0.93, P= .02 for C2. On multivariate analysis, BH significantly delayed onset of overt DCM (HR [benazepril/no ACEI] = 0.45, CI 0.26-0.78, P < .01, for C1; HR = 0.36, CI 0.21-0.63, P < .01, for C2). BH in particular and ACEIs in general might delay the progression of occult DCM. Prospective studies are warranted to test this theory.

  16. Prognostic significance of large perfusion defects on thallium-201 myocardial scintigraphy in dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Takata, Jun; Doi, Yoshinori; Chikamori, Taishiro; Yonezawa, Yoshihiro; Hamashige, Naohisa; Kuzume, Osamu; Ozawa, Toshio

    1989-01-01

    To evaluate the prognostic significance of perfusion abnormalities, particularly large defects, in dilated cardiomyopathy (DCM), we performed thallium-201 myocardial scintigraphy and 24-hour ambulatory ECG monitoring in 27 patients. The abnormal scintigraphic patterns and the presence of ventricular tachycardia (VT) were correlated with causes of death during a follow-up period of 30.0±19.4 months. Eight patients had large defects (LD), 11 had multiple small defects (MSD), and eight had no defects (NL). The patients with LD had extensive ventricular akinesis in the region of the perfusion defect, significantly elevated LVEDP (LD 20.6±7.4 mmHg, MSD 15.5±7.6 mmHg, NL 10.3±2.3 mmHg: LD vs NL; p<0.01, MSD vs NL; p<0.05), and reduced ejection fraction (LD 23.9±9.1%, MSD 32.7±7.2%, NL 40.3±7.7%: LD vs MSD; p<0.05, MSD vs NL; p<0.01). VT was detected in 11 patients; among whom three had LD, six had MSD, and two had no defects. Among seven patients who died during follow-up (five of heart failure, one sudden death, and one non-cardiac death), five had LD and two had MSD. There were no deaths among patients without defects. Among 11 patients with VT, only one died suddenly. In conclusion, large scintigraphic defects correlated well with severe LV dysfunction, and this is an important variable in predicting outcomes in DCM. (author)

  17. Homozygous EEF1A2 mutation causes dilated cardiomyopathy, failure to thrive, global developmental delay, epilepsy and early death.

    Science.gov (United States)

    Cao, Siqi; Smith, Laura L; Padilla-Lopez, Sergio R; Guida, Brandon S; Blume, Elizabeth; Shi, Jiahai; Morton, Sarah U; Brownstein, Catherine A; Beggs, Alan H; Kruer, Michael C; Agrawal, Pankaj B

    2017-09-15

    Eukaryotic elongation factor 1A (EEF1A), is encoded by two distinct isoforms, EEF1A1 and EEF1A2; whereas EEF1A1 is expressed almost ubiquitously, EEF1A2 expression is limited such that it is only detectable in skeletal muscle, heart, brain and spinal cord. Currently, the role of EEF1A2 in normal cardiac development and function is unclear. There have been several reports linking de novo dominant EEF1A2 mutations to neurological issues in humans. We report a pair of siblings carrying a homozygous missense mutation p.P333L in EEF1A2 who exhibited global developmental delay, failure to thrive, dilated cardiomyopathy and epilepsy, ultimately leading to death in early childhood. A third sibling also died of a similar presentation, but DNA was unavailable to confirm the mutation. Functional genomic analysis was performed in S. cerevisiae and zebrafish. In S. cerevisiae, there was no evidence for a dominant-negative effect. Previously identified putative de novo mutations failed to complement yeast strains lacking the EEF1A ortholog showing a major growth defect. In contrast, the introduction of the mutation seen in our family led to a milder growth defect. To evaluate its function in zebrafish, we knocked down eef1a2 expression using translation blocking and splice-site interfering morpholinos. EEF1A2-deficient zebrafish had skeletal muscle weakness, cardiac failure and small heads. Human EEF1A2 wild-type mRNA successfully rescued the morphant phenotype, but mutant RNA did not. Overall, EEF1A2 appears to be critical for normal heart function in humans, and its deficiency results in clinical abnormalities in neurologic function as well as in skeletal and cardiac muscle defects. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Genotype phenotype correlations of cardiac beta-myosin heavy chain mutations in Indian patients with hypertrophic and dilated cardiomyopathy

    DEFF Research Database (Denmark)

    Rai, Taranjit Singh; Ahmad, Shamim; Bahl, Ajay

    2009-01-01

    The aim of the current study was to determine the frequency of mutations in the beta-myosin heavy chain gene (MYH7) in a cohort of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) and their families, and to investigate correlations between genotype and phenotype. About 130...... consecutive patients diagnosed with HCM or DCM (69 with HCM and 61 with DCM) attending the cardiology clinic of Post Graduate Institute of Medical Education and Research were screened for mutations in the MYH7 gene. The control group for genetic studies consisted of 100 healthy subjects. We report 14...... mutations in 6 probands (5 probands in HCM and 1 proband in DCM) and their family members. Out of these 6 mutations, 3 are new and are being reported for the first time. One known mutation (p.Gly716Arg) was found to be "de novo" which resulted in severe asymmetric septal hypertrophy (31 mm) and resulted...

  19. A case of dilated cardiomyopathy with massive left ventricular thrombus after use of a sibutramine-containing slimming product.

    Science.gov (United States)

    Heo, Seung Hye; Kang, Min-Ho

    2013-09-01

    Sibutramine, which acts as an anti-obesity drug by inhibiting reuptake of serotonin and norepinephrine, has now been banned due to cardiovascular adverse effects. However, despite being banned, it is not uncommon for people to purchase products with sibutramine or its analogues used as adulterants in non-prescription slimming products or health foods available on the internet. Sibutramine has been associated with rare but serious adverse reactions such as cardiac arrhythmia including QT interval prolongation, myocardial infarction, and cardiomyopathy, as well as increases in blood pressure and pulse rate. Here, we report a case of a 32-year-old male who presented with dilated cardiomyopathy with massive left ventricular thrombus after taking unauthorized sibutramine-containing slimming pills sold over the internet.

  20. A case of reversible dilated cardiomyopathy after alpha-interferon therapy in a patient with renal cell carcinoma.

    Science.gov (United States)

    Kuwata, Akiko; Ohashi, Masuo; Sugiyama, Masaya; Ueda, Ryuzo; Dohi, Yasuaki

    2002-12-01

    A 47-year-old man with renal cell carcinoma underwent nephrectomy, and postoperative chemotherapy was performed with recombinant alpha-interferon. Five years later, he experienced dyspnea during physical exertion. An echocardiogram revealed dilatation and systolic dysfunction of the left ventricle, and thallium-201 myocardial scintigraphy showed diffuse heterogeneous perfusion. We diagnosed congestive heart failure because of cardiomyopathy induced by alpha-interferon therapy. Withdrawal of interferon therapy and the combination of an angiotensin-converting enzyme inhibitor, diuretics, and digitalis improved left ventricular systolic function. Furthermore, myocardial scintigraphy using [123I] beta-methyl-p-iodophenylpentadecanoic acid (123I-BMIPP) or [123 I]metaiodobenzylguanidine (123I-MIBG) revealed normal perfusion after the improvement of congestive heart failure. This is a rare case of interferon-induced cardiomyopathy that resulted in normal myocardial images in 123I-BMIPP and 123I-MIBG scintigrams after withdrawal of interferon therapy.

  1. Autologous transplantation of bone marrow mononuclear stem cells by mini-thoracotomy in dilated cardiomyopathy: technique and early results

    Directory of Open Access Journals (Sweden)

    Renato Abdala Karam Kalil

    Full Text Available CONTEXT AND OBJECTIVES: There are few studies concerning bone marrow mononuclear cell (BMMC transplantation in cases of nonischemic dilated cardiomyopathy. This study describes a novel technique of BMMC transplantation and the results up to one year after the procedure. DESIGN AND SETTING: This was a case series to evaluate the safety and viability of the procedure, at Instituto de Cardiologia do Rio Grande do Sul. METHODS: Nine patients with symptomatic dilated cardiomyopathy, functional class III/IV and left ventricular ejection fraction (LVEF < 35% received BMMC (9.6 ± 2.6 x 107 cells at 20 sites in the ventricular wall, by means of thoracotomy of length 5 cm in the fifth left intercostal space. Echocardiograms and nuclear magnetic resonance (NMR were performed. RESULTS: There were no major complications. The functional class results for the first six patients (preoperatively and at two, four, eight and twelve-month follow-ups, respectively were: [IV-2, III-4] to [I-5, II-1] to [I-3, II-3] to [I-2, II-3] and [I-2, II-3]. Echocardiograms showed LVEF: 25.9 ± 8.2; 32.9 ± 10.4; 29.4 ± 7.2; 25.1 ± 7.9; 25.4 ± 6.8% (p = 0.023; and % left ventricular (LV fiber shortening: 12.6 ± 4.4; 16.4 ± 5.4; 14.3 ± 3.7; 12.1 ± 4.0; 12.2 ± 3.4% (p = 0.021. LV performance variation seen on NMR was non-significant. CONCLUSION: Intramyocardial transplantation of BMMC in dilated cardiomyopathy cases is feasible and safe. There were early improvements in symptoms and LV performance. Medium-term evaluation revealed regression of LV function, although maintaining improved functional class.

  2. Knock-in mice harboring a Ca(2+) desensitizing mutation in cardiac troponin C develop early onset dilated cardiomyopathy.

    Science.gov (United States)

    McConnell, Bradley K; Singh, Sonal; Fan, Qiying; Hernandez, Adriana; Portillo, Jesus P; Reiser, Peter J; Tikunova, Svetlana B

    2015-01-01

    The physiological consequences of aberrant Ca(2+) binding and exchange with cardiac myofilaments are not clearly understood. In order to examine the effect of decreasing Ca(2+) sensitivity of cTnC on cardiac function, we generated knock-in mice carrying a D73N mutation (not known to be associated with heart disease in human patients) in cTnC. The D73N mutation was engineered into the regulatory N-domain of cTnC in order to reduce Ca(2+) sensitivity of reconstituted thin filaments by increasing the rate of Ca(2+) dissociation. In addition, the D73N mutation drastically blunted the extent of Ca(2+) desensitization of reconstituted thin filaments induced by cTnI pseudo-phosphorylation. Compared to wild-type mice, heterozygous knock-in mice carrying the D73N mutation exhibited a substantially decreased Ca(2+) sensitivity of force development in skinned ventricular trabeculae. Kaplan-Meier survival analysis revealed that median survival time for knock-in mice was 12 weeks. Echocardiographic analysis revealed that knock-in mice exhibited increased left ventricular dimensions with thinner walls. Echocardiographic analysis also revealed that measures of systolic function, such as ejection fraction (EF) and fractional shortening (FS), were dramatically reduced in knock-in mice. In addition, knock-in mice displayed electrophysiological abnormalities, namely prolonged QRS and QT intervals. Furthermore, ventricular myocytes isolated from knock-in mice did not respond to β-adrenergic stimulation. Thus, knock-in mice developed pathological features similar to those observed in human patients with dilated cardiomyopathy (DCM). In conclusion, our results suggest that decreasing Ca(2+) sensitivity of the regulatory N-domain of cTnC is sufficient to trigger the development of DCM.

  3. Dilated cardiomyopathy secondary to vitamin D deficiency and hypocalcaemia in the Irish paediatric population. A case report.

    LENUS (Irish Health Repository)

    Glackin, S

    2017-03-01

    We identified three infants with dilated cardiomyopathy (DCM) secondary to severe vitamin D deficieny and hypocalcaemia. All infants were exclusively breast fed, from dark skinned ethnic backgrounds, born and living in Ireland. None of these pregnant mothers or infants received the recommended vitamin D supplementation. Each infant presented in heart failure and required inotropic support as well as calcium and vitamin D replacement. Cardiac function subsequently improved. This highlights the public health issue that many high risk pregnant mothers and infants are not receiving the recommended vitamin D supplementation.

  4. Detection and comparison of microRNA expression in the serum of Doberman Pinschers with dilated cardiomyopathy and healthy controls.

    Science.gov (United States)

    Steudemann, Carola; Bauersachs, Stefan; Weber, Karin; Wess, Gerhard

    2013-01-17

    Dilated cardiomyopathy (DCM) is the most common heart disease in Doberman Pinschers. MicroRNAs (miRNAs) are short non-coding RNAs playing important roles in gene regulation. Different miRNA expression patterns have been described for DCM in humans and might represent potential diagnostic markers. There are no studies investigating miRNA expression profiles in canine DCM. The aims of this study were to screen the miRNA expression profile of canine serum using miRNA microarray and to compare expression patterns of a group of Doberman Pinschers with DCM and healthy controls. Eight Doberman Pinschers were examined by echocardiography and 24-hour-ECG and classified as healthy (n=4) or suffering from DCM (n=4). Total RNA was extracted from serum and hybridized on a custom-designed 8x60k miRNA microarray (Agilent) containing probes for 1368 individual miRNAs. Although total RNA concentrations were very low in serum samples, 404 different miRNAs were detectable with sufficient signal intensity on miRNA microarray. 22 miRNAs were differentially expressed in the two groups (p1.5), but did not reach statistical significance after multiple testing correction (false discovery rate adjusted p>0.05). Five miRNAs were selected for further analysis using quantitative Real-Time RT-PCR (qPCR) assays. No significant differences were found using specific miRNA qPCR assays (p>0.05). Numerous miRNAs can be detected in canine serum. Between healthy and DCM dogs, miRNA expression changes could be detected, but the results did not reach statistical significance most probably due to the small group size. miRNAs are potential new circulating biomarkers in veterinary medicine and should be investigated in larger patient groups and additional canine diseases.

  5. 2-Deoxyadenosine triphosphate restores the contractile function of cardiac myofibril from adult dogs with naturally occurring dilated cardiomyopathy.

    Science.gov (United States)

    Cheng, Yuanhua; Hogarth, Kaley A; O'Sullivan, M Lynne; Regnier, Michael; Pyle, W Glen

    2016-01-01

    Dilated cardiomyopathy (DCM) is a major type of heart failure resulting from loss of systolic function. Naturally occurring canine DCM is a widely accepted experimental paradigm for studying human DCM. 2-Deoxyadenosine triphosphate (dATP) can be used by myosin and is a superior energy substrate over ATP for cross-bridge formation and increased systolic function. The objective of this study was to evaluate the beneficial effect of dATP on contractile function of cardiac myofibrils from dogs with naturally occurring DCM. We measured actomyosin NTPase activity and contraction/relaxation properties of isolated myofibrils from nonfailing (NF) and DCM canine hearts. NTPase assays indicated replacement of ATP with dATP significantly increased myofilament activity in both NF and DCM samples. dATP significantly improved maximal tension of DCM myofibrils to the NF sample level. dATP also restored Ca(2+) sensitivity of tension that was reduced in DCM samples. Similarly, dATP increased the kinetics of contractile activation (kACT), with no impact on the rate of cross-bridge tension redevelopment (kTR). Thus, the activation kinetics (kACT/kTR) that were reduced in DCM samples were restored for dATP to NF sample levels. dATP had little effect on relaxation. The rate of early slow-phase relaxation was slightly reduced with dATP, but its duration was not, nor was the fast-phase relaxation or times to 50 and 90% relaxation. Our findings suggest that myosin utilization of dATP improves cardiac myofibril contractile properties of naturally occurring DCM canine samples, restoring them to NF levels, without compromising relaxation. This suggests elevation of cardiac dATP is a promising approach for the treatment of DCM. Copyright © 2016 the American Physiological Society.

  6. A novel mutation and first report of dilated cardiomyopathy in ALG6-CDG (CDG-Ic: a case report

    Directory of Open Access Journals (Sweden)

    Zagal Ahmad

    2010-04-01

    Full Text Available Abstract Congenital disorders of glycosylation (CDG are an expanding group of inherited metabolic diseases with multisystem involvement. ALG6-CDG (CDGIc is an endoplasmatic reticulum defect in N-glycan assembly. It is usually milder than PMM2-CDG (CDG-Ia and so is its natural course. It is characterized by psychomotor retardation, seizures, ataxia, and hypotonia. In contrast to PMM2-CDG (CDGIa, there is no cerebellar hypoplasia. Cardiomyopathy has been reported in a few CDG types and in a number of patients with unexplained CDG. We report an 11 year old Saudi boy with severe psychomotor retardation, seizures, strabismus, inverted nipples, dilated cardiomyopathy, and a type 1 pattern of serum transferrin isoelectrofocusing. Phosphomannomutase and phosphomannose isomerase activities were normal in fibroblasts. Full gene sequencing of the ALG6 gene revealed a novel mutation namely c.482A>G (p.Y161C and heterozygosity in the parents. This report highlights the importance to consider CDG in the differential diagnosis of unexplained cardiomyopathy.

  7. Regional evidence of modulation of cardiac adiponectin level in dilated cardiomyopathy: pilot study in a porcine animal model

    Directory of Open Access Journals (Sweden)

    Caselli Chiara

    2012-11-01

    Full Text Available Abstract Background The role of systemic and myocardial adiponectin (ADN in dilated cardiomyopathy is still debated. We tested the regulation of both systemic and myocardial ADN and the relationship with AMP-activated protein kinase (AMPK activity in a swine model of non-ischemic dilated cardiomyopathy. Methods and results Cardiac tissue was collected from seven instrumented adult male minipigs by pacing the left ventricular (LV free wall (180 beats/min, 3 weeks, both from pacing (PS and opposite sites (OS, and from five controls. Circulating ADN levels were inversely related to global and regional cardiac function. Myocardial ADN in PS was down-regulated compared to control (p Conclusions Paradoxically, circulating ADN did not show any cardioprotective effect, confirming its role as negative prognostic biomarker of heart failure. Myocardial ADN was reduced in PS compared to control in an AMPK-independent fashion, suggesting the occurrence of novel mechanisms by which reduced cardiac ADN levels may regionally mediate the decline of cardiac function.

  8. Ivabradine, a novel heart rate slower: is it a sword of double blades in patients with idiopathic dilated cardiomyopathy?

    Science.gov (United States)

    Rayan, Mona; Tawfik, Mazen; Alabd, Ali; Gamal, Amr

    2011-08-01

    To prospectively assess the safety and efficacy of ivabradine in patients with idiopathic dilated cardiomyopathy. We included 35 patients with idiopathic dilated cardiomyopathy with an ejection fraction (EF) 70 beats/min despite optimal medical therapy, according to the international guidelines in this prospective, non-randomized, single-arm, open-label safety study. Ivabradine was used as an add-on therapy to the maximally tolerated b-blocker in an increasing titrated dose till a target dose of 15 mg/day or resting heart rate of 60 beats/min for 3 months. During follow-up period the safety, patient tolerance and efficacy of this drug were assessed. All patients underwent 12-lead resting electrocardiography and Holter monitoring at inclusion and after 3 months. Statistical analysis was accomplished using paired t-test and Pearson correlation analysis. We found a significant reduction in the resting heart rate by a mean of 25.9 ± 9.4%, without a significant change of blood pressure. There was no prolongation of PR, QTc or QRS durations. Ventricular ectopic activity showed significant reduction (p<0.001). There was a significant correlation between the resting heart rate, NYHA and left ventricular ejection fraction (p<0.001 for both). One patient developed photopsia and decompensation was observed in another patient. Ivabradine is a safe and effective drug in reducing resting heart rate, improving NYHA functional class without undesirable effects on conduction parameters or ectopic activity.

  9. Determinants of Atrial Electromechanical Delay in Patients with Functional Mitral Regurgitation and Non-ischemic Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Bengi Bakal Ruken

    2014-12-01

    Full Text Available Introduction: Atrial conduction time has important hemodynamic effects on ventricular filling and is accepted as a predictor of atrial fibrillation. In this study we assessed atrial conduction time in patients with non ischemic dilated cardiomyopathy (NIDCMP and functional mitral regurgitation (MR and aimed to determine factors predicting atrial conduction time prolongation. Methods: Sixty five patients with non ischemic dilated cardiomyopathy who have moderate to severe MR and 60 control subjects were included in the study. In addition to conventional echocardiographic measures used to asses left ventricle and MR, atrial electromechanical coupling (time interval from the onset of P wave on surface electrocardiogram [ECG] to the beginning of A wave interval with tissue Doppler echocardiography [PA], intra- and interatrial electromechanical delay (intra and inter AEMD were measured. Results: The correlations between inter AEMD and left atrial (LA size, MR volume, isovolumetric relaxation time (IVRT, deceleration time (DT, systolic pulmonary artery pressure (PAPs, E/A ratio and E/e’ were very poor. Similarly, intra AEMD was not correlated to LA size , MR volume, IVRT, DT, PAPs, E/A ratio and E/e’. However, both inter AEMD and intra AEMD had good correlation with left ventricular mass index, tenting area (TA, tenting distance (TD, coaptation septal distance (CSD, sphericity index (SI. Conclusion: Prolongation of inter and intra AEMDs were found to be well correlated with parameters reflecting left ventricular and mitral annular remodeling.

  10. Cardiomyocyte-Specific Ablation of Med1 Subunit of the Mediator Complex Causes Lethal Dilated Cardiomyopathy in Mice.

    Science.gov (United States)

    Jia, Yuzhi; Chang, Hsiang-Chun; Schipma, Matthew J; Liu, Jing; Shete, Varsha; Liu, Ning; Sato, Tatsuya; Thorp, Edward B; Barger, Philip M; Zhu, Yi-Jun; Viswakarma, Navin; Kanwar, Yashpal S; Ardehali, Hossein; Thimmapaya, Bayar; Reddy, Janardan K

    2016-01-01

    Mediator, an evolutionarily conserved multi-protein complex consisting of about 30 subunits, is a key component of the polymerase II mediated gene transcription. Germline deletion of the Mediator subunit 1 (Med1) of the Mediator in mice results in mid-gestational embryonic lethality with developmental impairment of multiple organs including heart. Here we show that cardiomyocyte-specific deletion of Med1 in mice (csMed1-/-) during late gestational and early postnatal development by intercrossing Med1fl/fl mice to α-MyHC-Cre transgenic mice results in lethality within 10 days after weaning due to dilated cardiomyopathy-related ventricular dilation and heart failure. The csMed1-/- mouse heart manifests mitochondrial damage, increased apoptosis and interstitial fibrosis. Global gene expression analysis revealed that loss of Med1 in heart down-regulates more than 200 genes including Acadm, Cacna1s, Atp2a2, Ryr2, Pde1c, Pln, PGC1α, and PGC1β that are critical for calcium signaling, cardiac muscle contraction, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy and peroxisome proliferator-activated receptor regulated energy metabolism. Many genes essential for oxidative phosphorylation and proper mitochondrial function such as genes coding for the succinate dehydrogenase subunits of the mitochondrial complex II are also down-regulated in csMed1-/- heart contributing to myocardial injury. Data also showed up-regulation of about 180 genes including Tgfb2, Ace, Atf3, Ctgf, Angpt14, Col9a2, Wisp2, Nppa, Nppb, and Actn1 that are linked to cardiac muscle contraction, cardiac hypertrophy, cardiac fibrosis and myocardial injury. Furthermore, we demonstrate that cardiac specific deletion of Med1 in adult mice using tamoxifen-inducible Cre approach (TmcsMed1-/-), results in rapid development of cardiomyopathy and death within 4 weeks. We found that the key findings of the csMed1-/- studies described above are highly reproducible in TmcsMed1-/- mouse heart

  11. Mitochondrial cardiomyopathies

    Directory of Open Access Journals (Sweden)

    Ayman W. El-Hattab

    2016-07-01

    Full Text Available Mitochondria are found in all nucleated human cells and perform a variety of essential functions, including the generation of cellular energy. Mitochondria are under dual genome control. Only a small fraction of their proteins are encoded by mitochondrial DNA (mtDNA while more than 99% of them are encoded by nuclear DNA (nDNA. Mutations in mtDNA or mitochondria-related nDNA genes result in mitochondrial dysfunction leading to insufficient energy production required to meet the needs of various organs, particularly those with high energy requirements, including the central nervous system, skeletal and cardiac muscles, kidneys, liver, and endocrine system. Because cardiac muscles are one of the high energy demanding tissues, cardiac involvement occurs in mitochondrial diseases with cardiomyopathies being one of the most frequent cardiac manifestations found in these disorders. Cardiomyopathy is estimated to occur in 20-40% of children with mitochondrial diseases. Mitochondrial cardiomyopathies can vary in severity from asymptomatic status to severe manifestations including heart failure, arrhythmias, and sudden cardiac death. Hypertrophic cardiomyopathy is the most common type; however, mitochondrial cardiomyopathies might also present as dilated, restrictive, left ventricular noncompaction, and histiocytoid cardiomyopathies. Cardiomyopathies are frequent manifestations of mitochondrial diseases associated with defects in electron transport chain (ETC complexes subunits and their assembly factors, mitochondrial tRNAs, rRNAs, ribosomal proteins, and translation factors, mtDNA maintenance, and coenzyme Q10 synthesis. Other mitochondrial diseases with cardiomyopathies include Barth syndrome, Sengers syndrome, TMEM70-related mitochondrial complex V deficiency, and Friedreich ataxia.

  12. A splice site mutation in a gene encoding for PDK4, a mitochondrial protein, is associated with the development of dilated cardiomyopathy in the Doberman pinscher.

    Science.gov (United States)

    Meurs, Kathryn M; Lahmers, Sunshine; Keene, Bruce W; White, Stephen N; Oyama, Mark A; Mauceli, Evan; Lindblad-Toh, Kerstin

    2012-08-01

    Familial dilated cardiomyopathy is a primary myocardial disease that can result in the development of congestive heart failure and sudden cardiac death. Spontaneous animal models of familial dilated cardiomyopathy exist and the Doberman pinscher dog is one of the most commonly reported canine breeds. The objective of this study was to evaluate familial dilated cardiomyopathy in the Doberman pinscher dog using a genome-wide association study for a genetic alteration(s) associated with the development of this disease in this canine model. Genome-wide association analysis identified an area of statistical significance on canine chromosome 14 (p(raw) = 9.999e-05 corrected for genome-wide significance), fine-mapping of additional SNPs flanking this region localized a signal to 23,774,190-23,781,919 (p = 0.001) and DNA sequencing identified a 16-base pair deletion in the 5' donor splice site of intron 10 of the pyruvate dehydrogenase kinase 4 gene in affected dogs (p dilation, marked pleomorphic mitochondrial alterations with megamitochondria, scattered mitochondria with whorling and vacuolization and mild aggregates of lipofuscin granules. In conclusion, we report the identification of a splice site deletion in the PDK4 gene that is associated with the development of familial dilated cardiomyopathy in the Doberman pinscher dog.

  13. Neuregulin-1/erbB-activation improves cardiac function and survival in models of ischemic, dilated, and viral cardiomyopathy.

    Science.gov (United States)

    Liu, Xifu; Gu, Xinhua; Li, Zhaoming; Li, Xinyan; Li, Hui; Chang, Jianjie; Chen, Ping; Jin, Jing; Xi, Bing; Chen, Denghong; Lai, Donna; Graham, Robert M; Zhou, Mingdong

    2006-10-03

    We evaluated the therapeutic potential of a recombinant 61-residue neuregulin-1 (beta2a isoform) receptor-active peptide (rhNRG-1) in multiple animal models of heart disease. Activation of the erbB family of receptor tyrosine kinases by rhNRG-1 could provide a treatment option for heart failure, because neuregulin-stimulated erbB2/erbB4 heterodimerization is not only critical for myocardium formation in early heart development but prevents severe dysfunction of the adult heart and premature death. Disabled erbB-signaling is also implicated in the transition from compensatory hypertrophy to failure, whereas erbB receptor-activation promotes myocardial cell growth and survival and protects against anthracycline-induced cardiomyopathy. rhNRG-1 was administered IV to animal models of ischemic, dilated, and viral cardiomyopathy, and cardiac function and survival were evaluated. Short-term intravenous administration of rhNRG-1 to normal dogs and rats did not alter hemodynamics or cardiac contractility. In contrast, rhNRG-1 improved cardiac performance, attenuated pathological changes, and prolonged survival in rodent models of ischemic, dilated, and viral cardiomyopathy, with the survival benefits in the ischemic model being additive to those of angiotensin-converting enzyme inhibitor therapy. In addition, despite continued pacing, rhNRG-1 produced global improvements in cardiac function in a canine model of pacing-induced heart failure. These beneficial effects make rhNRG-1 promising as a broad-spectrum therapeutic for the treatment of heart failure due to a variety of common cardiac diseases.

  14. Usefulness of Serial N-terminal Pro-B-type Natriuretic Peptide Measurements to Predict Cardiac Death in Acute and Chronic Dilated Cardiomyopathy in Children

    NARCIS (Netherlands)

    Boer, S.L. den; Rizopoulos, D.; Sarvaas, G.J.; Backx, A.P.; Harkel, A.D. Ten; Iperen, G.G. van; Rammeloo, L.A.; Tanke, R.B.; Boersma, E.; Helbing, W.A.; Dalinghaus, M.

    2016-01-01

    N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an important predictor of outcome in adults with heart failure. In children with heart failure secondary to dilated cardiomyopathy (DC) markers that reliably predict disease progression and outcome during follow-up are scarce. We investigated

  15. Expression and biochemical characteristics of two different aldosterone receptors in both healthy and dilated cardiomyopathy dog heart tissue.

    Science.gov (United States)

    Reynoso Palomar, Alejandro R; Rodriguez Bravo, Moncerrat; Villa Mancera, Abel E; Mucha, Carlos J

    2017-03-01

    Recently, replicates of the aldosterone receptor expression have been done in healthy heart dog tissues through immunohistochemistry, showing an apparent heterogeneous distribution in the four chambers. Recent studies have also identified immediate effects of aldosterone, suggesting aldosterone also produces non-genomic effects caused by an unidentified receptor. In order to study the molecular and quantitative expression characteristics of aldosterone binding receptors in the canine heart, we conducted studies, using Western Blot, in the heart from both healthy animals and animals with dilated cardiomyopathy. The results show the presence and distribution of two aldosterone receptors; one of 110/120 kDa molecular weight, suggested as cytosolic/nuclear and the other of undetermined location with a 250 kDa molecular weight.

  16. Assessment of regional systolic and diastolic myocardial function using tissue Doppler and strain imaging in dogs with dilated cardiomyopathy.

    Science.gov (United States)

    Chetboul, Valérie; Gouni, Vassiliki; Sampedrano, Carolina Carlos; Tissier, Renaud; Serres, François; Pouchelon, Jean-Louis

    2007-01-01

    Tissue Doppler Imaging (TDI) or strain (St) imaging could provide sensitive indices for early detection and treatment follow-up of canine dilated cardiomyopathy (DCM). Analysis of TDI and St features in dogs with overt DCM is a prerequisite before using these new criteria in prospective screenings of predisposed families or in clinical trials. Radial and longitudinal right and left myocardial motion, assessed by TDI and St variables, is altered in dogs with DCM. Case records for 26 dogs; 14 with DCM and 12 healthy controls of comparable age and weight were reviewed. A retrospective analysis was conducted of conventional echocardiography, 2-dimensional color TDI, and St imaging data. The DCM group was characterized by decreases in radial and longitudinal systolic velocity gradients of the left ventricular free wall (LVFW), radial and longitudinal absolute values of peak systolic St of the LVFW, and longitudinal systolic right ventricular (RV) velocities (all P canine DCM.

  17. Improvement in cardiac function and free fatty acid metabolism in a case of dilated cardiomyopathy with CD36 deficiency.

    Science.gov (United States)

    Hirooka, K; Yasumura, Y; Ishida, Y; Komamura, K; Hanatani, A; Nakatani, S; Yamagishi, M; Miyatake, K

    2000-09-01

    A 27-year-old man diagnosed as having dilated cardiomyopathy (DCM) without myocardial accumulation of 123I-beta-methyl-iodophenylpentadecanoic acid, and he was found to have type I CD36 deficiency. This abnormality of cardiac free fatty acid metabolism was also confirmed by other methods: 18F-fluoro-2-deoxyglucose positron emission tomography, measurements of myocardial respiratory quotient and cardiac fatty acid uptake. Although the type I CD36 deficiency was reconfirmed after 3 months, the abnormal free fatty acid metabolism improved after carvedilol therapy and was accompanied by improved cardiac function. Apart from a cause-and-effect relationship, carvedilol can improve cardiac function and increase free fatty acid metabolism in patients with both DCM and CD36 deficiency.

  18. Th17-related cytokines in systemic lupus erythematosus patients with dilated cardiomyopathies: a possible linkage to parvovirus B19 infection.

    Directory of Open Access Journals (Sweden)

    Der-Yuan Chen

    Full Text Available Dilated cardiomyopathies (DCM are a major cause of mortality in patients with systemic lupus erythematosus (SLE. Immune responses induced by human parvovirus B19 (B19 are considered an important pathogenic mechanism in myocarditis or DCM. However, little is known about Th17-related cytokines in SLE patients with DCM about the linkage with B19 infection. IgM and IgG against B19 viral protein, and serum levels of Th17-related cytokines were determined using ELISA in eight SLE patients with DCM and six patients with valvular heart disease (VHD. Humoral responses of anti-B19-VP1u and anti-B19-NS1 antibody were assessed using Western blot and B19 DNA was detected by nested Polymerase Chain Reaction (PCR. Levels of interleukin (IL-17, IL-6, IL-1β, and tumor necrosis factor (TNF-α were significantly higher in SLE patients with DCM (mean ± SEM, 390.99±125.48 pg/ml, 370.24±114.09 pg/ml, 36.01±16.90 pg/ml, and 183.84±82.94 pg/ml, respectively compared to healthy controls (51.32±3.04 pg/ml, p<0.001; 36.88±6.64 pg/ml, p<0.001; 5.39±0.62 pg/ml, p<0.005; and 82.13±2.42 pg/ml, p<0.005, respectively. Levels of IL-17 and IL-6 were higher in SLE patients with DCM versus those with VHD (both p<0.01. Five (62.5% of DCM patients had detectable anti-B19-NS1 IgG and four (50.0% of them had anti-B19-VP1u IgG, whereas only one (16.7% of VHD patients had detectable anti-B19-NS1 IgG and anti-B19-VP1u IgG. Serum levels of IL-17, IL-6 and IL-1β were markedly higher in SLE patients with anti-B19-VP1u IgG and anti-B19-NS1 IgG compared to those without anti-B19-VP1u IgG or anti-B19-NS1 IgG, respectively. These suggest a potential association of B19 with DCM and Th17-related cytokines implicated in the pathogenesis of DCM in SLE patients.

  19. Th17-Related Cytokines in Systemic Lupus Erythematosus Patients with Dilated Cardiomyopathies: A Possible Linkage to Parvovirus B19 Infection

    Science.gov (United States)

    Chen, Der-Yuan; Chen, Yi-Ming; Lan, Joung-Liang

    2014-01-01

    Dilated cardiomyopathies (DCM) are a major cause of mortality in patients with systemic lupus erythematosus (SLE). Immune responses induced by human parvovirus B19 (B19) are considered an important pathogenic mechanism in myocarditis or DCM. However, little is known about Th17-related cytokines in SLE patients with DCM about the linkage with B19 infection. IgM and IgG against B19 viral protein, and serum levels of Th17-related cytokines were determined using ELISA in eight SLE patients with DCM and six patients with valvular heart disease (VHD). Humoral responses of anti-B19-VP1u and anti-B19-NS1 antibody were assessed using Western blot and B19 DNA was detected by nested Polymerase Chain Reaction (PCR). Levels of interleukin (IL)-17, IL-6, IL-1β, and tumor necrosis factor (TNF)-α were significantly higher in SLE patients with DCM (mean ± SEM, 390.99±125.48 pg/ml, 370.24±114.09 pg/ml, 36.01±16.90 pg/ml, and 183.84±82.94 pg/ml, respectively) compared to healthy controls (51.32±3.04 pg/ml, pB19-NS1 IgG and four (50.0%) of them had anti-B19-VP1u IgG, whereas only one (16.7%) of VHD patients had detectable anti-B19-NS1 IgG and anti-B19-VP1u IgG. Serum levels of IL-17, IL-6 and IL-1β were markedly higher in SLE patients with anti-B19-VP1u IgG and anti-B19-NS1 IgG compared to those without anti-B19-VP1u IgG or anti-B19-NS1 IgG, respectively. These suggest a potential association of B19 with DCM and Th17-related cytokines implicated in the pathogenesis of DCM in SLE patients. PMID:25462010

  20. Correlation between changes in diastolic dysfunction and health-related quality of life after cardiac rehabilitation program in dilated cardiomyopathy

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    Sherin H.M. Mehani

    2013-03-01

    Full Text Available Chronic heart failure (CHF is a complex syndrome characterized by progressive decline in left ventricular function, low exercise tolerance and raised mortality and morbidity. Left ventricular diastolic dysfunction plays a major role in CHF and progression of most cardiac diseases. The current recommended goals can theoretically be accomplished via exercise and pharmacological therapy so the aim of the present study was to evaluate the impact of cardiac rehabilitation program on diastolic dysfunction and health related quality of life and to determine the correlation between changes in left ventricular diastolic dysfunction and domains of health-related quality of life (HRQoL. Forty patients with chronic heart failure were diagnosed as having dilated cardiomyopathy (DCM with systolic and diastolic dysfunction. The patients were equally and randomly divided into training and control groups. Only 30 of them completed the study duration. The training group participated in rehabilitation program in the form of circuit-interval aerobic training adjusted according to 55–80% of heart rate reserve for a period of 7 months. Circuit training improved both diastolic and systolic dysfunction in the training group. On the other hand, only a significant correlation was found between improvement in diastolic dysfunction and health related quality of life measured by Kansas City Cardiomyopathy Questionnaire. It was concluded that improvement in diastolic dysfunction as a result of rehabilitation program is one of the important underlying mechanisms responsible for improvement in health-related quality of life in DCM patients.

  1. Cardiomyopathy

    Science.gov (United States)

    ... as a disorder that causes the buildup of abnormal proteins (amyloidosis), a disease that causes inflammation and can cause lumps of ... Cardiomyopathy can lead to abnormal heart rhythms. These abnormal heart rhythms ... other types of heart disease by living a heart-healthy lifestyle and making ...

  2. Assessment of inotropic and vasodilating effects of milrinone lactate in patients with dilated cardiomyopathy and severe heart failure

    Directory of Open Access Journals (Sweden)

    Edson Antonio Bregagnollo

    1999-02-01

    Full Text Available OBJECTIVE: To assess the hemodynamic and vasodilating effects of milrinone lactate (ML in patients with dilated cardiomyopathy (DCM and New York Heart Association (NYHA class III and IV heart failure. METHODS: Twenty patients with DCM and NYHA class III and IV heart failure were studied. The hemodynamic and vasodilating effects of ML, administered intravenously, were evaluated. The following variables were compared before and during drug infusion: cardiac output (CO and cardiac index (CI; pulmonary capillary wedge pressure (PCWP; mean aortic pressure (MAP; mean pulmonary artery pressure (MPAP; mean right atrial pressure (MRAP; left ventricular systolic and end-diastolic pressures (LVSP and LVEDP, respectively; peak rate of left ventricular pressure rise (dP/dt; systemic vascular resistance (SVR; pulmonary vascular resistance (PVR; and heart rate (HR. RESULTS: All patients showed a significant improvement of the analysed parameters of cardiac performance with an increase of CO and CI; a significant improvement in myocardial contractility (dP/dt and reduction of the LVEDP; PCWP; PAP; MAP; MRAP; SVR; PVR. Were observed no significant increase in HR occurred. CONCLUSION: Milrinone lactate is an inotropic dilating drug that, when administered intravenously, has beneficial effects on cardiac performance and myocardial contractility. It also promotes reduction of SVR and PVR in patients with DCM and NYHA class III and IV of heart failure.

  3. [Competitive sports and dilated cardiomyopathy: the case of a 32-year-old soccer player with ventricular tachycardia].

    Science.gov (United States)

    Scharhag, J; Meyer, T; Görge, G; Kindermann, W

    2003-01-24

    A 32-year-old competitive soccer player presented with palpitations he had felt for 4 weeks during maximal activity (soccer training and match). The physical examination and an exercise electrocardiogram were carried out by his general practitioner up to 19 s at 350 W and a heart rate of 147/min without showing any abnormalities. All blood parameters revealed no signs of illness. During treadmill exercise at a heart rate of 181/min, a non-sustained ventricular tachycardia was induced. Echocardiography showed a dilated left ventricle with an enddiastolic diameter of 70 mm and low fractional shortening (28 %). Cardiac catheterization demonstrated a diminished left ventricular ejection fraction (38 %) and an enlarged enddiastolic volume (199 ml) without signs of coronary artery disease. Electrophysiologic testing induced a non-sustained ventricular tachycardia. The echocardiographic and angiographic results indicated a dilated cardiomyopathy. Competitive sports activities were stopped and treatment with a beta-blocker (metoprolol) and an ACE-antagonist (ramipril) was started. In young male and female athletes, the possibility of severe cardiac abnormalities have to be considered even in the presence of good physical fitness and performance. To reach a high sensitivity for diagnostic ergometry, the work-load must reach the maximal capacity of the cardio-pulmonary system. Differences in the exercise performance of athletes and untrained subjects have to be considered.

  4. Locally expressed IGF1 propeptide improves mouse heart function in induced dilated cardiomyopathy by blocking myocardial fibrosis and SRF-dependent CTGF induction

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    Melissa Touvron

    2012-07-01

    Cardiac fibrosis is critically involved in the adverse remodeling accompanying dilated cardiomyopathies (DCMs, which leads to cardiac dysfunction and heart failure (HF. Connective tissue growth factor (CTGF, a profibrotic cytokine, plays a key role in this deleterious process. Some beneficial effects of IGF1 on cardiomyopathy have been described, but its potential role in improving DCM is less well characterized. We investigated the consequences of expressing a cardiac-specific transgene encoding locally acting IGF1 propeptide (muscle-produced IGF1; mIGF1 on disease progression in a mouse model of DCM [cardiac-specific and inducible serum response factor (SRF gene disruption] that mimics some forms of human DCM. Cardiac-specific mIGF1 expression substantially extended the lifespan of SRF mutant mice, markedly improved cardiac functions, and delayed both DCM and HF. These protective effects were accompanied by an overall improvement in cardiomyocyte architecture and a massive reduction of myocardial fibrosis with a concomitant amelioration of inflammation. At least some of the beneficial effects of mIGF1 transgene expression were due to mIGF1 counteracting the strong increase in CTGF expression within cardiomyocytes caused by SRF deficiency, resulting in the blockade of fibroblast proliferation and related myocardial fibrosis. These findings demonstrate that SRF plays a key role in the modulation of cardiac fibrosis through repression of cardiomyocyte CTGF expression in a paracrine fashion. They also explain how impaired SRF function observed in human HF promotes fibrosis and adverse cardiac remodeling. Locally acting mIGF1 efficiently protects the myocardium from these adverse processes, and might thus represent a therapeutic avenue to counter DCM.

  5. The X-linked gene G4.5 is responsible for different infantile dilated cardiomyopathies

    NARCIS (Netherlands)

    D'Adamo, P.; Fassone, L.; Gedeon, A.; Janssen, E. A.; Bione, S.; Bolhuis, P. A.; Barth, P. G.; Wilson, M.; Haan, E.; Orstavik, K. H.; Patton, M. A.; Green, A. J.; Zammarchi, E.; Donati, M. A.; Toniolo, D.

    1997-01-01

    Barth syndrome (BTHS) is an X-linked disorder characterized clinically by the associated features of cardiac and skeletal myopathy, short stature, and neutropenia. The clinical manifestations of the disease are, in general, quite variable, but cardiac failure as a consequence of cardiac dilatation

  6. A new surgical approach for treating dilated cardiomyopathy with mitral regurgitation

    Directory of Open Access Journals (Sweden)

    Buffolo Enio

    2000-01-01

    Full Text Available OBJECTIVE: To evaluate the early outcome of mitral valve prostheses implantation and left ventricular remodeling in 23 patients with end-stage cardiomyopathy and secondary mitral regurgitation (NYHA class III and IV. METHODS: Mitral valvular prosthesis implantation with preservation of papillary muscles and chordae tendinae, and plasty of anteriun cuspid for remodeling of the left ventricle. RESULTS: The surgery was performed in 23 patients, preoperative ejection fraction (echocardiography varied from 13% to 44% (median: 30%. In 13 patients associated procedures were performed: myocardial revascularization (9, left ventricle plicature repair (3 and aortic prosthese implantation (1. Early deaths (2 occurred on the 4th PO day (cardiogenic shock and on the 20th PO day (upper gastrointestinal bleeding, and a late death in the second month PO (ventricular arrhythmia. Improvement occurred in NYHA class in 82.6% of the patients (P<0.0001, with a survival rate of 86.9% (mean of 8.9 months of follow-up. CONCLUSION: This technique offers a promising therapeutic alternative for the treatment of patients in refractory heart failure with cardiomyopathy and secondary mitral regurgitation.

  7. Long-Term Outcomes of Catheter Ablation of Electrical Storm in Nonischemic Dilated Cardiomyopathy Compared With Ischemic Cardiomyopathy.

    Science.gov (United States)

    Muser, Daniele; Liang, Jackson J; Pathak, Rajeev K; Magnani, Silvia; Castro, Simon A; Hayashi, Tatsuya; Garcia, Fermin C; Supple, Gregory E; Riley, Michael P; Lin, David; Dixit, Sanjay; Zado, Erica S; Frankel, David S; Callans, David J; Marchlinski, Francis E; Santangeli, Pasquale

    2017-07-01

    The goal of this study was to determine the long-term outcomes of catheter ablation (CA) of electrical storm in patients with nonischemic dilated cardiomyopathy (NIDCM) compared with patients with ischemic cardiomyopathy (ICM). CA of ventricular tachycardia (VT) electrical storm has been shown to improve VT-free survival in patients with ICM. Data on the outcomes of CA of electrical storm in patients with NIDCM are insufficient. The study included 267 consecutive patients with NIDCM (n = 71; ejection fraction 32 ± 14%) and ICM (n = 196; ejection fraction 28 ± 12%). Endo-epicardial CA was performed in 59 (22%) patients. CA was guided by activation and entrainment mapping for tolerated VT and pacemapping/targeting of abnormal substrate for unmappable VT. After a median follow-up of 45 (25th to 75th percentile: 9 to 71) months and 1 (25th to 75th percentile: 1 to 8) procedures, 76 (29%) patients died, 25 (9%) underwent heart transplantation, 87 (33%) experienced VT recurrence, and 13 (5%) had recurrence of electrical storm. Overall VT-free survival was 54% at 60 months (48% in NIDCM and 54% in ICM; p = 0.128). Patients with VT recurrence experienced a median of 2 (1 to 10) VT episodes in the 5 (1 to 14) months after the procedure. Death/transplantation-free survival was 62% at 60 months (53% in NIDCM and 64% in ICM; p = 0.067). Persistent inducibility of any VT with cycle length ≥250 ms at programmed stimulation at the end of the procedure was the only independent predictor of VT recurrence. Low ejection fraction, New York Heart Association functional class, and VT recurrence over follow-up independently predicted death/transplantation. CA of electrical storm was similarly effective in patients with NIDCM compared with patients with ICM, with elimination of electrical storm in 95% of cases and achievement of complete VT control at long-term follow-up in most patients. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc

  8. The canine sarcoglycan delta gene: BAC clone contig assembly, chromosome assignment and interrogation as a candidate gene for dilated cardiomyopathy in Dobermann dogs.

    Science.gov (United States)

    Stabej, P; Leegwater, P A J; Imholz, S; Versteeg, S A; Zijlstra, C; Stokhof, A A; Domanjko-Petriè, A; van Oost, B A

    2005-01-01

    Dilated cardiomyopathy (DCM) is a common disease of the myocardium recognized in human, dog and experimental animals. Genetic factors are responsible for a large proportion of cases in humans, and 17 genes with DCM causing mutations have been identified. The genetic origin of DCM in the Dobermann dogs has been suggested, but no disease genes have been identified to date. In this paper, we describe the characterization and evaluation of the canine sarcoglycan delta (SGCD), a gene implicated in DCM in human and hamster. Bacterial artificial chromosomes (BACs) containing the canine SGCD gene were isolated with probes for exon 3 and exons 4-8 and were characterized by Southern blot analysis. BAC end sequences were obtained for four BACs. Three of the BACs overlapped and could be ordered relative to each other and the end sequences of all four BACs could be anchored on the preliminary assembly of the dog genome sequence (www. ensembl.org). One of the BACs of the partial contig was localized by fluorescent in situ hybridization to canine chromosome 4q22, in agreement with the dog genome sequence. Two highly informative polymorphic microsatellite markers in intron 7 of the SGCD gene were identified. In 25 DCM-affected and 13 non DCM-affected dogs seven different haplotypes could be distinguished. However, no association between any of the SGCD variants and the disease locus was apparent.

  9. Molecular genetic and functional characterization implicate muscle-restricted coiled-coil gene (MURC) as a causal gene for familial dilated cardiomyopathy.

    Science.gov (United States)

    Rodriguez, Gabriela; Ueyama, Tomomi; Ogata, Takehiro; Czernuszewicz, Grazyna; Tan, Yanli; Dorn, Gerald W; Bogaev, Roberta; Amano, Katsuya; Oh, Hidemasa; Matsubara, Hiroaki; Willerson, James T; Marian, Ali J

    2011-08-01

    Dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) are classic forms of systolic and diastolic heart failure, respectively. Mutations in genes encoding sarcomere and cytoskeletal proteins are major causes of HCM and DCM. MURC, encoding muscle-restricted coiled-coil, a Z-line protein, regulates cardiac function in mice. We investigated potential causal role of MURC in human cardiomyopathies. We sequenced MURC in 1199 individuals, including 383 probands with DCM, 307 with HCM, and 509 healthy control subjects. We found 6 heterozygous DCM-specific missense variants (p.N128K, p.R140W, p.L153P, p.S307T, p.P324L, and p.S364L) in 8 unrelated probands. Variants p.N128K and p.S307T segregated with inheritance of DCM in small families (χ(2)=8.5, P=0.003). Variants p.N128K, p.R140W, p.L153P, and p.S364L were considered probably or possibly damaging. Variant p.P324L recurred in 3 independent probands, including 1 proband with a TPM1 mutation (p.M245T). A deletion variant (p.L232-R238del) was present in 3 unrelated HCM probands, but it did not segregate with HCM in a family who also had a MYH7 mutation (p.L907V). The phenotype in mutation carriers was notable for progressive heart failure leading to heart transplantation in 4 patients, conduction defects, and atrial arrhythmias. Expression of mutant MURC proteins in neonatal rat cardiac myocytes transduced with recombinant adenoviruses was associated with reduced RhoA activity, lower mRNA levels of hypertrophic markers and smaller myocyte size as compared with wild-type MURC. MURC mutations impart loss-of-function effects on MURC functions and probably are causal variants in human DCM. The causal role of a deletion mutation in HCM is uncertain.

  10. First description of a novel mitochondrial mutation in the MT-TI gene associated with multiple mitochondrial DNA deletion and depletion in family with severe dilated mitochondrial cardiomyopathy.

    Science.gov (United States)

    Alila-Fersi, Olfa; Tabebi, Mouna; Maalej, Marwa; Belguith, Neila; Keskes, Leila; Mkaouar-Rebai, Emna; Fakhfakh, Faiza

    2018-03-18

    Mitochondria are essential for early cardiac development and impaired mitochondrial function was described associated with heart diseases such as hypertrophic or dilated mitochondrial cardiomyopathy. In this study, we report a family including two individuals with severe dilated mitochondrial cardiomyopathy. The whole mitochondrial genome screening showed the presence of several variations and a novel homoplasmic mutation m.4318-4322delC in the MT-TI gene shared by the two patients and their mother and leading to a disruption of the tRNA Ile secondary structure. In addition, a mitochondrial depletion was present in blood leucocyte of the two affected brother whereas a de novo heteroplasmic multiple deletion in the major arc of mtDNA was present in blood leucocyte and mucosa of only one of them. These deletions in the major arc of the mtDNA resulted to the loss of several protein-encoding genes and also some tRNA genes. The mtDNA deletion and depletion could result to an impairment of the oxidative phosphorylation and energy metabolism in the respiratory chain in the studied patients. Our report is the first description of a family with severe lethal dilated mitochondrial cardiomyopathy and presenting several mtDNA abnormalities including punctual mutation, deletion and depletion. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. I(f) current inhibitor ivabradine in patients with idiopathic dilated cardiomyopathy: Impact on the exercise tolerance and quality of life.

    Science.gov (United States)

    Abdel-Salam, Zainab; Rayan, Mona; Saleh, Ayman; Abdel-Barr, Mohamed G; Hussain, Mohamed; Nammas, Wail

    2015-01-01

    Evidence supported a beneficial effect of ivabradine on clinical outcome of patients with systolic heart failure, and a sinus heart rate (HR) ≥ 70 bpm. We explored the effect of ivabradine, vs. placebo, added to evidence-based treatment on exercise tolerance and quality of life in patients with idiopathic dilated cardiomyopathy. We enrolled 43 consecutive patients with dilated cardiomyopathy of no apparent cause, a left ventricular ejection fraction (LVEF) 0.05 for all). At 3 months, mean dose of ivabradine was 6.8 mg bid. Ivabradine-treated patients had a lower HR, and improved left ventricular dimensions and systolic function, versus placebo-treated ones (p < 0.05 for all). HR dropped by a mean of 14 bpm in the ivabradine group, corrected for placebo. Both exercise tolerance, and Minnesota questionnaire score were better in the ivabradine group (p < 0.05 both). Ivabradine was well-tolerated. In symptomatic patients with idiopathic dilated cardiomyopathy, the addition of ivabradine, vs. placebo, to evidence-based treatment, reduced HR, and improved functional capacity, at short-term follow-up.

  12. Dilated cardiomyopathy and amebic gastritis in a giant anteater (Myrmecophaga tridactyla).

    Science.gov (United States)

    Coke, Rob L; Carpenter, James W; Aboellail, Tawfk; Armbrust, Laura; Isaza, Ramiro

    2002-09-01

    An approximately 11-mo-old female giant anteater (Myrmecophaga tridactyla) exhibited anorexia, lethargy, hypothermia, depression, and minimal response to external stimuli. Radiography and ultrasonography revealed an enlarged heart, with free gas and fluid in the abdomen. Abdominocentesis produced a clear brown fluid with an acute to subacute septic suppurative exudate. Cardiac ultrasonography revealed a dilated, thin-walled left ventricle with a comparatively low fractional shortening. Despite intensive supportive care, the anteater died. Postmortem findings included gastric ulceration with perforation near the pylorus. Entameba spp. and Acanthamoeba spp. were both identified in large numbers at the site of the gastric ulceration and perforation.

  13. Evaluation of sympathetic activity by 123I-metaiodobenzylguanidine myocardial scintigraphy in dilated cardiomyopathy patients with sleep breathing disorder

    International Nuclear Information System (INIS)

    Nanjo, Shuji; Fujimoto, Shinichiro; Yamashiro, Yoshihiro

    2009-01-01

    Because increased sympathetic nervous activity (SNA) in patients with dilated cardiomyopathy (DCM) associated with sleep breathing disorder (SBD) is known to deteriorate the prognosis of cardiac failure, 123 I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was used as the investigative tool in the present study. The study group comprised 53 patients (47 men, 6 women; mean age 56±3 years) with chronic stable DCM. Patients were divided into SBD(+) or SBD(-) group according to 24-h pulse oximetry results. SBD(+) was defined when the 3% oxygen desaturation index was more than 15/h during sleep. In total, 32 patients were SBD(-) and 21 were SBD(+). In both groups, pulse oximetry were performed during sleep and awakening pulse rate, and measurement of the blood levels of catecholamines and B-type natriuretic peptide was performed. MIBG myocardial scintigraphy and echocardiography were performed at the same time. No significant difference was found between the 2 groups in catecholamine levels or left ventricular ejection fraction. However, MIBG had a significantly increased washout rate and a significantly decreased delayed heart to mediastinum ratio in the SBD(+) group compared with the SBD(-) group. SNA is increased in DCM patients when associated with SBD. MIBG myocardial scintigraphy may be a sensitive method of detecting increased SNA. (author)

  14. Improvement of Left Ventricular Function by Permanent Direct His-Bundle Pacing in a Case with Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Yukiko Sashida, MD

    2006-01-01

    Full Text Available The patient was a 67-year-old female diagnosed with dilated cardiomyopathy. She had chronic atrial fibrillation (AF with bradycardia and low left ventricular function (left ventricular ejection fraction (LVEF 40%. She was admitted for congestive heart failure. She remained New York Heart Association (NYHA functional class III due to AF bradycardia. Pacemaker implantation was necessary for treatment of heart failure and administration of dose intensive β-blockers. As she had normal His-Purkinje activation, we examined the optimal pacing sites. Hemodynamics of His-bundle pacing and biventricular pacing were compared. Pulmonary capillary wedge pressure (PCWP was significantly lower on Hisbundle pacing than right ventricular (RV apical pacing and biventricular pacing (13mmHg, 19mmHg, and 19mmHg, respectively with an almost equal cardiac index. Based on the examination we implanted a permanent pacemaker for Direct His-bundle pacing (DHBP. After the DHBP implantation, the LVEF immediately improved from 40% to 55%, and BNP level decreased from 422 pg/ml to 42 pg/ml. The number of premature ventricular complex (PVC was decreased, and non sustained ventricular tachycardia (NSVT disappeared. Pacing threshold for His-bundle pacing has remained at the same level. His-bundle pacing has been maintained during 27 months and her long-term DHBP can improve cardiac function and the NYHA functional class.

  15. Effect of Atorvastatin vs. Rosuvastatin on cardiac sympathetic nerve activity in non-diabetic patients with dilated cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Tsutamoto, Takayoshi; Ibe, Kunihiro [Toyosato Hospital, Toyosato, Shiga (Japan); Sakai, Hiroshi; Yamaji, Masayuki; Kawahara, Chiho; Nakae, Ichiro; Fujii, Masanori; Yamamoto, Takashi; Horie, Minoru [Shiga Univ. of Medical Science, Faculty of Medicine, Otsu, Shiga (Japan)

    2011-08-15

    Effects of statin therapy on cardiac sympathetic nerve activity in patients with chronic heart failure (CHF) have not previously been evaluated. To compare the effects of lipophilic atorvastatin and hydrophilic rosuvastatin on cardiac sympathetic nerve activity in CHF patients with dilated cardiomyopathy (DCM), 63 stable outpatients with DCM, who were already receiving standard therapy for CHF, were randomized to atorvastatin (n=32) or rosuvastatin (n=31). We evaluated cardiac sympathetic nerve activity by cardiac {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy, hemodynamic parameters and neurohumoral factors before and after 6 months of treatment. There were no differences in the baseline characteristics of the 2 groups. In the rosuvastatin group, there were no changes in MIBG parameters, left ventricular ejection fraction or plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) after 6 months of treatment. In contrast, the atorvastatin group showed a significant increase in the delayed heart/mediastinum count ratio (2.18{+-}0.4 vs. 2.36{+-}0.4, P<0.0001), and the washout rate was significantly decreased (34.8{+-}5.7 vs. 32.6{+-}6.3%, P=0.0001) after 6 months of treatment compared with the baseline values. The plasma NT-proBNP level was also significantly decreased (729{+-}858 vs. 558{+-}747 pg/ml, P=0.0139). Lipophilic atorvastatin but not hydrophilic rosuvastatin improves cardiac sympathetic nerve activity in CHF patients with DCM. (author)

  16. Amiodarone and Catheter Ablation as Cardiac Resynchronization Therapy for Children with Dilated Cardiomyopathy and Wolff-Parkinson-White Syndrome

    Science.gov (United States)

    Kim, Sung Hoon; Jeong, Soo In; Kang, I-Seok; Lee, Heung Jae

    2013-01-01

    Preexcitation by accessory pathways (APs) is known to cause dyssynchrony of the ventricle, related to ventricular dysfunction. Correction of ventricular dyssynchrony can improve heart failure in cases of dilated cardiomyopathy (DCMP) with preexcitation. Here, we report the first case of a child with DCMP and Wolff-Parkinson-White (WPW) syndrome treated with amiodarone and radiofrequency catheter ablation (RFCA) in Korea. A 7-year-old boy, who suffered from DCMP and WPW syndrome, showed improved left ventricular function and clinical functional class after treatment with amiodarone to eliminate preexcitation. QRS duration and left ventricular ejection fraction (LVEF) were inversely correlated with amiodarone dosage. After confirming the reduction of preexcitation effects in DCMP, successful RFCA of the right anterior AP resulted in LVEF improvement, along with the disappearance of preexcitation. Our findings suggest that ventricular dyssynchrony, caused by preexcitation in DCMP with WPW syndrome, can worsen ventricular function and amiodarone, as well as RFCA, which should be considered as a treatment option, even in young children. PMID:23407697

  17. Dyssynchronous Ventricular Activation in Asymptomatic Wolff-Parkinson-White Syndrome: A Risk Factor for Development of Dilated Cardiomyopathy

    Science.gov (United States)

    Udink ten Cate, Floris EA; Wiesner, Nathalie; Trieschmann, Uwe; Khalil, Markus; Sreeram, Narayanswami

    2010-01-01

    A subset of children and adults with Wolff-Parkinson-White (WPW) syndrome develop dilated cardiomyopathy (DCM). Although DCM may occur in symptomatic WPW patients with sustained tachyarrhythmias, emerging evidence suggests that significant left ventricular dysfunction may arise in WPW in the absence of incessant tachyarrhythmias. An invariable electrophysiological feature in this non-tachyarrhythmia type of DCM is the presence of a right-sided septal or paraseptal accessory pathway. It is thought that premature ventricular activation over these accessory pathways induces septal wall motion abnormalities and ventricular dyssynchrony. LV dyssynchrony induces cellular and structural ventricular remodelling, which may have detrimental effects on cardiac performance. This review summarizes recent evidence for development of DCM in asymptomatic patients with WPW, discusses its pathogenesis, clinical presentation, management and treatment. The prognosis of accessory pathway-induced DCM is excellent. LV dysfunction reverses following catheter ablation of the accessory pathway, suggesting an association between DCM and ventricular preexcitation. Accessory pathway-induced DCM should be suspected in all patients presenting with heart failure and overt ventricular preexcitation, in whom no cause for their DCM can be found. PMID:20552060

  18. Predictors of electrical storm in patients with idiopathic dilated cardiomyopathy--how to stratify the risk of electrical storm.

    Science.gov (United States)

    Takigawa, Masateru; Noda, Takashi; Kurita, Takashi; Aihara, Naohiko; Yamada, Yuko; Okamura, Hideo; Satomi, Kazuhiro; Suyama, Kazuhiro; Shimizu, Wataru; Kamakura, Shiro

    2010-09-01

    Electrical storm (ES) is a serious problem in patients with an implantable cardioverter defibrillator (ICD). However, insufficient reports have indicated the predictors of ES in ICD patients with idiopathic dilated cardiomyopathy (DCM). The purpose of this study was to clarify the predictors of ES for risk stratification in DCM patients with an ICD. Of 446 ICD patients, 53 DCM patients were included in this study. During a mean follow-up of 55+/-36 months, ES (> or =3 times appropriate ICD therapy within 24 h) occurred in 18/53 (34%) patients. According to multivariate Cox proportional hazard regression analysis, a duration of the terminal low amplitude signals of <40 microV (LAS40) (HR 1.4/10 ms increase, 95% confidence interval (CI) 1.1-2.1; P=0.0049) or root mean square voltage of the last 40 ms of the QRS complex (RMS40) (HR 0.88/1 microV, 95%CI 0.77-0.96; P=0.001) on the signal averaged electrocardiogram, and a history of atrial fibrillation (AF) before ICD implantation (HR 2.3, 95%CI 1.2-5.0; P=0.013) were independently associated with an increased risk of ES. Our data indicated that a longer LAS40, lower RMS40 and history of AF before ICD implantation could strongly predict ES, and the combination of those parameters could effectively stratify the risk of ES in DCM patients.

  19. Assessment of left ventricular torsion and untwisting in patients suffering from dilated cardiomyopathy by velocity vector imaging

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    Xiao-juan ZHANG

    2015-10-01

    Full Text Available Objective To evaluate the characteristics of left ventricular twisting (LVtw and untwisting (LVuntw in patients with dilated cardiomyopathy (DCM. Methods Nineteen DCM patients (aged 18-82 years, mean 50.52±17.52 years, 2 females and 21 normal controls (aged 18-80 years, mean 49.05±16.94 years, 5 females were enrolled in present study. Basal and apical short axis view of two-dimensional images of left ventricle were obtained to analyze LV rotation, and the LV rotation velocity was detected by velocity vector imaging (VVI. LVtw, LVtw velocity, untwisting velocity and untwisting rate (untwR were calculated. Results The rotated degree and velocity of the basal and apical parts of LV myocardium were irregularly changed along with the cardiac cycle in the DCM group. The rotation degree and rotation velocity at the basal and apex axis decreased in DCM group compared with that in normal group, while the peak of twisting (Ptw [(6.49±1.82°] and the peak of twisting velocity (PTV [(67.84±15.60°/s] decreased significantly in DCM group. The untwR and peak of untwisting velocity (PUV were also decreased significantly in DCM patients. Conclusion The Ptw, PTV and PUV decrease significantly, and the LV untwR, impacted by the preload, is also decreased significantly in DCM patients. DOI: 10.11855/j.issn.0577-7402.2015.09.13

  20. Noninvasive measurements of cardiac high-energy phosphate metabolites in dilated cardiomyopathy by using 31P spectroscopic chemical shift imaging

    International Nuclear Information System (INIS)

    Hansch, A.; Rzanny, R.; Heyne, J.-P.; Reichenbach, J.R.; Kaiser, W.A.; Leder, U.

    2005-01-01

    Dilated cardiomyopathy (DCM) is accompanied by an impaired cardiac energy metabolism. The aim of this study was to investigate metabolic ratios in patients with DCM compared to controls by using spectroscopic two-dimensional chemical shift imaging (2D-CSI). Twenty volunteers and 15 patients with severe symptoms (left ventricular ejection fraction, LVEF 30%) of DCM were investigated. Cardiac 31 P MR 2D-CSI measurements (voxel size: 40 x 40 x 100 mm 3 ) were performed with a 1.5 T whole-body scanner. Measurement time ranged from 15 min to 30 min. Peak areas and ratios of different metabolites were evaluated, including high-energy phosphates (PCr, ATP), 2,3-diphosphoglycerate (2,3-DPG) and phosphodiesters (PDE). In addition, we evaluated how PCr/ATP ratios correlate with LVEF as an established prognostic factor of heart failure. The PCr/γ-ATP ratio was significantly decreased in patients with moderate and severe DCM and showed a linear correlation with reduced LVEFs. PDE/ATP ratios were significantly increased only in patients with severe DCM as compared to volunteers. Applying 31 P MRS with commonly-available 2D-CSI sequences is a valuable technique to evaluate DCM by determining PCr/ATP ratios noninvasively. In addition to reduced PCr/ATP ratios observed in patients suffering from DCM, significantly-increased PDE/ATP ratios were found in patients with severe DCM. (orig.)

  1. Left ventricular epicardial activation increases transmural dispersion of repolarization in healthy, long QT, and dilated cardiomyopathy dogs.

    Science.gov (United States)

    Bai, Rong; Lü, Jiagao; Pu, Jun; Liu, Nian; Zhou, Qiang; Ruan, Yanfei; Niu, Huiyan; Zhang, Cuntai; Wang, Lin; Kam, Ruth

    2005-10-01

    Benefits of cardiac resynchronization therapy (CRT) are well established. However, less is understood concerning its effects on myocardial repolarization and the potential proarrhythmic risk. Healthy dogs (n = 8) were compared to a long QT interval (LQT) model (n = 8, induced by cesium chloride, CsCl) and a dilated cardiomyopathy with congestive heart failure (DCM-CHF, induced by rapid ventricular pacing, n = 5). Monophasic action potential (MAP) recordings were obtained from the subendocardium, midmyocardium, subepicardium, and the transmural dispersion of repolarization (TDR) was calculated. The QT interval and the interval from the peak to the end of the T wave (T(p-e)) were measured. All these characteristics were compared during left ventricular epicardial (LV-Epi), right ventricular endocardial (RV-Endo), and biventricular (Bi-V) pacing. In healthy dogs, TDR prolonged to 37.54 ms for Bi-V pacing and to 47.16 ms for LV-Epi pacing as compared to 26.75 ms for RV-Endo pacing (P canine models in addition to their intrinsic transmural heterogeneity in the intact heart. This mechanism may contribute to the development of malignant ventricular arrhythmias, such as torsades de pointes (TdP) in congestive heart failure (CHF) patients treated with CRT.

  2. Correlation of mitochondrial protein expression in complexes I to V with natural and induced forms of canine idiopathic dilated cardiomyopathy.

    Science.gov (United States)

    Lopes, Rosana; Solter, Philip F; Sisson, D David; Oyama, Mark A; Prosek, Robert

    2006-06-01

    To identify qualitative and quantitative differences in cardiac mitochondrial protein expression in complexes I to V between healthy dogs and dogs with natural or induced dilated cardiomyopathy (DCM). Left ventricle samples were obtained from 7 healthy dogs, 7 Doberman Pinschers with naturally occurring DCM, and 7 dogs with DCM induced by rapid right ventricular pacing. Fresh and frozen mitochondrial fractions were isolated from the left ventricular free wall and analyzed by 2-dimensional electrophoresis. Protein spots that increased or decreased in density by 2-fold or greater between groups were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or quadrupole selecting, quadrupole collision cell, time-of-flight mass spectrometry. A total of 22 altered mitochondrial proteins were identified in complexes I to V. Ten and 12 were found in complex I and complexes II to V, respectively. Five were mitochondrial encoded, and 17 were nuclear encoded. Most altered mitochondrial proteins in tissue specimens from dogs with naturally occurring DCM were associated with complexes I and V, whereas in tissue specimens from dogs subjected to rapid ventricular pacing, complexes I and IV were more affected. In the experimentally induced form of DCM, only nuclear-encoded subunits were changed in complex I. In both disease groups, the 22-kd subunit was downregulated. Natural and induced forms of DCM resulted in altered mitochondrial protein expression in complexes I to V. However, subcellular differences between the experimental and naturally occurring forms of DCM may exist.

  3. PDK4 Deficiency Induces Intrinsic Apoptosis in Response to Starvation in Fibroblasts from Doberman Pinschers with Dilated Cardiomyopathy.

    Science.gov (United States)

    Taggart, Kathryn; Estrada, Amara; Thompson, Patrick; Lourenco, Francisco; Kirmani, Sara; Suzuki-Hatano, Silveli; Pacak, Christina A

    2017-01-01

    The Doberman pinscher (DP) canine breed displays a high incidence of idiopathic, nonischemic dilated cardiomyopathy (DCM) with increased mortality. A common mutation in DPs is a splice site deletion in the pyruvate dehydrogenase kinase 4 (PDK4) gene that shows a positive correlation with DCM development. PDK4, a vital mitochondrial protein, controls the switch between glycolysis and oxidative phosphorylation based upon nutrient availability. It is likely, although unproven, that DPs with the PDK4 mutation are unable to switch to oxidative phosphorylation during periods of low nutrient availability, and thus are highly susceptible to mitochondrial-mediated apoptosis. This study investigated cell viability, mitochondrial stress, and activation of the intrinsic (mitochondrial mediated) apoptotic pathway in dermal fibroblasts from DPs that were healthy (PDK4 wt/wt ), heterozygous (PDK4 wt/del ), and homozygous (PDK4 del/del ) for the PDK4 mutation under conditions of high (unstarved) and low (starved) nutrient availability in vitro . As hypothesized, PDK4 wt/del and PDK4 del/del cells showed evidence of mitochondrial stress and activation of the intrinsic apoptotic pathway following starvation, while the PDK4 wt/wt cells remained healthy and viable under these conditions. Adeno-associated virus (AAV) PDK4-mediated gene replacement experiments confirmed cause-effect relationships between PDK4 deficiency and apoptosis activation. The restoration of function observed following administration of AAV-PDK4 provides strong support for the translation of this gene therapy approach into the clinical realm for PDK4-affected Dobermans.

  4. Polymerase chain reaction analysis for viruses in paraffin-embedded myocardium from dogs with dilated cardiomyopathy or myocarditis.

    Science.gov (United States)

    Maxson, T R; Meurs, K M; Lehmkuhl, L B; Magnon, A L; Weisbrode, S E; Atkins, C E

    2001-01-01

    To perform polymerase chain reaction (PCR) analysis on paraffin-embedded myocardium from dogs with dilated cardiomyopathy (DCM) and dogs with myocarditis to screen for canine parvovirus, adenovirus types 1 and 2, and herpesvirus. Myocardial specimens from 18 dogs with an antemortem diagnosis of DCM and 9 dogs with a histopathologic diagnosis of myocarditis were evaluated. Paraffin-embedded myocardial specimens were screened for viral genome by PCR analysis. Positive-control specimens were developed from cell cultures as well as paraffin-embedded tissue specimens from dogs with clinical and histopathologic diagnoses of viral infection with canine parvovirus, adenovirus types 1 and 2, and herpesvirus. The histologic characteristics of all myocardial specimens were classified regarding extent, location, and type of inflammation and fibrosis. Canine adenovirus type 1 was amplified from 1 specimen from a dog with DCM. Canine parvovirus, adenovirus type 2, and herpesvirus were not amplified from any myocardial specimens. Histologic analysis of specimens from dogs with DCM revealed variable amounts of fibrosis; myocardial inflammation was observed in 1 affected dog. Histopathologic analysis of specimens from dogs with myocarditis disclosed variable degrees of inflammation and fibrosis. Viral agents canine parvovirus, adenovirus types 1 and 2, and herpesvirus are not commonly associated with DCM or active myocarditis in dogs. Additional studies evaluating for nucleic acid from viruses that less commonly affect dogs or different types of infectious agents may be warranted to gain insight into the cause of DCM and myocarditis in dogs.

  5. The Role of Serum Adiponectin for Outcome Prediction in Patients with Dilated Cardiomyopathy and Advanced Heart Failure

    Directory of Open Access Journals (Sweden)

    Vaida Baltrūnienė

    2017-01-01

    Full Text Available Clinical interpretation of patients’ plasma adiponectin (APN remains challenging; its value as biomarker in dilated cardiomyopathy (DCM is equivocal. We evaluated whether circulating APN level is an independent predictor of composite outcome: death, left ventricle assist device (LVAD implantation, and heart transplantation (HT in patients with nonischemic DCM. 57 patients with nonischemic DCM (average LV diastolic diameter 6.85 cm, LV ejection fraction 26.63%, and pulmonary capillary wedge pressure 22.06  mmHg were enrolled. Patients underwent echocardiography, right heart catheterization, and endomyocardial biopsy. During a mean follow-up of 33.42 months, 15 (26% patients died, 12 (21% patients underwent HT, and 8 (14% patients were implanted with LVAD. APN level was significantly higher in patients who experienced study endpoints (23.4 versus 10.9 ug/ml, p=0.01. APN was associated with worse outcome in univariate Cox proportional hazards model (HR 1.04, CI 1.02–1.07, p=0.001 but lost significance adjusting for other covariates. Average global strain (AGS is an independent outcome predictor (HR 1.42, CI 1.081–1.866, p=0.012. Increased circulating APN level was associated with higher mortality and may be an additive prognostic marker in DCM with advanced HF. Combination of serum (APN, BNP, TNF-α and echocardiographic (AGS markers may increase the HF predicting power for the nonischemic DCM patients.

  6. The importance of the family history in caring for families with long QT syndrome and dilated cardiomyopathy.

    Science.gov (United States)

    Ruiter, Jolien S; Berkenbosch-Nieuwhof, Karin; van den Berg, Maarten P; van Dijk, Rene; Middel, Berrie; van Tintelen, J Peter

    2010-03-01

    In potentially inherited cardiac diseases, the family history is of great importance. We looked at the way cardiologists take a family history in patients with idiopathic dilated cardiomyopathy (DCM) or long QT syndrome (LQTS) and whether this led to screening of relatives or other follow-up. We performed retrospective cross-sectional analyses of adult index patients with DCM or LQTS in a general hospital (GH) or a University Medical Center (UMC). We identified 82 index patients with DCM (34 GH; 48 UMC) and 20 with LQTS (all UMC) between 1996 and 2005. Mean follow-up was 58 months. A family history was recorded in 90% of both LQTS and DCM patients most of the cases restricted to first-degree family members. The genetic aspects, counseling and screening of family members was discussed significantly more often with LQTS than DCM patients (all P family members, DNA analysis and referral) was performed significantly more often in LQTS than DCM patients. Cardiologists in the UMC referred DCM index patients for genetic counseling more often than those in the GH (25% vs. 6%; P familial. Since early recognition and treatment may reduce morbidity and mortality we recommend cardiologists take a more thorough family history and always consider referring to a clinical genetics department in such index patients. (c) 2010 Wiley-Liss, Inc.

  7. Sokolow-Lyon voltage is suitable for monitoring improvement in cardiac function and prognosis of patients with idiopathic dilated cardiomyopathy.

    Science.gov (United States)

    Fukaya, Kenji; Takeshita, Kyosuke; Okumura, Takahiro; Hiraiwa, Hiroaki; Aoki, Soichiro; Ichii, Takeo; Sugiura, Yuki; Kitagawa, Katsuhide; Kondo, Toru; Watanabe, Naoki; Kano, Naoaki; Furusawa, Kenji; Sawamura, Akinori; Morimoto, Ryota; Bando, Yasuko; Murohara, Toyoaki

    2017-09-01

    The clinical significance of electrocardiogram in the assessment of patients with idiopathic dilated cardiomyopathy (IDCM) is currently unknown. The aim of this study was to determine the feasibility of recording serial changes in Sokolow-Lyon voltage (∆%QRS-voltage) in one year to estimate left ventricular reverse remodeling (LVRR) and predict a prognosis of IDCM patients under tailored medical therapy. Sixty-eight consecutive patients with mild symptoms (52.1 ± 13 years old; 69% men; NYHA I/II/III/IV; 33/29/6/0) underwent electrocardiography and echocardiography at baseline and 12 month follow-up (follow-up period: 3.9 years). LVRR was observed in 30 patients (44.1%). The ∆%QRS-voltage was significantly lower in the LVRR group (LVRR; -26.9%, non-LVRR: -9.2%, p voltage correlated with ∆%LV end-diastolic diameter (r = .634, p voltage group (voltage is associated with improvement in cardiac function and favorable prognosis in IDCM patients on medical therapy, suggesting that this index is a feasible marker for response to treatment of IDCM. © 2017 Wiley Periodicals, Inc.

  8. [Signal transducer and activator of transcription 4 gene polymorphisms associated with dilated cardiomyopathy in Chinese Han population].

    Science.gov (United States)

    Fu, Kai; Peng, Ying; Li, Ya-Jiao; Xie, Qiu; Yang, Hao; Zhou, Bin; Rao, Li

    2013-07-01

    To investigate the association between signal transducer and activator of transcription 4 (STAT4) gene polymorphism and dilated cardiomyopathy (DCM). Two single nucleotide polymorphisms (SNP) (rs7574865 and rs11889341) in STAT4 gene were determined using PCR-RFLP method. The genotype and allele frequencies of these two SNPs were compared between 294 DCM patients and 334 normal controls to test whether SNPs in STAT4 was associated with DCM. Compared to healthy controls, the frequency of GG genotype (55.8% in patients vs. 47.9% in controls, P = 0.039) and the G allele in rs11889341 (76.4% in patients vs. 70.7% in controls, P = 0.023) were significantly increased in D C M patients. We found that increased DCM risk is associated with CC+AC genotypes of rs574865 (94.2% in patients vs. 89.2% in controls, P = 0.025). No significant difference was observed in the distribution of allele frequency in rs7874865 between DCM patients and the controls. SNPs in STAT4 gene is associated with DCM. G allele and GG genotype in rs11889341, and CC+AC genotypes in rs7574865, may be associated with significantly increased risk of DCM.

  9. Impact of shocks on mortality in patients with ischemic or dilated cardiomyopathy and defibrillators implanted for primary prevention.

    Directory of Open Access Journals (Sweden)

    Florian Streitner

    Full Text Available BACKGROUND: Emerging interest is seen in the paradox of defibrillator shocks for ventricular tachyarrhythmia and increased mortality risk. Particularly in patients with dilated cardiomyopathy (DCM, the prognostic importance of shocks is unclear. The purpose of this study was to compare the outcome after shocks in patients with ischemic cardiomyopathy (ICM or DCM and defibrillators (ICD implanted for primary prevention. METHODS AND RESULTS: Data of 561 patients were analyzed (mean age 68.6±10.6 years, mean left ventricular ejection fraction 28.6±7.3%. During a median follow-up of 49.3 months, occurrence of device therapies and all-cause mortality were recorded. 74 out of 561 patients (13.2% experienced ≥1 appropriate and 51 out of 561 patients (9.1% ≥1 inappropriate shock. All-cause mortality was 24.2% (136 out of 561 subjects. Appropriate shock was associated with a trend to higher mortality in the overall patient population (HR 1.48, 95% CI 0.96-2.28, log rank p = 0.072. The effect was significant in ICM patients (HR 1.61, 95% CI 1.00-2.59, log rank p = 0.049 but not in DCM patients (HR 1.03, 95% CI 0.36-2.96, log rank p = 0.96. Appropriate shocks occurring before the median follow-up revealed a much stronger impact on mortality (HR for the overall patient population 2.12, 95% CI 1.24-3.63, p = 0.005. The effect was driven by ICM patients (HR 2.48, 95% CI 1.41-4.37, p = 0.001, as appropriate shocks again did not influence survival of DCM patients (HR 0.63, 95% CI 0.083-4.75, p = 0.65. Appropriate shocks occurring after the median follow-up and inappropriate shocks occurring at any time revealed no impact on survival in any of the groups (p = ns. CONCLUSION: Appropriate shocks are associated with reduced survival in patients with ICM but not in patients with DCM and ICDs implanted for primary prevention. Furthermore, the negative effect of appropriate shocks on survival in ICM patients is only evident within the

  10. Lone ventricular cardiomyopathy,

    African Journals Online (AJOL)

    ... (I) cardiac catheterisation, including coronary arteriography and pulmonary ... described existence of lone ventricular idiopathic ... spectrum of classic idiopathic dilated cardiomyopathy. ... endomyocardial fibrosis, and from discussions at an.

  11. Usefulness of {sup 123}I-MIBG scintigraphy for prediction of effect of {beta}-blocker therapy in dilated cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Tawarahara, Kei; Sugiyama, Tsuyoshi; Nakano, Tomoyasu; Matou, Fumitaka [Hamamatsu Red Cross Hospital, Shizuoka (Japan); Kurata, Chinori; Wakabayashi, Yasushi; Shouda, Sakae; Mikami, Tadashi

    1998-07-01

    To determine whether {sup 123}I-MIBG (MIBG) scintigraphy is useful for predicting the effect of {beta}-blocker therapy in patients with dilated cardiomyopathy (DCM), we studied MIBG scintigraphy in 11 controls and 9 patients with DCM before starting {beta}-blocker therapy. First, initial and delayed heart-to-mediastinum ratios (H/M ratio) of MIBG activity in patients with DCM were significantly lower than those in 11 controls, respectively (initial H/M; 1.8{+-}0.3 vs. 2.1{+-}0.3, p<0.02, delayed H/M; 1.6{+-}0.3 vs. 2.4{+-}0.2, p<0.0001), and MIBG washout rate from the heart was significantly higher in patients than in controls (washout rate; 33{+-}7% vs. 22{+-}4%, p<0.0005). Second, {beta}-blocker therapy improved LVEF in 7 patients (improved group), while it resulted in deterioration of heart failure, followed by death in 2 patients (deteriorated group). Although initial and delayed H/M ratios in the improved group were not significantly different from those in the deteriorated group, respectively, MIBG washout rate was significantly higher in the deteriorated group than in the improved group (45{+-}8% vs. 30{+-}3%, p=0.04). Our study suggests that DCM patients with markedly rapid MIBG clearance may be deteriorated by {beta}-blocker therapy. In contrast, there were no differences in LVEF and plasma norepinephrine between improved and deteriorated groups. In conclusion, {sup 123}I-MIBG scintigraphy is useful for predicting the effects of {beta}-blocker therapy in patients with DCM. (author)

  12. Dyssynchronous ventricular contraction in Wolff-Parkinson-White syndrome: a risk factor for the development of dilated cardiomyopathy.

    Science.gov (United States)

    Dai, Chen-Cheng; Guo, Bao-Jing; Li, Wen-Xiu; Xiao, Yan-Yan; Jin, Mei; Han, Lin; Sun, Jing-Ping; Yu, Cheuk-Man; Dong, Jian-Zeng

    2013-11-01

    Emerging evidence suggests that significant left ventricular dysfunction may arise in right-sided septal or paraseptal accessory pathways (APs) with Wolff-Parkinson-White syndrome, even in the absence of recurrent or incessant tachycardia. During 1 year and 9 months, we identified four consecutive female children with median age of 8 years diagnosed as having dilated cardiomyopathy (DCM) combined with overt right-sided APs several years ago. Incessant or recurrent tachycardia as the cause of DCM could be excluded. Anti-heart failure chemotherapy did not produce satisfactory effects. The patients underwent radiofrequency ablations (RFCAs). This report describes the clinical and echocardiographic characteristics of the cases before and after the ablation. Dyssynchronous ventricular contraction was observed in all patients. The locations of the APs were the right-sided anteroseptum and the free wall (n = 2 each). All patients received successful RFCAs. Their physical activities and growth improved greatly, and the echocardiographic data demonstrated that their left ventricular (LV) contraction recovered to synchrony shortly after the ablation and that their LV function recovered to normal gradually during the follow-up. A causal relationship between overt ventricular preexcitation and the development of DCM is supported by the complete recovery of LV function and reversed LV remodeling after the loss of ventricular preexcitation. Preexcitation-related dyssynchrony was probably the crucial mechanism. Not only right-sided septal or paraseptal but also free wall overt APs may induce LV dysfunction and even DCM. AP-induced DCM is an indication for ablation with a good prognosis.

  13. Oxidative Stress Markers and C-Reactive Protein Are Related to Severity of Heart Failure in Patients with Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Celina Wojciechowska

    2014-01-01

    Full Text Available Background. The aim of study was to determine relationships between functional capacity (NYHA class, left ventricle ejection fraction (LVEF, hemodynamic parameters, and biomarkers of redox state and inflammation in patients with dilated cardiomyopathy (DCM. Methods. DCM patients (n=109, aged 45.97±10.82 years, NYHA class IIV, and LVEF 2.94±7.1% were studied. Controls comprised age-matched healthy volunteers (n=28. Echocardiography and right heart catheterization were performed. Serum activities of superoxide dismutase isoenzymes (MnSOD and CuZnSOD, concentrations of uric acid (UA, malondialdehyde (MDA, and C-reactive protein (hs-CRP were measured. Results. MnSOD, UA, hs-CRP, and MDA were significantly higher in DCM patients compared to controls. Except MDA concentration, above parameters were higher in patients in III-IV NYHA class or with lower LVEF. hsCRP correlated with of MnSOD (P<0.05 and CuZnSOD activity (P<0.01. Both isoenzymes positively correlated with mPAP and pulmonary capillary wedge pressure (MnSOD, resp., P<0.01 and P<0.05 and CuZnSOD P<0.05; P<0.05. UA positively correlated with MnSOD (P<0.05, mPAP (P<0.05, and PVRI (P<0.05. The negative correlation between LVEF and UA (P<0.01 was detected. Conclusion. There are relationships among the severity of symptoms of heart failure, echocardiographic hemodynamic parameters, oxidative stress, and inflammatory activation. Increased MnSOD activity indicates the mitochondrial source of ROS in patients with advanced heart failure.

  14. PDK4 Deficiency Induces Intrinsic Apoptosis in Response to Starvation in Fibroblasts from Doberman Pinschers with Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Kathryn Taggart

    2017-12-01

    Full Text Available The Doberman pinscher (DP canine breed displays a high incidence of idiopathic, nonischemic dilated cardiomyopathy (DCM with increased mortality. A common mutation in DPs is a splice site deletion in the pyruvate dehydrogenase kinase 4 (PDK4 gene that shows a positive correlation with DCM development. PDK4, a vital mitochondrial protein, controls the switch between glycolysis and oxidative phosphorylation based upon nutrient availability. It is likely, although unproven, that DPs with the PDK4 mutation are unable to switch to oxidative phosphorylation during periods of low nutrient availability, and thus are highly susceptible to mitochondrial-mediated apoptosis. This study investigated cell viability, mitochondrial stress, and activation of the intrinsic (mitochondrial mediated apoptotic pathway in dermal fibroblasts from DPs that were healthy (PDK4wt/wt, heterozygous (PDK4wt/del, and homozygous (PDK4del/del for the PDK4 mutation under conditions of high (unstarved and low (starved nutrient availability in vitro. As hypothesized, PDK4wt/del and PDK4del/del cells showed evidence of mitochondrial stress and activation of the intrinsic apoptotic pathway following starvation, while the PDK4wt/wt cells remained healthy and viable under these conditions. Adeno-associated virus (AAV PDK4-mediated gene replacement experiments confirmed cause-effect relationships between PDK4 deficiency and apoptosis activation. The restoration of function observed following administration of AAV-PDK4 provides strong support for the translation of this gene therapy approach into the clinical realm for PDK4-affected Dobermans.

  15. A comparison of the histopathologic pattern of the left atrium in canine dilated cardiomyopathy and chronic mitral valve disease.

    Science.gov (United States)

    Janus, Izabela; Noszczyk-Nowak, Agnieszka; Nowak, Marcin; Ciaputa, Rafał; Kandefer-Gola, Małgorzata; Pasławska, Urszula

    2016-01-05

    Dilated cardiomyopathy (DCM) and chronic mitral valve disease (CMVD) in dogs are associated with heart chamber enlargement, also of the left atrium. DCM is often accompanied by rhythm disturbances (mainly atrial fibrillation or ventricular arrhythmias). In CMVD, arrhythmias are observed less frequently. It is still unclear whether left atrial enlargement in these diseases results from volume overload or if it is also connected with other factors (e.g. rhythm disturbances). This study was conducted on the left atrial myocardial specimens from 31 dogs, including those from 16 dogs with clinically diagnosed DCM and 15 dogs with CMVD. After fixation and staining (using haematoxylin-eosin and Masson-Goldner trichrome stain), the specimens underwent evaluation. Parenchymal changes (fibrosis, fatty infiltration, and vessel narrowing), degenerative changes (loss of striation, changes in cardiomyocyte structure, and abnormal cell nuclei) and the presence of inflammatory infiltrates were assessed. More interstitial fibrosis (median 4 vs. 2.5 grid fields; p < 0.05) and less perivascular fibrosis (median score 1 vs. 2; p < 0.05) was observed in the DCM group compared to the CMVD group. Moreover, less distinct vessel narrowing was observed in the DCM group than in the CMVD group (median lumen area ratio 0.3 vs. 0.26 respectively; p < 0.05). Dogs with DCM showed more strongly defined degenerative changes than the CMVD dogs (median nuclei enlargement score 3 vs. 1, median loss of striation score 3 vs. 2 and median structural alterations score 3 vs. 2, respectively; p < 0.05). The obtained results indicate a different nature of changes occurring in the left atrial myocardium of dogs with DCM compared to dogs with mitral valve disease, including differences in vessel narrowing, cardiomyocyte degeneration and in the distribution of connective tissue.

  16. Sphericity index and E-point-to-septal-separation (EPSS) to diagnose dilated cardiomyopathy in Doberman Pinschers.

    Science.gov (United States)

    Holler, P J; Wess, G

    2014-01-01

    E-point-to-septal-separation (EPSS) and the sphericity index (SI) are echocardiographic parameters that are recommended in the ESVC-DCM guidelines. However, SI cutoff values to diagnose dilated cardiomyopathy (DCM) have never been evaluated. To establish reference ranges, calculate cutoff values, and assess the clinical value of SI and EPSS to diagnose DCM in Doberman Pinschers. One hundred seventy-nine client-owned Doberman Pinschers. Three groups were formed in this prospective longitudinal study according to established Holter and echocardiographic criteria using the Simpson method of disk (SMOD): control group (97 dogs), DCM with echocardiographic changes (75 dogs) and "last normal" group (n = 7), which included dogs that developed DCM within 1.5 years, but were still normal at this time point. In a substudy, dogs with early DCM based upon SMOD values above the reference range but still normal M-Mode measurements were selected, to evaluate if EPSS or SI were abnormal using the established cutoff values. ROC-curve analysis determined 6.5 mm for EPSS (sensitivity 100%; specificity 99.0%) as optimal cutoff values to diagnose DCM. Both parameters were significantly different between the control group and the DCM group (P < 0.001), but were not abnormal in the "last normal" group. In the substudy, EPSS was abnormal in 13/13 dogs and SI in 2/13 dogs. E-point-to-septal-separation is a valuable additional parameter for the diagnosis of DCM, which can enhance diagnostic capabilities of M-Mode and which performs similar as well as SMOD. Copyright © 2013 by the American College of Veterinary Internal Medicine.

  17. Determination of the prevalence of whole blood taurine in Irish wolfhound dogs with and without echocardiographic evidence of dilated cardiomyopathy.

    Science.gov (United States)

    Vollmar, Andrea C; Fox, Philip R; Servet, Eric; Biourge, Vincent

    2013-09-01

    Taurine plays an important role in maintaining myocardial function. Irish wolfhound dogs (IW) are at risk for dilated cardiomyopathy (DCM), but a relationship between whole blood taurine (WBT) deficiency and DCM has not been established. Our aim was to determine prevalence of WBT deficiency in IW with and without DCM and assess its association with diet. 115 privately owned IW. Whole blood taurine was measured in IW that received cardiovascular examination. Dietary history was recorded; crude protein and energy intake were estimated. Forty-nine (42.6%) had DCM; 66 (57.4%) had no DCM. Dogs with DCM were older ([median; inter-quartile range or IQR] 5.3; 4.3, 6.2 years) than dogs without heart disease (3; 2, 4 years; P < 0.001). There was no significant relationship between WBT concentration and age (P = 0.64). Whole blood taurine was severely reduced (<130 nmol/mL) in 8 dogs (4 with and 4 without DCM) and moderately reduced (130-179.9 nmol/mL) in 32 dogs (12 with DCM and 20 without DCM). Follow up of dogs without DCM revealed that a higher proportion of dogs with any degree of WBT deficiency developed DCM later compared to dogs with normal WBT (P < 0.001). Whole blood taurine deficiency occurred in IW with and without DCM. Based on taurine measurement on a single occasion, there was no clear relationship between low WBT and presence of DCM in this population. Regardless of WBT, DCM affected predominantly older dogs, suggesting a relatively late onset disease in the IW. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Relationship between cardiac 123I-Metaiodobenzylguanidine imaging and the transcardiac gradient of neurohumoral factors in patients with dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Matsui, Toshiki; Tsutamoto, Takayoshi; Kinoshita, Masahiko

    2001-01-01

    Cardiac sympathetic nervous function is altered in congestive heart failure (CHF) and the uptake and washout rate of cardiac 123 I-metaiodobenzylguanidine (MIBG) are useful markers for evaluating the severity of it. To assess what parameters predict decreased uptake or increased washout rate of MIBG, the concentrations of neurohumoral factor in both the aorta (Ao) and coronary sinus (CS) were measured, as well as hemodynamic parameters by catheterization, in patients with dilated cardiomyopathy (DCM). MIBG imaging was performed within 1 week of cardiac catheterization. Regarding MIBG parameters, the correlation with the transcardiac gradient of norepinephrine (NE), brain natriuretic peptide (BNP) and hemodynamics was investigated. Stepwise multivariate regression analysis was used to determine which variables closely correlated with cardiac MIBG parameters. There was a significant increase in the NE level between the Ao (446 pg/ml) and the CS (727 pg/ml). According to stepwise multivariate regression analysis, the heart/mediastinum (H/M) ratio independently correlated with the transcardiac gradient of BNP (r=-0.480, p<0.01), and the washout rate independently correlated with the transcardiac gradient of NE (r=0.481, p<0.01). These findings indicate that the H/M ratio may reflect the transcardiac gradient of BNP, which implies the degree of left ventricular dysfunction and/or damage and the washout rate may reflect altered cardiac sympathetic nerve terminal in DCM patients with CHF, suggesting that both the H/M ratio and washout rate provide important information about the failing ventricle. (author)

  19. The BAG3 gene variants in Polish patients with dilated cardiomyopathy: four novel mutations and a genotype-phenotype correlation.

    Science.gov (United States)

    Franaszczyk, Maria; Bilinska, Zofia T; Sobieszczańska-Małek, Małgorzata; Michalak, Ewa; Sleszycka, Justyna; Sioma, Agnieszka; Małek, Łukasz A; Kaczmarska, Dorota; Walczak, Ewa; Włodarski, Paweł; Hutnik, Łukasz; Milanowska, Blanka; Dzielinska, Zofia; Religa, Grzegorz; Grzybowski, Jacek; Zieliński, Tomasz; Ploski, Rafal

    2014-07-09

    BAG3 gene mutations have been recently implicated as a novel cause of dilated cardiomyopathy (DCM). Our aim was to evaluate the prevalence of BAG3 mutations in Polish patients with DCM and to search for genotype-phenotype correlations. We studied 90 unrelated probands by direct sequencing of BAG3 exons and splice sites. Large deletions/insertions were screened for by quantitative real time polymerase chain reaction (qPCR). We found 5 different mutations in 6 probands and a total of 21 mutations among their relatives: the known p.Glu455Lys mutation (2 families), 4 novel mutations: p.Gln353ArgfsX10 (c.1055delC), p.Gly379AlafsX45 (c.1135delG), p.Tyr451X (c.1353C>A) and a large deletion of 17,990 bp removing BAG3 exons 3-4. Analysis of mutation positive relatives of the probands from this study pooled with those previously reported showed higher DCM prevalence among those with missense vs. truncating mutations (OR = 8.33, P = 0.0058) as well as a difference in age at disease onset between the former and the latter in Kaplan-Meier survival analysis (P = 0.006). Clinical data from our study suggested that in BAG3 mutation carriers acute onset DCM with hemodynamic compromise may be triggered by infection. BAG3 point mutations and large deletions are relatively frequent cause of DCM. Delayed DCM onset associated with truncating vs. non-truncating mutations may be important for genetic counseling.

  20. Mitochondrial-related gene expression profiles suggest an important role of PGC-1alpha in the compensatory mechanism of endemic dilated cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    He, Shu-Lan [Key Laboratory of Environment and Gene Related Diseases, Xi' an Jiaotong University, Ministry Education, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Key Laboratory of Trace Elements and Endemic Diseases, Xi' an Jiaotong University, Ministry of Health, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Tan, Wu-Hong, E-mail: tanwh@mail.xjtu.edu.cn [Key Laboratory of Environment and Gene Related Diseases, Xi' an Jiaotong University, Ministry Education, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Key Laboratory of Trace Elements and Endemic Diseases, Xi' an Jiaotong University, Ministry of Health, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Zhang, Zeng-Tie; Zhang, Feng [Key Laboratory of Environment and Gene Related Diseases, Xi' an Jiaotong University, Ministry Education, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Key Laboratory of Trace Elements and Endemic Diseases, Xi' an Jiaotong University, Ministry of Health, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Qu, Cheng-Juan [Institute of Biomedicine, University of Eastern Finland, Kuopio (Finland); Lei, Yan-Xia; Zhu, Yan-He [Key Laboratory of Environment and Gene Related Diseases, Xi' an Jiaotong University, Ministry Education, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Key Laboratory of Trace Elements and Endemic Diseases, Xi' an Jiaotong University, Ministry of Health, No. 76 Yanta West Road, Xi' an, Shaanxi 710061 (China); Yu, Han-Jie [Department of Biotechnology, Northwest University, Xi' an, Shaanxi 710069 (China); Xiang, You-Zhang [Shandong Institute for prevention and Treatment of Endemic Disease, Jinan, Shandong 250014 (China); and others

    2013-10-15

    Keshan disease (KD) is an endemic dilated cardiomyopathy with unclear etiology. In this study, we compared mitochondrial-related gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from 16 KD patients and 16 normal controls in KD areas. Total RNA was isolated, amplified, labeled and hybridized to Agilent human 4×44k whole genome microarrays. Mitochondrial-related genes were screened out by the Third-Generation Human Mitochondria-Focused cDNA Microarray (hMitChip3). Quantitative real-time PCR, immunohistochemical and biochemical parameters related mitochondrial metabolism were conducted to validate our microarray results. In KD samples, 34 up-regulated genes (ratios≥2.0) were detected by significance analysis of microarrays and ingenuity systems pathway analysis (IPA). The highest ranked molecular and cellular functions of the differentially regulated genes were closely related to amino acid metabolism, free radical scavenging, carbohydrate metabolism, and energy production. Using IPA, 40 significant pathways and four significant networks, involved mainly in apoptosis, mitochondrion dysfunction, and nuclear receptor signaling were identified. Based on our results, we suggest that PGC-1alpha regulated energy metabolism and anti-apoptosis might play an important role in the compensatory mechanism of KD. Our results may lead to the identification of potential diagnostic biomarkers for KD in PBMCs, and may help to understand the pathogenesis of KD. Highlights: • Thirty-four up-regulated genes were detected in KD versus health controls. • Forty pathways and four networks were detected in KD. • PGC-1alpha regulated energy metabolism and anti-apoptosis in KD.

  1. Cardiomyopathy in neurological disorders.

    Science.gov (United States)

    Finsterer, Josef; Stöllberger, Claudia; Wahbi, Karim

    2013-01-01

    According to the American Heart Association, cardiomyopathies are classified as primary (solely or predominantly confined to heart muscle), secondary (those showing pathological myocardial involvement as part of a neuromuscular disorder) and those in which cardiomyopathy is the first/predominant manifestation of a neuromuscular disorder. Cardiomyopathies may be further classified as hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, or unclassified cardiomyopathy (noncompaction, Takotsubo-cardiomyopathy). This review focuses on secondary cardiomyopathies and those in which cardiomyopathy is the predominant manifestation of a myopathy. Any of them may cause neurological disease, and any of them may be a manifestation of a neurological disorder. Neurological disease most frequently caused by cardiomyopathies is ischemic stroke, followed by transitory ischemic attack, syncope, or vertigo. Neurological disease, which most frequently manifests with cardiomyopathies are the neuromuscular disorders. Most commonly associated with cardiomyopathies are muscular dystrophies, myofibrillar myopathies, congenital myopathies and metabolic myopathies. Management of neurological disease caused by cardiomyopathies is not at variance from the same neurological disorders due to other causes. Management of secondary cardiomyopathies is not different from that of cardiomyopathies due to other causes either. Patients with neuromuscular disorders require early cardiologic investigations and close follow-ups, patients with cardiomyopathies require neurological investigation and avoidance of muscle toxic medication if a neuromuscular disorder is diagnosed. Which patients with cardiomyopathy profit most from primary stroke prevention is unsolved and requires further investigations. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. The LMNA mutation p.Arg321Ter associated with dilated cardiomyopathy leads to reduced expression and a skewed ratio of lamin A and lamin C proteins

    DEFF Research Database (Denmark)

    Al-Saaidi, Rasha Abdelkadhem; Rasmussen, Torsten Bloch; Palmfeldt, Johan

    2013-01-01

    Dilated cardiomyopathy (DCM) is a disease of the heart muscle characterized by cardiac chamber enlargement and reduced systolic function of the left ventricle. Mutations in the LMNA gene represent the most frequent known genetic cause of DCM associated with disease of the conduction systems...... however are still not clearly established. In this study, we used a representative LMNA nonsense mutation, p.Arg321Ter, to shed light on the molecular disease mechanisms. Cultured fibroblasts from three DCM patients carrying this mutation were analyzed. Quantitative reverse transcriptase PCR...

  3. Therapeutic effects of coenzyme Q10 on dilated cardiomyopathy. Assessment by {sup 123}I-BMIPP myocardial single photon emission computed tomography (SPECT). A multicenter trial in Osaka University Medical School Group

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, Tsunehiko; Hori, Masatsugu [Osaka Univ. (Japan). Faculty of Medicine

    1996-01-01

    To evaluate therapeutic effects of Coenzyme Q10 (CoQ10), 15 patients with dilated cardiomyopathy were investigated by {sup 123}I-BMIPP myocardial single photon emission computed tomography (SPECT). The BMIPP defect score was determined semiquantitatively by using representative short and long axial SPECT images. Mean BMIPP defect score with CoQ10 treatment was significantly low, 7.7{+-}6.1 compared to 12.7{+-}7.4 without CoQ10 treatment. On the other hand, in 8 patients of dilated cardiomyopathy, % fractional shortening using echocardiography was not different before and after CoQ10 treatment. In conclusion, {sup 123}I-BMIPP myocardial SPECT was proved to be sensitive to evaluate the therapeutic effects of CoQ10, which improve myocardial mitochondrial function, in the cases of dilated cardiomyopathy. (author).

  4. Assessment of right ventricular oxidative metabolism by PET in patients with idiopathic dilated cardiomyopathy undergoing cardiac resynchronisation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Knuuti, Juhani; Naum, Alexandru; Stolen, Kira Q.; Kalliokoski, Riikka [University of Turku, Turku PET Centre, P.O. Box 52, Turku (Finland); Sundell, Jan [University of Turku, Turku PET Centre, P.O. Box 52, Turku (Finland); University of Turku, Department of Medicine, Turku (Finland); Engblom, Erik; Koistinen, Juhani; Airaksinen, K.E. Juhani [University of Turku, Department of Medicine, Turku (Finland); Ylitalo, Antti [Satakunta Central Hospital, Department of Medicine, Pori (Finland); Nekolla, Stephan G. [Klinikum rechts der Isar der Technischen Universitaet Muenchen, Klinik und Poliklinik fuer Nuklearmedizin, Munich (Germany); Bax, K.E. Jeroen J. [Leiden University, Department of Cardiology, Leiden (Netherlands)

    2004-12-01

    Right ventricular (RV) performance is known to have prognostic value in patients with congestive heart failure (CHF). Cardiac resynchronisation therapy (CRT) has been found to enhance left ventricular (LV) energetics and metabolic reserve in patients with heart failure. The interplay between the LV and RV may play an important role in CRT response. The purpose of the study was to investigate RV oxidative metabolism, metabolic reserve and the effects of CRT in patients with CHF and left bundle brach block. In addition, the role of the RV in the response to CRT was evaluated. Ten patients with idiopathic dilated cardiomyopathy who had undergone implantation of a biventricular pacemaker 8{+-}5 months earlier were studied under two conditions: CRT ON and after CRT had been switched OFF for 24 h. Oxidative metabolism was measured using [{sup 11}C]acetate positron emission tomography (K{sub mono}). The measurements were performed at rest and during dobutamine-induced stress (5 {mu}g/kg per minute). LV performance and interventricular mechanical delay (interventricular asynchrony) were measured using echocardiography. CRT had no effect on RV K{sub mono} at rest (ON: 0.052{+-}0.014, OFF: 0.047{+-}0.018, NS). Dobutamine-induced stress increased RV K{sub mono} significantly under both conditions but oxidative metabolism was more enhanced when CRT was ON (0.076{+-}0.026 vs 0.065{+-}0.027, p=0.003). CRT shortened interventricular delay significantly (45{+-}33 vs 19{+-}35 ms, p=0.05). In five patients the response to CRT was striking (32% increase in mean LV stroke volume, range 18-36%), while in the other five patients no response was observed (mean change +2%, range -6% to +4%). RV K{sub mono} and LV stroke volume response to CRT correlated inversely (r=-0.66, p=0.034). None of the other measured parameters, including all LV parameters and electromechanical parameters, were associated with the response to CRT. In responders, RV K{sub mono} with CRT OFF was significantly lower

  5. Association of Nicotinamide Phosphoribosyltransferase (NAMPT Gene Polymorphisms and of Serum NAMPT Levels with Dilated Cardiomyopathy in a Chinese Population

    Directory of Open Access Journals (Sweden)

    Qingyu Dou

    2015-09-01

    Full Text Available Nicotinamide phosphoribosyltransferase (NAMPT has crucial roles for myocardial development, cardiomyocyte energy metabolism and cell death/survival by regulating NAD+-dependent sirtuin-1 (SIRT1 deacetylase. This study aimed to determine if the single nucleotide polymorphisms (SNPs of the NAMPT gene may affect the susceptibility and prognosis for patients with dilated cardiomyopathy (DCM and to describe the association of serum NAMPT levels with clinical features of DCM. Three SNPs (rs61330082, rs2505568, and rs9034 were analyzed by the polymerase chain reaction-restriction fragment length polymorphism method in a case-control study of 394 DCM patients and 395 controls from China. Serum NAMPT levels were measured by enzyme-linked immunosorbent assay kits. The homozygote for the minor allele at rs2505568 and rs9034 could not be detected in this study. Rs9034 T allele and CT genotype were associated with increased DCM risk (OR: 1.63, 95% CI = 1.16–2.27, p = 0.005 and OR: 1.72, 95% CI = 1.20–2.50, p = 0.0027, respectively. Nominally significant decreased DCM risk was found to be associated with the A allele and AT genotype of rs2505568 (OR: 0.48, 95% CI = 0.35–0.67, p < 0.0001 and OR: 0.44, 95% CI = 0.31–0.62, p < 0.0001, respectively, but it should be interpreted with caution because of Hardy-Weinberg disequilibrium in the control group. Of five haplotypes constructed, TAC (rs61330082-rs2505568-rs9034 was a protective haplotype to DCM (OR: 0.22, 95% CI = 0.13–0.39, p = 1.84 × 10−8. The Cox multivariate survival analysis indicated that the rs9034 CT genotype (hazard ratio (HR: 0.59, 95% CI = 0.37–0.96, p = 0.03 was an independently multivariate predictor for longer overall survival in DCM patients. Serum NAMPT levels were significantly higher in the DCM group than controls (p < 0.0001 and gradually increased with the increase of New York Heart Association grade in DCM patients. However, there was a lack of association of the three

  6. Incidence, risk factors, and mortality of neonatal and late-onset dilated cardiomyopathy associated with cardiac neonatal lupus.

    Science.gov (United States)

    Morel, Nathalie; Lévesque, Kateri; Maltret, Alice; Baron, Gabriel; Hamidou, Mohamed; Orquevaux, Pauline; Piette, Jean-Charles; Barriere, François; Le Bidois, Jérôme; Fermont, Laurent; Fain, Olivier; Theulin, Arnaud; Sassolas, François; Hauet, Quentin; Guettrot-Imbert, Gaëlle; Georgin-Lavialle, Sophie; Deligny, Christophe; Hachulla, Eric; Mouthon, Luc; Le Jeunne, Claire; Ravaud, Philippe; Le Mercier, Delphine; Romefort, Bénédicte; Villain, Elisabeth; Bonnet, Damien; Costedoat-Chalumeau, Nathalie

    2017-12-01

    Dilated cardiomyopathy (DCM), a well-known complication of cardiac neonatal lupus, is associated with high mortality rate. Its risk factors remain unclear. We analyzed occurrence of postnatal DCM among children with high-degree congenital heart block (CHB) and mothers with anti-SSA and/or anti-SSB antibodies. Among 187 neonates with CHB, 35 (18.8%, one missing data) had DCM and 22 (11.8%) died during a median follow-up of 7years [range: birth-36years]. On multivariate analysis, factors associated with postnatal DCM were in utero DCM (P=0.0199; HR=3.13 [95% CI: 1.20-8.16]), non-European origin (P=0.0052; HR=4.10 [95% CI: 1.81-9.28]) and pacemaker implantation (P=0.0013; HR=5.48 [95% CI: 1.94-15.47]). Postnatal DCM could be categorized in two subgroups: neonatal DCM (n=13, diagnosed at a median age of 0day [birth-4days]) and late-onset DCM (n=22, diagnosed at a median age of 15.2months [3.6months-22.8years]). Factors associated with neonatal DCM were in utero DCM, hydrops, endocardial fibroelastosis and pericardial effusion, whereas those associated with late-onset DCM were non-European origin, in utero mitral valve insufficiency, and pacemaker implantation. Fluorinated steroids showed no protective effect against late-onset DCM (P=0.27; HR=1.65 [95% CI: 0.63-4.25]). Probability of survival at 10years was 23.1% for newborns diagnosed neonatally with DCM, 53.9% for those who developed late-onset DCM, and 98.6% for those without DCM. Neonatal and late-onset DCM appear to be two different entities. None of the known risk factors associated with neonatal DCM predicted late-onset DCM. Long-term follow-up of cardiac function is warranted in all children with CHB. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Extension of myocardial necrosis differently affects MIBG retention in heart failure caused by ischaemic heart disease or by dilated cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Marini, Cecilia; Giorgetti, Assuero; Gimelli, Alessia; Kusch, Annette; Sereni, Nadia; Marzullo, Paolo; Sambuceti, Gianmario [CNR Institute of Clinical Physiology, Pisa (Italy); L' Abbate, Antonio [Scuola Superiore di Studi Universitari Sant' Anna, Pisa (Italy)

    2005-06-01

    This study aims to investigate the relationship between cardiac sympathetic nervous function (CSNF) and myocardial perfusion/function in patients with heart failure (HF) due to dilated cardiomyopathy (DCM) or ischaemic heart disease (CAD). Twenty patients (10 DCM, 10 CAD, 17 males, age 69{+-}5 years) with NYHA class IIIb HF were studied. CSNF was evaluated by early/delayed {sup 123}I-metaiodobenzylguanidine (MIBG) uptake and regional washout (WO). Myocardial perfusion and function were evaluated by {sup 99m}Tc-tetrofosmin gated single-photon emission tomography (G-SPECT) using a 20-segment model for 400 segments. In each segment, regional MIBG WO was computed as (count density in early images-count density in delayed images/count density in early images) x 100. DCM and CAD showed similar summed rest perfusion score (6.7{+-}5 vs 9.5{+-}5, p=NS) and mean ejection fraction values (29{+-}7% vs 30{+-}9%, p=NS). By contrast, the summed thickening score was higher in DCM than in CAD patients (26{+-}7 vs 17{+-}6, p<0.05). QGS analysis identified akinesis/dyskinesis in 129/137 (94%) severely hypoperfused segments which were considered as damaged. According to the underlying aetiology of HF, marked differences in regional MIBG WO were observed. In fact, within the CAD group, regional MIBG WO was lower in reference than in damaged segments (38{+-}21% vs 46{+-}19%, p<0.05). By contrast, in DCM patients, regional MIBG WO was faster in reference than in damaged segments (49{+-}18% vs 41{+-}30%, p<0.05). When the two groups were directly compared, regional MIBG WO from damaged areas was similar irrespective of the underlying disease, while it was faster in DCM than in CAD patients from reference segments. These data confirm the hypothesis that the presence of myocardial necrosis in HF due to CAD and the consequent loss of neuronal endings cause alterations in regional MIBG WO different from those observed in DCM. (orig.)

  8. Intracoronary Cytoprotective Gene Therapy: A Study of VEGF-B167 in a Pre-Clinical Animal Model of Dilated Cardiomyopathy.

    Science.gov (United States)

    Woitek, Felix; Zentilin, Lorena; Hoffman, Nicholas E; Powers, Jeffery C; Ottiger, Isabel; Parikh, Suraj; Kulczycki, Anna M; Hurst, Marykathryn; Ring, Nadja; Wang, Tao; Shaikh, Farah; Gross, Polina; Singh, Harinder; Kolpakov, Mikhail A; Linke, Axel; Houser, Steven R; Rizzo, Victor; Sabri, Abdelkarim; Madesh, Muniswamy; Giacca, Mauro; Recchia, Fabio A

    2015-07-14

    Vascular endothelial growth factor (VEGF)-B activates cytoprotective/antiapoptotic and minimally angiogenic mechanisms via VEGF receptors. Therefore, VEGF-B might be an ideal candidate for the treatment of dilated cardiomyopathy, which displays modest microvascular rarefaction and increased rate of apoptosis. This study evaluated VEGF-B gene therapy in a canine model of tachypacing-induced dilated cardiomyopathy. Chronically instrumented dogs underwent cardiac tachypacing for 28 days. Adeno-associated virus serotype 9 viral vectors carrying VEGF-B167 genes were infused intracoronarily at the beginning of the pacing protocol or during compensated heart failure. Moreover, we tested a novel VEGF-B167 transgene controlled by the atrial natriuretic factor promoter. Compared with control subjects, VEGF-B167 markedly preserved diastolic and contractile function and attenuated ventricular chamber remodeling, halting the progression from compensated to decompensated heart failure. Atrial natriuretic factor-VEGF-B167 expression was low in normally functioning hearts and stimulated by cardiac pacing; it thus functioned as an ideal therapeutic transgene, active only under pathological conditions. Our results, obtained with a standard technique of interventional cardiology in a clinically relevant animal model, support VEGF-B167 gene transfer as an affordable and effective new therapy for nonischemic heart failure. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  9. [Influence of pacing site on myocardial transmural dispersion of repolarization in intact normal and dilated cardiomyopathy dogs].

    Science.gov (United States)

    Bai, Rong; Pu, Jun; Liu, Nian; Lu, Jia-Gao; Zhou, Qiang; Ruan, Yan-Fei; Niu, Hui-Yan; Wang, Lin

    2003-12-25

    In order to verify the hypothesis that left ventricular epicardial (LV-Epi) pacing and biventricular (BiV) pacing unavoidably influence the myocardial electrophysiological characters and may result in high risk of malignant ventricular arrhythmia, we calculated, in both normal mongrel dogs and dog models with rapid-right-ventricular-pacing induced dilated cardiomyopathy congestive heart failure (DCM-CHF), the monophasic action potential duration (MAPD) and the transmural dispersion of repolarization (TDR) in intracardiac electrogram together with the QT interval and T(peak)-T(end) (T(p(-T(e)) interval in surface electrocardiogram (ECG) during LV-Epi and BiV pacing, compared with those during right ventricular endocardial (RV-Endo) pacing. To prepare the DCM-CHF dog model, rapid right ventricular pacing (250 bpm) was performed for 23.6+/-2.57 days to the dog. All the normal and DCM-CHF dogs were given radio frequency catheter ablation (RFCA) to His bundle with the guide of X-ray fluoroscopy. After the RFCA procedures, the animals were under the situation of complete atrioventricular block so that the canine heart rates could be voluntarily controlled in the following experiments. After a thoracotomy, ECG and monophasic action potentials (MAP) of subendocardial, subepicardial and mid-layer myocardium were recorded synchronously in 8 normal and 5 DCM-CHF dogs during pacing from endocardium of RV apex (RV-Endo), epicardium of LV anterior wall (LV-Epi) and simultaneously both of the above (biventricular, BiV), the later was similar to the ventricular resynchronization therapy to congestive heart failure patients in clinic. The Tp-Te) meant the interval from the peak to the end of T wave, which was a representative index of TDR in surface ECG. The TDR was defined as the difference between the longest and the shortest MAPD of subendocardial, subepicardial and mid-layer myocardium. Our results showed that in normal dogs, pacing participating of LV (LV-Epi, BiV) prolonged

  10. Novel Genetic Variants in BAG3 and TNNT2 in a Swedish Family with a History of Dilated Cardiomyopathy and Sudden Cardiac Death.

    Science.gov (United States)

    Fernlund, Eva; Österberg, A Wålinder; Kuchinskaya, E; Gustafsson, M; Jansson, K; Gunnarsson, C

    2017-08-01

    Familial dilated cardiomyopathy is a rare cause of dilated cardiomyopathy (DCM), especially in childhood. Our aim was to describe the clinical course and the genetic variants in a family where the proband was a four-month-old infant presenting with respiratory problems due to DCM. In the family, there was a strong family history of DCM and sudden cardiac death in four generations. DNA was analyzed initially from the deceased girl using next-generation sequencing including 50 genes involved in cardiomyopathy. A cascade family screening was performed in the family after identification of the TNNT2 and the BAG3 variants in the proband. The first-degree relatives underwent clinical examination including biochemistry panel, cardiac ultrasound, Holter ECG, exercise stress test, and targeted genetic testing. The index patient presented with advanced DCM. After a severe clinical course, the baby had external left ventricular assist as a bridge to heart transplantation. 1.5 months after transplantation, the baby suffered sudden cardiac death (SCD) despite maximal treatment in the pediatric intensive care unit. The patient was shown to carry two heterozygous genetic variants in the TNNT2 gene [TNNT2 c.518G>A(p.Arg173Gln)] and BAG3 [BAG3 c.785C>T(p.Ala262Val)]. Two of the screened individuals (two females) appeared to carry both the familial variants. All the individuals carrying the TNNT2 variant presented with DCM, the two adult patients had mild or moderate symptoms of heart failure and reported palpitations but no syncope or presyncopal attacks prior to the genetic diagnosis. The female carriers of TNNT2 and BAG3 variants had more advanced DCM. In the family history, there were three additional cases of SCD due to DCM, diagnosed by autopsy, but no genetic analysis was possible in these cases. Our findings suggest that the variants in TNNT2 and BAG3 are associated with a high propensity to life-threatening cardiomyopathy presenting from childhood and young adulthood.

  11. Association of myocardial inotropic reserve and adrenergic nerve alterations in idiopathic dilated cardiomyopathy. A dobutamine stress echocardiographic and 123-I-MIBG scintigraphic study

    International Nuclear Information System (INIS)

    Prassopoulos, V.P.; Koukouraki, S.; Velidaki, A.; Karkavitsas, N.; Parthenakis, F.; Patrianakos, A.; Kochiadakis, G.; Papadimitriou, E.; Vardas, P.

    2002-01-01

    Aim: Evaluation of contractile reserve is important in congestive hear failure. The aim of this study was to examine the relationship between the myocardial response to dobutamine by stress echocardiography and the sympathetic nerve alterations by 123-I-Metaiodobenzylguanidine (MIBG)scintigraphy and how both contribute to predict exercise capacity in patients with idiopathic dilated cardiomyopathy. Materials-Methods: We studied 20 patients with idiopathic dilated cardiomyopathy (IDC) and ejection fraction < 45% (M/F 13/7, age 56±11 years) while 15 healthy individuals served as controls. Echocardiography and myocardial scintigraphic study with 123-I- MIBG, provided quantitative assessment of left ventricular (LV) wall motion and heart to mediastinum uptake(H/M) ratio and washout. All patients underwent a cardiopulmonary exercise test with a modified Naughton protocol and gas exchange data were analyzed. According to LV response to dobutamine, patients were divided into two groups: those in whom contractility improved in ≥ five segments (Group I: 11 patients) and those in whom contractility improved in < 5 segments (Group II : 9 patients). Results: MIBG uptake was significantly lower in patients than in controls (p < 0.001). MIBG uptake and washout was higher in Group I compared to Group II (P<0,01 and p<0,05). Late MIBG H/M was correlated with resting ejection fraction (r=0,70), wall motion score index (WMSI) (r=-0,50), end systolic wall stress (r=-0,61), washout (r=-0,57), and oxygen consumption at peak exercise (r=0,64) and at anaerobic threshold (r=0,67). LV ejection fraction increased in both groups at Dobutamine, with a higher increase in Group I (p=0,008). WMSI changes at dobutamine correlated significantly with resting ejection fraction (r=0,46) early (r=0,53) and late (r=0,54) MIBG. Multivariate analysis revealed that only the late MIBG uptake was independently associated with the improvement in WMSI. Conclusions: The present data indicate that in

  12. Brain natriuretic peptide is not predictive of dilated cardiomyopathy in Becker and Duchenne muscular dystrophy patients and carriers

    NARCIS (Netherlands)

    Schade van Westrum, Steven; Dekker, Lukas; de Haan, Rob; Endert, Erik; Ginjaar, Ieke; de Visser, Marianne; van der Kooi, Anneke

    2013-01-01

    Cardiomyopathy is reported in Duchenne and Becker muscle dystrophy patients and female carriers. Brain Natriuretic peptide (BNP) is a hormone produced mainly by ventricular cardiomyocytes and its production is up regulated in reaction to increased wall stretching. N-terminal-proBNP (NT-proBNP) has

  13. Systemic autoimmunity induced by the TLR7/8 agonist Resiquimod causes myocarditis and dilated cardiomyopathy in a new mouse model of autoimmune heart disease

    Directory of Open Access Journals (Sweden)

    Muneer G. Hasham

    2017-03-01

    Full Text Available Systemic autoimmune diseases such as systemic lupus erythematosus (SLE and rheumatoid arthritis (RA show significant heart involvement and cardiovascular morbidity, which can be due to systemically increased levels of inflammation or direct autoreactivity targeting cardiac tissue. Despite high clinical relevance, cardiac damage secondary to systemic autoimmunity lacks inducible rodent models. Here, we characterise immune-mediated cardiac tissue damage in a new model of SLE induced by topical application of the Toll-like receptor 7/8 (TLR7/8 agonist Resiquimod. We observe a cardiac phenotype reminiscent of autoimmune-mediated dilated cardiomyopathy, and identify auto-antibodies as major contributors to cardiac tissue damage. Resiquimod-induced heart disease is a highly relevant mouse model for mechanistic and therapeutic studies aiming to protect the heart during autoimmunity.

  14. Prediction of effect of {beta}-blocker therapy in patients with dilated cardiomyopathy by using {sup 123}I-BMIPP, {sup 123}I-MIBG scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Aritomo; Yamazaki, Junichi; Nanjou, Shuji; Togane, Yuko; Amano, Hideo [Toho Univ., Tokyo (Japan). School of Medicine

    2001-03-01

    We investigated prediction of the efficacy of {beta}-blocker therapy in patients with dilated cardiomyopathy (DCM) by using myocardial scintigraphy with {sup 123}I-BMIPP (BMIPP) and {sup 123}I-MIBG (MIBG). Thirty-seven patients with DCM were examined by myocardial scintigraphy with BMIPP and MIBG before {beta}-blocker therapy. Patients were classified into two groups, based on whether they improved >10% of the left ventricular ejection fraction (LVEF) (improved group, n=21) or not (unimproved group, n=16). The extent and severity score of BMIPP for the improved group was significantly lower (p<0.001) than that for unimproved group. It has been suggested that BMIPP is useful in evaluating the prediction of efficacy of {beta}-blocker therapy in patients with DCM. (author)

  15. Left Ventricular Dysfunction and Dilated Cardiomyopathy in Infants and Children with Wolff-Parkinson-White Syndrome in the Absence of Tachyarrhythmias

    Science.gov (United States)

    2012-01-01

    Left ventricular (LV) dysfunction and dilated cardiomyopathy (DCM) are rarely attributable to sustained or incessant tachyarrhythmias in infants and children with Wolff-Parkinson-White (WPW) syndrome. However, several recent reports suggested that significant LV dysfunction may develop in WPW syndrome in the absence of tachyarrhythmias. It is assumed that an asynchronous ventricular activation over the accessory pathway, especially right-sided, induces septal wall motion abnormalities, ventricular remodeling and ventricular dysfunction. The prognosis of DCM associated with asymptomatic WPW is excellent. Loss of ventricular pre-excitation results in mechanical resynchronization and reverse remodeling where LV function recovers completely. The reversible nature of LV dysfunction after loss of ventricular pre-excitation supports the causal relationship between LV dysfunction and ventricular pre-excitation. This review summarizes recent clinical and electrophysiological evidence for development of LV dysfunction or DCM in asymptomatic WPW syndrome, and discusses the underlying pathophysiological mechanism. PMID:23323117

  16. Echocardiographic assessment of right ventricular function in routine practice: Which parameters are useful to predict one-year outcome in advanced heart failure patients with dilated cardiomyopathy?

    Science.gov (United States)

    Kawata, Takayuki; Daimon, Masao; Kimura, Koichi; Nakao, Tomoko; Lee, Seitetsu L; Hirokawa, Megumi; Kato, Tomoko S; Watanabe, Masafumi; Yatomi, Yutaka; Komuro, Issei

    2017-10-01

    Right ventricular (RV) function has recently gained attention as a prognostic predictor of outcome even in patients who have left-sided heart failure. Since several conventional echocardiographic parameters of RV systolic function have been proposed, our aim was to determine if any of these parameters (tricuspid annular plane systolic excursion: TAPSE, tissue Doppler derived systolic tricuspid annular motion velocity: S', fractional area change: FAC) are associated with outcome in advanced heart failure patients with dilated cardiomyopathy (DCM). We retrospectively enrolled 68 DCM patients, who were New York Heart Association (NYHA) Class III or IV and had a left ventricular (LV) ejection fraction functional class IV, plasma brain natriuretic peptide concentration, intravenous inotrope use, left atrial volume index, and FAC were associated with outcome, whereas TAPSE and S' were not. Receiver-operating characteristic curve analysis showed that the optimal FAC cut-off value to identify patients with an event was rights reserved.

  17. Use of {sup 123}I-MIBG scintigraphy to assess the impact of carvedilol on cardiac adrenergic neuronal function in childhood dilated cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Maunoury, Christophe [Service de Medecine Nucleaire, Hopital Necker-Enfants Malades, 149 rue de Sevres, 75743, Paris Cedex 15 (France); Acar, Philippe; Sidi, Daniel [Service de Cardiologie Pediatrique, Hopital Necker-Enfants Malades, Paris (France)

    2003-12-01

    Iodine-123 metaiodobenzylguanidine (MIBG) cardiac scintigraphy is a useful tool for the assessment of cardiac adrenergic neuronal function, which is impaired in children with idiopathic dilated cardiomyopathy (DCM). In adults with DCM, long-term treatment with carvedilol improves both cardiac adrenergic neuronal function and left ventricular function. The aim of this prospective study was to evaluate the impact of carvedilol on cardiac adrenergic neuronal function using {sup 123}I-MIBG scintigraphy and on left ventricular function using equilibrium radionuclide angiography in children with DCM. Seventeen patients (11 female, six male; mean age 39{+-}57 months, range 1-168 months) with DCM and left ventricular dysfunction underwent {sup 123}I-MIBG cardiac scintigraphy and equilibrium radionuclide angiography before and after a 6-month period of carvedilol therapy. A static anterior view of the chest was acquired 4 h after intravenous injection of 20-75 MBq of {sup 123}I-MIBG. Cardiac neuronal uptake of {sup 123}I-MIBG was measured using the heart to mediastinum count ratio (HMR). Radionuclide left ventricular ejection fraction (LVEF) was assessed following a standard protocol. MIBG cardiac uptake and left ventricular function respectively increased by 38% and 65% after 6 months of treatment with carvedilol (HMR=223%{+-}49% vs 162%{+-}26%, P<0.0001, and LVEF=43%{+-}17% vs 26%{+-}11%, P<0.0001). Carvedilol can improve cardiac adrenergic neuronal and left ventricular function in children with dilated cardiomyopathy. Further studies are needed to assess the relationship between improvement in MIBG cardiac uptake and the beneficial effects of carvedilol on morbidity and mortality. (orig.)

  18. Use of 123I-MIBG scintigraphy to assess the impact of carvedilol on cardiac adrenergic neuronal function in childhood dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Maunoury, Christophe; Acar, Philippe; Sidi, Daniel

    2003-01-01

    Iodine-123 metaiodobenzylguanidine (MIBG) cardiac scintigraphy is a useful tool for the assessment of cardiac adrenergic neuronal function, which is impaired in children with idiopathic dilated cardiomyopathy (DCM). In adults with DCM, long-term treatment with carvedilol improves both cardiac adrenergic neuronal function and left ventricular function. The aim of this prospective study was to evaluate the impact of carvedilol on cardiac adrenergic neuronal function using 123 I-MIBG scintigraphy and on left ventricular function using equilibrium radionuclide angiography in children with DCM. Seventeen patients (11 female, six male; mean age 39±57 months, range 1-168 months) with DCM and left ventricular dysfunction underwent 123 I-MIBG cardiac scintigraphy and equilibrium radionuclide angiography before and after a 6-month period of carvedilol therapy. A static anterior view of the chest was acquired 4 h after intravenous injection of 20-75 MBq of 123 I-MIBG. Cardiac neuronal uptake of 123 I-MIBG was measured using the heart to mediastinum count ratio (HMR). Radionuclide left ventricular ejection fraction (LVEF) was assessed following a standard protocol. MIBG cardiac uptake and left ventricular function respectively increased by 38% and 65% after 6 months of treatment with carvedilol (HMR=223%±49% vs 162%±26%, P<0.0001, and LVEF=43%±17% vs 26%±11%, P<0.0001). Carvedilol can improve cardiac adrenergic neuronal and left ventricular function in children with dilated cardiomyopathy. Further studies are needed to assess the relationship between improvement in MIBG cardiac uptake and the beneficial effects of carvedilol on morbidity and mortality. (orig.)

  19. Prediction of cardiac sympathetic nerve activity and cardiac functional outcome after treatment in patients with dilated cardiomyopathy. Examination using dobutamine gated blood pool scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Kasama, Shu; Toyama, Takuji; Iwasaki, Tsutomu; Suzuki, Tadashi [Gunma Univ., Maebashi (Japan). School of Medicine; Hoshizaki, Hiroshi; Oshima, Shigeru; Taniguchi, Koichi; Nagai, Ryozo

    2000-07-01

    This study evaluated whether dobutamine gated blood pool scintigraphy can predict improvement of cardiac sympathetic nerve activity and cardiac function. Sixteen patients (10 men and 6 women, mean age 59{+-}13 years) with dilated cardiomyopathy underwent dobutamine gated blood pool scintigraphy to measure left ventricular ejection fraction (LVEF) using tracer at 0, 5, 10 and 15 {mu}g/kg/min before treatment. Patients were divided into good responders (LVEF increase {>=}15%) 8 patients (GR Group) and poor responders (LVEF increase <15%) 8 patients (PR Group) after treatment with {beta}-blocker or amiodarone with a background treatment of digitalis, diuretics and angiotensin converting enzyme inhibitor. I-123 metaiodobenzylguanidine (MIBG) imaging to evaluate cardiac sympathetic nerve activity and echocardiography were performed before and at one year after treatment. MIBG imaging was obtained 4 hours after tracer injection, and the heart/mediastinum count ratio (H/M ratio) calculated from the anterior planar image and the total defect score (TDS) from the single photon emission computed tomography image. LVEF and left ventricular endo-diastolic dimension (LVDd) were measured by echocardiography and New York Heart Association (NYHA) functional class was evaluated. The GR Group showed TDS decreased from 28{+-}6 to 17{+-}12 (p<0.05), H/M ratio increased from 1.79{+-}0.26 to 2.07{+-}0.32 (p<0.05), LVEF increased from 29{+-}8% to 48{+-}10% (p<0.01), and LVDd decreased from 65{+-}4 mm to 58{+-}5 mm (p<0.05). In contrast, the PR group showed no significant changes in TDS. H/M ratio, LVEF and LVDd. NYHA functional class improved in both groups. The improvement was better in the GR Group than in the PR group. Dobutamine gated blood pool scintigraphy is useful to predict the improvement of the cardiac sympathetic nerve activity and cardiac function, and symptoms after treatment in patients with dilated cardiomyopathy. (author)

  20. Parent reports of health-related quality of life and heart failure severity score independently predict outcome in children with dilated cardiomyopathy.

    Science.gov (United States)

    den Boer, Susanna L; Baart, Sara J; van der Meulen, Marijke H; van Iperen, Gabriëlle G; Backx, Ad P; Ten Harkel, Arend D; Rammeloo, Lukas A; du Marchie Sarvaas, Gideon J; Tanke, Ronald B; Helbing, Willem A; Utens, Elisabeth M; Dalinghaus, Michiel

    2017-08-01

    Dilated cardiomyopathy in children causes heart failure and has a poor prognosis. Health-related quality of life in this patient group is unknown. Moreover, results may provide detailed information of parents' sense of their child's functioning. We hypothesised that health-related quality of life, as rated by parents, and the paediatric heart failure score, as assessed by physicians, have both predictive value on outcome. Methods and results In this prospective study, health-related quality of life was assessed by parent reports: the Infant Toddler Quality of Life questionnaire (0-4 years) or Child Health Questionnaire-Parent Form 50 (4-18 years) at 3-6-month intervals. We included 90 children (median age 3.8 years, interquartile range (IQR) 0.9-12.3) whose parents completed 515 questionnaires. At the same visit, physicians completed the New York University Pediatric Heart Failure Index. Compared with Dutch normative data, quality of life was severely impaired at diagnosis (0-4 years: 7/10 subscales and 4-18 years: 8/11 subscales) and ⩾1 year after diagnosis (3/10 and 6/11 subscales). Older children were more impaired (pFailure Index were independently predictive of the risk of death and heart transplantation (hazard ratio 1.24 per 10% decrease of predicted, 95% confidence interval (CI) 1.06-1.47 and hazard ratio 1.38 per unit, 95% CI 1.19-1.61, respectively). Physical impairment rated by parents and heart failure severity assessed by physicians independently predicted the risk of death or heart transplantation in children with dilated cardiomyopathy.

  1. Mena/VASP and αII-Spectrin complexes regulate cytoplasmic actin networks in cardiomyocytes and protect from conduction abnormalities and dilated cardiomyopathy.

    Science.gov (United States)

    Benz, Peter M; Merkel, Carla J; Offner, Kristin; Abeßer, Marco; Ullrich, Melanie; Fischer, Tobias; Bayer, Barbara; Wagner, Helga; Gambaryan, Stepan; Ursitti, Jeanine A; Adham, Ibrahim M; Linke, Wolfgang A; Feller, Stephan M; Fleming, Ingrid; Renné, Thomas; Frantz, Stefan; Unger, Andreas; Schuh, Kai

    2013-08-12

    In the heart, cytoplasmic actin networks are thought to have important roles in mechanical support, myofibrillogenesis, and ion channel function. However, subcellular localization of cytoplasmic actin isoforms and proteins involved in the modulation of the cytoplasmic actin networks are elusive. Mena and VASP are important regulators of actin dynamics. Due to the lethal phenotype of mice with combined deficiency in Mena and VASP, however, distinct cardiac roles of the proteins remain speculative. In the present study, we analyzed the physiological functions of Mena and VASP in the heart and also investigated the role of the proteins in the organization of cytoplasmic actin networks. We generated a mouse model, which simultaneously lacks Mena and VASP in the heart. Mena/VASP double-deficiency induced dilated cardiomyopathy and conduction abnormalities. In wild-type mice, Mena and VASP specifically interacted with a distinct αII-Spectrin splice variant (SH3i), which is in cardiomyocytes exclusively localized at Z- and intercalated discs. At Z- and intercalated discs, Mena and β-actin localized to the edges of the sarcomeres, where the thin filaments are anchored. In Mena/VASP double-deficient mice, β-actin networks were disrupted and the integrity of Z- and intercalated discs was markedly impaired. Together, our data suggest that Mena, VASP, and αII-Spectrin assemble cardiac multi-protein complexes, which regulate cytoplasmic actin networks. Conversely, Mena/VASP deficiency results in disrupted β-actin assembly, Z- and intercalated disc malformation, and induces dilated cardiomyopathy and conduction abnormalities.

  2. Embryonic Stem Cell Therapy of Heart Failure in Genetic Cardiomyopathy

    OpenAIRE

    Yamada, Satsuki; Nelson, Timothy J.; Crespo-Diaz, Ruben J.; Perez-Terzic, Carmen; Liu, Xiao-Ke; Miki, Takashi; Seino, Susumu; Behfar, Atta; Terzic, Andre

    2008-01-01

    Pathogenic causes underlying nonischemic cardiomyopathies are increasingly being resolved, yet repair therapies for these commonly heritable forms of heart failure are lacking. A case in point is human dilated cardiomyopathy 10 (CMD10; Online Mendelian Inheritance in Man #608569), a progressive organ dysfunction syndrome refractory to conventional therapies and linked to mutations in cardiac ATP-sensitive K+ (KATP) channel sub-units. Embryonic stem cell therapy demonstrates benefit in ischemi...

  3. CLINICAL AND MORPHOLOGICAL APPROACH TO DIAGNOSIS OF "IDIOPATHIC" ARRHYTHMIAS AND DILATED CARDIOMYOPATHY SYNDROME AS A BASIS FOR DIFFERENTIATED THERAPY. Part II (Treatment

    Directory of Open Access Journals (Sweden)

    O. V. Blagova

    2014-01-01

    Full Text Available Part I (Diagnostics, was published in the journal “Rational Pharmacotherapy in Cardiology” 2014;10(1:62-72Aim. To develop a comprehensive clinical and morphological approach to the nosological diagnosis and treatment of "idiopathic" arrhythmias (IA and the syndrome of dilated cardiomyopathy (DCM.Material and methods. Patients (n=320 with IA (n=190; 117 women, age 45.3±14.8 years and DCM (n=130, 41 women, age 46.9±12.5 years were included in the main group. 51 people (patients with ischemic heart disease; heart valve disease, hypertrophic cardiomyopathy, who underwent open-heart surgery; healthy volunteers were included in the control group. Along with the standard tests evaluation of the level of anti-heart antibodies (185 patients with IA and 122 with DCM, viral serology (166 and 122, multispiral computed tomography (42 and 88, cardiac magnetic resonance imaging (41 and 22, coronary angiography (19 and 54, myocardial biopsy/autopsy (19/0 and 33/9 were performed.Results. According to morphological study infectious-immune myocarditis was found in 78.9% patients with IA and 66.7% patients with DCM, arrhythmogenic right ventricular dysplasia in 5.3% and 4.8% of patients, respectively. Other genetic cardiomyopathies, including combination with myocarditis were revealed in other patients. The frequency of the viral genome detection in the myocardium in IA, DCM and the control group was 17.6%, 66.7% and 77.1%, respectively. However in the control group the incidence of myocarditis and anti-heart antibodies titers were significantly lower than in the main group, where a strong correlation between myocarditis and anti-heart antibodies titers was found. The algorithm of noninvasive nosological diagnostics was developed; it allowed to verify diagnosis in 95% of IA patients and 89% DCM patientsThe basic therapy (antiviral drugs, corticosteroids, hydroxychloroquine, azathioprine was performed in some patients with myocarditis. Improving of the

  4. CLINICAL AND MORPHOLOGICAL APPROACH TO DIAGNOSIS OF "IDIOPATHIC" ARRHYTHMIAS AND DILATED CARDIOMYOPATHY SYNDROME AS A BASIS FOR DIFFERENTIATED THERAPY. Part II (Treatment

    Directory of Open Access Journals (Sweden)

    O. V. Blagova

    2015-09-01

    Full Text Available Part I (Diagnostics, was published in the journal “Rational Pharmacotherapy in Cardiology” 2014;10(1:62-72Aim. To develop a comprehensive clinical and morphological approach to the nosological diagnosis and treatment of "idiopathic" arrhythmias (IA and the syndrome of dilated cardiomyopathy (DCM.Material and methods. Patients (n=320 with IA (n=190; 117 women, age 45.3±14.8 years and DCM (n=130, 41 women, age 46.9±12.5 years were included in the main group. 51 people (patients with ischemic heart disease; heart valve disease, hypertrophic cardiomyopathy, who underwent open-heart surgery; healthy volunteers were included in the control group. Along with the standard tests evaluation of the level of anti-heart antibodies (185 patients with IA and 122 with DCM, viral serology (166 and 122, multispiral computed tomography (42 and 88, cardiac magnetic resonance imaging (41 and 22, coronary angiography (19 and 54, myocardial biopsy/autopsy (19/0 and 33/9 were performed.Results. According to morphological study infectious-immune myocarditis was found in 78.9% patients with IA and 66.7% patients with DCM, arrhythmogenic right ventricular dysplasia in 5.3% and 4.8% of patients, respectively. Other genetic cardiomyopathies, including combination with myocarditis were revealed in other patients. The frequency of the viral genome detection in the myocardium in IA, DCM and the control group was 17.6%, 66.7% and 77.1%, respectively. However in the control group the incidence of myocarditis and anti-heart antibodies titers were significantly lower than in the main group, where a strong correlation between myocarditis and anti-heart antibodies titers was found. The algorithm of noninvasive nosological diagnostics was developed; it allowed to verify diagnosis in 95% of IA patients and 89% DCM patientsThe basic therapy (antiviral drugs, corticosteroids, hydroxychloroquine, azathioprine was performed in some patients with myocarditis. Improving of the

  5. Relation between myocardial response to dobutamine stress and sympathetic nerve activation in patients with idiopathic dilated cardiomyopathy. A comparison of 123I-MIBG scintigraphic and echocardiographic data

    International Nuclear Information System (INIS)

    Naruse, Hitoshi; Arii, Tohru; Kondo, Tomohiro

    2000-01-01

    It is likely that a close association exists between findings obtained by two methods: dobutamine stress echocardiography and 123 I-MIBG scintigraphy. Both of these methods are associated with β-adrenergic receptor mechanisms. This study was conducted to demonstrate the relation between myocardial response to dobutamine stress and sympathetic nerve release of norepinephrine in the failing heart. In 12 patents with heart failure due to idiopathic dilated cardiomyopathy, the myocardial effects of dobutamine stress were evaluated by low-dose dobutamine stress echocardiography; and sympathetic nerve function was evaluated by scintigraphic imaging with iodine-123[ 123 I]meta-iodobenzylguanidine (MIBG), an analogue of norepinephrine. Echocardiography provided quantitative assessment of wall motion and left ventricular dilation; radiotracer studies with 123 I-MIBG provided quantitative assessment of the heart-to-mediastinum (H/M) uptake ratio and washout rate. Results showed that H/M correlated with baseline wall motion (r=0.682, p=0.0146), wall motion after dobutamine stress (r=0.758, p=0.0043), the change in wall motion (r=0.667, p=0.0178), and with left ventricular diastolic diameter (r=0.837, p=0.0007). In addition, the 123 I-MIBG washout rate correlated with baseline wall motion (r=0.608, p=0.0360), wall motion after dobutamine stress (r=0.703, p=0.0107), and with the change in wall motion (r=0.664, p=0.0185). Wall motion, especially in the myocardial response to dobutamine stress, is related to sympathetic nerve activity in heart failure. (author)

  6. O uso da L-carnitina como adjuvante no tratamento da miocardiopatia dilatada em criança com Aids Usage of L-carnitine as adjuvant in the treatment of dilated cardiomyopathy in a child with Aids

    Directory of Open Access Journals (Sweden)

    Lourdes Zélia Zanoni

    2011-06-01

    Full Text Available OBJETIVO: Apresentar a resposta cardiovascular à L-carnitina de um paciente com insuficiência cardíaca congestiva decorrente de miocardiopatia dilatada pelo vírus da imunodeficiência humana. DESCRIÇÃO DO CASO: Criança com quadro clínico de insuficiência cardíaca congestiva grave devido à miocardiopatia dilatada pela síndrome de imunodeficiência adquirida. O tratamento para as manifestações clínicas foi instituído, com pouca resposta clínica. Com objetivo de melhorar o desempenho energético/metabólico dos cardiomiócitos, foi instituída terapia com L-carnitina. Observou-se significativa melhora clínica do paciente, em relação ao desempenho cardíaco, mesmo antes do início do tratamento com os fármacos antirretrovirais. COMENTÁRIOS: A L-carnitina é um composto que facilita o transporte dos ácidos graxos de cadeia longa para dentro da mitocôndria. Nesse caso, o uso da L-carnitina parece ser clinica e bioquimicamente justificado.OBJECTIVE: To present the cardiovascular response to L-carnitine of a patient with congestive heart failure caused by dilated cardiomyopathy and human immunodeficiency virus. CASE DESCRIPTION: Child with a clinical history of severe congestive heart failure due to dilated cardiomyopathy caused by acquired immunodeficiency syndrome. The treatment for the symptoms resulted in a poor clinical response. In order to improve the energetic performance/metabolism of cardiomyocytes, therapy with L-carnitine was established. There was significant clinical improvement of the cardiac performance of the patient, even before starting the treatment with antiretroviral drugs. COMMENTS: L-carnitine is a compound that facilitates the transport of long-chain fatty acids into the mitochondria. In this case the administration of L-carnitine appears to be clinically and biochemical justified.

  7. Early-progressive dilated cardiomyopathy in a family with Becker muscular dystrophy related to a novel frameshift mutation in the dystrophin gene exon 27.

    Science.gov (United States)

    Tsuda, Takeshi; Fitzgerald, Kristi; Scavena, Mena; Gidding, Samuel; Cox, Mary O; Marks, Harold; Flanigan, Kevin M; Moore, Steven A

    2015-03-01

    We report a family in which two male siblings with Becker muscular dystrophy (BMD) developed severe dilated cardiomyopathy (DCM) and progressive heart failure (HF) at age 11 years; one died at age 14 years while awaiting heart transplant and the other underwent left ventricular assist device implantation at the same age. Genetic analysis of one sibling showed a novel frameshift mutation in exon 27 of Duchenne muscular dystrophy (DMD) gene (c.3779_3785delCTTTGGAinsGG), in which seven base pairs are deleted and two are inserted. Although this predicts an amino-acid substitution and premature termination (p.Thr1260Argfs*8), muscle biopsy dystrophin immunostaining instead indicates that the mutation is more likely to alter splicing. Despite relatively preserved skeletal muscular performance, both the siblings developed progressive HF secondary to early-onset DCM. In addition, their 7-year-old nephew with delayed gross motor development, mild proximal muscle weakness and markedly elevated serum creatine kinase level (>13 000 IU l(-1)) at 16 months was recently demonstrated to have the familial DMD mutation. Here, we report a novel genotype of BMD with early-onset DCM and progressive lethal HF during early adolescence.

  8. The prognostic value of right ventricular long axis strain in non-ischaemic dilated cardiomyopathies using standard cardiac magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Arenja, Nisha [University of Heidelberg, Department of Cardiology, Angiology and Pneumology, Heidelberg (Germany); Kantonsspital Olten, Department of Cardiology, Solothurner Spitaeler AG, Olten (Switzerland); Riffel, Johannes H.; Halder, Manuel; Djiokou, Charly N.; Fritz, Thomas; Andre, Florian; Siepen, Fabian aus dem; Zelniker, Thomas; Meder, Benjamin; Kayvanpour, Elham; Korosoglou, Grigorios [University of Heidelberg, Department of Cardiology, Angiology and Pneumology, Heidelberg (Germany); Katus, Hugo A. [University of Heidelberg, Department of Cardiology, Angiology and Pneumology, Heidelberg (Germany); DZHK (German Centre for Cardiovascular Research), partner site Heidelberg, Heidelberg (Germany); Buss, Sebastian J. [University of Heidelberg, Department of Cardiology, Angiology and Pneumology, Heidelberg (Germany); Das Radiologische Zentrum - Radiology Center, Sinsheim-Eberbach-Erbach-Walldorf-Heidelberg (Germany)

    2017-09-15

    To investigate the association of right ventricular long axis strain (RV-LAS), a parameter of longitudinal function, with outcome in patients with non-ischaemic dilated cardiomyopathy (NIDCM). In 441 patients with NIDCM, RV-LAS was analysed retrospectively by measuring the length between the epicardial border of the left ventricular apex and the middle of a line connecting the origins of the tricuspidal valve leaflets in end-diastole and end-systole on non-contrast standard cine sequences. The primary endpoint (cardiac death or heart transplantation) occurred in 41 patients, whereas 95 reached the combined endpoint (including cardiac decompensation and sustained ventricular arrhythmias) during a median follow-up of 4.2 years. Kaplan-Meier survival curves showed a poor outcome in patients with RV-LAS values below -10% (log-rank, p < 0.0001). In a risk stratification model RV-LAS improved prediction of outcome in addition to RV ejection fraction (RVEF) and presence of late gadolinium enhancement. Assessment of RV-LAS offered incremental information compared to clinical symptoms, biomarkers and RVEF. Even in the subgroup with normal RVEF (>45%, n = 213) reduced RV-LAS was still associated with poor outcome. Assessment of RV-LAS is an independent indicator of outcome in patients with NIDCM and offers incremental information beyond clinical and cardiac MR parameters. (orig.)

  9. Effects of carvedilol in heart failure due to dilated cardiomyopathy. Results of a double-blind randomized placebo-controlled study (CARIBE study

    Directory of Open Access Journals (Sweden)

    Paulo Roberto Chizzola

    2000-03-01

    Full Text Available OBJECTIVE: To assess the effects of carvedilol in patients with idiopathic dilated cardiomyopathy. METHODS: In a double-blind randomized placebo-controlled study, 30 patients (7 women with functional class II and III heart failure were assessed. Their ages ranged from 28 to 66 years (mean of 43±9 years, and their left ventricular ejection fraction varied from 8% to 35%. Carvedilol was added to the usual therapy of 20 patients; placebo was added to the usual therapy of 10 patients. The initial dose of carvedilol was 12.5 mg, which was increased weekly until it reached 75 mg/day, according to the patient's tolerance. Clinical assessment, electrocardiogram, echocardiogram, and radionuclide ventriculography were performed in the pretreatment phase, being repeated after 2 and 6 months of medication use. RESULTS: A reduction in heart rate (p=0.016 as well as an increase in left ventricular shortening fraction (p=0.02 and in left ventricular ejection fraction (p=0.017 occurred in the group using carvedilol as compared with that using placebo. CONCLUSION: Carvedilol added to the usual therapy for heart failure resulted in better heart function.

  10. Oxaliplatin-induced acquired long QT syndrome with torsades de pointes and myocardial injury in a patient with dilated cardiomyopathy and rectal cancer

    Directory of Open Access Journals (Sweden)

    Rei-Yeuh Chang

    2013-08-01

    Full Text Available A 67-year-old woman presented with a history of dilated cardiomyopathy with congestive heart failure since 2003, who subsequently developed lower rectal cancer (adenocarcinoma with liver, bone, and lymph node metastasis. Abdominoperineal resection and hepatectomy were performed. The patient received two rounds of intravenous chemotherapy, including 12 and six courses of FOLFOX4 (5-fluorouracil, leucovorin, and oxaliplatin; 85 mg/m2 per cycle. She underwent a third round of intravenous FOLFOX4 because of tumor progression. During the 21st course of FOLFOX4 regimen, the patient developed ST segment depression in lead II and prolongation of QT interval with polymorphic ventricular tachycardia, torsades de pointes right after the start of oxaliplatin infusion. Immediate defibrillation and cardiopulmonary resuscitation were administered, and the patient regained spontaneous circulation and consciousness. Twelve-lead electrocardiogram showed ST segment elevation in III, aVF, and ST segment depression in V4–6 after resuscitation. To our knowledge, prolongation of QT interval with torsades de pointes and coronary spasm with myocardial injury that were stabilized in one patient following oxaliplatin infusion has not been reported. We present a patient with these rare complications.

  11. Use of iodine-123 metaiodobenzylguanidine myocardial imaging to predict the effectiveness of {beta}-blocker therapy in patients with dilated cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Fukuoka, Shuji [Department of Radiology, National Cardiovascular Center, Osaka (Japan); Hayashida, Kohei [Department of Radiology, National Cardiovascular Center, Osaka (Japan); Hirose, Yoshiaki [Department of Radiology, National Cardiovascular Center, Osaka (Japan); Shimotsu, Yoriko [Department of Radiology, National Cardiovascular Center, Osaka (Japan); Ishida, Yoshio [Department of Radiology, National Cardiovascular Center, Osaka (Japan); Kakuchi, Hiroyuki [Department of Internal Medicine, National Cardiovascular Center, Osaka (Japan); Eto, Tanenao [First Department of Internal Medicine, Miyazaki Medical College, Miyazaki (Japan)

    1997-05-01

    We studied 13 patients with dilated cardiomyopathy (DCM) and seven normal subjects. We obtained myocardial SPET images 15 min and 4 h after administration of {sup 123}I-MIBG (111 MBq). Studies were performed in the patients with DCM before and 1 and 3 months after the administration of metoprolol and in the normal subjects. We calculated the regional {sup 123}I-MIBG washout rate (r-WR) in the SPET image, and the global {sup 123}I-MIBG washout rate (g-WR) and heart-mediastinum activity ratio (H/M) using the anterior planar image. We classified patients into those showing a {>=}5% increase in LV ejection fraction (LVEF) at 3 months compared with LVEF values before the treatment (group I, n=7) and those showing a <5% increase in LVEF (group II, n=6). In normal subjects, the r-WR values in each of the anterior, lateral, septal and inferior segments were significantly lower than those in groups I and II. These values were 18%{+-}9%, 18%{+-}15%, 20%{+-}12% and 21%{+-}15%, respectively. This study demonstrated that with regional assessment {sup 123}I-MIBG SPET imaging can be used to predict the functional improvement of LVEF at 1 month of {beta}-blocker therapy in patients with DCM. (orig./VHE). With 4 figs., 1 tab.

  12. Use of iodine-123 metaiodobenzylguanidine myocardial imaging to predict the effectiveness of β-blocker therapy in patients with dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Fukuoka, Shuji; Hayashida, Kohei; Hirose, Yoshiaki; Shimotsu, Yoriko; Ishida, Yoshio; Kakuchi, Hiroyuki; Eto, Tanenao

    1997-01-01

    We studied 13 patients with dilated cardiomyopathy (DCM) and seven normal subjects. We obtained myocardial SPET images 15 min and 4 h after administration of 123 I-MIBG (111 MBq). Studies were performed in the patients with DCM before and 1 and 3 months after the administration of metoprolol and in the normal subjects. We calculated the regional 123 I-MIBG washout rate (r-WR) in the SPET image, and the global 123 I-MIBG washout rate (g-WR) and heart-mediastinum activity ratio (H/M) using the anterior planar image. We classified patients into those showing a ≥5% increase in LV ejection fraction (LVEF) at 3 months compared with LVEF values before the treatment (group I, n=7) and those showing a 123 I-MIBG SPET imaging can be used to predict the functional improvement of LVEF at 1 month of β-blocker therapy in patients with DCM. (orig./VHE). With 4 figs., 1 tab

  13. Immunohistochemical evidence for expression of fast-twitch type sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA1) in German shepherd dogs with dilated cardiomyopathy myocardium.

    Science.gov (United States)

    Summerfield, Nuala; Peters, Mary E; Hercock, Carol A; Mobasheri, Ali; Young, Iain S

    2010-04-01

    Dilated cardiomyopathy (DCM) is one of the most common acquired canine heart diseases. It is particularly common in large and giant breed dogs. Although a great deal is known about the clinical progression and manifestations of the disease, the underlying cellular and molecular mechanisms remain poorly understood. One widely held belief is that calcium-handling abnormalities are critically involved in the disease process. This study investigates the changes in expression of the sarco(endo)plasmic reticulum calcium ATPase (SERCA) isoforms in DCM myocardium from German shepherd dogs. Affected tissue samples were obtained from German shepherd dogs with DCM, euthanized for intractable congestive heart failure while normal myocardial tissue samples were obtained from German shepherd dogs, euthanized for non-cardiovascular reasons. Tissue microarrays containing normal and DCM myocardium samples were prepared, immunostained with SERCA1 and SERCA2 antibodies and analyzed. We were able to demonstrate, for the first time, that while there is little change in the expression of the cardiac isoform (SERCA2), there is clear expression of the fast-twitch skeletal muscle isoform SERCA1 in the myocardium of dogs diagnosed with DCM. We propose that SERCA1 expression is evidence of a natural adaptive response to the impaired Ca2+ handling thought to occur in German shepherd dogs with DCM and heart failure. Copyright 2010 Elsevier B.V. All rights reserved.

  14. The Prognostic Value of Late Gadolinium-Enhanced Cardiac Magnetic Resonance Imaging in Nonischemic Dilated Cardiomyopathy: A Review and Meta-Analysis.

    Science.gov (United States)

    Becker, Marthe A J; Cornel, Jan H; van de Ven, Peter M; van Rossum, Albert C; Allaart, Cornelis P; Germans, Tjeerd

    2018-04-13

    This review and meta-analysis reviews the prognostic value of cardiac magnetic resonance (CMR) in nonischemic dilated cardiomyopathy (DCM). Late gadolinium-enhanced (LGE) CMR is a noninvasive method to determine the underlying cause of DCM and previous studies reported the prognostic value of the presence of LGE to identify patients at risk of major adverse cardiovascular events. PubMed was searched for studies describing the prognostic implication of LGE in patients with DCM for the specified endpoints cardiovascular mortality, major ventricular arrhythmic events including appropriate implantable cardioverter-defibrillator therapy, rehospitalization for heart failure, and left ventricular reverse remodeling. Data from 34 studies were included, with a total of 4,554 patients. Contrast enhancement was present in 44.8% of DCM patients. Patients with LGE had increased cardiovascular mortality (odds ratio [OR]: 3.40; 95% confidence interval [CI]: 2.04 to 5.67), ventricular arrhythmic events (OR: 4.52; 95% CI: 3.41 to 5.99), and rehospitalization for heart failure (OR: 2.66; 95% CI: 1.67 to 4.24) compared with those without LGE. Moreover, the absence of LGE predicted left ventricular reverse remodeling (OR: 0.15; 95% CI: 0.06 to 0.36). The presence of LGE on CMR substantially worsens prognosis for adverse cardiovascular events in DCM patients, and the absence indicates left ventricular reverse remodeling. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  15. Left ventricular responses to dopamine in dilated cardiomyopathy as assessed by two-dimensional echocardiography and compared with findings of thallium-201 scintigraphy

    International Nuclear Information System (INIS)

    Oda, Hirotaka

    1987-01-01

    The effects of dopamine on the left ventricular regional wall motion were studied in 11 patients with dilated cardiomyopathy by use of two-dimentional echocardiography and compared with the findings on the uptake of thallium-201. There were no significant changes in heart rate after dopamine infusion (6 μg/kg/min). However, the administration of dopamine significantly reduced PEP/ET and increased the systolic blood pressure, fractional shortening, ejection fraction and mV cf. The percentage of segments with reduced thallium-uptake area was significantly higher in abnormal wall motion segments than in normal wall segments both before and after dopamine administration. The percentage of segments with reduced thallium-uptake area was significantly higher in abnormal wall motion segments after loading than in normal wall segments before loading or in dopamine responding segments. However, in reduced uptake area, the asynergy of the left ventricle was improved significantly after dopamine administration. These results demonstrated that the abnormality of Tl-uptake was correlated roughly to the asynergy of the left ventricle, but that the state of remaining myocardium was not necessarily evaluated correctly by Tl-uptake. Dopamine loading seemed to be useful for more accurate evaluation of myocardial residual function. (author)

  16. Contrast-enhanced T1 mapping-based extracellular volume fraction independently predicts clinical outcome in patients with non-ischemic dilated cardiomyopathy: a prospective cohort study

    Energy Technology Data Exchange (ETDEWEB)

    Youn, Jong-Chan [Hallym University College of Medicine, Division of Cardiology, Dongtan Sacred Heart Hospital, Hwaseong (Korea, Republic of); Yonsei University College of Medicine, Division of Cardiology, Severance Cardiovascular Hospital, Seoul (Korea, Republic of); Hong, Yoo Jin; Lee, Hye-Jeong; Han, Kyunghwa; Suh, Young Joo; Hur, Jin; Kim, Young Jin; Choi, Byoung Wook [Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Seoul (Korea, Republic of); Shim, Chi Young; Hong, Geu-Ru; Kang, Seok-Min [Yonsei University College of Medicine, Division of Cardiology, Severance Cardiovascular Hospital, Seoul (Korea, Republic of)

    2017-09-15

    We aimed to evaluate the prognostic role of cardiac magnetic resonance imaging (CMR)-based extracellular volume fraction (ECV) in patients with non-ischemic dilated cardiomyopathy (NIDCM) and compare it with late gadolinium enhancement (LGE) parameters. This was a single-center, prospective, cohort study of 117 NIDCM patients (71 men, 51.9 ± 16.7 years) who underwent clinical 3.0-T CMR. Myocardial ECV and LGE were quantified on the left ventricular myocardium. The presence of midwall LGE was also detected. Nineteen healthy subjects served as controls. The primary end points were cardiovascular (CV) events defined by CV death, rehospitalization due to heart failure, and heart transplantation. During the follow-up period (median duration, 11.2 months; 25{sup th}-75{sup th} percentile, 7.8-21.9 months), the primary end points occurred in 19 patients (16.2%). The ECV (per 3% and 1% increase) was associated with a hazard ratio of 1.80 and 1.22 (95% confidence interval [CI], 1.48-2.20 and 1.14-1.30, respectively; p < 0.001) for the CV events. Multivariable analysis also indicated that ECV was an independent prognostic factor and had a higher prognostic value (Harrell's c statistic, 0.88) than LGE quantification values (0.77) or midwall LGE (0.80). CMR-based ECV independently predicts the clinical outcome in NIDCM patients. (orig.)

  17. Prognostic value of repeated {sup 123}I-metaiodobenzylguanidine imaging in patients with dilated cardiomyopathy with congestive heart failure before and after optimized treatments. Comparison with neurohumoral factors

    Energy Technology Data Exchange (ETDEWEB)

    Matsui, Toshiki; Tsutamoto, Takayoshi; Maeda, Keiko; Kusukawa, Junya; Kinoshita, Masahiko [Shiga Univ. of Medical Science, Otsu (Japan)

    2002-06-01

    The present study was undertaken to assess whether repeated measurement of cardiac {sup 123}I-metaiodobenzylguanidine (MIBG) imaging parameters before and after optimized treatments is useful for predicting the prognosis of patients with congestive heart failure (CHF) resulting from dilated cardiomyopathy (DCM). The subjects were 85 consecutive patients with DCM who had a left ventricular ejection fraction (LVEF) of less than 45%. The MIBG and the concentrations of neurohumoral factors were measured at baseline and after 6 months of optimized treatments. Cox proportional hazards analysis was performed to assess the various parameters before and after treatment. Twenty-three patients had a cardiac event (12 died; 11 hospitalized) during a mean follow-up period of 2 years. Although there was no difference between the baseline heart to mediastinum (H/M) ratio measured by MIBG between survivors and nonsurvivors, the H/M ratio was significantly decreased in nonsurvivors after 6 months. Multivariate analysis revealed that a high plasma concentration of brain natriuretic peptide level after 6 months (p=0.0049) and absolute changes in the H/M ratio (p=0.0046) were independent predictors of mortality. Comparison of the H/M ratio on MIBG imaging before and after optimized additional treatment provided useful information for predicting mortality and was independent of clinical and neurohumoral factors previously shown to be associated with poor prognosis in patients with DCM. (author)

  18. MR imaging in cardiomyopathies

    International Nuclear Information System (INIS)

    Miller, S.; Riessen, R.

    2005-01-01

    According to the WHO classification, cardiomyopathies are a group of diseases which are associated with myocardial dysfunction and can be classified either as primary or secondary cardiomyopathies. Genetic disorders have been identified in certain primary cardiomyopathies, however often the etiology remains unknown. The term ''secondary cardiomyopathy'' is used to specify diseases with the clinical indications of a cardiomyopathy, but can be attributed to a certain pathophysiological mechanism such as exposure to toxic substances, metabolic syndromes or systemic diseases. Based on morphological and functional criteria, primary cardiomyopathies are divided into dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular cardiomyopathy (ARVC) and restrictive cardiomyopathy (RCM). During the last two decades MR imaging has emerged to a well established diagnostic tool for the understanding and treatment of cardiomyopathies. Morphological and functional information can be achieved with a high level of accuracy and reproducibility. Tissue alteration of the myocardium can be detected assessing regional contrast enhancement, T1- and T2-signal intensities and chemical shift phenomena. This article describes characteristic aspects of MR imaging for the diagnosis of primary and secondary cardiomyopathies. (orig.)

  19. The LMNA mutation p.Arg321Ter associated with dilated cardiomyopathy leads to reduced expression and a skewed ratio of lamin A and lamin C proteins

    Energy Technology Data Exchange (ETDEWEB)

    Al-Saaidi, Rasha [Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Aarhus (Denmark); Rasmussen, Torsten B. [Department of Cardiology, Aarhus University Hospital, Aarhus (Denmark); Palmfeldt, Johan [Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Aarhus (Denmark); Nissen, Peter H. [Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus (Denmark); Beqqali, Abdelaziz [Heart Failure Research Center, Academic Medical Center, Amsterdam (Netherlands); Hansen, Jakob [Department of Forensic Medicine, Bioanalytical Unit, University of Aarhus (Denmark); Pinto, Yigal M. [Heart Failure Research Center, Academic Medical Center, Amsterdam (Netherlands); Boesen, Thomas [Department of Molecular Biology and Genetics, University of Aarhus (Denmark); Mogensen, Jens [Department of Cardiology, Odense University Hospital, Odense (Denmark); Bross, Peter, E-mail: peter.bross@ki.au.dk [Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Aarhus (Denmark)

    2013-11-15

    Dilated cardiomyopathy (DCM) is a disease of the heart muscle characterized by cardiac chamber enlargement and reduced systolic function of the left ventricle. Mutations in the LMNA gene represent the most frequent known genetic cause of DCM associated with disease of the conduction systems. The LMNA gene generates two major transcripts encoding the nuclear lamina major components lamin A and lamin C by alternative splicing. Both haploinsuffiency and dominant negative effects have been proposed as disease mechanism for premature termination codon (PTC) mutations in LMNA. These mechanisms however are still not clearly established. In this study, we used a representative LMNA nonsense mutation, p.Arg321Ter, to shed light on the molecular disease mechanisms. Cultured fibroblasts from three DCM patients carrying this mutation were analyzed. Quantitative reverse transcriptase PCR and sequencing of these PCR products indicated that transcripts from the mutant allele were degraded by the nonsense-mediated mRNA decay (NMD) mechanism. The fact that no truncated mutant protein was detectable in western blot (WB) analysis strengthens the notion that the mutant transcript is efficiently degraded. Furthermore, WB analysis showed that the expression of lamin C protein was reduced by the expected approximately 50%. Clearly decreased lamin A and lamin C levels were also observed by immunofluorescence microscopy analysis. However, results from both WB and nano-liquid chromatography/mass spectrometry demonstrated that the levels of lamin A protein were more reduced suggesting an effect on expression of lamin A from the wild type allele. PCR analysis of the ratio of lamin A to lamin C transcripts showed unchanged relative amounts of lamin A transcript suggesting that the effect on the wild type allele was operative at the protein level. Immunofluorescence microscopy analysis showed no abnormal nuclear morphology of patient fibroblast cells. Based on these data, we propose that

  20. Therapeutic effect of immunoadsorption and subsequent immunoglobulin substitution in patients with dilated cardiomyopathy: Results from the observational prospective Bad Berka Registry.

    Science.gov (United States)

    Ohlow, Marc-Alexander; Brunelli, Michele; Schreiber, Matthias; Lauer, Bernward

    2017-02-01

    Elimination of cardiac autoantibodies, frequently detected in patients with dilated cardiomyopathy (DCM), with immunoadsorption (IA) improves functional capacity and left ventricular (LV) function. This study aimed to prospectively address this issue in a large cohort of unselected patients. Consecutive patients undergoing IA followed by IgG substitution were included. Clinical and echocardiographic parameters were assessed at baseline (BL) and 12-month follow-up (FU). Patients were classified as IA responders when ≥2 of the following criteria were achieved: improvement in the Minnesota Living with Heart Failure Questionnaire (MLHFQ) ≥5 points, symptoms [≥1 New York Heart Association (NYHA) class], LV ejection fraction (EF) ≥10% or decrease in LV end-diastolic diameter (EDD) ≥10%, or N-terminal pro B-type natriuretic peptide (NT-pro-BNP) ≥50%. 93 patients (median age 61 years, LVEF 30%, duration of symptoms 14 months, 87% in NYHA class III/IV, >90% treated with β-blocker/angiotensin-converting enzyme inhibitor) were included. When the entire cohort was analyzed, a significant improvement in MLHFQ (50 vs. 26 points), NYHA-class (median 3.0 vs. 2.0), LVEF (30% vs. 38%), LVEDD (62 vs. 59mm), NT-pro-BNP (892 vs. 523pg/ml) was observed at FU (p1 viral genome, and higher values of mononuclear inflammatory cells at endomyocardial biopsy. Sixteen (17.2%) patients experienced IA related complications. A positive response is observed in 48% of inflammatory DCM patients undergoing IA, and this translates into a significant improvement in clinical and echocardiographic parameters. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  1. Use of thallium-201 myocardial scintigraphy for the prediction of the response to {beta}-blocker therapy in patients with dilated cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Hara, Yuji; Hamada, Mareomi; Ohtsuka, Tomoaki; Ogimoto, Akiyoshi; Saeki, Hideyuki; Suzuki, Jun; Matsunaka, Tsuyoshi; Nakata, Shigeru; Shigematsu, Yuji [Ehime Univ., Shigenobu (Japan). School of Medicine

    2002-12-01

    This study was performed to evaluate whether thallium-201 myocardial scintigraphy (Tl-201) and iodine-123-metaiodobenzylguanidine (MIBG) myocardial scintigraphy could predit the usefulness of {beta}-blocker therapy in patients with dilated cardiomyopathy (DCM). Tl-201 and MIBG were performed in 47 patients before {beta}-blocker therapy. Patients were classified into group A, if their cardiac function improved, and group B, whose function remained unchanged Two types of extent score (ES) by Tl-201 were proposed to quantitate myocardial damage, mean-2SD (ES-2) and mean -3SD (ES-3). The ES difference between ES-2 and ES-3 was calculated, and according to ES and ES difference, DCM cases were classified into 3 groups: mild-defect type (mild-type), moderate-defect type (moderate-type) and severe-defect type (severe-type). The heart-to-mediastinum (H/M) MIBG uptake ratio was evaluated, and the percent washout ratio of myocardial MIBG was obtained from these data. Group A comprised 18 mild-type, 14 moderate-type and 1 severe-type cases, and group B comprised 5 mild-type, 4 moderate-type and 5 severe-type cases. A significant relation was observed between the defect type on Tl-201 and the response to {beta}-blocker therapy (p=0.0090). Both H/M MIBG uptake ratios and washout ratio were not significantly different in the 2 groups. Tl-201 may be useful for predicting the response to {beta}-blocker therapy in patients with DCM. (author)

  2. Evaluation of left ventricular function and volume in patients with dilated cardiomyopathy: Gated myocardial single-photon emission tomography (SPECT) versus echocardiography

    International Nuclear Information System (INIS)

    Berk, Fatma; Isgoren, S.; Demir, H.; Kozdag, G.; Ural, D.; Komsuoglu, B.

    2005-01-01

    Left ventricular function, volumes and regional wall motion provide valuable diagnostic information and are of long-term prognostic importance in patients with dilated cardiomyopathy (DCM). This study was designed to compare the effectiveness of 2D-echocardiography and gated single-photon emission tomography (SPECT) for evaluation of these parameters in patients with DCM. Gated SPECT and 2D-echocardiography were performed in 33 patients having DCM. Gated SPECT data, including left ventricular ejection fraction (LVEF), were processed using an automated algorithm. Standard technique was used for 2D-echocardiography. Regional wall motion was evaluated using both modalities and was scored by two independent observers using a 16-sement model with a 5-point scoring system. The overall agreement between the two imaging modalities for the assessment of regional wall motion was 56% (298/528 segments). With gated SPECT, LEVF, end-diastolic volume (EDV), and end-diastolic volume (EDV), and end-systolic volume (ESV) were 27+-9%, 217+-73mL, respectively, and 30.8%, 195+-58mL and, 137+-48 mL with echocardiography. The correlation between gated SPECT and 2-D-echocardiography was good (r=0.76, P<0.01) for the assessment of LVEF. The correlation for EDV and ESV were also good, but with wider limits of agreement (r=0.72, P<0.01 and r=0.73, P<0.01, respectively) and significantly higher values were obtained with gated SPECT (P<0.01). Gated SPECT and 2D-echocardiography correlate well for the assessment of LV function and LV volumes. Like 2D-echocardiography, gated SPECT provides reliable information about LV function and dimension with the additional advantage of perfusion data. (author)

  3. Relationship between evaluation by quantitative fatty acid myocardial scintigraphy and response to {beta}-blockade therapy in patients with dilated cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Tatsuo; Hoshida, Shiro; Nishino, Masami; Aoi, Toshiyuki; Egami, Yasuyuki; Takeda, Toshihiro; Kawabata, Masayoshi; Tanouchi, Jun; Yamada, Yoshio; Kamada, Takenobu [Div. of Cardiology, Osaka Rosai Hospital (Japan)

    2001-12-01

    Predicting the effect of {beta}-blockade therapy on the clinical outcome of patients with dilated cardiomyopathy (DCM) is difficult prior to the initiation of therapy. Myocardial fatty acid metabolism has been shown to be impaired in patients with DCM. We examined whether the extent of myocardial injury, as assessed by iodine-123 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) myocardial scintigraphy, is related to the response of patients with DCM to {beta}-blockade therapy. Thirty-seven patients with DCM were examined using BMIPP myocardial scintigraphy before and after 6 months of treatment with metoprolol. Myocardial BMIPP uptake (%BM uptake) was estimated quantitatively as a percentage of the total injected count ratio. The left ventricular end-diastolic and end-systolic dimensions (LVDd, LVDs) and ejection fraction (LVEF) were also evaluated. The patients were divided into two groups according to their functional improvement (>10% elevation of LVEF) after 6 months of metoprolol therapy. Twenty-eight patients responded to the therapy, while nine did not. Prior to the therapy, no significant differences in LVDd, LVDs or LVEF were observed between the responders and non-responders. However, the %BM uptake was significantly lower in the non-responders than in the responders (1.0%{+-}0.2% vs 2.1%{+-}0.5%, P<0.001). The %BM uptake could be used to distinguish the responders from the non-responders with a sensitivity of 0.93 and a specificity of 1.00 at a threshold value of 1.4. After the metoprolol therapy, the %BM uptake improved significantly in the responders (2.5%{+-}0.5%, P<0.01) but did not change in the non-responders. These results indicate that myocardial BMIPP uptake could predict the response of DCM patients to {beta}-blockade therapy. (orig.)

  4. Relationship between myocardial extracellular space expansion estimated with post-contrast T1 mapping MRI and left ventricular remodeling and neurohormonal activation in patients with dilated cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Ji Hyun; Son, Jung Woo; Chung, Hye Moon [Cardiology Division, Dept. of Internal Medicine, Yonsei University College of Medicine, Seoul (Korea, Republic of); and others

    2015-10-15

    Post-contrast T1 values are closely related to the degree of myocardial extracellular space expansion. We determined the relationship between post-contrast T1 values and left ventricular (LV) diastolic function, LV remodeling, and neurohormonal activation in patients with dilated cardiomyopathy (DCM). Fifty-nine patients with DCM (mean age, 55 ± 15 years; 41 males and 18 females) who underwent both 1.5T magnetic resonance imaging and echocardiography were enrolled. The post-contrast 10-minute T1 value was generated from inversion time scout images obtained using the Look-Locker inversion recovery sequence and a curve-fitting algorithm. The T1 sample volume was obtained from three interventricular septal points, and the mean T1 value was used for analysis. The N-Terminal pro-B-type natriuretic peptide (NT-proBNP) level was measured in 40 patients. The mean LV ejection fraction was 24 ± 9% and the post-T1 value was 254.5 ± 46.4 ms. The post-contrast T1 value was significantly correlated with systolic longitudinal septal velocity (s'), peak late diastolic velocity of the mitral annulus (a'), the diastolic elastance index (Ed, [E/e']/stroke volume), LV mass/volume ratio, LV end-diastolic wall stress, and LV end-systolic wall stress. In a multivariate analysis without NT-proBNP, T1 values were independently correlated with Ed (β = -0.351, p = 0.016) and the LV mass/volume ratio (β = 0.495, p = 0.001). When NT-proBNP was used in the analysis, NT-proBNP was independently correlated with the T1 values (β = -0.339, p = 0.017). Post-contrast T1 is closely related to LV remodeling, diastolic function, and neurohormonal activation in patients with DCM.

  5. Diagnostic and Prognostic Value of Long-Axis Strain and Myocardial Contraction Fraction Using Standard Cardiovascular MR Imaging in Patients with Nonischemic Dilated Cardiomyopathies.

    Science.gov (United States)

    Arenja, Nisha; Riffel, Johannes H; Fritz, Thomas; André, Florian; Aus dem Siepen, Fabian; Mueller-Hennessen, Matthias; Giannitsis, Evangelos; Katus, Hugo A; Friedrich, Matthias G; Buss, Sebastian J

    2017-06-01

    Purpose To assess the utility of established functional markers versus two additional functional markers derived from standard cardiovascular magnetic resonance (MR) images for their incremental diagnostic and prognostic information in patients with nonischemic dilated cardiomyopathy (NIDCM). Materials and Methods Approval was obtained from the local ethics committee. MR images from 453 patients with NIDCM and 150 healthy control subjects were included between 2005 and 2013 and were analyzed retrospectively. Myocardial contraction fraction (MCF) was calculated by dividing left ventricular (LV) stroke volume by LV myocardial volume, and long-axis strain (LAS) was calculated from the distances between the epicardial border of the LV apex and the midpoint of a line connecting the origins of the mitral valve leaflets at end systole and end diastole. Receiver operating characteristic curve, Kaplan-Meier method, Cox regression, and classification and regression tree (CART) analyses were performed for diagnostic and prognostic performances. Results LAS (area under the receiver operating characteristic curve [AUC] = 0.93, P < .001) and MCF (AUC = 0.92, P < .001) can be used to discriminate patients with NIDCM from age- and sex-matched control subjects. A total of 97 patients reached the combined end point during a median follow-up of 4.8 years. In multivariate Cox regression analysis, only LV ejection fraction (EF) and LAS independently indicated the combined end point (hazard ratio = 2.8 and 1.9, respectively; P < .001 for both). In a risk stratification approach with classification and regression tree analysis, combined LV EF and LAS cutoff values were used to stratify patients into three risk groups (log-rank test, P < .001). Conclusion Cardiovascular MR-derived MCF and LAS serve as reliable diagnostic and prognostic markers in patients with NIDCM. LAS, as a marker for longitudinal contractile function, is an independent parameter for outcome and offers incremental

  6. Fibrosis of extracellular matrix is related to the duration of the disease but is unrelated to the dynamics of collagen metabolism in dilated cardiomyopathy.

    Science.gov (United States)

    Rubiś, Paweł; Wiśniowska-Śmialek, Sylwia; Wypasek, Ewa; Biernacka-Fijalkowska, Barbara; Rudnicka-Sosin, Lucyna; Dziewiecka, Ewa; Faltyn, Patrycja; Khachatryan, Lusine; Karabinowska, Aleksandra; Kozanecki, Artur; Tomkiewicz-Pająk, Lidia; Podolec, Piotr

    2016-12-01

    Fibrosis of extracellular matrix (ECM) in dilated cardiomyopathy (DCM) corresponds to the myocardial over-production of various types of collagens. However, mechanism of this process is poorly understood. To investigate whether enhanced metabolism of ECM occur in DCM. Seventy consecutive DCM patients (pts) (48 ± 12.1 years, EF 24.4 ± 7.4 %) and 20 healthy volunteers were studied. Based on symptoms duration, pts were divided into new-onset (n = 35, 6 months) and chronic DCM (n = 35, >6 months). Markers of collagen type I and III synthesis-procollagen type I carboxy- and amino-terminal peptides (PICP and PINP) and procollagen type III carboxy- and amino-terminal peptides (PIIICP and PIIINP), collagen 1 (col-1), ECM metabolism controlling factors-tumor growth factor beta-1 (TGF1-β), connective tissue growth factor (CTGF), and ECM degradation enzymes-matrix metalloproteinases (MMP-2, MMP-9) and their tissue inhibitor (TIMP-1) were measured in serum. All pts underwent right ventricular endomyocardial biopsy to study ECM fibrosis. The presence of fibrosis was detected in 24 (34.3 %) pts and was more prevalent in chronic DCM [17 (48.6 %) vs. 7 (20 %), p collagen type III prevailed over collagen type I. ECM metabolism was not different in DCM regardless of the duration of the disease and status of myocardial fibrosis. Serum markers of ECM metabolism were found not to be useful for the prediction of myocardial fibrosis in DCM.

  7. Use of I-123 MIBG cardiac scintigraphy to assess the impact of carvedilol on cardiac adrenergic neuronal function in childhood dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Maunoury, C.; Acar, P.; Sidi, D.

    2006-01-01

    I-123 MIBG cardiac scintigraphy is a useful tool to assess cardiac adrenergic neuronal function, which is impaired in children with dilated cardiomyopathy (DCM). In adults with DCM, long-term treatment with carvedilol improves both cardiac adrenergic neuronal function and left ventricular function. The aim of this prospective study was to evaluate the impact of carvedilol on cardiac adrenergic neuronal function and on left ventricular function in seventeen patients (11 female, 6 male, mean age 39 ± 57 months, range 1 - 168 months) with DCM. All patients underwent I-123 MIBG cardiac scintigraphy and equilibrium radio-nuclide angiography before and after a 6 month period of carvedilol therapy. A static anterior view of the chest was acquired 4 hours after intravenous injection of 20 to 75 MBq of I-123 MIBG. Cardiac neuronal uptake of I-123 MIBG was measured using the heart to mediastinum count ratio (HMR). Radionuclide left ventricular ejection fraction (LVEF) was assessed following a standard protocol. There was no major cardiac events (death or transplantation) during the follow-up period. I-123 MIBG cardiac uptake and left ventricular function respectively increased by 38% and 65% after 6 months of treatment with carvedilol (HMR 223 ± 49% vs 162 ± 26%, p < 0.0001 and LVEF = 43 ± 17% vs 26 ± 11%, p < 0.0001). Carvedilol can improve cardiac adrenergic neuronal function and left ventricular function in children with DCM. Further studies are needed to assess the relationship between improvement in I-123 MIBG cardiac uptake and the beneficial effects of carvedilol on morbidity and mortality. (authors)

  8. A new methodological approach to assess cardiac work by pressure-volume and stress-length relations in patients with aortic valve stenosis and dilated cardiomyopathy.

    Science.gov (United States)

    Alter, P; Rupp, H; Rominger, M B; Klose, K J; Maisch, B

    2008-01-01

    In experimental animals, cardiac work is derived from pressure-volume area and analyzed further using stress-length relations. Lack of methods for determining accurately myocardial mass has until now prevented the use of stress-length relations in patients. We hypothesized, therefore, that not only pressure-volume loops but also stress-length diagrams can be derived from cardiac volume and cardiac mass as assessed by cardiac magnetic resonance imaging (CMR) and invasively measured pressure. Left ventricular (LV) volume and myocardial mass were assessed in seven patients with aortic valve stenosis (AS), eight with dilated cardiomyopathy (DCM), and eight controls using electrocardiogram (ECG)-gated CMR. LV pressure was measured invasively. Pressure-volume curves were calculated based on ECG triggering. Stroke work was assessed as area within the pressure-volume loop. LV wall stress was calculated using a thick-wall sphere model. Similarly, stress-length loops were calculated to quantify stress-length-based work. Taking the LV geometry into account, the normalization with regard to ventricular circumference resulted in "myocardial work." Patients with AS (valve area 0.73+/-0.18 cm(2)) exhibited an increased LV myocardial mass when compared with controls (Pwork of AS was unchanged when compared with controls (0.539+/-0.272 vs 0.621+/-0.138 Nm, not significant), whereas DCM exhibited a significant depression (0.367+/-0.157 Nm, Pwork was significantly reduced in both AS and DCM when compared with controls (129.8+/-69.6, 200.6+/-80.1, 332.2+/-89.6 Nm/m(2), Pmethodological approach of using CMR and invasive pressure measurement. Myocardial work was reduced in patients with DCM and noteworthy also in AS, while stroke work was reduced in DCM only. Most likely, deterioration of myocardial work is crucial for the prognosis. It is suggested to include these basic physiological procedures in the clinical assessment of the pump function of the heart.

  9. Evaluation of therapy for dilated cardiomyopathy with heart failure by iodine-123 metaiodobenzyl-guanidine imaging. Comparison with heart rate variability power spectral analysis

    Energy Technology Data Exchange (ETDEWEB)

    Li, Shou-lin; Ikeda, Jun; Takita, Tamotsu; Sekiguchi, Yohei; Demachi, Jun; Chikama, Hisao; Goto, Atsushi; Shirato, Kunio [Tohoku Univ., Sendai (Japan). School of Medicine

    1998-11-01

    The relationship between the myocardial uptake of iodine-123 metaiodobenzylguanidine ({sup 123}I-MIBG) and heart rate variability parameters has not been determined. This study determined the relationship between the change in myocardial uptake of {sup 123}I-MIBG and improvement in left ventricular function after treatment, to determine the usefulness of {sup 123}I-MIBG imaging to assess the effect of therapy on heart failure due to dilated cardiomyopathy (DCM). {sup 123}I-MIBG imaging and power spectral analysis of heart rate variability were performed before and after treatment in 17 patients with heart failure due to DCM. The following parameters were compared before and after treatment: New York Heart Association (NYHA) functional class, radiographic cardiothoracic ratio (CTR), blood pressure, echocardiographic data (left ventricular end-systolic (LVDs) and end-diastolic (LVDd) diameters, left ventricular ejection fraction (LVEF)), plasma concentrations of norepinephrine and epinephrine, heart rate variability power spectral analysis data (mean low frequency (MLF) and high frequency power (MHF)) and the myocardium to mediastinum activity ratio (MYO/M) obtained in early and late images, and washout rate calculated by anterior planar imaging of {sup 123}I-MIBG. The NYHA functional class, LVEF, LVDs, CTR, MLF and MHF improved after treatment. Early MYO/M and late MYO/M improved after treatment. The rate of increase in late MYO/M was positively correlated with the rate of improvement of LVEF after treatment. Furthermore, the late MYO/M was negatively correlated with MLF. Washout rate revealed no correlation with hemodynamic parameters. These findings suggest that late MYO/M is more useful than washout rate to assess the effect of treatment on heart failure due to DCM. Furthermore, the {sup 123}I-MIBG imaging and heart rate variability parameters are useful to assess the autonomic tone in DCM with heart failure. (author)

  10. Activated nuclear transcription factor κB in patients with myocarditis and dilated cardiomyopathy-relation to inflammation and cardiac function

    International Nuclear Information System (INIS)

    Alter, Peter; Rupp, Heinz; Maisch, Bernhard

    2006-01-01

    Objectives and background: Myocarditis is caused by various agents and autoimmune processes. It is unknown whether viral genome persistence represents inactive remnants of previous infections or whether it is attributed to ongoing adverse processes. The latter also applies to the course of autoimmune myocarditis. One principal candidate for an adverse remodeling is nuclear factor-κB (NFκB). Methods: A total of 93 patients with suspected myocarditis/cardiomyopathy was examined. Hemodynamics were assessed by echocardiography as well as right and left heart catheterization. Endomyocardial biopsies were taken from the left ventricle. Biopsies were examined by immunohistochemistry and PCR for viral genomes. Selective immunostaining of activated NFκB was performed. Results: NFκB was increased in patients with myocarditis when compared with controls (11.1 ± 7.1% vs. 5.0 ± 5.3%, P 2 = 0.72, P 2 = 0.43, P < 0.02). Increased activated NFκB was found in adenovirus persistence when compared with controls (P = 0.001). Only a trend of increased NFκB activation was seen in cytomegalovirus persistence. Parvovirus B19 persistence did not affect NFκB activation. Conclusions: Increased activation of NFκB is related to inflammatory processes in myocarditis. Since activated NFκB correlates with left ventricular function, it could be assumed that NFκB activation occurs at early stages of inflammation. Potentially, NFκB could inhibit loss of cardiomyocytes by apoptosis and protect from cardiac dilation. Since NFκB is a crucial key transcription factor of inflammation, its prognostic and future therapeutic relevance should be addressed

  11. Evaluation of therapy for dilated cardiomyopathy with heart failure by iodine-123 metaiodobenzyl-guanidine imaging. Comparison with heart rate variability power spectral analysis

    International Nuclear Information System (INIS)

    Li, Shou-lin; Ikeda, Jun; Takita, Tamotsu; Sekiguchi, Yohei; Demachi, Jun; Chikama, Hisao; Goto, Atsushi; Shirato, Kunio

    1998-01-01

    The relationship between the myocardial uptake of iodine-123 metaiodobenzylguanidine ( 123 I-MIBG) and heart rate variability parameters has not been determined. This study determined the relationship between the change in myocardial uptake of 123 I-MIBG and improvement in left ventricular function after treatment, to determine the usefulness of 123 I-MIBG imaging to assess the effect of therapy on heart failure due to dilated cardiomyopathy (DCM). 123 I-MIBG imaging and power spectral analysis of heart rate variability were performed before and after treatment in 17 patients with heart failure due to DCM. The following parameters were compared before and after treatment: New York Heart Association (NYHA) functional class, radiographic cardiothoracic ratio (CTR), blood pressure, echocardiographic data (left ventricular end-systolic (LVDs) and end-diastolic (LVDd) diameters, left ventricular ejection fraction (LVEF)), plasma concentrations of norepinephrine and epinephrine, heart rate variability power spectral analysis data (mean low frequency (MLF) and high frequency power (MHF)) and the myocardium to mediastinum activity ratio (MYO/M) obtained in early and late images, and washout rate calculated by anterior planar imaging of 123 I-MIBG. The NYHA functional class, LVEF, LVDs, CTR, MLF and MHF improved after treatment. Early MYO/M and late MYO/M improved after treatment. The rate of increase in late MYO/M was positively correlated with the rate of improvement of LVEF after treatment. Furthermore, the late MYO/M was negatively correlated with MLF. Washout rate revealed no correlation with hemodynamic parameters. These findings suggest that late MYO/M is more useful than washout rate to assess the effect of treatment on heart failure due to DCM. Furthermore, the 123 I-MIBG imaging and heart rate variability parameters are useful to assess the autonomic tone in DCM with heart failure. (author)

  12. Reduction of myocardial blood flow reserve in idiopathic dilated cardiomyopathy without overt heart failure and its relation with functional indices: an echo-Doppler and positron emission tomography study.

    Science.gov (United States)

    Morales, Maria-Aurora; Neglia, Danilo; L'Abbate, Antonio

    2008-08-01

    Myocardial blood flow during pharmacological vasodilatation is depressed in patients with idiopathic dilated cardiomyopathy even the in absence of overt heart failure; the extent of myocardial blood flow abnormalities is not predictable by left ventricular ejection fraction (LVEF) and diastolic dimensions. To assess whether myocardial blood flow impairment in idiopathic dilated cardiomyopathy without overt heart failure can be related to Doppler-derived dP/dt and to echocardiographically determined left ventricular end systolic stress - which is linked to myocardial blood flow reserve in advanced disease. Twenty-six patients, New York Heart Association Class I-II, (LVEF 37.4 +/- 1.4%, left ventricular diastolic dimensions 62.6 +/- 0.9 mm) underwent resting/dipyridamole [13N]NH3 flow positron emission tomography and an ultrasonic study. Regional myocardial blood flow values (ml/min per g) were computed from positron emission tomography data in 13 left ventricular (LV) myocardial regions and averaged to provide mean myocardial blood flow and myocardial blood flow reserve, defined as dipyridamole/resting mean myocardial blood flow ratio. Resting myocardial blood flow was 0.686 +/- 0.045, dipyridamole myocardial blood flow 1.39 +/- 0.15 and myocardial blood flow reserve 2.12 +/- 0.2, lower than in controls (P < 0.01). The ratio dP/dt was directly related to dipyridamole myocardial blood flow and myocardial blood flow reserve (r = 0.552 and 0.703, P < 0.005 and P < 0.0001); no relation was found between myocardial blood flow and LVEF left ventricular diastolic dimensions, and left ventricular end systolic stress. In idiopathic dilated cardiomyopathy patients without overt heart failure, the extent of myocardial blood flow reserve impairment is related to dP/dt but not to more classical indices of left ventricular function.

  13. Heterozygous Lmna(delK32) mice develop dilated cardiomyopathy through a combined pathomechanism of haploinsufficiency and peptide toxicity

    DEFF Research Database (Denmark)

    Cattin, M. E.; Bertrand, A. T.; Schlossarek, S.

    2013-01-01

    itself has a clear deleterious effect on engineered heart tissues force of contraction, it also leads to the nuclear aggregation of viral-mediated expression of K32-lamin. In conclusion, Het mice are the first knock-in Lmna model with cardiac-specific phenotype at the heterozygous state. Altogether, our....... The pathomechanisms linking mutations to DCM remain to be elucidated. We investigated the phenotype and associated pathomechanisms of heterozygous Lmna(K32/) (Het) knock-in mice, which carry a human mutation. Het mice developed a cardiac-specific phenotype. Two phases, with two different pathomechanisms, could...... be observed that lead to the development of cardiac dysfunction, DCM and death between 35 and 70 weeks of age. In young Het hearts, there was a clear reduction in lamin A/C level, mainly due to the degradation of toxic K32-lamin. As a side effect, lamin A/C haploinsufficiency probably triggers the cardiac...

  14. Assessment of central chemosensitivity and cardiac sympathetic nerve activity using I-123 MIBG imaging in central sleep apnea syndrome in patients with dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Meguro, Kentaro; Nagai, Ryozo; Toyama, Takuji; Adachi, Hitoshi; Ohshima, Shigeru; Taniguchi, Koichi

    2007-01-01

    Iodine-123 m-iodobenzylguanidine (MIBG) imaging has been used to study cardiac sympathetic function in various cardiac diseases. Central sleep apnea syndrome (CSAS) occurs frequently in patients with chronic heart failure (CHF) and is reported to be associated with a poor prognosis. One of the mechanisms of its poor prognosis may be related to impaired cardiac sympathetic activity. However, the relationship between chemosensitivity to carbon dioxide, which is reported to correlate with the severity of CSAS, and cardiac sympathetic activity has not been investigated. Therefore, this study was undertaken to assess cardiac sympathetic function and chemosensitivity to carbon dioxide in CHF patients. The oxygen desaturation index (ODI) was evaluated in 21 patients with dilated cardiomyopathy (male/female: 19/2, left ventricular ejection fraction (LVEF) 5 times/h underwent polysomnography. Patients with an apnea hypopnea index >15/h but without evidence of obstructive apnea were defined as having CSAS. Early (15 min) and delayed (4 hr) planar MIBG images were obtained from these patients. The mean counts in the whole heart and the mediastinum were obtained. The heart-to-mediastinum count ratio of the delayed image (H/M) and the corrected myocardial washout rate (WR) were also calculated. The central chemoreflex was assessed with the rebreathing method using a hypercapnic gas mixture (7% CO 2 and 93% O 2 ). Ten of the 21 patients had CSAS. The H/M ratio was similar in patients both with and without CSAS (1.57±0.18 vs. 1.59±0.14, p=0.82). However, the WR was higher in patients with CSAS than in patients without CSAS (40±8% vs. 30±12%, p<0.05). ODI significantly correlated with central chemosensitivity to carbon dioxide. Moreover, there was a highly significant correlation between WR and central chemosensitivity (r=0.65, p<0.05). However, there was no correlation between ODI and the WR (r=0.36, p=0.11). Cardiac sympathetic nerve activity in patients with CHF and CSAS is

  15. 99 mTc-MIBI washout as a complementary factor in the evaluation of idiopathic dilated cardiomyopathy (IDCM) using myocardial perfusion imaging.

    Science.gov (United States)

    Shiroodi, Mohammad Kazem; Shafiei, Babak; Baharfard, Nastaran; Gheidari, Mohammad Esmail; Nazari, Babak; Pirayesh, Elaheh; Kiasat, Ali; Hoseinzadeh, Samaneh; Hashemi, Abolghassem; Akbarzadeh, Mohammad Ali; Javadi, Hamid; Nabipour, Iraj; Assadi, Majid

    2012-01-01

    Rapid technetium-99 m methoxyisobutylisonitrile (99 mTc-MIBI) washout has been shown to occur in impaired myocardia. This study is based on the hypothesis that scintigraphy can be applied to calculate the myocardial 99 mTc-MIBI washout rate (WR) to diagnose and evaluate heart failure severity and other left ventricular functional parameters specifically in idiopathic dilated cardiomyopathy (IDCM) patients. Patients with IDCMP (n = 17; 52.65 ± 11.47 years) and normal subjects (n = 6; 49.67 ± 10.15 years) were intravenously administered 99 mTc-hexakis-2-methoxyisobutylisonitrile (99 mTc-MIBI). Next, early and delayed planar data were acquired (at 3.5-h intervals), and electrocardiogram (ECG)-gated myocardial perfusion single photon emission computed tomography (SPECT) was performed. The 99 mTc-MIBI WR was calculated using early and delayed planar images. Left ventricular functional parameters were also analyzed using quantitative gated SPECT (QGS) data. In target group, myocardial WRs (29.13 ± 6.68%) were significantly higher than those of control subjects (14.17 ± 3.31%; P 99 mTc-MIBI WR increased with the increasing severity of the NYHA functional class (23.16 ± 1.72% for class I, 30.25 ± 0.95% for class II, 32.60 ± 6.73% for class III, and 37.50 ± 7.77% for class IV; P = 0.02). The WR was positively correlated with the end-diastolic volume (EDV) index (r (2) = 0.216; β = 0.464; P = 0.02 [ml/m(2)], the end-systolic volume (ESV) index (r (2) = 0.234; β = 0.484; P = 0.01 [ml/m(2)]), the summed motion score (SMS) (r (2) = 0.544; β = 0.738; P = 0.00), and the summed thickening score (STS) (r (2) = 0.656; β = 0.810; P = 0.00); it was negatively correlated with the left ventricular ejection fraction (LVEF) (r (2) = 0.679; β = -0.824; P = 0.00). It can be concluded that 99 mTc-MIBI scintigraphy might be a valuable molecular imaging tool for the diagnosis and evaluation of myocardial damage or dysfunction severity.

  16. The effect of β-blocker on hamster model BIO 53.58 with dilated cardiomyopathy determined using 123I-MIBG myocardial scintigraphy

    International Nuclear Information System (INIS)

    Inoue, Aritomo; Yamashina, Shohei; Yamazaki, Junichi

    2003-01-01

    123 I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy is currently used to evaluate cardiac sympathetic nerve function, but MIBG also has the capacity to evaluate dilated cardiomyopathy (DCM) severity and therapeutic effectiveness. In this study, we administered β-blockers to a DCM hamster model and evaluated the effect of therapy using MIBG. We also pathologically compared the effects of myocardial fibrosis suppression. BIO 53.58 hamsters were divided into the following five groups based on β-blocker administration: vehicle (COT), 2 mg/kg/day carvedilol (CLT), 20 mg/kg/day (CHT) carvedilol, 4 mg/kg/day (MLT) metoprolol, 40 mg/kg/day (MHT) metoprolol. F1B hamsters were administered a vehicle (COF). Plasma catecholamine, noradrenaline (p-NADR), adrenaline (p-ADR), and dopamine (p-DOPA) were assayed, and MIBG was performed. The count ratio of the heart to the mediastinum (H/M) and left ventricle myocardial washout ratio (WR) were calculated. We then performed an autopsy and calculated the percent change in fibrotic area from myocardial sections. H/M of the initial image in the COT group was significantly lower at 2.4±0.2 than the 2.9±0.7 in the COF group (p<0.05). The CLT and CHT groups had higher H/M values compared to the COT group (3.1±0.6, 3.0±0.6 versus 2.4±0.2: p<0.05). Significant correlations were evident between the H/M of the delayed image and p-NADR and p-DOPA (p<0.05, p<0.01, respectively) as well as between WR and p-NADR and p-DOPA (p<0.05). Percent change in fibrotic area was significantly lower in the β-blocker groups than in the COT group (p<0.05). Significant negative correlations were seen between the H/M of the delayed image and the percent change in fibrosis area. The delayed image H/M and WR acutely reflected cardiac disorder and sympathetic nerve function disorder in BIO 53.58 hamsters. In the carvedilol-administered groups, there was improvement compared to the initial H/M image, indicating the efficacy of the β-blocker in DCM

  17. Phase analysis of gated blood pool SPECT for multiple stress testing assessments of ventricular mechanical dyssynchrony in a tachycardia-induced dilated cardiomyopathy canine model.

    Science.gov (United States)

    Salimian, Samaneh; Thibault, Bernard; Finnerty, Vincent; Grégoire, Jean; Harel, François

    2017-02-01

    Stress-induced dyssynchrony has been shown to be independently correlated with clinical outcomes in patients with dilated cardiomyopathy (DCM) and narrow QRS complexes. However, the extent to which stress levels affect inter- and intraventricular dyssynchrony parameters remains unknown. Ten large dogs were submitted to tachycardia-induced DCM by pacing the right ventricular apex for 3-4 weeks to reach a target ejection fraction (EF) of 35% or less. Stress was then induced in DCM dogs by administering intravenous dobutamine up to a maximum of 20 μg·kg -1 ·min -1 . Hemodynamic and ventricular dyssynchrony data were analyzed by left ventricular (LV) pressure measurements and gated blood pool SPECT (GBPS) imaging. In order to assess mechanical dyssynchrony in DCM subjects and compare it with that of 8 normal counterparts, we extracted the following data: count-based indices of LV contraction homogeneity index (CHI), entropy and phase standard deviation, and interventricular dyssynchrony index. A significant LV intraventricular dyssynchrony (CHI: 96.4 ± 1.3% in control vs 78.6% ± 10.9% in DCM subjects) resulted in an intense LV dysfunction in DCM subjects (EF: 49.5% ± 8.4% in control vs 22.6% ± 6.0% in DCM), compared to control subjects. However, interventricular dyssynchrony did not vary significantly between the two groups. Under stress, DCM subjects showed a significant improvement in ventricular functional parameters at each level (EF: 22.6% ± 6.0% at rest vs 48.1% ± 5.8% at maximum stress). All intraventricular dyssynchrony indices showed a significant increase in magnitude of synchrony from baseline to stress levels of greater than or equal to 5 μg·kg -1 ·min -1 dobutamine. There were individual differences in the magnitude and pattern of change in interventricular dyssynchrony during the various levels of stress. Based on GBPS analyses, different levels of functional stress, even in close intervals, can have a significant impact on

  18. Evidence for shear stress-mediated dilation of the internal carotid artery in humans

    DEFF Research Database (Denmark)

    Carter, Howard Henry; Atkinson, Ceri L; Heinonen, Ilkka H A

    2016-01-01

    -mediated dilation of larger conduit arteries in humans. There was a strong association between change in shear and diameter of the internal carotid (r=0.68; Ptime in humans, that shear stress is an important stimulus for hypercapnic vasodilation of the internal carotid...... increases carotid shear stress, a known stimulus to vasodilation in other conduit arteries. To explore the hypothesis that shear stress contributes to hypercapnic internal carotid dilation in humans, temporal changes in internal and common carotid shear rate and diameter, along with changes in middle.......01) carotids. Diameter also increased (Ptime course is associated with shear...

  19. Whole exome sequencing identified 1 base pair novel deletion in BCL2-associated athanogene 3 (BAG3) gene associated with severe dilated cardiomyopathy (DCM) requiring heart transplant in multiple family members.

    Science.gov (United States)

    Rafiq, Muhammad Arshad; Chaudhry, Ayeshah; Care, Melanie; Spears, Danna A; Morel, Chantal F; Hamilton, Robert M

    2017-03-01

    Dilated cardiomyopathy (DCM) is characterized by dilation and impaired contraction of the left ventricle or both ventricles. Among hereditary DCM, the genetic causes are heterogeneous, and include mutations encoding cytoskeletal, nucleoskeletal, mitochondrial, and calcium-handling proteins. We report three severely affected males, in a four-generation pedigree, with DCM phenotype who underwent cardiac transplant. Cardiomegaly with marked biventricular dilation and fibrosis were noticeable histopathological findings. The affected males had tested negative on a 46-gene pancardiomyopathy panel. Whole Exome Sequencing (WES) was performed to reveal mutation in the gene responsible in generation of DCM phenotypes. The 1-bp (Chr10:121435979delC; c.913delC) novel heterozygous deletion in exon 4 of BAG3, was identified in three affected males, resulted in frame-shift and a premature termination codon (p.Met306-Stop) producing a truncated BAG3 protein lacking functionally important PXXP and BAG domains. WES data were further utilized to map 10 SNP markers around the discovered mutation to generate shared disease haplotype in all affected individuals encompassing 11 Mb on 10q25.3-26.2 harboring BAG3. Finally genotypes were inferred for the unavailable/deceased individuals in the pedigrees. Here we propose that Chr10:121435979delC in BAG3 is a causal mutation in these subjects. Our and earlier studies indicate that BAG3 mutations are associated with DCM phenotypes. BAG3 should be added to cardiomyopathy gene panels for screening of DCM patients, and patients previously considered gene elusive should undergo sequencing of the BAG3 gene. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  20. Depressed heart rate variability as an independent predictor of death in chronic congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

    Science.gov (United States)

    Ponikowski, P; Anker, S D; Chua, T P; Szelemej, R; Piepoli, M; Adamopoulos, S; Webb-Peploe, K; Harrington, D; Banasiak, W; Wrabec, K; Coats, A J

    1997-06-15

    After acute myocardial infarction, depressed heart rate variability (HRV) has been proven to be a powerful independent predictor of a poor outcome. Although patients with chronic congestive heart failure (CHF) have also markedly impaired HRV, the prognostic value of HRV analysis in these patients remains unknown. The aim of this study was to investigate whether HRV parameters could predict survival in 102 consecutive patients with moderate to severe CHF (90 men, mean age 58 years, New York Heart Association [NYHA] class II to IV, CHF due to idiopathic dilated cardiomyopathy in 24 patients and ischemic heart disease in 78 patients, ejection fraction [EF], 26%; peak oxygen consumption, 16.9 ml/kg/min) after exclusion of patients in atrial fibrilation with diabetes or with chronic renal failure. In the prognostic analysis (Cox proportional-hazards model, Kaplan-Meier survival analysis), the following factors were investigated: age, CHF etiology, NYHA class, EF, peak oxygen consumption, presence of ventricular tachycardia on Holter monitoring, and HRV measures derived from 24-hour electrocardiography monitoring, calculated in the time (standard deviation of all normal RR intervals [SDNN], standard deviation of 5-minute RR intervals [SDANN], mean of all 5-minute standard deviations of RR intervals [SD], root-mean-square of difference of successive RR intervals [rMSSD], and percentage of adjacent RR intervals >50 ms different [pNN50]) and frequency domain (total power [TP], power within low-frequency band [LF], and power within high-frequency band [HF]). During follow-up of 584 +/- 405 days (365 days in all who survived), 19 patients (19%) died (mean time to death: 307 +/- 315 days, range 3 to 989). Cox's univariate analysis identified the following factors to be predictors of death: NYHA (p = 0.003), peak oxygen consumption (p = 0.01), EF (p = 0.02), ventricular tachycardia on Holter monitoring (p = 0.05), and among HRV measures: SDNN (p = 0.004), SDANN (p = 0.003), SD

  1. Monitorização eletrocardiográfica ambulatorial por 24-horas em cães com cardiomiopatia dilatada idiopática Twenty-four-hour ambulatory electrocardiographic monitoring in dogs with idiopathic dilated cardiomyopathy

    Directory of Open Access Journals (Sweden)

    F.L. Yamaki

    2007-12-01

    Full Text Available Caracterizou-se monitorização eletrocardiográfica ambulatorial por 24 horas (ou monitorização Holter em cães com cardiomiopatia dilatada idiopática, visando principalmente à detecção de arritmias ventriculares não detectadas pela eletrocardiografia convencional (de repouso. Para tanto, avaliaram-se 40 pacientes com diagnóstico de cardiomiopatia dilatada idiopática, por meio de exame físico e mensuração indireta da pressão arterial, além de exames eletrocardiográfico, ecocardiográfico, radiográfico de tórax e da monitorização Holter. Extra-sístoles ventriculares foram detectadas, por monitorização Holter, em 97,5% dos animais e taquicardia ventricular, em 45%. Não houve correlação entre o número de extra-sístoles ventriculares e a fração de encurtamento. Considerando as manifestações clínicas, apenas houve associação entre presença de taquicardia ventricular e histórico de síncopes. Conclui-se que a incidência de arritmias ventriculares em cães com cardiomiopatia dilatada idiopática é bastante alta, sendo a taquicardia ventricular relativamente freqüente, ocorrendo mais sob a forma não sustentada.This study aimed to characterize 24-hour ambulatory electrocardiographic monitoring (Holter monitoring in dogs with idiopathic dilated cardiomyopathy. Physical examination and indirect (Doppler blood pressure measurement, and also electrocardiography, thoracic radiography, echocardiography, and 24-hour ambulatory electrocardiographic exams were performed in 40 dogs with idiopathic dilated cardiomyopathy. Ventricular extrasystoles were detected in 97.5% of the animals, and ventricular tachycardia in 45%. No correlation between the number of ventricular extrasystoles and the shortening fraction was observed. Concerning the clinical symptoms, there was only association between the presence of ventricular tachycardia and past report of syncope. It was concluded that the incidence of ventricular arrhythmias is

  2. [Sepsis, cardiomyopathy and human immunodeficiency virus infection: presentation of a case].

    Science.gov (United States)

    Llagunes, J; Arastey, S; Cobo Del Prado, I; Carmona, P; Peña, J J; Mínguez, C

    2014-04-01

    Sepsis in patients with human immunodeficiency virus (HIV) may be associated with the appearance of cardiac dysfunction. This is a challenge, both when making the differential diagnosis and determining the proper treatment, as there are numerous risk factors: Myocarditis due to the HIV itself, the presence or absence of highly active antiretroviral therapy, toxic substances, and cardiomyopathy associated with sepsis. The diagnostic and therapeutic approach to an HIV positive patient with septic shock and cardiac dysfunction is described, as well as a brief review of the different causes of cardiomyopathy which may affect this group of patients is also presented. Copyright © 2012 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  3. Myocardial scintigraphy using iodine-123 15-(p-Iodophenyl)-3-R, S-methylpentadecanoic acid predicts the response to beta-blocker therapy in patients with dilated cardiomyopathy but does not reflect therapeutic effect

    Energy Technology Data Exchange (ETDEWEB)

    Yoshinaga, Keiichiro; Tahara, Minoru; Torii, Hiroyuki; Akimoto, Masaki [Kagoshima City Medical Association Hopital (Japan); Kihara, Koichi; Tei, Chuwa

    2000-05-01

    Myocardial fatty acid metabolism is disturbed in patients with idiopathic dilated cardiomyopathy. Myocardial scintigraphy using iodine-123 15-(p-iodophenyl)-3-R, S-methylpentadecanoic acid (BMIPP) was used to assess the response to {beta}-blocker therapy in 19 patients with dilated cardiomyopathy. BMIPP myocardial scintigraphy was performed before and 6 months after initiating {beta}-blocker therapy with metoprolol. Cardiac BMIPP uptake was assessed as the total defect score (TDS) and heart-to-mediastinum activity (H/M) ratio. Patients were classified retrospectively as responders with an improvement of at least one functional class (New York Heart Association) or an increase in ejection fraction of {>=}0.10 at 6 months, or as nonresponders meeting neither criterion. Responders had a significantly better pretreatment TDS (p<0.005) and H/M ratio (p<0.0001) than nonresponders. TDS exhibited no significant changes over 6 months in either group (responders: 13.2{+-}3.7 vs 12.5{+-}3.3; nonresponders: 20.8{+-}6.5 vs 20.5{+-}3.0). Responders showed no significant changes in H/M ratio (2.47{+-}0.28 vs 2.43{+-}0.42); paradoxically, nonresponders showed a significant increase from 1.82{+-}0.11 to 2.10{+-}0.19 (p<0.05), suggesting that {beta}-blocker therapy protected the myocardial fatty acid metabolism even in the absence of clinical improvement. BMIPP myocardial scintigraphy provides a prediction of response to {beta}-blocker treatment, but does not reflect the therapeutic effect in responders at 6 months. (author)

  4. Animal Models of Congenital Cardiomyopathies Associated With Mutations in Z-Line Proteins.

    Science.gov (United States)

    Bang, Marie-Louise

    2017-01-01

    The cardiac Z-line at the boundary between sarcomeres is a multiprotein complex connecting the contractile apparatus with the cytoskeleton and the extracellular matrix. The Z-line is important for efficient force generation and transmission as well as the maintenance of structural stability and integrity. Furthermore, it is a nodal point for intracellular signaling, in particular mechanosensing and mechanotransduction. Mutations in various genes encoding Z-line proteins have been associated with different cardiomyopathies, including dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, and left ventricular noncompaction, and mutations even within the same gene can cause widely different pathologies. Animal models have contributed to a great advancement in the understanding of the physiological function of Z-line proteins and the pathways leading from mutations in Z-line proteins to cardiomyopathy, although genotype-phenotype prediction remains a great challenge. This review presents an overview of the currently available animal models for Z-line and Z-line associated proteins involved in human cardiomyopathies with special emphasis on knock-in and transgenic mouse models recapitulating the clinical phenotypes of human cardiomyopathy patients carrying mutations in Z-line proteins. Pros and cons of mouse models will be discussed and a future outlook will be given. J. Cell. Physiol. 232: 38-52, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Therapeutic effect of co-enzyme Q10 on idiopathic dilated cardiomyopathy: assessment by iodine-123 labelled 15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid myocardial single-photon emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yong-ih [Department of Internal Medicine, Nishiyodo Hospital, Nishiyodo (Japan); Sawada, Yoshihiro [Department of Internal Medicine, Nishiyodo Hospital, Nishiyodo (Japan); Fujiwara, Go [Department of Radiology, Nishiyodo Hospital, Nishiyodo (Japan); Chiba, Hiroshi [Department of Internal Medicine, Mimihara General Hospital, Mimihara (Japan); Nishimura, Tsunehiko [Division of Tracer Kinetics, Biomedical Research Center, Osaka University Medical School, Osaka (Japan)

    1997-06-10

    It has been reported that myocardial mitochondrial function can be improved by the administration of co-enzyme Q10 (CoQ10). Recently, iodine-123 labelled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) was developed for metabolic imaging using single-photon emission tomography (SPET). This study was conducted to determine whether the therapeutic effects of CoQ10 on idiopathic dilated cardiomyopathy can be evaluated by BMIPP myocardial SPET. Fifteen patients, comprising 14 men and one woman (mean age: 64{+-}12 years), were examined. CoQ10 was administered at 30 mg/day for a period of 35.7{+-}12.4 days. BMIPP myocardial SPET was carried out before and after CoQ10 treatment. The count ratio of the heart (H) to the upper mediastinum (M) (H/M ratio) was calculated using a region of interest method with anterior planar imaging. Representative short-axis tomograms were divided into 27 segments (three slices x nine segments). Each segmental score was analysed semiquantitatively using a four-point scoring system (normal=0, mild low uptake=1, severe low uptake=2, defect=3). The H/M ratio showed a significant improvement, from 2.39{+-}0.39 to 2.54{+-}0.47, after treatment (P<0.05). The BMIPP total defect score after CoQ10 treatment was significantly decreased to 10.1{+-}4.3, compared to 13.9{+-}4.5 without CoQ10 treatment (P<0.001). However, the percent fractional shortening measured using echocardiography was not significantly different before and after CoQ treatment (19.2{+-}8.1 vs 19.7{+-}7.1). BMIPP myocardial SPET was confirmed to be sensitive in evaluating the therapeutic effects of CoQ10 in patients with idiopathic dilated cardiomyopathy. This method is unique, since the therapeutic effects can be estimated from the perspective of metabolic SPET imaging. (orig.). With 5 figs., 1 tab.

  6. Disease modeling and phenotypic drug screening for diabetic cardiomyopathy using human induced pluripotent stem cells.

    Science.gov (United States)

    Drawnel, Faye M; Boccardo, Stefano; Prummer, Michael; Delobel, Frédéric; Graff, Alexandra; Weber, Michael; Gérard, Régine; Badi, Laura; Kam-Thong, Tony; Bu, Lei; Jiang, Xin; Hoflack, Jean-Christophe; Kiialainen, Anna; Jeworutzki, Elena; Aoyama, Natsuyo; Carlson, Coby; Burcin, Mark; Gromo, Gianni; Boehringer, Markus; Stahlberg, Henning; Hall, Benjamin J; Magnone, Maria Chiara; Kolaja, Kyle; Chien, Kenneth R; Bailly, Jacques; Iacone, Roberto

    2014-11-06

    Diabetic cardiomyopathy is a complication of type 2 diabetes, with known contributions of lifestyle and genetics. We develop environmentally and genetically driven in vitro models of the condition using human-induced-pluripotent-stem-cell-derived cardiomyocytes. First, we mimic diabetic clinical chemistry to induce a phenotypic surrogate of diabetic cardiomyopathy, observing structural and functional disarray. Next, we consider genetic effects by deriving cardiomyocytes from two diabetic patients with variable disease progression. The cardiomyopathic phenotype is recapitulated in the patient-specific cells basally, with a severity dependent on their original clinical status. These models are incorporated into successive levels of a screening platform, identifying drugs that preserve cardiomyocyte phenotype in vitro during diabetic stress. In this work, we present a patient-specific induced pluripotent stem cell (iPSC) model of a complex metabolic condition, showing the power of this technique for discovery and testing of therapeutic strategies for a disease with ever-increasing clinical significance. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Disease Modeling and Phenotypic Drug Screening for Diabetic Cardiomyopathy using Human Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Faye M. Drawnel

    2014-11-01

    Full Text Available Diabetic cardiomyopathy is a complication of type 2 diabetes, with known contributions of lifestyle and genetics. We develop environmentally and genetically driven in vitro models of the condition using human-induced-pluripotent-stem-cell-derived cardiomyocytes. First, we mimic diabetic clinical chemistry to induce a phenotypic surrogate of diabetic cardiomyopathy, observing structural and functional disarray. Next, we consider genetic effects by deriving cardiomyocytes from two diabetic patients with variable disease progression. The cardiomyopathic phenotype is recapitulated in the patient-specific cells basally, with a severity dependent on their original clinical status. These models are incorporated into successive levels of a screening platform, identifying drugs that preserve cardiomyocyte phenotype in vitro during diabetic stress. In this work, we present a patient-specific induced pluripotent stem cell (iPSC model of a complex metabolic condition, showing the power of this technique for discovery and testing of therapeutic strategies for a disease with ever-increasing clinical significance.

  8. Vidarabine, an Anti-Herpes Virus Agent, Protects Against the Development of Heart Failure With Relatively Mild Side-Effects on Cardiac Function in a Canine Model of Pacing-Induced Dilated Cardiomyopathy.

    Science.gov (United States)

    Nakamura, Takashi; Fujita, Takayuki; Kishimura, Megumi; Suita, Kenji; Hidaka, Yuko; Cai, Wenqian; Umemura, Masanari; Yokoyama, Utako; Uechi, Masami; Ishikawa, Yoshihiro

    2016-11-25

    In heart failure patients, chronic hyperactivation of sympathetic signaling is known to exacerbate cardiac dysfunction. In this study, the cardioprotective effect of vidarabine, an anti-herpes virus agent, which we identified as a cardiac adenylyl cyclase inhibitor, in dogs with pacing-induced dilated cardiomyopathy (DCM) was evaluated. In addition, the adverse effects of vidarabine on basal cardiac function was compared to those of the β-blocker, carvedilol.Methods and Results:Vidarabine and carvedilol attenuated the development of pacing-induced systolic dysfunction significantly and with equal effectiveness. Both agents also inhibited the development of cardiac apoptosis and fibrosis and reduced the Na + -Ca 2+ exchanger-1 protein level in the heart. Importantly, carvedilol significantly enlarged the left ventricle and atrium; vidarabine, in contrast, did not. Vidarabine-treated dogs maintained cardiac response to β-AR stimulation better than carvedilol-treated dogs did. Vidarabine may protect against pacing-induced DCM with less suppression of basal cardiac function than carvedilol in a dog model. (Circ J 2016; 80: 2496-2505).

  9. Relationship between late ventricular potentials and myocardial 123I-metaiodobenzylguanidine scintigraphy in patients with dilated cardiomyopathy with mild to moderate heart failure: results of a prospective study of sudden death events

    International Nuclear Information System (INIS)

    Kasama, Shu; Toyama, Takuji; Kaneko, Yoshiaki; Kurabayashi, Masahiko; Iwasaki, Toshiya; Sumino, Hiroyuki; Kumakura, Hisao; Minami, Kazutomo; Ichikawa, Shuichi; Matsumoto, Naoya; Sato, Yuichi

    2012-01-01

    Late ventricular potentials (LPs) are considered to be useful for identifying patients with heart failure at risk of developing ventricular arrhythmias. 123 I-metaiodobenzylguanidine (MIBG) scintigraphy, which is used to evaluate cardiac sympathetic activity, has demonstrated cardiac sympathetic denervation in patients with malignant ventricular tachyarrhythmias. This study was undertaken to clarify the relationship between LPs and 123 I-MIBG scintigraphy findings in patients with dilated cardiomyopathy (DCM). A total of 56 patients with DCM were divided into an LP-positive group (n = 24) and an LP-negative group (n = 32). During the compensated period, the delayed heart/mediastinum count (H/M) ratio, delayed total defect score (TDS), and washout rate (WR) were determined from 123 I-MIBG images and plasma brain natriuretic peptide (BNP) concentrations were measured. Left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and left ventricular ejection fraction (LVEF) were simultaneously determined by echocardiography. LVEDV, LVESV, LVEF and plasma BNP concentrations were similar in the two groups. However, TDS was significantly higher (35 ± 8 vs. 28 ± 6, p 123 I-MIBG scintigraphic parameters were worse in LP-positive DCM patients than in LP-negative DCM patients. Furthermore, in LP-positive DCM patients with a high WR, the incidence of sudden death events was higher than that in other subgroups of DCM patients. (orig.)

  10. Human pupillary dilation response to deviant auditory stimuli: Effects of stimulus properties and voluntary attention

    Directory of Open Access Journals (Sweden)

    Hsin-I eLiao

    2016-02-01

    Full Text Available A unique sound that deviates from a repetitive background sound induces signature neural responses, such as mismatch negativity and novelty P3 response in electro-encephalography studies. Here we show that a deviant auditory stimulus induces a human pupillary dilation response (PDR that is sensitive to the stimulus properties and irrespective whether attention is directed to the sounds or not. In an auditory oddball sequence, we used white noise and 2000-Hz tones as oddballs against repeated 1000-Hz tones. Participants’ pupillary responses were recorded while they listened to the auditory oddball sequence. In Experiment 1, they were not involved in any task. Results show that pupils dilated to the noise oddballs for approximately 4 s, but no such PDR was found for the 2000-Hz tone oddballs. In Experiments 2, two types of visual oddballs were presented synchronously with the auditory oddballs. Participants discriminated the auditory or visual oddballs while trying to ignore stimuli from the other modality. The purpose of this manipulation was to direct attention to or away from the auditory sequence. In Experiment 3, the visual oddballs and the auditory oddballs were always presented asynchronously to prevent residuals of attention on to-be-ignored oddballs due to the concurrence with the attended oddballs. Results show that pupils dilated to both the noise and 2000-Hz tone oddballs in all conditions. Most importantly, PDRs to noise were larger than those to the 2000-Hz tone oddballs regardless of the attention condition in both experiments. The overall results suggest that the stimulus-dependent factor of the PDR appears to be independent of attention.

  11. Human Pupillary Dilation Response to Deviant Auditory Stimuli: Effects of Stimulus Properties and Voluntary Attention.

    Science.gov (United States)

    Liao, Hsin-I; Yoneya, Makoto; Kidani, Shunsuke; Kashino, Makio; Furukawa, Shigeto

    2016-01-01

    A unique sound that deviates from a repetitive background sound induces signature neural responses, such as mismatch negativity and novelty P3 response in electro-encephalography studies. Here we show that a deviant auditory stimulus induces a human pupillary dilation response (PDR) that is sensitive to the stimulus properties and irrespective whether attention is directed to the sounds or not. In an auditory oddball sequence, we used white noise and 2000-Hz tones as oddballs against repeated 1000-Hz tones. Participants' pupillary responses were recorded while they listened to the auditory oddball sequence. In Experiment 1, they were not involved in any task. Results show that pupils dilated to the noise oddballs for approximately 4 s, but no such PDR was found for the 2000-Hz tone oddballs. In Experiments 2, two types of visual oddballs were presented synchronously with the auditory oddballs. Participants discriminated the auditory or visual oddballs while trying to ignore stimuli from the other modality. The purpose of this manipulation was to direct attention to or away from the auditory sequence. In Experiment 3, the visual oddballs and the auditory oddballs were always presented asynchronously to prevent residuals of attention on to-be-ignored oddballs due to the concurrence with the attended oddballs. Results show that pupils dilated to both the noise and 2000-Hz tone oddballs in all conditions. Most importantly, PDRs to noise were larger than those to the 2000-Hz tone oddballs regardless of the attention condition in both experiments. The overall results suggest that the stimulus-dependent factor of the PDR appears to be independent of attention.

  12. Como o ecocardiograma pode ser útil em predizer a morte em crianças com cardiomiopatia dilatada idiopática? How can the echocardiogram be useful for predicting death in children with idiopathic dilated cardiomyopathy?

    Directory of Open Access Journals (Sweden)

    Vitor Manuel Pereira Azevedo

    2004-06-01

    Full Text Available OBJETIVO: Determinar os fatores preditores ecocardiográficos de morte em crianças com cardiomiopatia dilatada idiopática. MÉTODOS: Estudo retrospectivo de 148 crianças com cardiomiopatia dilatada idiopática diagnosticadas entre setembro/1979 a março/2003. Critérios para inclusão: insuficiência cardíaca e redução da contratilidade no ecocardiograma, na ausência de cardiopatia congênita ou secundária. Foram analisados 470 exames, durante 244,8 meses de evolução. Parâmetros analisados: dimensão do átrio esquerdo (DAE, relação átrio esquerdo/aorta (DAE/Ao, dimensão sistólica (DSVE e diastólica (DDVE do VE, massa do VE (massa, dimensão do ventrículo direito (DVD, fração de ejeção do VE (FE, percentagem de encurtamento do VE (%EC, gravidade da insuficiência das valvas atrioventriculares e da valva pulmonar e medida da pressão sistólica (PsVD e diastólica (PdVD do VD. Foi considerado significativo erro alfa OBJECTIVE: To determine the echocardiographic predicting factors of death in children with idiopathic dilated cardiomyopathy. METHODS: A retrospective study of 148 children with idiopathic dilated cardiomyopathy diagnosed between September 1979 and March 2003 was carried out. The inclusion criteria were as follows: heart failure and a reduction in contractility on the echocardiogram in the absence of congenital or secondary heart disease. Four hundred and seventy examinations during a period of 244.8 months of evolution were analyzed. The following parameters were assessed: left atrial dimension (LAD; left atrium/aorta ratio (LAD/Ao; left ventricular systolic (LVSD and diastolic (LVDD dimensions; left ventricular mass (LVmass; right ventricular dimension (RVD; left ventricular ejection fraction (LVEF; left ventricular shortening fraction (% SH; severity of the insufficiency of the atrioventricular and pulmonary valves; and right ventricular systolic (RVSP and diastolic (RVDP pressures. The significance level

  13. Hipotiroidismo, miocardiopatía dilatada y síndrome nefrótico durante el embarazo Hypothyroidism, dilated cardiomyopathy and nephrotic syndrome during pregnancy

    Directory of Open Access Journals (Sweden)

    Ariel K. Saad

    2011-02-01

    Full Text Available El hipotiroidismo en el embarazo es infrecuente, pero cuando ocurre suele asociarse con complicaciones maternas y fetales. Se presenta el caso de una mujer joven sin antecedentes de enfermedad cardiovascular que consulta por ortopnea, dolor torácico y edema de miembros inferiores. Los exámenes pusieron en evidencia la existencia de insuficiencia cardíaca, hipotiroidismo, síndrome nefrótico e insuficiencia renal. El eco-Doppler mostró dilatación de las cuatro cavidades cardíacas con deterioro grave de la función sistólica. El tratamiento con levotiroxina por vía intravenosa mejoró el cuadro clínico y los parámetros de laboratorio. Se analizan los efectos de la hormona tiroidea sobre el aparato cardiovascular y se comentan los mecanismos fisiopatológicos de la insuficiencia cardíaca en el embarazo.Hypothyroidism during pregnancy is infrequent, but its presence is associated with maternal and fetal complications. We present the case of a young pregnant woman with no previous history of cardiovascular disease, who consulted for orthopnea, chest pain and edema in both legs. Laboratory tests demonstrated a hypothyroid condition and a nephrotic syndrome with renal failure. The echo-Doppler exam showed a four chamber dilatation with systolic dysfunction. Treatment with intravenous levothyroxine improved her medical condition. We analyze the effects of thyroid hormone on the heart and vascular system and discuss the pathophysiologic mechanisms of heart failure during pregnancy.

  14. Survival and echocardiographic evaluation of dogs with idiopathic dilated cardiomyopathy treated with carvedilol Avaliação ecocardiográfica e de sobrevida de cães com cardiomiopatia dilatada idiopática tratados com carvedilol

    Directory of Open Access Journals (Sweden)

    E.C. Soares

    2010-06-01

    Full Text Available Sixty dogs with idiopathic dilated cardiomyopathy were randomly treated with traditional therapy - digitalis, diuretics, angiotensin-converting inhibitors - (group A or treated with these drugs plus carvedilol (group B. Echocardiographic variables were measured before and after 3, 13, 26, and 52 weeks of treatment or until death. Comparisons between groups and time were performed. No significant differences between groups were found in the most of the echocardiographic variables. The left ventricular end-systolic diameter indexed to body surface area (LVESDi increased significantly in the group A dogs compared to the group B animals. The survival of groups A and B dogs were not different (P-value=0.1137. In conclusion, the stability of the LVESDi observed in the group treated with carvedilol may represent the beneficial effect over the ventricular remodeling.Sessenta cães com cardiomiopatia dilatada idiopática receberam, aleatoriamente, tratamento convencional - digitálicos, diuréticos, inibidores da enzima conversora de angiotensina - (grupo A ou esses fármacos mais carvedilol (grupo B. As variáveis ecocardiográficas foram avaliadas antes e depois de três, 13, 26 e 52 semanas de tratamento ou até o óbito. Não foram encontradas diferenças significativas entre os grupos de animais quanto à maioria das variáveis ecocardiográficas. O diâmetro sistólico final do ventrículo esquerdo indexado à superfície corpórea (DSVEi aumentou de forma significativa no grupo A quando comparado ao grupo B. Não se observou diferença na sobrevida dos grupos A e B (P=0,1137. Concluiu-se que a estabilização do DSVEi no grupo tratado com carvedilol pode representar o efeito benéfico deste fármaco sobre o remodelamento ventricular.

  15. Usefulness of {sup 123}I-metaiodobenzylguanidine myocardial scintigraphy for predicting the effectiveness of {beta}-blockers in patients with dilated cardiomyopathy from the standpoint of long-term prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Fujimoto, Shinichiro; Inoue, Aritomo; Hisatake, Shinji; Yamashina, Shohei; Yamashina, Hisayo; Nakano, Hajime; Yamazaki, Junichi [Toho University School of Medicine, Division of Cardiovascular Medicine, Department of Internal Medicine, Ohmori Hospital, Tokyo (Japan)

    2004-10-01

    The usefulness of {sup 123}I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in predicting the effectiveness of {beta}-blocker therapy in dilated cardiomyopathy (DCM) was investigated from the standpoint of long-term prognosis. The subjects were 53 DCM patients in whom {beta}-blockers had been successfully introduced and used for 6 months or longer. When symptoms were stable before the introduction of {beta}-blockers and for up to 1 year thereafter, MIBG myocardial single-photon emission computed tomography was performed and the images analysed to obtain the extent score (EXT), severity score (SEV) and washout rate (WR). At the same time, echocardiography was performed to measure left ventricular ejection fraction (LVEF). Thereafter, patients were placed under observation for an average of 1,314{+-}986 days, with the occurrence of cardiac events as the endpoint. The degree of improvement in WR after introduction of {beta}-blockers was a significant predictor of cardiac events. In fact, none of the patients whose improvement in WR was valued at 10 or higher had cardiac events. Accordingly, using improvement in WR of 10 as the cut-off value, the patients were divided into two groups, ''improved'' and ''unimproved''. There were significant differences between the groups in respect of early EXT, early SEV and WR before the introduction of {beta}-blockers. As regards predictors of WR improvement, multivariate logistic regression analysis demonstrated that early EXT, WR and LVEF were significant predictors. This study shows that, from the standpoint of long-term prognosis, DCM patients who would benefit the most from {beta}-blocker therapy are those with low early EXT and early SEV and high WR before {beta}-blocker introduction regardless of LVEF values. (orig.)

  16. Predicting the effects on patients with dilated cardiomyopathy of {beta}-blocker therapy, by using iodine-123 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) myocardial scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Yoshinaga, Keiichiro; Tahara, Minoru; Torii, Hiroyuki [Kagoshima City Medical Association Hospital (Japan); Kihara, Koichi

    1998-12-01

    We examined whether the iodine-123 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) myocardial scintigraphy was useful for predicting the treatment response to {beta}-blocker in patients with dilated cardiomyopathy (DCM). Sixteen patients with DCM were studied. BMIPP single photon emission computed tomography (SPECT) was performed before {beta}-blocker therapy. The count ratio of the heart (H) to the upper mediastinum (M) (H/M ratio) was calculated. Several measurements including the BMIPP H/M ratio before the administration of metoprorol were retrospectively compared among the 10 ``good responders`` (showing improvement by at least one NYHA class or an increase in the ejection fraction of {>=}0.10, 6 months after the start of the drug therapy) and the 6 ``poor responders.`` The bull`s eye map of BMIPP was divided into 17 areas. Each segmental score was analyzed quantitatively by means of a two-point scoring system (good uptake {>=}67%, poor uptake <67%). The total score was regarded as the uptake score. The H/M ratio was significantly higher in the good responders than in the poor responders (2.41{+-}0.24 vs. 1.86{+-}0.17 p<0.01). There were no significant differences between the two groups in any other variable data at entry. The uptake score was also a good index for predicting the therapeutic effect. When a relative uptake of 67% or higher was scored as 1, uptake scores of 9 to 17 corresponded to good responses (sensitivity=100%, specificity=100%, accuracy=100%, positive and negative predictive value=100%). Although the number of patients studied is small, our results suggest that BMIPP myocardial scintigraphy can predict the response to a {beta}-blocker in patients with DCM. (author)

  17. Missense mutation Lys18Asn in dystrophin that triggers X-linked dilated cardiomyopathy decreases protein stability, increases protein unfolding, and perturbs protein structure, but does not affect protein function.

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    Surinder M Singh

    Full Text Available Genetic mutations in a vital muscle protein dystrophin trigger X-linked dilated cardiomyopathy (XLDCM. However, disease mechanisms at the fundamental protein level are not understood. Such molecular knowledge is essential for developing therapies for XLDCM. Our main objective is to understand the effect of disease-causing mutations on the structure and function of dystrophin. This study is on a missense mutation K18N. The K18N mutation occurs in the N-terminal actin binding domain (N-ABD. We created and expressed the wild-type (WT N-ABD and its K18N mutant, and purified to homogeneity. Reversible folding experiments demonstrated that both mutant and WT did not aggregate upon refolding. Mutation did not affect the protein's overall secondary structure, as indicated by no changes in circular dichroism of the protein. However, the mutant is thermodynamically less stable than the WT (denaturant melts, and unfolds faster than the WT (stopped-flow kinetics. Despite having global secondary structure similar to that of the WT, mutant showed significant local structural changes at many amino acids when compared with the WT (heteronuclear NMR experiments. These structural changes indicate that the effect of mutation is propagated over long distances in the protein structure. Contrary to these structural and stability changes, the mutant had no significant effect on the actin-binding function as evident from co-sedimentation and depolymerization assays. These results summarize that the K18N mutation decreases thermodynamic stability, accelerates unfolding, perturbs protein structure, but does not affect the function. Therefore, K18N is a stability defect rather than a functional defect. Decrease in stability and increase in unfolding decrease the net population of dystrophin molecules available for function, which might trigger XLDCM. Consistently, XLDCM patients have decreased levels of dystrophin in cardiac muscle.

  18. The mitochondrial DNA T16189C polymorphism and HIV-associated cardiomyopathy: a genotype-phenotype association study

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    Poulton Joanna

    2009-04-01

    Full Text Available Abstract Background The mitochondrial DNA (mtDNA T16189C polymorphism, with a homopolymeric C-tract of 10–12 cytosines, is a putative genetic risk factor for idiopathic dilated cardiomyopathy in the African and British populations. We hypothesized that this variant may predispose to dilated cardiomyopathy in people who are infected with the human immunodeficiency virus (HIV. Methods A case-control study of 30 HIV-positive cases with dilated cardiomyopathy and 37 HIV-positive controls without dilated cardiomyopathy was conducted. The study was confined to persons of black African ancestry to minimize confounding of results by population admixture. HIV-positive patients with an echocardiographically confirmed diagnosis of dilated cardiomyopathy and HIV-positive controls with echocardiographically normal hearts were studied. Patients with secondary causes of cardiomyopathy (such as hypertension, diabetes, pregnancy, alcoholism, valvular heart disease, and opportunistic infection were excluded from the study. DNA samples were sequenced for the mtDNA T16189C polymorphism with a homopolymeric C-tract in the forward and reverse directions on an ABI3100 sequencer. Results The cases and controls were well matched for age (median 35 years versus 34 years, P = 0.93, gender (males 60% vs 53%, P = 0.54, and stage of HIV disease (mean CD4 T cell count 260.7/μL vs. 176/μL, P = 0.21. The mtDNA T16189C variant with a homopolymeric C-tract was detected at a frequency of 26.7% (8/30 in the HIV-associated cardiomyopathy cases and 13.5% (5/37 in the HIV-positive controls. There was no significant difference between cases and controls (Odds Ratio 2.33, 95% Confidence Interval 0.67–8.06, p = 0.11. Conclusion The mtDNA T16189C variant with a homopolymeric C-tract is not associated with dilated cardiomyopathy in black African people infected with HIV.

  19. Clínica de cães com cardiomiopatia dilatada idiopática, tratados ou não com carvedilol Clinic of dogs with dilated cardiomyopathy (DCM treated or not by carvedilol

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    Moacir Leomil Neto

    2011-04-01

    -arrhythmics. Carvedilol is a third generation non-selective β-blocker which blocks equally and competitively (β1, β2 and α1 receptors. Produces an evident peripheral vasodilation, exerts anti-oxidative effects, removing free radicals of oxygen and preventing lipidic peroxydation of cardiac membranes, and the loss of myocytes and arrhythmias, as well as reducing mortality rate in human patients. The aim of the present study was to evaluate by physical examination, electrocardiography, radiography, and echocardiography the evolution of dogs with dilated cardiomyopathy (DCM treated by conventional therapy associated to carvedilol. Forty-nine dogs with DCM were divided in two groups: group NT: treated with conventional therapy, and group T: treated with conventional therapy associated to carvedilol. The animals were submitted to clinical and complementary examinations during one year. The results demonstrated that carvedilol therapy presented good tolerability on the dose of 0.3mg kg-1 each 12 hours, prolonged lifetime of the dogs in 30.9%, did not alter systolic or diastolic pressure, reduced heart frequency after three weeks of treatment, significantly enhanced shortening and ejection fractions after six months of treatment, did not promote radiographic or E-septum distance alterations, decreased patients letality, as demonstrated by improvement of clinical score and functional class (heart failure according to NYHA of the animals, obtained three weeks after the beginning of cavedilol therapy.

  20. MRI of the cardiomyopathies

    International Nuclear Information System (INIS)

    Di Cesare, Ernesto

    2001-01-01

    We examined the potentialities of Magnetic resonance imaging (MRI) in the evaluation of the main cardiomyopathies: hypertrophic, dilated, restrictive and arrhythmogenic right ventricular. The hypertrophic cardiomyopathy is generally adequately investigated by echocardiography, that well defines the myocardial thickening and the obstruction of the left ventricular output. However, by echocardiography we still have difficulties in the evaluation of the apex of the left ventricle and the right ventricle involvement. MRI provides a complete evaluation of the heart with a clear evidence also of the echocardiographic dark zones by means of a clear evidence of the apex of the right ventricle. The dilated form is also well investigated by MRI that provides a clear evaluation of the volumes, mass and ejection fraction by means of the 3D analysis including conditions of the ventricular remodelling. Moreover, this technique helps in the differential diagnosis of acute myocarditis. In the acute phase of myocarditis (first 2 weeks), in fact, the myocardium produces high signal intensity on the T2 weighted sequences due to the presence of oedema. The third form of cardiomyopathy is the restrictive one, characterised by reduced diastolic filling and diastolic volume, normality of the systolic function and parietal thickness, interstitial fibrosis and enlargement of both atria. The mean potentiality of MRI is related to the differential diagnosis with constrictive pericarditis. Only in the former, the pericardium appears irregularly thickened with areas exceeding 4 mm of pericardial thickness. Finally, the right ventricular arrhythmogenic cardiomyopathy represents the main indication to MRI evaluation. With this imaging modality we are can obtain a clear morpho-functional evaluation of the right ventricle and distinguish the intramyocardial adipose substitution characterised by areas of high signal in the myocardium

  1. Autologous bone marrow mononuclear cell delivery to dilated ...

    African Journals Online (AJOL)

    Autologous bone marrow mononuclear cell delivery to dilated cardiomyopathy patients: A clinical trial. PLN Kaparthi, G Namita, LK Chelluri, VSP Rao, PK Shah, A Vasantha, SK Ratnakar, K Ravindhranath ...

  2. Genetics Home Reference: early-onset myopathy with fatal cardiomyopathy

    Science.gov (United States)

    ... in childhood, people with EOMFC may also develop joint deformities called contractures that restrict the movement of ... Home Edition for Patients and Caregivers: Dilated Cardiomyopathy Neuromuscular Disease Center, Washington University Orphanet: Early-onset myopathy ...

  3. Embryonic stem cell therapy of heart failure in genetic cardiomyopathy.

    Science.gov (United States)

    Yamada, Satsuki; Nelson, Timothy J; Crespo-Diaz, Ruben J; Perez-Terzic, Carmen; Liu, Xiao-Ke; Miki, Takashi; Seino, Susumu; Behfar, Atta; Terzic, Andre

    2008-10-01

    Pathogenic causes underlying nonischemic cardiomyopathies are increasingly being resolved, yet repair therapies for these commonly heritable forms of heart failure are lacking. A case in point is human dilated cardiomyopathy 10 (CMD10; Online Mendelian Inheritance in Man #608569), a progressive organ dysfunction syndrome refractory to conventional therapies and linked to mutations in cardiac ATP-sensitive K(+) (K(ATP)) channel subunits. Embryonic stem cell therapy demonstrates benefit in ischemic heart disease, but the reparative capacity of this allogeneic regenerative cell source has not been tested in inherited cardiomyopathy. Here, in a Kir6.2-knockout model lacking functional K(ATP) channels, we recapitulated under the imposed stress of pressure overload the gene-environment substrate of CMD10. Salient features of the human malignant heart failure phenotype were reproduced, including compromised contractility, ventricular dilatation, and poor survival. Embryonic stem cells were delivered through the epicardial route into the left ventricular wall of cardiomyopathic stressed Kir6.2-null mutants. At 1 month of therapy, transplantation of 200,000 cells per heart achieved teratoma-free reversal of systolic dysfunction and electrical synchronization and halted maladaptive remodeling, thereby preventing end-stage organ failure. Tracked using the lacZ reporter transgene, stem cells engrafted into host heart. Beyond formation of cardiac tissue positive for Kir6.2, transplantation induced cell cycle activation and halved fibrotic zones, normalizing sarcomeric and gap junction organization within remuscularized hearts. Improved systemic function induced by stem cell therapy translated into increased stamina, absence of anasarca, and benefit to overall survivorship. Embryonic stem cells thus achieve functional repair in nonischemic genetic cardiomyopathy, expanding indications to the therapy of heritable heart failure. Disclosure of potential conflicts of interest is

  4. Tratamento de insuficiência cardíaca com benazepril em cães com cardiomiopatia dilatada e endocardiose Treatment of congestive heart failure with benazepril in dogs with dilated cardiomyopathy and endocardiosis

    Directory of Open Access Journals (Sweden)

    P.M. Pereira

    2005-09-01

    Full Text Available Foram avaliados os efeitos clínicos do benazepril, um inibidor da enzima de conversão da angiotensina de ação prolongada, em cães com insuficiência cardíaca congestiva (ICC secundária à endocardiose de mitral ou cardiomiopatia dilatada. O medicamento foi administrado na dose de 0,25 a 0,5mg/kg/dia. Diuréticos, digitálicos e f��rmacos antiarrítmicos foram usados de acordo com a necessidade de cada paciente. Exames físico, radiográfico e eletrocardiográfico foram realizados nos dias 0, 7, 28 e 56. A gasometria arterial e a bioquímica sérica foram avaliadas nos dias 0 e 56. Os sinais de dispnéia e o estado geral dos pacientes melhoraram em todos os cães após o início do tratamento. Houve diminuição na freqüência da tosse e não houve alterações no eletrocardiograma, exceto pela diminuição na amplitude e na duração da onda P. Nenhum efeito colateral foi observado. Conclui-se que o benazepril é um inibidor da enzima de conversão da angiotensina, eficaz e bem tolerado no tratamento da ICC no cão.Clinical effects of benazepril, a long acting angiotensin-converting enzyme (ACEi, in dogs with naturally-occurring congestive heart failure (CHF caused by mitral endocardiosis or dilated cardiomyopathy were studied. The drug was given orally at a dose of 0.25 to 0.5mg/kg/day. Diuretics, digitalics, and antiarrhtyhmic drugs were given as needed. Physical, radiographic, and eletrocardiographic examination were performed at days 0, 7, 28, and 56. Serum biochemistry and arterial blood gases were obtained at days 0 and 56. Signs of dyspnea and general condition improved in all dogs. Cough decreased in frequency. The electrocardiogram did not change with benazepril use except for a decrease in P wave amplitude and duration. No adverse effects related to the use of benazepril were observed. Benazepril is an effective and well tolerated ACEi for the treatment of CHF in dogs.

  5. Relationship between late ventricular potentials and myocardial {sup 123}I-metaiodobenzylguanidine scintigraphy in patients with dilated cardiomyopathy with mild to moderate heart failure: results of a prospective study of sudden death events

    Energy Technology Data Exchange (ETDEWEB)

    Kasama, Shu [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Gunma (Japan); Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Toyama, Takuji; Kaneko, Yoshiaki; Kurabayashi, Masahiko [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Gunma (Japan); Iwasaki, Toshiya; Sumino, Hiroyuki; Kumakura, Hisao; Minami, Kazutomo; Ichikawa, Shuichi [Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Matsumoto, Naoya [Nihon University School of Medicine, Department of Cardiology, Tokyo (Japan); Sato, Yuichi [Health Park Clinic, Department of Imaging, Gunma (Japan)

    2012-06-15

    Late ventricular potentials (LPs) are considered to be useful for identifying patients with heart failure at risk of developing ventricular arrhythmias. {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy, which is used to evaluate cardiac sympathetic activity, has demonstrated cardiac sympathetic denervation in patients with malignant ventricular tachyarrhythmias. This study was undertaken to clarify the relationship between LPs and {sup 123}I-MIBG scintigraphy findings in patients with dilated cardiomyopathy (DCM). A total of 56 patients with DCM were divided into an LP-positive group (n = 24) and an LP-negative group (n = 32). During the compensated period, the delayed heart/mediastinum count (H/M) ratio, delayed total defect score (TDS), and washout rate (WR) were determined from {sup 123}I-MIBG images and plasma brain natriuretic peptide (BNP) concentrations were measured. Left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and left ventricular ejection fraction (LVEF) were simultaneously determined by echocardiography. LVEDV, LVESV, LVEF and plasma BNP concentrations were similar in the two groups. However, TDS was significantly higher (35 {+-} 8 vs. 28 {+-} 6, p < 0.005), the H/M ratio was significantly lower (1.57 {+-} 0.23 vs. 1.78 {+-} 0.20, p < 0.005), and the WR was significantly higher (60 {+-} 14% vs. 46 {+-} 12%, p < 0.001) in the LP-positive than in the LP-negative group. The average follow-up time was 4.5 years, and there were nine sudden deaths among the 56 patients (16.1%). In logistic regression analysis, the incidences of sudden death events were similar in those LP-negative with WR <50%, LP-negative with WR {>=}50% and LP-positive with WR <50% (0%, 10.0% and 14.3%, respectively), but was significantly higher (41.2%) in those LP-positive with WR {>=}50% (p < 0.01, p < 0.05, and p < 0.05, respectively). The present study demonstrated that the values of cardiac {sup 123}I-MIBG scintigraphic parameters

  6. Genetic Variation in Cardiomyopathy and Cardiovascular Disorders.

    Science.gov (United States)

    McNally, Elizabeth M; Puckelwartz, Megan J

    2015-01-01

    With the wider deployment of massively-parallel, next-generation sequencing, it is now possible to survey human genome data for research and clinical purposes. The reduced cost of producing short-read sequencing has now shifted the burden to data analysis. Analysis of genome sequencing remains challenged by the complexity of the human genome, including redundancy and the repetitive nature of genome elements and the large amount of variation in individual genomes. Public databases of human genome sequences greatly facilitate interpretation of common and rare genetic variation, although linking database sequence information to detailed clinical information is limited by privacy and practical issues. Genetic variation is a rich source of knowledge for cardiovascular disease because many, if not all, cardiovascular disorders are highly heritable. The role of rare genetic variation in predicting risk and complications of cardiovascular diseases has been well established for hypertrophic and dilated cardiomyopathy, where the number of genes that are linked to these disorders is growing. Bolstered by family data, where genetic variants segregate with disease, rare variation can be linked to specific genetic variation that offers profound diagnostic information. Understanding genetic variation in cardiomyopathy is likely to help stratify forms of heart failure and guide therapy. Ultimately, genetic variation may be amenable to gene correction and gene editing strategies.

  7. Acute limb heating improves macro- and microvascular dilator function in the leg of aged humans.

    Science.gov (United States)

    Romero, Steven A; Gagnon, Daniel; Adams, Amy N; Cramer, Matthew N; Kouda, Ken; Crandall, Craig G

    2017-01-01

    Local heating of an extremity increases blood flow and vascular shear stress throughout the arterial tree. Local heating acutely improves macrovascular dilator function in the upper limbs of young healthy adults through a shear stress-dependent mechanism but has no such effect in the lower limbs of this age group. The effect of acute limb heating on dilator function within the atherosclerotic prone vasculature of the lower limbs of aged adults is unknown. Therefore, the purpose of this study was to test the hypothesis that acute lower limb heating improves macro- and microvascular dilator function within the leg vasculature of aged adults. Nine young and nine aged adults immersed their lower limbs at a depth of ~33 cm into a heated (~42°C) circulated water bath for 45 min. Before and 30 min after heating, macro (flow-mediated dilation)- and microvascular (reactive hyperemia) dilator functions were assessed in the lower limb, following 5 min of arterial occlusion, via Doppler ultrasound. Compared with preheat, macrovascular dilator function was unchanged following heating in young adults (P = 0.6) but was improved in aged adults (P = 0.04). Similarly, microvascular dilator function, as assessed by peak reactive hyperemia, was unchanged following heating in young adults (P = 0.1) but was improved in aged adults (P lower limb heating improves both macro- and microvascular dilator function in an age dependent manner. We demonstrate that lower limb heating acutely improves macro- and microvascular dilator function within the atherosclerotic prone vasculature of the leg in aged adults. These findings provide evidence for a potential therapeutic use of chronic lower limb heating to improve vascular health in primary aging and various disease conditions. Copyright © 2017 the American Physiological Society.

  8. [Ventricular tachyarrhythmias in patients with cardiomyopathy

    DEFF Research Database (Denmark)

    Henningsen, K.; Christensen, A.H.; Svendsen, Jesper Hastrup

    2008-01-01

    by disease, gender, age, previous cardiac arrest and treatment with implantable cardioverter-defibrillator (ICD). RESULTS: 993 patients were screened and 128 patients with cardiomyopathy were identified, corresponding to 13% of the screened patients. 58 (45%) of the patients had dilated cardiomyopathy (DCM......), 57 (45%) patients had arrhythmogenic right ventricular cardiomyopathy (ARVC) and 13 (10%) had hypertrophic cardiomyopathy (HCM). The average age was 44 years for HCM, 41 years for ARVC and 58 years for DCM. The majority of the patients were male. ICD treatment was used in 95% of the patients...... with ARVC, 70% of the patients with HCM and 59% of the patients with DCM. Only 5 patients had previous cardiac arrest without reversible cause. CONCLUSION: The study shows that cardiomyopathies are relatively frequent causes of ventricular tachyarrhythmias in patients discharged from a specialised...

  9. Deficient regulatory T cell activity and low frequency of IL-17-producing T cells correlate with the extent of cardiomyopathy in human Chagas' disease.

    Directory of Open Access Journals (Sweden)

    Paulo Marcos Matta Guedes

    Full Text Available BACKGROUND: Myocardium damage during Chagas' disease results from the immunological imbalance between pro- and production of anti-inflammatory cytokines and has been explained based on the Th1-Th2 dichotomy and regulatory T cell activity. Recently, we demonstrated that IL-17 produced during experimental T. cruzi infection regulates Th1 cells differentiation and parasite induced myocarditis. Here, we investigated the role of IL-17 and regulatory T cell during human Chagas' disease. METHODOLOGY/PRINCIPAL FINDINGS: First, we observed CD4(+IL-17(+ T cells in culture of peripheral blood mononuclear cells (PBMC from Chagas' disease patients and we evaluated Th1, Th2, Th17 cytokine profile production in the PBMC cells from Chagas' disease patients (cardiomyopathy-free, and with mild, moderate or severe cardiomyopathy cultured with T. cruzi antigen. Cultures of PBMC from patients with moderate and severe cardiomyopathy produced high levels of TNF-α, IFN-γ and low levels of IL-10, when compared to mild cardiomyopathy or cardiomyopathy-free patients. Flow cytometry analysis showed higher CD4(+IL-17(+ cells in PBMC cultured from patients without or with mild cardiomyopathy, in comparison to patients with moderate or severe cardiomyopathy. We then analyzed the presence and function of regulatory T cells in all patients. All groups of Chagas' disease patients presented the same frequency of CD4(+CD25(+ regulatory T cells. However, CD4(+CD25(+ T cells from patients with mild cardiomyopathy or cardiomyopathy-free showed higher suppressive activity than those with moderate and severe cardiomyopathy. IFN-γ levels during chronic Chagas' disease are inversely correlated to the LVEF (P = 0.007, r = -0.614, while regulatory T cell activity is directly correlated with LVEF (P = 0.022, r = 0.500. CONCLUSION/SIGNIFICANCE: These results indicate that reduced production of the cytokines IL-10 and IL-17 in association with high levels of IFN-γ and TNF

  10. Restrictive cardiomyopathy

    Science.gov (United States)

    ... People with restrictive cardiomyopathy may be heart transplant candidates. The outlook depends on the cause of the ... www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. ...

  11. Peripartum Cardiomyopathy

    Science.gov (United States)

    ... short- ness of breath, and palpitations. •  Electrocardiogram (heart tracing) to assess heart rate and rhythm, to look ... Accessed January 22, 2013. The Peripartum Cardiomyopathy Network Web site. http: / / www. peripartumcmnetwork. pitt. edu. Accessed January ...

  12. Magnetic resonance imaging in familial hypertrophic cardiomyopathy associated with abnormal thallium perfusion and cardiac enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, Tsunehiko; Nagata, Seiki; Sakakibara, Hiroshi

    1988-05-01

    Gated magnetic resonance imaging (MRI) was performed in 6 patients with familial hypertrophic cardiomyopathy associated with abnormal thallium perfusion, and 12 patients with ordinary hypertrophic cardiomyopathy. The patients with ordinary hypertrophic cardiomyopathy and abnormal thickening of the septal wall and normal left ventricular dimensions, while the patients with familial hypertrophic cardiomyopathy had focal wall thinning (usually involving the apical-septal wall) and dilated left ventricle in addition to hypertrophied heart. The quantitative measurement for cardiac dimensions using MRI was similar to that found on echocardiography in all cases. In addition, inhomogeneous signal intensities at left ventricular wall were observed in 3 cases of familial hypertrophic cardiomyopathy, which may suggest the existence of myocardial fibrosis. Gated MRI should be performed for early detection and follow-up of hypertrophic cardiomyopathy, since some patients will progress from hypertrophic cardiomyopathy to dilated cardiomyopathy.

  13. Determinants of Thyrotoxic Cardiomyopathy Recovery

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    Lucia Oliveros-Ruiz

    2013-01-01

    Full Text Available The purpose was to evaluate the effect of the disease duration prior to treatment, thyroid hormones level, or both on the reversibility of dilated cardiomyopathy. Between January 2006 and December 2010, a longitudinal study with a 6 months follow-up was carried on. One hundred and seventy patients with hyperthyroidism were referred to the cardiologist, and 127 had a 6 months followup after antithyroid treatment and were evaluated by echocardiography. Dilated cardiomyopathy reversibility criteria were established according to echocardiographic parameters. Complete reversibility existed when all parameters were met, partial reversibility when LVEF was ≥55% plus two or three other parameters, and no reversibility when LVEF was ≤55% regardless of other parameters. The results showed that echocardiography parameters related to the regression of myocardial mass were associated with a disease duration shorter than 10.38 months. This was the main predictive variable for reversal of dilated cardiomyopathy, followed by β-blocker treatment, and the last predictive variable was the serum level of free triiodothyronine. This study showed that the effect on the myocardium related to thyrotoxicosis was associated with the disease duration before treatment.

  14. High resolution systematic digital histological quantification of cardiac fibrosis and adipose tissue in phospholamban p.Arg14del mutation associated cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Johannes M I H Gho

    Full Text Available Myocardial fibrosis can lead to heart failure and act as a substrate for cardiac arrhythmias. In dilated cardiomyopathy diffuse interstitial reactive fibrosis can be observed, whereas arrhythmogenic cardiomyopathy is characterized by fibrofatty replacement in predominantly the right ventricle. The p.Arg14del mutation in the phospholamban (PLN gene has been associated with dilated cardiomyopathy and recently also with arrhythmogenic cardiomyopathy. Aim of the present study is to determine the exact pattern of fibrosis and fatty replacement in PLN p.Arg14del mutation positive patients, with a novel method for high resolution systematic digital histological quantification of fibrosis and fatty tissue in cardiac tissue. Transversal mid-ventricular slices (n = 8 from whole hearts were collected from patients with the PLN p.Arg14del mutation (age 48±16 years; 4 (50% male. An in-house developed open source MATLAB script was used for digital analysis of Masson's trichrome stained slides (http://sourceforge.net/projects/fibroquant/. Slides were divided into trabecular, inner and outer compact myocardium. Per region the percentage of connective tissue, cardiomyocytes and fatty tissue was quantified. In PLN p.Arg14del mutation associated cardiomyopathy, myocardial fibrosis is predominantly present in the left posterolateral wall and to a lesser extent in the right ventricular wall, whereas fatty changes are more pronounced in the right ventricular wall. No difference in distribution pattern of fibrosis and adipocytes was observed between patients with a clinical predominantly dilated and arrhythmogenic cardiomyopathy phenotype. In the future, this novel method for quantifying fibrosis and fatty tissue can be used to assess cardiac fibrosis and fatty tissue in animal models and a broad range of human cardiomyopathies.

  15. Cardiomyopathy induced by anthracycline

    International Nuclear Information System (INIS)

    Quiroz, Isabel; Espinoza, Gerson; Poveda, Maria; Flores, Walter

    2002-01-01

    Anthracycline cardiomyopathy is less frequently encountered nowadays, due to the well recognized dose limitations and cardiac monitoring protocols used by chemotherapy centers. However, it is a condition that will persist due to the sensitivity of some patients to these drugs and the necessity for large doses to be used for certain individuals. We have demonstrated the benefit of angiotensin converting enzyme inhibitor therapy and would consider introducing these compounds at the earliest opportunity. The use of probucol and vitamins as antioxidants capable of preventing the onset of cardiomyopathy in humans appears to require further investigation but may significantly reduce the incidence of this condition in the future. (The author)

  16. Celiac disease with pulmonary haemosiderosis and cardiomyopathy

    OpenAIRE

    Işikay, Sedat; Yilmaz, Kutluhan; Kilinç, Metin

    2012-01-01

    Celiac disease or pulmonary haemosiderosis can be associated with several distinguished conditions. Pulmonary haemosiderosis is a rare, severe and fatal disease characterised by recurrent episodes of alveolar haemorrhage, haemoptysis and anaemia. Association of pulmonary haemosiderosis and celiac disease is extremely rare. We describe a case of celiac disease presented with dilated cardiomyopathy and pulmonary haemosiderosis without gastrointestinal symptoms of celiac disease. In addition, vi...

  17. MTO1 mutations are associated with hypertrophic cardiomyopathy and lactic acidosis and cause respiratory chain deficiency in humans and yeast.

    Science.gov (United States)

    Baruffini, Enrico; Dallabona, Cristina; Invernizzi, Federica; Yarham, John W; Melchionda, Laura; Blakely, Emma L; Lamantea, Eleonora; Donnini, Claudia; Santra, Saikat; Vijayaraghavan, Suresh; Roper, Helen P; Burlina, Alberto; Kopajtich, Robert; Walther, Anett; Strom, Tim M; Haack, Tobias B; Prokisch, Holger; Taylor, Robert W; Ferrero, Ileana; Zeviani, Massimo; Ghezzi, Daniele

    2013-11-01

    We report three families presenting with hypertrophic cardiomyopathy, lactic acidosis, and multiple defects of mitochondrial respiratory chain (MRC) activities. By direct sequencing of the candidate gene MTO1, encoding the mitochondrial-tRNA modifier 1, or whole exome sequencing analysis, we identified novel missense mutations. All MTO1 mutations were predicted to be deleterious on MTO1 function. Their pathogenic role was experimentally validated in a recombinant yeast model, by assessing oxidative growth, respiratory activity, mitochondrial protein synthesis, and complex IV activity. In one case, we also demonstrated that expression of wt MTO1 could rescue the respiratory defect in mutant fibroblasts. The severity of the yeast respiratory phenotypes partly correlated with the different clinical presentations observed in MTO1 mutant patients, although the clinical outcome was highly variable in patients with the same mutation and seemed also to depend on timely start of pharmacological treatment, centered on the control of lactic acidosis by dichloroacetate. Our results indicate that MTO1 mutations are commonly associated with a presentation of hypertrophic cardiomyopathy, lactic acidosis, and MRC deficiency, and that ad hoc recombinant yeast models represent a useful system to test the pathogenic potential of uncommon variants, and provide insight into their effects on the expression of a biochemical phenotype. © 2013 The Authors. *Human Mutation published by Wiley Periodicals, Inc.

  18. Restrictive Cardiomyopathy

    Science.gov (United States)

    ... up in the circulatory system. In time, the heart fails. What causes it? Restrictive cardiomyopathy is often caused by diseases in other parts of the body. One known cause is cardiac ... build up in the heart tissue, making the tissue stiff and thickened. Cardiac ...

  19. Angiotensin, transforming growth factor β and aortic dilatation in Marfan syndrome: Of mice and humans

    Directory of Open Access Journals (Sweden)

    Christopher Yu

    2018-03-01

    Full Text Available Marfan syndrome is consequent upon mutations in FBN1, which encodes the extracellular matrix microfibrillar protein fibrillin-1. The phenotype is characterised by development of thoracic aortic aneurysm. Current understanding of the pathogenesis of aneurysms in Marfan syndrome focuses upon abnormal vascular smooth muscle cell signalling through the transforming growth factor beta (TGFβ pathway. Angiotensin II (Ang II can directly induce aortic dilatation and also influence TGFβ synthesis and signalling. It has been hypothesised that antagonism of Ang II signalling may protect against aortic dilatation in Marfan syndrome. Experimental studies have been supportive of this hypothesis, however results from multiple clinical trials are conflicting. This paper examines current knowledge about the interactions of Ang II and TGFβ signalling in the vasculature, and critically interprets the experimental and clinical findings against these signalling interactions. Keywords: Aneurysm, Angiotensin blocker, Cell Signalling, Clinical trial

  20. Arrhythmogenic right ventricular cardiomyopathy in a dog : case report

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    A.J. Möhr

    2000-07-01

    Full Text Available An 8-month-old Labrador retriever bitch was evaluated for sudden-onset, progressive abdominal distension. Physical examination revealed an exaggerated inspiratory effort, severe ascites, bilateral jugular vein distension, and hypokinetic femoral arterial pulses. Thoracic auscultation detected tachycardia with muffled heart sounds, without audible cardiac murmurs. Thoracic radiographs identified severe right ventricular enlargement and pleural effusion. The electrocardiogram was consistent with incomplete right bundle branch block or right ventricular enlargement. Echocardiography demonstrated severe right ventricular and atrial dilation, secondary tricuspid regurgitation, and thinning and hypocontractility of the right ventricular myocardium. Left heart chamber sizes were slightly decreased, with normal left ventricular contractility. Adiagnosis of arrhythmogenic right ventricular cardiomyopathy was reached, based on the characteristic clinical, electrocardiographic, radiographic and echocardiographic findings, and the exclusion of other causes of isolated right ventricular failure. Treatment effected good control of clinical signs, until acutely decompensated congestive right heart failure led to euthanasia after 4 months. Arrhythmogenic right ventricular cardiomyopathy is a well-described clinical entity in humans, and has previously been documented in 3 male dogs. The condition is characterised by progressive fibro-adipose replacement of right ventricular myocardium, while the left ventricle usually remains unaffected. It should be considered a differential diagnosis in any young dog presented with isolated right heart failure, syncope, or unexplained ventricular tachyarrhythmias. This article reports the 1st case of arrhythmogenic right ventricular cardiomyopathy in a female dog, and highlights its echocardiographic features.

  1. Cardiomyocytes undergo apoptosis in human immunodeficiency virus cardiomyopathy through mitochondrion- and death receptor-controlled pathways.

    Science.gov (United States)

    Twu, Cheryl; Liu, Nancy Q; Popik, Waldemar; Bukrinsky, Michael; Sayre, James; Roberts, Jaclyn; Rania, Shammas; Bramhandam, Vishnu; Roos, Kenneth P; MacLellan, W Robb; Fiala, Milan

    2002-10-29

    We investigated 18 AIDS hearts (5 with and 13 without cardiomyopathy) by using immunocytochemistry and computerized image analysis regarding the roles of HIV-1 proteins and tumor necrosis factor ligands in HIV cardiomyopathy (HIVCM). HIVCM and cardiomyocyte apoptosis were significantly related to each other and to the expression by inflammatory cells of gp120 and tumor necrosis factor-alpha. In HIVCM heart, active caspase 9, a component of the mitochondrion-controlled apoptotic pathway, and the elements of the death receptor-mediated pathway, tumor necrosis factor-alpha and Fas ligand, were expressed strongly on macrophages and weakly on cardiomyocytes. HIVCM showed significantly greater macrophage infiltration and cardiomyocyte apoptosis rate compared with non-HIVCM. HIV-1 entered cultured neonatal rat ventricular myocytes by macropinocytosis but did not replicate. HIV-1- or gp120-induced apoptosis of rat myocytes through a mitochondrion-controlled pathway, which was inhibited by heparin, AOP-RANTES, or pertussis toxin, suggesting that cardiomyocyte apoptosis is induced by signaling through chemokine receptors. In conclusion, in patients with HIVCM, cardiomyocytes die through both mitochondrion- and death receptor-controlled apoptotic pathways.

  2. Substituição da valva mitral com tração dos músculos papilares em pacientes com miocardiopatia dilatada Mitral valve replacement with chordae tendineae preservation, traction and fixation in end-stage dilated cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Fabio Antonio Gaiotto

    2007-03-01

    Full Text Available OBJETIVO: Avaliar a geometria e a função do ventrículo esquerdo (VE após a troca mitral com tração e fixação dos papilares, em portadores de insuficiência cardíaca terminal com insuficiência mitral secundária. MÉTODO: Dos 20 pacientes avaliados, 70% eram homens, com idade média de 50,2 anos e 55% recebiam inotrópicos. A fração de ejeção (FEVE foi menor que 30% em todos; 85% estavam em classe funcional (CF IV. Dezoito receberam próteses de pericárdio bovino e dois, mecânicas. Os períodos considerados foram: 3, 6, 12 e 18 meses. As variáveis consideradas: volume sistólico do VE (VS, a FEVE, os diâmetros sistólico e diastólico finais (DSF e DDF e os volumes sistólico e diastólico finais (VSF e VDF. No estudo estatístico, empregou-se da análise de variância (AV e o teste de Friedmann (F. A sobrevida foi aferida pelo método de Kaplan-Meyer. RESULTADOS: Dois (10% faleceram no período imediato. A sobrevida no primeiro ano foi de 85%, no segundo, 44%, no terceiro, 44%, no quarto, 44% e no quinto, 44%. A comparação entre pré e 3 meses, empregando-se a AV, não revelou alteração significativa para o VS (p=0,086. Houve acréscimo da FEVE (p=0,008 e decréscimo do DDF (p=0,038; do DSF (p=0,008; do VDF (p=0,029 e do VSF (p=0,009. Os momentos pré, 3 e 6 meses, com o teste F, não revelaram alterações. Entre os momentos pré, 3 meses e final, empregando-se a AV, não houve significância. CONCLUSÃO: Há melhora da FEVE, dos VDF, VSF, DDF e DSF; até o terceiro mês. A partir de então, as variáveis permanecem estáveis.OBJECTIVE: This study aimed at evaluating results of mitral valve replacement using a new technique of complete chordae tendineae adjustment for left ventricular remodeling. METHODS: Twenty end-stage idiopathic dilated cardiomyopathy patients with severe functional mitral valve regurgitation underwent mitral valve replacement. Seventeen (85% were in functional class IV. Both anterior and posterior

  3. Takotsubo cardiomyopathy

    DEFF Research Database (Denmark)

    Nielsen, Lene Hüche; Munk, Kim; Goetzsche, Ole

    2009-01-01

    INTRODUCTION: Sparse information with regard to the electrocardiographic (ECG) changes in Takotsubo cardiomyopathy (TC) is available. The purpose of this study was to describe the clinical characteristics and electrocardiographic changes in a Danish cohort of patients with TC. We discuss the pote......INTRODUCTION: Sparse information with regard to the electrocardiographic (ECG) changes in Takotsubo cardiomyopathy (TC) is available. The purpose of this study was to describe the clinical characteristics and electrocardiographic changes in a Danish cohort of patients with TC. We discuss...... retrospectively from medical records and the hospitals laboratory database. RESULTS: Seven patients with TC were identified comprising six females and one male (mean age 70, range 53-81 years). In the acute phase all patients had ECG changes compatible with ST-elevation acute myocardial infarction (STEMI...

  4. Sincronia ventricular em portadores de miocardiopatia dilatada e indivíduos normais: avaliação através da ventriculografia radioisotópica Ventricular synchrony in patients with dilated cardiomyopathy and normal individuals: assessment by radionuclide ventriculography

    Directory of Open Access Journals (Sweden)

    Simone Cristina S. Brandão

    2007-05-01

    Full Text Available OBJETIVO: Estabelecer parâmetros de sincronia intra- e interventricular em indivíduos normais e compará-los aos de pacientes com miocardiopatia dilatada com e sem distúrbios de condução ao eletrocardiograma (ECG. MÉTODOS: Três grupos de pacientes foram incluídos no estudo: 18 indivíduos (G1 sem cardiopatia e com ECG normal (52+/-12 anos, 29% masculinos; 50 portadores de miocardiopatia dilatada e disfunção ventricular esquerda grave, sendo 20 pacientes (G2 com QRS 120 ms (57+/-12 anos, 60% masculinos. Todos foram submetidos à ventriculografia radioisotópica (VR. Para avaliar dissincronia intraventricular esquerda foi estudada a largura do histograma de fase e para avaliar dissincronia interventricular foi medida a diferença da média do ângulo de fase entre o ventrículo direito e o esquerdo (DifDE. RESULTADOS: As frações de ejeção do ventrículo esquerdo (FEVEs foram: 62±6% (G1, 27±6% (G2 e 22±7% (G3 e do VD foram: 46 ± 4% (G1, 38±9%(G2 e 37±9% (G3. A avaliação da largura do histograma de fase foi de: 89±18 ms (G1, 203±54 ms (G2 e 312±130 ms (G3, pOBJECTIVE: To establish the parameters of intra- and interventricular synchrony in normal individuals and to compare them with patients with dilated cardiomyopathy with and without conduction disorders shown in the electrocardiogram (ECG examination. METHODS: Three groups of patients were included in this study: 18 individuals (G1 with no cardiomyopathy and with a normal ECG (52±12 years, 29% male; 50 patients with dilated cardiomyopathy and severe left ventricular dysfunction, with 20 patients (G2 presenting QRS 120ms (57±12 years, 60% male. All patients underwent RV. Evaluation of left intraventricular dyssynchrony was carried out with the measurement of the phase histogram width and interventricular dyssynchrony was evaluated by the difference of the mean phase angle between the right and left ventricles (RLDif. RESULTS: Left ventricle ejection fractions (LVEFs were

  5. TREATMENT OF PERIPARTUM CARDIOMYOPATHY (REVIEW

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    N. T. Vatutin

    2017-01-01

    Full Text Available The presented review concerns discussion about current insights into treatment of peripartum cardiomyopathy. The definition of peripartum cardiomyopathy and general issues about diagnosis and pathogenesis of the disorder are provided at the head of the review. Particularly, the role of the system «prolactin — cathepsin D — prolactin 16 kDa» in cardiomyopathy development is disclosed. The general approaches to management of the patients are highlighted. The review provides detailed data about indications, adverse effects and derived clinical experience concerning the main pharmacological drugs which had been used in peripartum cardiomyopathy treatment given their possible unfavorable influence on fetus maturation and maternal lactation. The detailed description is provided on diuretics including loop, thiazide and potassium-sparing drugs. It was noted relative safety and efficiency of nitrates and hydralazine in conditions of limited choice from vasodilator group and, particularly, angiotensinconverting-enzyme inhibitors and angiotensin-II receptor blockers which are contraindicated in pregnancy. A special attention is paid to the group of inotropic drugs: levosimendan, milrinone, and cardiac glycosides. The role of β-blockers and ivabradine is disclosed in heart failure treatment of peripartum cardiomyopathy. Anticoagulants were presented in details given that these drugs are justified in severe cardiac chambers dilation, decrease in ejection fraction, and in presence of intracardiac thrombosis. The place of antiarrhythmic drugs administrating in various cardiac rhythm disorders is discussed in the review. The data is given with account of potential influence on fetus in antenatal peripartum cardiomyopathy in which lidocaine and sotalol are the most preferable drugs; adenosine, quinidine, and flecainide are useful with caution, but amiodarone and dronedarone are absolutely contraindicated. Taking into account proposed pathogenic

  6. Paschke Dilations

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    Abraham Westerbaan

    2017-01-01

    Full Text Available In 1973 Paschke defined a factorization for completely positive maps between C*-algebras. In this paper we show that for normal maps between von Neumann algebras, this factorization has a universal property, and coincides with Stinespring's dilation for normal maps into B(H.

  7. Exome Sequencing Identifies a Novel LMNA Splice-Site Mutation and Multigenic Heterozygosity of Potential Modifiers in a Family with Sick Sinus Syndrome, Dilated Cardiomyopathy, and Sudden Cardiac Death.

    Directory of Open Access Journals (Sweden)

    Michael V Zaragoza

    Full Text Available The goals are to understand the primary genetic mechanisms that cause Sick Sinus Syndrome and to identify potential modifiers that may result in intrafamilial variability within a multigenerational family. The proband is a 63-year-old male with a family history of individuals (>10 with sinus node dysfunction, ventricular arrhythmia, cardiomyopathy, heart failure, and sudden death. We used exome sequencing of a single individual to identify a novel LMNA mutation and demonstrated the importance of Sanger validation and family studies when evaluating candidates. After initial single-gene studies were negative, we conducted exome sequencing for the proband which produced 9 gigabases of sequencing data. Bioinformatics analysis showed 94% of the reads mapped to the reference and identified 128,563 unique variants with 108,795 (85% located in 16,319 genes of 19,056 target genes. We discovered multiple variants in known arrhythmia, cardiomyopathy, or ion channel associated genes that may serve as potential modifiers in disease expression. To identify candidate mutations, we focused on ~2,000 variants located in 237 genes of 283 known arrhythmia, cardiomyopathy, or ion channel associated genes. We filtered the candidates to 41 variants in 33 genes using zygosity, protein impact, database searches, and clinical association. Only 21 of 41 (51% variants were validated by Sanger sequencing. We selected nine confirmed variants with minor allele frequencies G, a novel heterozygous splice-site mutation as the primary mutation with rare or novel variants in HCN4, MYBPC3, PKP4, TMPO, TTN, DMPK and KCNJ10 as potential modifiers and a mechanism consistent with haploinsufficiency.

  8. An update on canine cardiomyopathies - is it all in the genes?

    Science.gov (United States)

    Dutton, E; López-Alvarez, J

    2018-04-17

    Dilated cardiomyopathy is the second most common cardiac disease in dogs and causes considerable morbidity and mortality. Primary dilated cardiomyopathy is suspected to be familial, and genetic loci have been associated with the disease in a number of breeds. Because it is an adult-onset disease, usually with late onset, testing breeding dogs and bitches before breeding for a genetic mutation that could lead to dilated cardiomyopathy would be helpful to prevent disease. There is growing evidence that the genetic basis may be multigenic rather than monogenic in the majority of studied breeds. This review article describes the known genetic aspects of canine dilated cardiomyopathy and the implications of genetic tests on heart testing and the future of veterinary cardiology. © 2018 British Small Animal Veterinary Association.

  9. Gallium 67 scintigraphic examination of dilated myocardiopathies

    International Nuclear Information System (INIS)

    Lanfranchi, J.; Sachs, R.N.; Beaudet, B.; Deblock, C.; Tellier, P.

    1989-01-01

    Twenty-seven patients were diagnosed as having dilated cardiomyopathies, based on increases in the cardiothoracic index > 0.50, in the diastolic and systolic diameters of the left ventricle, and in the telediastolic volume of the left ventricle, which was indexed by body surface determined by contrast ventriculography. They underwent gallium 67 scintigraphic examination of the myocardium, in order to non-invasively detect the presence of an inflammatory infiltrate. Fifteen of them also had endomyocardial biopsies and all had virology check-up. The results were disappointing. Only in one case was the scintigraphic image undeniably positive; in 20 other patients the findings were dubious or negative. This technique did not demonstrate the presence of an inflammatory infiltrate and thus an association between myocarditis and dilated cardiomyopathy, could not be established [fr

  10. RESTRICTIVE CARDIOMYOPATHY AND SECONDARY CONGESTIVE HEART FAILURE IN A MCDOWELL'S CARPET PYTHON (MORELIA SPILOTA MCDOWELLI).

    Science.gov (United States)

    Schilliger, Lionel; Chetboul, Valérie; Damoiseaux, Cécile; Nicolier, Alexandra

    2016-12-01

    Echocardiography is an established and noninvasive diagnostic tool used in herpetologic cardiology. Various cardiac lesions have been previously described in reptiles with the exception of restrictive cardiomyopathy. In this case report, restrictive cardiomyopathy and congestive heart failure associated with left atrial and sinus venosus dilation were diagnosed in a 2-yr-old captive lethargic McDowell's carpet python ( Morelia spilota mcdowelli), based on echocardiographic, Doppler, and histopathologic examinations. This cardiomyopathy was also associated with thrombosis within the sinus venosus.

  11. Cardiac chambers and their walls in cardiomyopathies as evaluated with CT

    International Nuclear Information System (INIS)

    Wojtowicz, J.; Pawlak, B.; Lehman, Z.; Karwowski, A.; Akademia Medyczna, Poznan

    1984-01-01

    Thirty-two patients with cardiomyopathy, 25 with hypertrophic and 7 with dilated form were examined by cardiac catheterisation, left ventriculography, selective coronary angiography and ungated cardiac computed tomography. Diffuse hypertrophy, localized hypertrophy and dilated cardiomyopathy were diagnosed and assessed quantitatively based on CT linear, surface and volumetric parameters of cardiac morphology. Absolute septal thickness and left ventricular mass measured in CT image are the most discriminative attributes. (orig.)

  12. Acute peritonitis as the first presentation of valvular cardiomyopathy.

    LENUS (Irish Health Repository)

    Higgins, Nikki

    2012-02-01

    Valvular cardiomyopathy can present a diagnostic challenge in the absence of overt cardiac symptoms. This report describes the case of a 46-year-old woman who presented with acute peritonitis associated with vomiting and abdominal distension. Subsequent abdominal computed tomography and ultrasound revealed bibasal pleural effusions, ascites, and normal ovaries. An echocardiogram revealed that all cardiac chambers were dilated with a global decrease in contractility and severe mitral, tricuspid, and aortic regurgitation. A diagnosis of cardiomyopathy with acute heart failure, secondary to valvular heart disease, was secured. Acute peritonitis as the presenting feature of valvular cardiomyopathy is a rare clinical entity.

  13. Reversible catecholamine-induced cardiomyopathy due to pheochromocytoma: case report.

    Science.gov (United States)

    Satendra, Milan; de Jesus, Cláudia; Bordalo e Sá, Armando L; Rosário, Luís; Rocha, José; Bicha Castelo, Henrique; Correia, Maria José; Nunes Diogo, António

    2014-03-01

    Pheochromocytoma is a tumor originating from chromaffin tissue. It commonly presents with symptoms and signs of catecholamine excess, such as hypertension, tachycardia, headache and sweating. Cardiovascular manifestations include catecholamine-induced cardiomyopathy, which may present as severe left ventricular dysfunction and congestive heart failure. We report a case of pheochromocytoma which was diagnosed following investigation of dilated cardiomyopathy. We highlight the dramatic symptomatic improvement and reversal of cardiomyopathy, with recovery of left ventricular function after treatment. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  14. Human Engineered Cardiac Tissues Created Using Induced Pluripotent Stem Cells Reveal Functional Characteristics of BRAF-Mediated Hypertrophic Cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Timothy J Cashman

    Full Text Available Hypertrophic cardiomyopathy (HCM is a leading cause of sudden cardiac death that often goes undetected in the general population. HCM is also prevalent in patients with cardio-facio-cutaneous syndrome (CFCS, which is a genetic disorder characterized by aberrant signaling in the RAS/MAPK signaling cascade. Understanding the mechanisms of HCM development in such RASopathies may lead to novel therapeutic strategies, but relevant experimental models of the human condition are lacking. Therefore, the objective of this study was to develop the first 3D human engineered cardiac tissue (hECT model of HCM. The hECTs were created using human cardiomyocytes obtained by directed differentiation of induced pluripotent stem cells derived from a patient with CFCS due to an activating BRAF mutation. The mutant myocytes were directly conjugated at a 3:1 ratio with a stromal cell population to create a tissue of defined composition. Compared to healthy patient control hECTs, BRAF-hECTs displayed a hypertrophic phenotype by culture day 6, with significantly increased tissue size, twitch force, and atrial natriuretic peptide (ANP gene expression. Twitch characteristics reflected increased contraction and relaxation rates and shorter twitch duration in BRAF-hECTs, which also had a significantly higher maximum capture rate and lower excitation threshold during electrical pacing, consistent with a more arrhythmogenic substrate. By culture day 11, twitch force was no longer different between BRAF and wild-type hECTs, revealing a temporal aspect of disease modeling with tissue engineering. Principal component analysis identified diastolic force as a key factor that changed from day 6 to day 11, supported by a higher passive stiffness in day 11 BRAF-hECTs. In summary, human engineered cardiac tissues created from BRAF mutant cells recapitulated, for the first time, key aspects of the HCM phenotype, offering a new in vitro model for studying intrinsic mechanisms and

  15. Genetic basis of arrhythmogenic cardiomyopathy.

    Science.gov (United States)

    Karmouch, Jennifer; Protonotarios, Alexandros; Syrris, Petros

    2018-05-01

    To date 16 genes have been associated with arrhythmogenic cardiomyopathy (ACM). Mutations in these genes can lead to a broad spectrum of phenotypic expression ranging from disease affecting predominantly the right or left ventricle, to biventricular subtypes. Understanding the genetic causes of ACM is important in diagnosis and management of the disorder. This review summarizes recent advances in molecular genetics and discusses the application of next-generation sequencing technology in genetic testing in ACM. Use of next-generation sequencing methods has resulted in the identification of novel causative variants and genes for ACM. The involvement of filamin C in ACM demonstrates the genetic overlap between ACM and other types of cardiomyopathy. Putative pathogenic variants have been detected in cadherin 2 gene, a protein involved in cell adhesion. Large genomic rearrangements in desmosome genes have been systematically investigated in a cohort of ACM patients. Recent studies have identified novel causes of ACM providing new insights into the genetic spectrum of the disease and highlighting an overlapping phenotype between ACM and dilated cardiomyopathy. Next-generation sequencing is a useful tool for research and genetic diagnostic screening but interpretation of identified sequence variants requires caution and should be performed in specialized centres.

  16. Mechanisms of pro-arrhythmic abnormalities in ventricular repolarisation and anti-arrhythmic therapies in human hypertrophic cardiomyopathy.

    Science.gov (United States)

    Passini, Elisa; Mincholé, Ana; Coppini, Raffaele; Cerbai, Elisabetta; Rodriguez, Blanca; Severi, Stefano; Bueno-Orovio, Alfonso

    2016-07-01

    Hypertrophic cardiomyopathy (HCM) is a cause of sudden arrhythmic death, but the understanding of its pro-arrhythmic mechanisms and an effective pharmacological treatment are lacking. HCM electrophysiological remodelling includes both increased inward and reduced outward currents, but their role in promoting repolarisation abnormalities remains unknown. The goal of this study is to identify key ionic mechanisms driving repolarisation abnormalities in human HCM, and to evaluate anti-arrhythmic effects of single and multichannel inward current blocks. Experimental ionic current, action potential (AP) and Ca(2+)-transient (CaT) recordings were used to construct populations of human non-diseased and HCM AP models (n=9118), accounting for inter-subject variability. Simulations were conducted for several degrees of selective and combined inward current block. Simulated HCM cardiomyocytes exhibited prolonged AP and CaT, diastolic Ca(2+) overload and decreased CaT amplitude, in agreement with experiments. Repolarisation abnormalities in HCM models were consistently driven by L-type Ca(2+) current (ICaL) re-activation, and ICaL block was the most effective intervention to normalise repolarisation and diastolic Ca(2+), but compromised CaT amplitude. Late Na(+) current (INaL) block partially abolished repolarisation abnormalities, with small impact on CaT. Na(+)/Ca(2+) exchanger (INCX) block effectively restored repolarisation and CaT amplitude, but increased Ca(2+) overload. Multichannel block increased efficacy in normalising repolarisation, AP biomarkers and CaT amplitude compared to selective block. Experimentally-calibrated populations of human AP models identify ICaL re-activation as the key mechanism for repolarisation abnormalities in HCM, and combined INCX, INaL and ICaL block as effective anti-arrhythmic therapies also able to partially reverse the HCM electrophysiological phenotype. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Percutaneous balloon dilation of pulmonary stenosis

    International Nuclear Information System (INIS)

    Hua Yangde; Huang Ming; Li Jinkang; Qian Jinqing; Chen Xiuyu; Yang Siyuan

    2003-01-01

    Objective: Review our experience of balloon dilation of valvular pulmonary stenosis in 32 cases. Methods: Totally 32 cases of pulmonary stenosis admitted from 1995-2001 with age of 1.5-13 yrs mean 6.8. Diagnosis was made by clinical manifestations, EKG, ECHO and angiocardiography. Results: Before dilation, the mean systolic pressure of right ventricle was (93.5 ± 28.5) mmHg, after the procedure it reduced to (42 ± 9.0) mmHg. The pressure gradient between right ventricle and pulmonary artery before dilation was (76 ± 30) mmHg and become (24.5 ± 8.5) mmHg after dilation. The gradient pressure after dilation was less than 25 mmHg in 90.6% cases. A case of Noonan syndrome showed no response to balloon dilation and died during valvulectomy from accompanying left ventricular cardiomyopathy. Conclusions: Balloon dilation of valvular pulmonary stenosis is effective and safe. The selection of proper diameter of pulmonary valvular rings and sized of the balloon are the major factors

  18. Metabolic imaging of patients with cardiomyopathy

    International Nuclear Information System (INIS)

    Geltman, E.M.

    1991-01-01

    The cardiomyopathies comprise a diverse group of illnesses that can be characterized functionally by several techniques. However, the delineation of derangements of regional perfusion and metabolism have been accomplished only relatively recently with positron emission tomography (PET). Regional myocardial accumulation and clearance of 11C-palmitate, the primary myocardial substrate under most conditions, demonstrate marked spatial heterogeneity when studied under fasting conditions or with glucose loading. PET with 11C-palmitate permits the noninvasive differentiation of patients with nonischemic from ischemic dilated cardiomyopathy, since patients with ischemic cardiomyopathy demonstrate large zones of intensely depressed accumulation of 11C-palmitate, probably reflecting prior infarction. Patients with hypertrophic cardiomyopathy and Duchenne's muscular dystrophy demonstrate relatively unique patterns of myocardial abnormalities of perfusion and metabolism. The availability of new tracers and techniques for the evaluation of myocardial metabolism (11C-acetate), perfusion (H2(15)O), and autonomic tone (11-C-hydroxyephedrine) should facilitate further understanding of the pathogenesis of the cardiomyopathies

  19. Fatores prognósticos e evolução da função ventricular em 5 anos de seguimento da ventriculectomia parcial esquerda no tratamento da cardiomiopatia dilatada Prognostic factors in the follow-up of patients with idiopathic dilated cardiomyopathy submitted to partial left ventriculectomy

    Directory of Open Access Journals (Sweden)

    Luiz Felipe P. MOREIRA

    2001-12-01

    Full Text Available OBJETIVO: Nesta investigação, os resultados tardios da ventriculectomia parcial esquerda, associada à correção da insuficiência das valvas atrioventriculares, foram estudados em 43 pacientes portadores de cardiomiopatia dilatada. CASUÍSTICA E MÉTODOS: Os pacientes estavam em classe funcional III (18 ou IV (25 no pré-operatório, sendo que 7 pacientes foram operados na vigência de choque cardiogênico. A redução cirúrgica do volume do ventrículo esquerdo (VE foi associada à anuloplastia mitral em 32 pacientes e à substituição daquela valva em 3. Em 10 pacientes, também foi realizada plastia de valva tricúspide. Doze pacientes foram submetidos ao implante de desfibriladores automáticos. RESULTADOS: Ocorreram 9 (20,9% óbitos hospitalares. O tempo de seguimento pós-operatório variou entre dois e 68 meses, com média de 34,2 meses. Aos seis meses de seguimento, 8 pacientes estavam em classe funcional I, 13 em classe II, 3 em classe III e 1 em classe IV (pOBJECTIVE: Partial left ventriculectomy has been performed in patients with severe cardiomyopathies. The purpose of this investigation is to document the clinical effects of this procedure, associated with mitral insufficiency correction, in 43 patients with idiopathic dilated cardiomyopathy. METHODS: Eighteen patients were in New York Heart Association class III and 25 were in persistent class IV. Seven of these patients were operated on in cardiogenic shock. The procedure was associated with mitral anuloplasty in 32 patients and with mitral replacement in three. Ten patients were also submitted to De Vega tricuspid valve anuloplasty. Automatic cardioverter-defibrillators were implanted in 12 patients. RESULTS: Nine (20.9% patients died during the hospital period. The follow-up time ranged from two to 57 months, with a mean of 28.3 months. At six months of follow-up, eight patients were in functional class I, 13 patients in class II, three patients in class III e one patient

  20. Peripartum cardiomyopathy

    International Nuclear Information System (INIS)

    Velasquez V, Jorge E; Duque R, Mauricio

    2008-01-01

    Peripartum cardiomyopathy is a clinical entity with a variable frequency according to the zone of the study. It is characterized by a systolic dysfunction of the left ventricle and posterior appearance of heart failure symptoms that occur during the last month of pregnancy and the first post-partum months. Its etiology isn't still clear, but different theories are proposed based on inflammatory, infectious and autoimmune processes. Alterations related to oxidative stress that could largely explain this pathology were recently described. Its clinical presentation has a big similitude with all other causes of heart failure although atypical presentations have been described. Its diagnosis requires a high suspicion level and must be considered in any woman with symptoms of heart failure during the peripartum. The conventional treatment of chronic heart failure that includes beta-blockers, angiotensin converting enzyme inhibitors and diuretics, in addition to the advances in diagnosis and management of acute heart failure, allowed changing the history of the disease by lowering mortality and recovering systolic function of the left ventricle. Gestations posterior to the development of this entity will depend on the complete recovery of heart function without lowering the risk of recurrence. There still remain many questions to answer in areas like etiology, risk factors, treatment and prognosis markers that may allow to prevent and to manage in an appropriate and safe way both the mother and her son.

  1. Effect of black tea consumption on brachial artery flow-mediated dilation and ischaemia-reperfusion in humans.

    Science.gov (United States)

    Schreuder, Tim H A; Eijsvogels, Thijs M H; Greyling, Arno; Draijer, Richard; Hopman, Maria T E; Thijssen, Dick H J

    2014-02-01

    Tea consumption is associated with reduced cardiovascular risk. Previous studies found that tea flavonoids work through direct effects on the vasculature, leading to dose-dependent improvements in endothelial function. Cardioprotective effects of regular tea consumption may relate to the prevention of endothelial ischaemia-reperfusion (IR) injury. Therefore, we examined the effect of black tea consumption on endothelial function and the ability of tea to prevent IR injury. In a randomized, crossover study, 20 healthy subjects underwent 7 days of tea consumption (3 cups per day) or abstinence from tea. We examined brachial artery (BA) endothelial function via flow-mediated dilation (FMD), using high resolution echo-Doppler, before and 90 min after tea or hot water consumption. Subsequently, we followed a 20-min ischaemia and 20-min reperfusion protocol of the BA after which we measured FMD to examine the potential of tea consumption to protect against IR injury. Tea consumption resulted in an immediate increase in FMD% (pre-consumption: 5.8 ± 2.5; post-consumption: 7.2 ± 3.2; p FMD (p FMD. However, the impact of the IR protocol on FMD was not influenced by tea consumption. Therefore, the cardioprotective association of tea ingestion relates to a direct effect of tea on the endothelium in humans in vivo.

  2. Different gene expression in human heart tissue and progenitor cells from control and diabetic subjects: relevance to the pathogenesis of human diabetic cardiomyopathy.

    Science.gov (United States)

    de Cillis, Emanuela; Leonardini, Anna; Laviola, Luigi; Giorgino, Francesco; Tupputi Schinosa, Luigi de Luca; Bortone, Alessandro Santo

    2010-04-01

    The The aim of our study is to investigate the molecular mechanisms of diabetic cardiomyopathy through the identification of remarkable genes for the myocardial function that are expressed differently between diabetic and normal subjects. Moreover, we intend to characterize both in human myocardial tissue and in the related cardiac progenitor cells the pattern of gene expression and the levels of expression and protein activation of molecular effectors involved in the regulation of the myocardial function and differentiation to clarify whether in specific human pathological conditions (type 2 diabetes mellitus, cardiac failure, coronary artery disease) specific alterations of the aforementioned factors could take place. Thirty-five patients scheduled for coronary artery bypass grafting (CABG) or for aortic or mitral valve replacement were recruited into the study. There were 13 men and 22 women with a mean age of 64.8 +/- 13.4 years. A list of anamnestic, anthropometric, clinical, and instrumental data required for an optimal phenotypical characterization of the patients is reported. The small cardiac biopsy specimens were placed in the nourishing buffer, in a sterile tube provided the day of the procedure, to maintain the stability of the sample for several hours at room temperature. The cells were isolated by a dedicated protocol and then cultured in vitro. The sample was processed for total RNA extraction and levels of gene expression and protein activation of molecular effectors involved in the regulation of function and differentiation of human myocardium was analyzed. In particular, cardiac genes that modulate the oxidative stress response or the stress induced by pro-inflammatory cytokines (p66Shc, SOCS-1, SOCS-3) were analyzed. From a small sample of myocardium cardiac stem cells and cardiomyoblasts were also isolated and characterized. These cells showed a considerable proliferative capacity due to the fact that they demonstrate stability up to the

  3. Echomorphology of cardiomyopathy: review of 217 cases from 1999 to 2010

    International Nuclear Information System (INIS)

    Ilyas, S.; Ilyas, H.; Fawad, A.; Hameed, A.; Fazli, A.

    2013-01-01

    Objective: To study echocardiogram features of different types of cardiomyopathy presenting over a 12 year period at a single centre in Peshawar. Methods: The series comprised a retrospective review of 13,788 consecutive echocardiograms carried out at the Muhammadi Hospital International Medical Research Centre, Hayatabad, Peshawar, from January 1999 to December 2010. Patients were split into two: Group I with paediatric and adolescent cases (0-18 years) and Group II with adults (>18 years). In the adult group, women with peripartum cardiomyopathy were subdivided into two groups of 18-30 years and 30 to 44 years. Standard Echo B and M modes and Doppler parameters were recorded to ascertain the diagnoses of common primary and secondary cardiomyopathies. Patients with myocarditis with chambers dilatation and global dysfunction, and cardiopathy associated with major cardiovascular diseases were excluded. SPSS 14 was used for statistical analysis. Results: Cardiomyopathy was diagnosed in 217 (1.57%) cases. There were 144 (66%) cases of dilated cardiomyopathy with a mean age of 13+-14.8 years; 17 (8%) cases of hypertrophic cardiomyopathy with a mean age of 12+-11.5 years; and 7 (3%) cases of restrictive cardiomyopathy with a mean age of 31+-7.8 years. Primary cardiac amyloidosis was confirmed in 9 (4%) cases, and peripartum cardiomyopathy in 25 (11%) females. Rare subtypes were found in 15 (7%) cases. Conclusion: DCM was the most frequently diagnosed subtype of cardiomyopathy followed by HCM in both the adult and paediatric age groups. (author)

  4. Harmonic Force Spectroscopy Reveals a Force-Velocity Curve from a Single Human Beta Cardiac Myosin Motor

    DEFF Research Database (Denmark)

    Sung, Jongmin; Nag, Suman; Vestergaard, Christian L.

    2014-01-01

    human beta cardiac myosin S1. We also compare load-velocity curves for wild-type motors with load-velocity curves of mutant forms that cause hypertrophic or dilated-cardiomyopathy (HCM or DCM), in order to understand the effects of mutations on the contractile cycle at the single molecule level....

  5. Cardiomyopathies in Noonan syndrome and the other RASopathies

    Science.gov (United States)

    Gelb, Bruce D.; Roberts, Amy E.; Tartaglia, Marco

    2015-01-01

    Noonan syndrome and related disorders (Noonan syndrome with multiple lentigines, Costello syndrome, cardiofaciocutaneous syndrome, Noonan syndrome with loose anagen hair, and other related traits) are autosomal dominant traits. Mutations causing these disorders alter proteins relevant for signaling through RAS. Thus, these traits are now collectively called the RASopathies. While the RASopathies have pleiomorphic features, this review will focus on the hypertrophic cardiomyopathy observed in varying percentages of all of these traits. In addition, inherited abnormalities in one pathway gene, RAF1, cause pediatric-onset dilated cardiomyopathy. The pathogeneses for the RASopathy-associated cardiomyopathies are being elucidated, principally using animal models, leading to genotype-specific insights into how signal transduction is perturbed. Based on those findings, small molecule therapies seem possible for RASopathy-associated cardiomyopathies. PMID:26380542

  6. Smooth muscle LDL receptor-related protein-1 deletion induces aortic insufficiency and promotes vascular cardiomyopathy in mice.

    Directory of Open Access Journals (Sweden)

    Joshua E Basford

    Full Text Available Valvular disease is common in patients with Marfan syndrome and can lead to cardiomyopathy. However, some patients develop cardiomyopathy in the absence of hemodynamically significant valve dysfunction, suggesting alternative mechanisms of disease progression. Disruption of LDL receptor-related protein-1 (Lrp1 in smooth muscle cells has been shown to cause vascular pathologies similar to Marfan syndrome, with activation of smooth muscle cells, vascular dysfunction and aortic aneurysms. This study used echocardiography and blood pressure monitoring in mouse models to determine whether inactivation of Lrp1 in vascular smooth muscle leads to cardiomyopathy, and if so, whether the mechanism is a consequence of valvular disease. Hemodynamic changes during treatment with captopril were also assessed. Dilation of aortic roots was observed in young Lrp1-knockout mice and progressed as they aged, whereas no significant aortic dilation was detected in wild type littermates. Diastolic blood pressure was lower and pulse pressure higher in Lrp1-knockout mice, which was normalized by treatment with captopril. Aortic dilation was followed by development of aortic insufficiency and subsequent dilated cardiomyopathy due to valvular disease. Thus, smooth muscle cell Lrp1 deficiency results in aortic dilation and insufficiency that causes secondary cardiomyopathy that can be improved by captopril. These findings provide novel insights into mechanisms of cardiomyopathy associated with vascular activation and offer a new model of valvular cardiomyopathy.

  7. A mutation in the mitochondrial fission gene Dnm1l leads to cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Houman Ashrafian

    2010-06-01

    Full Text Available Mutations in a number of genes have been linked to inherited dilated cardiomyopathy (DCM. However, such mutations account for only a small proportion of the clinical cases emphasising the need for alternative discovery approaches to uncovering novel pathogenic mutations in hitherto unidentified pathways. Accordingly, as part of a large-scale N-ethyl-N-nitrosourea mutagenesis screen, we identified a mouse mutant, Python, which develops DCM. We demonstrate that the Python phenotype is attributable to a dominant fully penetrant mutation in the dynamin-1-like (Dnm1l gene, which has been shown to be critical for mitochondrial fission. The C452F mutation is in a highly conserved region of the M domain of Dnm1l that alters protein interactions in a yeast two-hybrid system, suggesting that the mutation might alter intramolecular interactions within the Dnm1l monomer. Heterozygous Python fibroblasts exhibit abnormal mitochondria and peroxisomes. Homozygosity for the mutation results in the death of embryos midway though gestation. Heterozygous Python hearts show reduced levels of mitochondria enzyme complexes and suffer from cardiac ATP depletion. The resulting energy deficiency may contribute to cardiomyopathy. This is the first demonstration that a defect in a gene involved in mitochondrial remodelling can result in cardiomyopathy, showing that the function of this gene is needed for the maintenance of normal cellular function in a relatively tissue-specific manner. This disease model attests to the importance of mitochondrial remodelling in the heart; similar defects might underlie human heart muscle disease.

  8. A human type 5 adenovirus-based Trypanosoma cruzi therapeutic vaccine re-programs immune response and reverses chronic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Isabela Resende Pereira

    2015-01-01

    Full Text Available Chagas disease (CD, caused by the protozoan Trypanosoma cruzi, is a prototypical neglected tropical disease. Specific immunity promotes acute phase survival. Nevertheless, one-third of CD patients develop chronic chagasic cardiomyopathy (CCC associated with parasite persistence and immunological unbalance. Currently, the therapeutic management of patients only mitigates CCC symptoms. Therefore, a vaccine arises as an alternative to stimulate protective immunity and thereby prevent, delay progression and even reverse CCC. We examined this hypothesis by vaccinating mice with replication-defective human Type 5 recombinant adenoviruses (rAd carrying sequences of amastigote surface protein-2 (rAdASP2 and trans-sialidase (rAdTS T. cruzi antigens. For prophylactic vaccination, naïve C57BL/6 mice were immunized with rAdASP2+rAdTS (rAdVax using a homologous prime/boost protocol before challenge with the Colombian strain. For therapeutic vaccination, rAdVax administration was initiated at 120 days post-infection (dpi, when mice were afflicted by CCC. Mice were analyzed for electrical abnormalities, immune response and cardiac parasitism and tissue damage. Prophylactic immunization with rAdVax induced antibodies and H-2Kb-restricted cytotoxic and interferon (IFNγ-producing CD8+ T-cells, reduced acute heart parasitism and electrical abnormalities in the chronic phase. Therapeutic vaccination increased survival and reduced electrical abnormalities after the prime (analysis at 160 dpi and the boost (analysis at 180 and 230 dpi. Post-therapy mice exhibited less heart injury and electrical abnormalities compared with pre-therapy mice. rAdVax therapeutic vaccination preserved specific IFNγ-mediated immunity but reduced the response to polyclonal stimuli (anti-CD3 plus anti-CD28, CD107a+ CD8+ T-cell frequency and plasma nitric oxide (NO levels. Moreover, therapeutic rAdVax reshaped immunity in the heart tissue as reduced the number of perforin+ cells

  9. Increased myosin heavy chain-beta with atrial expression of ventricular light chain-2 in canine cardiomyopathy.

    Science.gov (United States)

    Fuller, Geraldine A; Bicer, Sabahattin; Hamlin, Robert L; Yamaguchi, Mamoru; Reiser, Peter J

    2007-10-01

    Dilated cardiomyopathy is a naturally occurring disease in humans and dogs. Human studies have shown increased levels of myosin heavy chain (MHC)-beta in failing ventricles and the left atria (LA) and of ventricular light chain (VLC)-2 in the right atria in dilated cardiomyopathy. This study evaluates the levels of MHC-beta in all heart chambers in prolonged canine right ventricular pacing. In addition, we determined whether levels of VLC2 were altered in these hearts. Failing hearts demonstrated significantly increased levels of MHC-beta in the right atria, right atrial appendage, LA, left atrial appendage (LAA), and right ventricle compared with controls. Significant levels of VLC2 were detected in the right atria of paced hearts. Differences in MHC-beta expression were observed between the LA and the LAA of paced and control dogs. MHC-beta expression was significantly greater in the LA of paced and control dogs compared with their respective LAA. The cardiac myosin isoform shifts in this study were similar to those observed in end-stage human heart failure and more severe than those reported in less prolonged pacing models, supporting the use of this model for further study of end-stage human heart failure. The observation of consistent differences between sampling sites, especially LA versus LAA, indicates the need for rigorous sampling consistency in future studies.

  10. Use of I-123 MIBG cardiac scintigraphy to assess the impact of carvedilol on cardiac adrenergic neuronal function in childhood dilated cardiomyopathy; Interet de la scintigraphie cardiaque a l'I-123 MIBG pour evaluer l'impact du carvedilol sur la fonction neuronale adrenergique cardiaque dans les myocardiopathies dilatees de l'enfant

    Energy Technology Data Exchange (ETDEWEB)

    Maunoury, C. [Hopital Europeen Georges Pompidou (HEGP), Dept. de Physiologie et Radio-Isotopes, 75 - Paris (France); Acar, P. [Centre Hospitalier Universitaire, Service de Cardiologie Pediatrique, Hopital des Enfants, 31 - Toulouse (France); Sidi, D. [Centre Hospitalier Universitaire Necker-Enfants-Malades, 75 - Paris (France)

    2006-04-15

    I-123 MIBG cardiac scintigraphy is a useful tool to assess cardiac adrenergic neuronal function, which is impaired in children with dilated cardiomyopathy (DCM). In adults with DCM, long-term treatment with carvedilol improves both cardiac adrenergic neuronal function and left ventricular function. The aim of this prospective study was to evaluate the impact of carvedilol on cardiac adrenergic neuronal function and on left ventricular function in seventeen patients (11 female, 6 male, mean age 39 {+-} 57 months, range 1 - 168 months) with DCM. All patients underwent I-123 MIBG cardiac scintigraphy and equilibrium radio-nuclide angiography before and after a 6 month period of carvedilol therapy. A static anterior view of the chest was acquired 4 hours after intravenous injection of 20 to 75 MBq of I-123 MIBG. Cardiac neuronal uptake of I-123 MIBG was measured using the heart to mediastinum count ratio (HMR). Radionuclide left ventricular ejection fraction (LVEF) was assessed following a standard protocol. There was no major cardiac events (death or transplantation) during the follow-up period. I-123 MIBG cardiac uptake and left ventricular function respectively increased by 38% and 65% after 6 months of treatment with carvedilol (HMR 223 {+-} 49% vs 162 {+-} 26%, p < 0.0001 and LVEF = 43 {+-} 17% vs 26 {+-} 11%, p < 0.0001). Carvedilol can improve cardiac adrenergic neuronal function and left ventricular function in children with DCM. Further studies are needed to assess the relationship between improvement in I-123 MIBG cardiac uptake and the beneficial effects of carvedilol on morbidity and mortality. (authors)

  11. Evolução clínica e capacidade funcional de pacientes com cardiomiopatia dilatada após quatro anos do transplante Clinical and functional capacity of patients with dilated cardiomyopathy after four years of transplantation

    Directory of Open Access Journals (Sweden)

    Daniela Gardano Bucharles Mont'Alverne

    2012-12-01

    Full Text Available OBJETIVO: Avaliar a evolução do paciente miocardiopata após transplante (Tx cardíaco, analisando sua sobrevida, complicações trans e pós-operatórias e respostas cardiovasculares após cerca de quatro anos do procedimento cirúrgico. MÉTODOS: A pesquisa foi realizada no período de fevereiro a maio de 2011, com pacientes submetidos a Tx cardíaco no Hospital Dr. Carlos Alberto Studart Gomes - Hospital de Messejana (HDM. A amostra foi composta de todos os pacientes transplantados no ano de 2007 no referido hospital. Inicialmente, foi aplicada uma ficha de avaliação, coletando dados dos prontuários, sobre a evolução do paciente no período trans e pós-operatório até a alta hospitalar. Após a coleta dessas informações, os pacientes foram submetidos ao teste da caminhada dos seis minutos (TC6. Os valores encontrados na distância percorrida foram comparados aos valores de referência esperados para a população utilizando a equação de Enright e Sherrill. RESULTADOS: Do total de 24 pacientes que realizaram Tx cardíaco no HDM no ano de 2007, 14 foram avaliados e 10 excluídos do estudo. Com relação às complicações, no período transoperatório, a mais evidenciada foi a disfunção do ventrículo direito (64,3% e, no pós-operatório, quadro de taquicardia (64,3%. Analisando o TC6 observou-se diminuição de 11,6% na distância percorrida quando comparada à distância estimada (486 ± 55 m, 550 ± 59 m, respectivamente. CONCLUSÃO: Os resultados obtidos neste estudo perante o TC6 evidenciam que as respostas cardiovasculares dos pacientes avaliados estão abaixo do estimado, contudo dentro da faixa de normalidade estabelecida.OBJECTIVE: To evaluate patient with cardiomyopathy's progress after cardiac transplant, by analyzing his survival, complications and cardiovascular responses after nearly four years of surgery. METHODS: The survey was conducted from February to May 2011, with patients undergoing cardiac transplantation

  12. O papel da L-carnitina no estado nutricional e na evolução ecocardiográfica da cardiomiopatia dilatada idiopática da infância The role of L-carnitine in nutritional status and echocardiographic parameters in idiopathic dilated cardiomyopathy in children

    Directory of Open Access Journals (Sweden)

    Vitor M. P. Azevedo

    2005-10-01

    Full Text Available OBJETIVO: A desnutrição é marcadora independente de óbito na cardiomiopatia dilatada idiopática. Foi analisada a repercussão da introdução da L-carnitina nos parâmetros nutricionais e ecocardiográficos em crianças com cardiomiopatia dilatada idiopática. MÉTODOS: Estudo prospectivo aberto de 11 crianças, comparadas com 40 controles, pareados para sexo e idade. Foi administrada L-carnitina oral (100 mg/kg/dia, além do tratamento padrão. Foram realizadas 118 pesagens no grupo L-carnitina e 264 nos controles, além de 65 ecocardiogramas no grupo L-carnitina e 144 nos controles. Análise estatística: qui-quadrado, teste t de Student, ANOVA e correlação de Pearson. Foi utilizado alfa = 0,05. RESULTADOS: Grupo L-carnitina: idade = 3,82 anos, 72,7% (p = 0,033 menores de 2 anos e do sexo feminino, e 90,9% (p = 0,001 em classe funcional III e IV. Não ocorreram óbitos no período. Não houve diferença no percentil de peso inicial (31,2±8,74 vs. 19,6±21,2 (p = 0,29 nem no índice z (-0,68±1,05 vs. -1,16±0,89 (p = 0,24. Ocorreu aumento do percentil (p = 0,026 e do índice z (p = 0,033 após a L-carnitina. Não houve diferença na fração de ejeção na apresentação (54,9%±3,8 vs. 49,3%±6,6 (p = 0,19, porém a massa VE/SC foi superior no grupo L-carnitina (169,12 g/m²±26,24 vs. 110,67 g/m²±15,62 (p = 0,0005. Após a L-carnitina, a ANOVA demonstrou aumento da fração de ejeção (48,3±7 para 67,2±7 (p = 0,044, e a massa do VE/SC foi reduzida (164,29g/m²±28,14 para 110,88g/m²±28,88, porém sem significância estatística (p = 0,089. CONCLUSÃO: Na cardiomiopatia dilatada idiopática na infância, a suplementação com L-carnitina pode auxiliar na recuperação nutricional e na melhora da fração de ejeção, facilitando a reversão do quadro de caquexia e da insuficiência cardíaca.OBJECTIVES: Malnutrition is an independent predictor of death in idiopathic dilated cardiomyopathy. An analysis was performed of the

  13. Cardiovascular magnetic resonance in hypertrophic cardiomyopathy

    International Nuclear Information System (INIS)

    Shiozaki, Afonso Akio; Parga, Jose Rodrigues; Arteaga, Edmundo; Rochitte, Carlos Eduardo; Tassi, Eduardo Marinho

    2007-01-01

    Hypertrophic cardiomyopathy (HCM) is the most frequent genetic cardiac disease that causes sudden death in young people, with an incidence of 1:500 adults. The routinely used criteria for worst prognosis have limited sensitivity and specificity. Thus, the estimated risk of evolving to dilated cardiomyopathy or sudden death is somewhat inaccurate, leading to management uncertainty of HCM patients. Therefore, an accurate noninvasive method for the diagnosis of HCM with prognostic value is of great importance. In the last years, Cardiovascular Magnetic Resonance (CMR) emerged not only as a diagnostic tool, but also as a study with prognostic values, by characterizing myocardial fibrosis with great accuracy in HCM patients. Additionally, CMR identifies the types of hypertrophy, analyses the ventricular function, estimates the intraventricular gradient and allows the determination of differential diagnosis. Moreover, CMR can uniquely access myocardial fibrosis in HCM. (author)

  14. Esophageal dilatation using the Eder Puestow dilators.

    Science.gov (United States)

    Royston, C M; Dowling, B L; Gear, M W

    1976-06-01

    We have performed fifty-one dilatations in twenty-six patients using an end-viewing fiberoptic endoscope and Eder Puestow dilators. All (except two) were performed using intravenous diazepam, the majority on an outpatient basis. The only complication has been a single case of aspiration pneumonia. We have found this method of esophageal dilatation particularly useful in the preoperative dilatation of benign strictures, and in those elderly frail patients who are unsuitable for surgery. Transthoracic resection of the stricture is avoided and thus transabdominal repair of the hiatus hernia may be undertaken.

  15. EBCT in diagnosis on primary cardiomyopathy

    International Nuclear Information System (INIS)

    Li Xiangmin; Zhou Xuhui; Meng Quanfei; Li Weiduo; Peng Qian; Tan Zhiyu

    2000-01-01

    Objective: To evaluate the diagnostic value of electron beam CT (EBCT) in primary cardiomyopathy (PCM). Methods: EBCT including coronary scanning and heart movie study was performed in 15 patients. The diagnosis of PCM was established by clinical and imaging findings or/and pathologic examination. Results: BECT findings related to the classification of PCM drawn up by WHO/ISFC were as follows: (1) dilated PCM (8 cases): dilated left ventricle (LV) was found in 7 of 8 cases and dilated right ventricle (RV) in the remaining one. Hypokinetic contraction of the LV wall with (250 ± 101) ml LVEDV and (18.9 ±6.6)% LVEF presented in the patients with dilated LV. (2) Hypertrophic PCM (5 cases): Hypertrophic ventricular septum (16.5 ± 2.3) mm was demonstrated in all cases, hypertrophy of the LV wall or the apex in 3 of 5 cases, and stenosis of the LV outflow tract in 2 cases. (3) Restrictive PCM (2 cases): Thickening of endocardium with lower density than cardiac muscle, reduced RV, obliteration of apex, hypokinetic contraction of the RV wall, and dilatation of right atrium (RA) with parietal thrombus formation of RA was identified in one patient. Both the LV and the RV were involved, with enlargement of atrium. Conclusion: The findings of PCM on EBCT seem to reflect pathologic and functional changes of PCM, and may be useful for diagnosis and classification of PCM

  16. [Congestive cardiomyopathy in addiction to clobenzorex, an anorexigenic drug].

    Science.gov (United States)

    Cornaert, P; Camblin, J; Graux, P; Anaye, B; Dutoit, A; Croccel, L

    1986-04-01

    Cardiac failure caused by high doses of amphetamine-like drugs is rare. We report a case of decompensated congestive cardiomyopathy occurring in a 29 year old woman addicted to clobenzorex (Dinintel). This patient had been taking 5 to 7 capsules per day for 5 years. No other cause of cardiac failure was detected. A rapid improvement was obtained by digitalis and diuretic therapy; no further episodes of cardiac failure were observed after one year. However, the drug could not be completely withdrawn and echocardiography has shown increasing left ventricular dilatation. The possible mechanisms of amphetamine induced myocardial toxicity are discussed and the analogy with the group of adrenergic cardiomyopathies is underlined.

  17. Avaliação hemodinâmica e evolução clínica de crianças portadoras de cardiomiopatia dilatada grave candidatas a transplante cardíaco Hemodynamic evaluation and clinical outcome of children candidates for heart transplantation with severe dilated cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Estela Azeka

    1998-11-01

    were calculated. RESULTS: Ten (41.6% children were transplanted (group A, 5 (20.8% are still waiting heart transplantation (group B and 9 (37.6% died (group C. The mean age of the B and C group were significantly different. The PVRI, MPAP and TPG were significant lower in group A than group C (p=0.01; p=0.044 and p=0.023 respectively. CONCLUSION: The profile of the hemodynamic parameters of children with severe dilated cardiomyopathy was compatible with the clinical findings. The age was the only difference comparing groups B and C. PVRI, MPAP and TPG were significant factors between group A and C. The older the patient, the worse was the prognosis.

  18. Genetics Home Reference: arrhythmogenic right ventricular cardiomyopathy

    Science.gov (United States)

    ... cardiomyopathy Merck Manual Consumer Version: Cardiomyopathy Merck Manual Consumer Version: Overview of Abnormal Heart Rhythms Orphanet: Arrhythmogenic right ventricular cardiomyopathy Orphanet: Familial isolated arrhythmogenic right ventricular ...

  19. Dilations and interaction

    International Nuclear Information System (INIS)

    Buchholz, D.; Fredenhagen, K.

    1976-07-01

    As a consequence of the geometrical features of dilations massless particles do not interact in a local, dilationally invariant quantum theory. This result also holds in models in which dilations are only an asymptotically visible symmetry of the S-matrix. (orig.) [de

  20. A Systematic Review of Phenotypic Features Associated With Cardiac Troponin I Mutations in Hereditary Cardiomyopathies

    DEFF Research Database (Denmark)

    Mogensen, Jens; Hey, Thomas; Lambrecht, Sascha

    2015-01-01

    BACKGROUND: Genetic investigations have established that mutations in proteins of the contractile unit of the myocardium, known as the sarcomere, may be associated with hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), and dilated cardiomyopathy (DCM). It has become clinical...... to be the most frequent disease gene in RCM. CONCLUSIONS: To further explore if there is a genotype-phenotype relation, long-term follow-up studies are needed. It is essential to investigate the natural history of the condition among affected individuals and to provide clinical follow-up on disease development...

  1. Mice long-term high-fat diet feeding recapitulates human cardiovascular alterations: an animal model to study the early phases of diabetic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Sebastián D Calligaris

    Full Text Available BACKGROUND/AIM: Hypercaloric diet ingestion and sedentary lifestyle result in obesity. Metabolic syndrome is a cluster of clinical features secondary to obesity, considered as a pre-diabetic condition and recognized as an independent risk factor for cardiovascular diseases. To better understand the relationship between obesity, metabolic syndrome and cardiovascular disease as well as for the development of novel therapeutic strategies, animal models that reproduce the etiology, course and outcomes of these pathologies are required. The aim of this work was to characterize the long-term effects of high-fat diet-induced obesity on the mice cardiovascular system, in order to make available a new animal model for diabetic cardiomyopathy. METHODS/RESULTS: Male C57BL/6 mice were fed with a standardized high-fat diet (obese or regular diet (normal for 16 months. Metabolic syndrome was evaluated testing plasma glucose, triglycerides, cholesterol, insulin, and glucose tolerance. Arterial pressure was measured using a sphygmomanometer (non invasive method and by hemodynamic parameters (invasive method. Cardiac anatomy was described based on echocardiography and histological studies. Cardiac function was assessed by cardiac catheterization under a stress test. Cardiac remodelling and metabolic biomarkers were assessed by RT-qPCR and immunoblotting. As of month eight, the obese mice were overweight, hyperglycaemic, insulin resistant, hyperinsulinemic and hypercholesterolemic. At month 16, they also presented normal arterial pressure but altered vascular reactivity (vasoconstriction, and cardiac contractility reserve reduction, heart mass increase, cardiomyocyte hypertrophy, cardiac fibrosis, and heart metabolic compensations. By contrast, the normal mice remained healthy throughout the study. CONCLUSIONS: Mice fed with a high-fat diet for prolonged time recapitulates the etiology, course and outcomes of the early phases of human diabetic cardiomyopathy.

  2. Dilated thin-walled blood and lymphatic vessels in human endometrium: a potential role for VEGF-D in progestin-induced break-through bleeding.

    Directory of Open Access Journals (Sweden)

    Jacqueline F Donoghue

    Full Text Available Progestins provide safe, effective and cheap options for contraception as well as the treatment of a variety of gynaecological disorders. Episodes of irregular endometrial bleeding or breakthrough bleeding (BTB are a major unwanted side effect of progestin treatment, such that BTB is the leading cause for discontinued use of an otherwise effective and popular medication. The cellular mechanisms leading to BTB are poorly understood. In this study, we make the novel finding that the large, dilated, thin walled vessels characteristic of human progestin-treated endometrium include both blood and lymphatic vessels. Increased blood and lymphatic vessel diameter are features of VEGF-D action in other tissues and we show by immunolocalisation and Western blotting that stromal cell decidualisation results in a significant increase in VEGF-D protein production, particularly of the proteolytically processed 21 kD form. Using a NOD/scid mouse model with xenografted human endometrium we were able to show that progestin treatment causes decidualisation, VEGF-D production and endometrial vessel dilation. Our results lead to a novel hypothesis to explain BTB, with stromal cell decidualisation rather than progestin treatment per se being the proposed causative event, and VEGF-D being the proposed effector agent.

  3. Dystrophic Cardiomyopathy: Complex Pathobiological Processes to Generate Clinical Phenotype

    Directory of Open Access Journals (Sweden)

    Takeshi Tsuda

    2017-09-01

    Full Text Available Duchenne muscular dystrophy (DMD, Becker muscular dystrophy (BMD, and X-linked dilated cardiomyopathy (XL-DCM consist of a unique clinical entity, the dystrophinopathies, which are due to variable mutations in the dystrophin gene. Dilated cardiomyopathy (DCM is a common complication of dystrophinopathies, but the onset, progression, and severity of heart disease differ among these subgroups. Extensive molecular genetic studies have been conducted to assess genotype-phenotype correlation in DMD, BMD, and XL-DCM to understand the underlying mechanisms of these diseases, but the results are not always conclusive, suggesting the involvement of complex multi-layers of pathological processes that generate the final clinical phenotype. Dystrophin protein is a part of dystrophin-glycoprotein complex (DGC that is localized in skeletal muscles, myocardium, smooth muscles, and neuronal tissues. Diversity of cardiac phenotype in dystrophinopathies suggests multiple layers of pathogenetic mechanisms in forming dystrophic cardiomyopathy. In this review article, we review the complex molecular interactions involving the pathogenesis of dystrophic cardiomyopathy, including primary gene mutations and loss of structural integrity, secondary cellular responses, and certain epigenetic and other factors that modulate gene expressions. Involvement of epigenetic gene regulation appears to lead to specific cardiac phenotypes in dystrophic hearts.

  4. What Is Cardiomyopathy?

    Science.gov (United States)

    ... underlying conditions, such as diabetes and high blood pressure . Cardiomyopathy often runs in families. Your doctor may suggest that your parents, brothers and sisters, and children get checked to see whether they have the ...

  5. Investigating the role of uncoupling of Troponin I phosphorylation from changes in myofibrillar Ca2+-sensitivity in the pathogenesis of Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Andrew Easton Messer

    2014-08-01

    Full Text Available Contraction in the mammalian heart is controlled by the intracellular Ca2+ concentration as it is in all striated muscle, but the heart has an additional signalling system that comes into play to increase heart rate and cardiac output during exercise or stress. β-adrenergic stimulation of heart muscle cells leads to release of cyclic-AMP and the activation of protein kinase A which phosphorylates key proteins in the sarcolemma, sarcoplasmic reticulum and contractile apparatus. Troponin I (TnI and Myosin Binding Protein C (MyBP-C are the prime targets in the myofilaments. TnI phosphorylation lowers myofibrillar Ca2+-sensitivity and increases the speed of Ca2+-dissociation and relaxation (lusitropic effect.Recent studies have shown that this relationship between Ca2+-sensitivity and TnI phosphorylation may be unstable. In familial cardiomyopathies, both dilated and hypertrophic (DCM and HCM, a mutation in one of the proteins of the thin filament often results in the loss of the relationship (uncoupling and blunting of the lusitropic response. For familial dilated cardiomyopathy in thin filament proteins it has been proposed that this uncoupling is causative of the phenotype. Uncoupling has also been found in human heart tissue from patients with hypertrophic obstructive cardiomyopathy as a secondary effect. Recently, it has been found that Ca2+-sensitizing drugs can promote uncoupling, whilst one Ca2+-desensitising drug Epigallocatechin 3-Gallate (EGCG can reverse uncoupling.We will discuss recent findings about the role of uncoupling in the development of cardiomyopathies and the molecular mechanism of the process.

  6. Resolution of dilated cardiomyopathy in an adolescent with change ...

    African Journals Online (AJOL)

    Uganda Heart Institute, Mulago Hospital Complex. Abstract. Background: Cardiovascular dysfunction is a recognized complication of HIV infection in children. Cardiac complications of HIV usually occur late in the course of the disease; they may be associated with drug therapy, and hence become more common as therapy ...

  7. Resolution of dilated cardiomyopathy in an adolescent with change ...

    African Journals Online (AJOL)

    Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.4314/ahs.v15i1.39 · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners · Terms and Conditions of ...

  8. Dilated cardiomyopathy in a child with abdominal neuroblastoma ...

    African Journals Online (AJOL)

    Case report. A three-year-old female presented with a two-week history of fever ... arterial blood pressure monitoring and central venous pressure monitoring was .... Placement of an epidural catheter at the lower thoracic segments helped us ...

  9. [Hypertrophic cardiomyopathy showing no 123I-BMIPP myocardial accumulation with type I CD36 deficiency].

    Science.gov (United States)

    Watanabe, K; Miyajima, S; Kusano, Y; Tanabe, N; Hirokawa, Y

    1997-07-01

    A 57 years old male consulted our hospital in complaining chest oppression and short of breath. Familial and dilated phase hypertrophic cardiomyopathy (HCM) was detected by ECG, echocardiography, left ventriculography and left ventricular endomyocardial biopsy. 201T1 SPECT showed regional increased accumulation in the ventricular septum, however, no myocardial accumulation of 123I-beta-methyl-p-iodophenylpentadecanoic acid (123I-BMIPP) was observed. We analyzed CD36 in this patient, and found he had type 1 CD36 deficiency. Myocardial uptake of long-chain fatty acids occurs via a specific transporter, which is homologous with human CD36. We hypothesize that CD36 deficiency, especially type 1 CD36 deficiency, might be one factor of no myocardial 123I-BMIPP uptake.

  10. Genetic engineering and therapy for inherited and acquired cardiomyopathies.

    Science.gov (United States)

    Day, Sharlene; Davis, Jennifer; Westfall, Margaret; Metzger, Joseph

    2006-10-01

    The cardiac myofilaments consist of a highly ordered assembly of proteins that collectively generate force in a calcium-dependent manner. Defects in myofilament function and its regulation have been implicated in various forms of acquired and inherited human heart disease. For example, during cardiac ischemia, cardiac myocyte contractile performance is dramatically downregulated due in part to a reduced sensitivity of the myofilaments to calcium under acidic pH conditions. Over the last several years, the thin filament regulatory protein, troponin I, has been identified as an important mediator of this response. Mutations in troponin I and other sarcomere genes are also linked to several distinct inherited cardiomyopathic phenotypes, including hypertrophic, dilated, and restrictive cardiomyopathies. With the cardiac sarcomere emerging as a central player for such a diverse array of human heart diseases, genetic-based strategies that target the myofilament will likely have broad therapeutic potential. The development of safe vector systems for efficient gene delivery will be a critical hurdle to overcome before these types of therapies can be successfully applied. Nonetheless, studies focusing on the principles of acute genetic engineering of the sarcomere hold value as they lay the essential foundation on which to build potential gene-based therapies for heart disease.

  11. Pnematic Dilation in Achalasia

    Directory of Open Access Journals (Sweden)

    Maximilian Bittinger

    2001-01-01

    Full Text Available Pneumatic dilation is the most common first-line therapy for the treatment of achalasia. The aim of dilation is a controlled disruption of circular muscle fibres of the lower esophageal sphincter to reduce the functional obstruction. Several types of dilators and different dilation techniques are used, but the achieved results are similar. The mean success rate is about 80% in the short term, but some patients need redilation in the further course (particularly young patients. Best long term results are obtained if the lower esophageal sphincter pressure can be reduced below 10 mmHg. Major complications are rare after pneumatic dilation; the most serious complication is esophageal perforation, which occurs at a mean rate of about 2.5%. Considering the pros and cons of other effective forms of treatment of achalasia (esophagomyotomy and intrasphincteric injection of botulinum toxin, pneumatic dilation is still the treatment of choice in the majority of patients with achalasia.

  12. New population-based exome data are questioning the pathogenicity of previously cardiomyopathy-associated genetic variants

    DEFF Research Database (Denmark)

    Andreasen, Charlotte Hartig; Nielsen, Jonas B; Refsgaard, Lena

    2013-01-01

    Cardiomyopathies are a heterogeneous group of diseases with various etiologies. We focused on three genetically determined cardiomyopathies: hypertrophic (HCM), dilated (DCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC). Eighty-four genes have so far been associated with these card......Cardiomyopathies are a heterogeneous group of diseases with various etiologies. We focused on three genetically determined cardiomyopathies: hypertrophic (HCM), dilated (DCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC). Eighty-four genes have so far been associated...... with these cardiomyopathies, but the disease-causing effect of reported variants is often dubious. In order to identify possible false-positive variants, we investigated the prevalence of previously reported cardiomyopathy-associated variants in recently published exome data. We searched for reported missense and nonsense...... variants in the NHLBI-Go Exome Sequencing Project (ESP) containing exome data from 6500 individuals. In ESP, we identified 94 variants out of 687 (14%) variants previously associated with HCM, 58 out of 337 (17%) variants associated with DCM, and 38 variants out of 209 (18%) associated with ARVC...

  13. Mutation Glu82Lys in lamin A/C gene is associated with cardiomyopathy and conduction defect

    International Nuclear Information System (INIS)

    Wang Hu; Wang Jizheng; Zheng Weiyue; Wang Xiaojian; Wang Shuxia; Song Lei; Zou Yubao; Yao Yan; Hui Rutai

    2006-01-01

    Dilated cardiomyopathy is a form of heart muscle disease characterized by impaired systolic function and ventricular dilation. The mutations in lamin A/C gene have been linked to dilated cardiomyopathy. We screened genetic mutations in a large Chinese family of 50 members including members with dilated cardiomyopathy and found a Glu82Lys substitution mutation in the rod domain of the lamin A/C protein in eight family members, three of them have been diagnosed as dilated cardiomyopathy, one presented with heart dilation. The pathogenic mechanism of lamin A/C gene defect is poorly understood. Glu82Lys mutated lamin A/C and wild type protein was transfected into HEK293 cells. The mutated protein was not properly localized at the inner nuclear membrane and the emerin protein, which interacts with lamin A/C, was also aberrantly distributed. The nuclear membrane structure was disrupted and heterochromatin was aggregated aberrantly in the nucleus of the HEK293 cells stably transfected with mutated lamin A/C gene as determined by transmission electron microscopy

  14. Divergent effects of adrenaline in human induced pluripotent stem cell-derived cardiomyocytes obtained from hypertrophic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Chandra Prajapati

    2018-02-01

    Full Text Available Hypertrophic cardiomyopathy (HCM is a common inherited cardiac disease that affects the heart muscle with diverse clinical outcomes. HCM can cause sudden cardiac death (SCD during or immediately after mild to rigorous physical activity in young patients. However, the mechanism causing SCD as a result of exercise remains unknown, but exercise-induced ventricular arrhythmias are thought to be responsible for this fatal consequence. To understand the disease mechanism behind HCM in a better way, we generated patient-specific induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs from HCM patients carrying either the MYBPC3-Gln1061X or TPM1-Asp175Asn mutation. We extensively investigated the effects of low to high concentrations of adrenaline on action potential characteristics, and the occurrence of arrhythmias in the presence of various concentrations of adrenaline and in wash-out condition. We classified and quantified different types of arrhythmias observed in hiPSC-CMs, and found that the occurrence of arrhythmias was dependent on concentrations of adrenaline and positions of mutations in genes causing HCM. In addition, we observed ventricular tachycardia types of arrhythmias in hiPSC-CMs carrying the TPM1-Asp175Asn mutation. We additionally examined the antiarrhythmic potency of bisoprolol in HCM-specific hiPSC-CMs. However, bisoprolol could not reduce the occurrence of arrhythmias during administration or during the wash-out condition of adrenaline in HCM-specific hiPSC-CMs. Our study demonstrates hiPSC-CMs as a promising tool for studying HCM. The experimental design used in this study could be suitable and beneficial for studying other components and drugs related to cardiac disease in general.

  15. Interação entre especialidades: miocardiopatia dilatada e neoplasia de mama HER2 positiva Interacción entre especialidades: miocardiopatía dilatada y neoplasia de mama HER2 positiva Interaction between specialties: dilated cardiomyopathy and HER2-positive breast Cancer

    Directory of Open Access Journals (Sweden)

    Solange Moraes Sanches

    2010-01-01

    en la miocardiopatía dilatada, de una forma muy interesante.Basic research may result in unexpected benefit in terms of progress in the understanding of mechanisms responsible for different diseases and their potential treatment alternatives. This is seen, for instance, when a specific situation, defined in clinical practice, may be translated into laboratory findings which suggest a new therapy for an unrelated disease, representing the inverse of the more usual bench-to-bedside path. During the past few years, the use of the monoclonal antibody trastuzumab, in the adjuvant and therapeutic context, has become of fundamental importance in the treatment of breast cancer with amplification/overexpression of HER2, resulting in significant increase in survival rates. The observation that trastuzumab also induces cardiotoxicity, and the identification of mechanisms involved in this side effect, have allowed the investigation of these factors as a therapeutic alternative for dilated cardiomyopathy, in a highly interesting fashion.

  16. Takotsubo cardiomyopathy following subarachnoid hemorrhage

    International Nuclear Information System (INIS)

    Wajnberg, Eduardo

    2012-01-01

    Takotsubo cardiomyopathy corresponds to a syndrome characterized by a transient myocardial dysfunction affecting the left ventricular apex that classically occurs after major physical or emotional stress (also called 'broken heart syndrome' or 'stress-induced cardiomyopathy'). The author describes the case of a patient with takotsubo cardiomyopathy induced by subarachnoid hemorrhage. (author)

  17. Effect of cocoa/chocolate ingestion on brachial artery flow-mediated dilation and its relevance to cardiovascular health and disease in humans.

    Science.gov (United States)

    Monahan, Kevin D

    2012-11-15

    Prospective studies indicate that high intake of dietary flavanols, such as those contained in cocoa/chocolate, are associated with reduced rates of cardiovascular-related morbidity and mortality in humans. Numerous mechanisms may underlie these associations such as favorable effects of flavanols on blood pressure, platelet aggregation, thrombosis, inflammation, and the vascular endothelium. The brachial artery flow-mediated dilation (FMD) technique has emerged as a robust method to quantify endothelial function in humans. Collectively, the preponderance of evidence indicates that FMD is a powerful surrogate measure for firm cardiovascular endpoints, such as cardiovascular-related mortality, in humans. Thus, literally thousands of studies have utilized this technique to document group differences in FMD, as well as to assess the effects of various interventions on FMD. In regards to the latter, numerous studies indicate that both acute and chronic ingestion of cocoa/chocolate increases FMD in humans. Increases in FMD after cocoa/chocolate ingestion appear to be dose-dependent such that greater increases in FMD are observed after ingestion of larger quantities. The mechanisms underlying these responses are likely diverse, however most data suggest an effect of increased nitric oxide bioavailability. Thus, positive vascular effects of cocoa/chocolate on the endothelium may underlie (i.e., be linked mechanistically to) reductions in cardiovascular risk in humans. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Clinical Characteristics and Outcomes of Patients with Amphetamine-Associated Cardiomyopathy in South Auckland, New Zealand.

    Science.gov (United States)

    Kueh, Shaw-Hua Anthony; Gabriel, Ruvin S; Lund, Mayanna; Sutton, Tim; Bradley, Joshua; Kerr, Andrew J; Looi, Jen-Li

    2016-11-01

    Amphetamine-associated cardiomyopathy (AAC) is becoming an increasingly recognised entity. The characteristics and outcomes of these patients are poorly understood. Thirty patients admitted with heart failure and echocardiographic evidence of cardiomyopathy between 2005 and 2014 and who had a documented history of amphetamine abuse that was considered an important factor in the causation of their cardiomyopathy were retrospectively identified. Mean age at presentation was 40±10 years with a male predominance (n=25, 83%). The majority were of indigenous Maori ethnicity. At presentation, four patients were in cardiogenic shock. Five patients required intensive care unit (ICU) admission for inotropic support and mechanical ventilation. Fifteen had severe left ventricular (LV) dilation (mean LV end-diastolic dimension 6.8±1.0cm) and all patients had severe LV dysfunction (mean LV ejection fraction 22±8%). Despite optimal heart failure therapy, LV size remained significantly dilated with minimal improvement in LV function. During median follow-up of 18 months, five patients died from end-stage heart failure and 17 had at least one readmission with decompensated heart failure. Amphetamine-associated cardiomyopathy was seen predominantly in young indigenous Maori men. They presented with severe cardiomyopathy, often requiring ICU admission. Severe LV dilation and significant LV dysfunction persisted despite treatment and mortality was high. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  19. Hypertrophic cardiomyopathy-linked mutation in troponin T causes myofibrillar disarray and pro-arrhythmic action potential changes in human iPSC cardiomyocytes.

    Science.gov (United States)

    Wang, Lili; Kim, Kyungsoo; Parikh, Shan; Cadar, Adrian Gabriel; Bersell, Kevin R; He, Huan; Pinto, Jose R; Kryshtal, Dmytro O; Knollmann, Bjorn C

    2018-01-01

    Mutations in cardiac troponin T (TnT) are linked to increased risk of ventricular arrhythmia and sudden death despite causing little to no cardiac hypertrophy. Studies in mice suggest that the hypertrophic cardiomyopathy (HCM)-associated TnT-I79N mutation increases myofilament Ca sensitivity and is arrhythmogenic, but whether findings from mice translate to human cardiomyocyte electrophysiology is not known. To study the effects of the TnT-I79N mutation in human cardiomyocytes. Using CRISPR/Cas9, the TnT-I79N mutation was introduced into human induced pluripotent stem cells (hiPSCs). We then used the matrigel mattress method to generate single rod-shaped cardiomyocytes (CMs) and studied contractility, Ca handling and electrophysiology. Compared to isogenic control hiPSC-CMs, TnT-I79N hiPSC-CMs exhibited sarcomere disorganization, increased systolic function and impaired relaxation. The Ca-dependence of contractility was leftward shifted in mutation containing cardiomyocytes, demonstrating increased myofilament Ca sensitivity. In voltage-clamped hiPSC-CMs, TnT-I79N reduced intracellular Ca transients by enhancing cytosolic Ca buffering. These changes in Ca handling resulted in beat-to-beat instability and triangulation of the cardiac action potential, which are predictors of arrhythmia risk. The myofilament Ca sensitizer EMD57033 produced similar action potential triangulation in control hiPSC-CMs. The TnT-I79N hiPSC-CM model not only reproduces key cellular features of TnT-linked HCM such as myofilament disarray, hypercontractility and diastolic dysfunction, but also suggests that this TnT mutation causes pro-arrhythmic changes of the human ventricular action potential. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Advanced Electrocardiography Can Identify Occult Cardiomyopathy in Doberman Pinschers

    Science.gov (United States)

    Spiljak, M.; Petric, A. Domanjko; Wilberg, M.; Olsen, L. H.; Stepancic, A.; Schlegel, T. T.; Starc, V.

    2011-01-01

    Recently, multiple advanced resting electrocardiographic (A-ECG) techniques have improved the diagnostic value of short-duration ECG in detection of dilated cardiomyopathy (DCM) in humans. This study investigated whether 12-lead A-ECG recordings could accurately identify the occult phase of DCM in dogs. Short-duration (3-5 min) high-fidelity 12-lead ECG recordings were obtained from 31 privately-owned, clinically healthy Doberman Pinschers (5.4 +/- 1.7 years, 11/20 males/females). Dogs were divided into 2 groups: 1) 19 healthy dogs with normal echocardiographic M-mode measurements: left ventricular internal diameter in diastole (LVIDd . 47mm) and in systole (LVIDs . 38mm) and normal 24-hour ECG recordings (100 VPCs/24h; 1/12 dogs had only abnormal 24-hour ECG recordings (>100 VPCs/24h). ECG recordings were evaluated via custom software programs to calculate multiple parameters of high-frequency (HF) QRS ECG, heart rate variability, QT variability, waveform complexity and 3-D ECG. Student's t-tests determined 19 ECG parameters that were significantly different (P canine DCM as five selected ECG parameters can with reasonable accuracy identify occult DCM in Doberman Pinschers. Future extensive clinical studies need to clarify if 12-lead A-ECG could be useful as an additional screening test for canine DCM.

  1. Recurrent major depression, ataxia, and cardiomyopathy: association with a novel POLG mutation?

    Directory of Open Access Journals (Sweden)

    Verhoeven WMA

    2011-05-01

    Full Text Available Willem MA Verhoeven1,2, Jos IM Egger1,3,4, Berry PH Kremer5, Boudewijn JHB de Pont1, Carlo LM Marcelis61Vincent van Gogh Institute for Psychiatry, Centre of Excellence for Neuropsychiatry, Venray, The Netherlands; 2Erasmus University Medical Centre, Department of Psychiatry, Rotterdam, The Netherlands; 3Behavioural Science Institute, Radboud University Nijmegen, Nijmegen, The Netherlands; 4Donders Institute for Brain, Cognition and Behaviour, Centre for Cognition, Radboud University Nijmegen, Nijmegen, The Netherlands; 5Department of Neurology, University Medical Centre Groningen, The Netherlands; 6Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The NetherlandsAbstract: At present, more than 100 disease mutations in mitochondrial DNA polymerase γ (POLG have been indentified that are causally related to an array of neuropsychiatric diseases affecting multiple systems. Both autosomal recessive and autosomal dominant forms can be delineated, the latter being associated with Parkinsonism and depressive or psychotic syndromes. In this report, a middle-aged female patient with recurrent major depression with melancholic features, slowly progressive gait instability, and dilated cardiomyopathy is described. Detailed diagnostic evaluation was performed to elucidate the supposed relationship between ataxia, cardiomyopathy, and major depression with melancholia. After extensive genetic and metabolic investigation, a nucleotide substitution c.2207 A→G in the POLG gene resulting in amino acid change Asn 736Ser in exon 13 was demonstrated. This mutation was considered to be compatible with a mitochondrial disorder and implicated in the pathophysiology of the neuropsychiatric syndrome. It is concluded that this novel POLG mutation forms the most parsimonious etiological explanation for the here-described combination of ataxia, major depression, and cardiomyopathy. Therefore, in patients with a complex neuropsychiatric

  2. Pacing-induced Cardiomyopathy

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    Alex Koo

    2017-10-01

    Full Text Available We present a case of pacing-induced cardiomyopathy. The patient presented with clinical symptoms of dyspnea, leg swelling, and orthopnea several months after a dual-chambered pacemaker was placed for third-degree heart block. The echocardiogram demonstrated a depressed ejection fraction. Coronary angiography was performed, which showed widely patent vessels. Single- and dual-chambered pacemakers create ventricular dyssynchrony, which in turn can cause structural, molecular changes leading to cardiomyopathy. With early intervention of biventricular pacemaker replacement, these changes can be reversible; thus, a timely diagnosis and awareness is warranted.

  3. Analysis of selected genes associated with cardiomyopathy by next-generation sequencing.

    Science.gov (United States)

    Szabadosova, Viktoria; Boronova, Iveta; Ferenc, Peter; Tothova, Iveta; Bernasovska, Jarmila; Zigova, Michaela; Kmec, Jan; Bernasovsky, Ivan

    2018-02-01

    As the leading cause of congestive heart failure, cardiomyopathy represents a heterogenous group of heart muscle disorders. Despite considerable progress being made in the genetic diagnosis of cardiomyopathy by detection of the mutations in the most prevalent cardiomyopathy genes, the cause remains unsolved in many patients. High-throughput mutation screening in the disease genes for cardiomyopathy is now possible because of using target enrichment followed by next-generation sequencing. The aim of the study was to analyze a panel of genes associated with dilated or hypertrophic cardiomyopathy based on previously published results in order to identify the subjects at risk. The method of next-generation sequencing by IlluminaHiSeq 2500 platform was used to detect sequence variants in 16 individuals diagnosed with dilated or hypertrophic cardiomyopathy. Detected variants were filtered and the functional impact of amino acid changes was predicted by computational programs. DNA samples of the 16 patients were analyzed by whole exome sequencing. We identified six nonsynonymous variants that were shown to be pathogenic in all used prediction softwares: rs3744998 (EPG5), rs11551768 (MGME1), rs148374985 (MURC), rs78461695 (PLEC), rs17158558 (RET) and rs2295190 (SYNE1). Two of the analyzed sequence variants had minor allele frequency (MAF)MURC), rs34580776 (MYBPC3). Our data support the potential role of the detected variants in pathogenesis of dilated or hypertrophic cardiomyopathy; however, the possibility that these variants might not be true disease-causing variants but are susceptibility alleles that require additional mutations or injury to cause the clinical phenotype of disease must be considered. © 2017 Wiley Periodicals, Inc.

  4. Cardiomyopathy Following Latrodectus Envenomation

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    Levine, Michael

    2010-12-01

    Full Text Available Latrodectus envenomations are common throughout the United States and the world. While many envenomations can result in catecholamine release with resultant hypertension and tachycardia, myocarditis is very rare. We describe a case of a 22- year-old male who sustained a Latrodectus envenomation complicated by cardiomyopathy. [West J Emerg Med. 2010; 11(5:521-523.

  5. Hypertrophic Cardiomyopathy Association

    Science.gov (United States)

    ... be donated to Hypertrophic Cardiomyopathy Association. iGive.com - Online Shopping Joing iGive.com to earn money for the ... it works, check out the iGive website . AmazonSmile - Online Shopping Amazon donates 0.5% of the purchase price ...

  6. Hormones and postpartum cardiomyopathy.

    NARCIS (Netherlands)

    Clapp, C.; Thebault, S.C.; Martinez de la Escalera, G.M.

    2007-01-01

    Prolactin, a hormone fundamental for lactation, was recently shown to mediate postpartum cardiomyopathy, a life-threatening disease in late-term and lactating mothers. The detrimental effect of prolactin results from myocardial upregulation of cathepsin-D, which in turn cleaves prolactin to a 16 kDa

  7. A Review of the Giant Protein Titin in Clinical Molecular Diagnostics of Cardiomyopathies

    Directory of Open Access Journals (Sweden)

    Marta Gigli

    2016-07-01

    Full Text Available Titin (TTN is known as the largest sarcomeric protein that resides within the heart muscle. Due to alternative splicing of TTN the heart expresses two major isoforms (N2B and N2BA that incorporate four distinct regions termed the Z-line, I-band, A-band, and M-line. Next-generation sequencing allows a large number of genes to be sequenced simultaneously and provides the opportunity to easily analyze giant genes such as TTN. Mutations in the TTN gene can cause cardiomyopathies, in particular dilated cardiomyopathy (DCM. DCM is the most common form of cardiomyopathy and it is characterized by systolic dysfunction and dilation of the left ventricle. TTN truncating variants have been described as the most common cause of DCM while the real impact of TTN missense variants in the pathogenesis of DCM is still unclear. In a recent population screening study, rare missense variants potentially pathogenic based on bioinformatic filtering represented only 12.6% of the several hundred rare TTN missense variants found, suggesting that missense variants are very common in TTN and frequently benign. The aim of this review is to understand the clinical role of TTN mutations in DCM and in other cardiomyopathies. Whereas TTN truncations are common in DCM, there is evidence that TTN truncations are rare in the HCM phenotype. Furthermore TTN mutations can also cause arrhythmogenic right ventricular cardiomyopathy (ARVC with distinct clinical features and outcomes. Finally, the identification of a rare missense variant in TTN cosegregating with the restrictive cardiomyopathy (RCM phenotype suggests that TTN is a novel gene in this disease. Clinical diagnostic testing is currently able to analyze over 100 cardiomyopathy genes, including TTN, however, the size and presence of extensive genetic variation in TTN presents clinical challenges in determining significant disease-causing mutations. This review discusses the current knowledge of TTN genetic variations in

  8. [Plasma selenium and peripartum cardiomyopathy in Bamako, Mali].

    Science.gov (United States)

    Cénac, A; Touré, K; Diarra, M B; Sergeant, C; Jobic, Y; Sanogo, K; Dembele, M; Fayol, V; Simonoff, M

    2004-01-01

    Peripartum heart failure due to unexplained dilated cardiomyopathy is a common disorder as Savannak-Sahelian Africa. One of the many suspected risk factors identified is selenium deficiency. The purpose of this study was to measure plasma selenium levels in patients with peripartum heart failure due to cardiomyopathy in Bamako, Republic of Mali and compare data with healthy Sahalian women with the same obstetrical status. Plasma selenium was measured in a patient group consisting of 28 Malian women presenting peripartum heart failure and in a control group of 28 healthy breast-feeding Nigerien women of comparable age. The criteria for matching the two groups was parity (similar number of deliveries) since multiparity is a risk factor for peripartum cardiomyopathy. The Wilcoxon test (nonparametric) was used to compare the 2 groups considering up value < 0.05 as significant. Plasma selenium was significantly lower in patients from Mali than in controls from Niger (65 +/- 17 ng/ml vs. 78 +/- 17 ng/ml, p = 0.01). The results of this study showing lower plasma selenium in Bamako patients with peripartum cardiomyopathy than in a matching healthy control population confirms the previous data from the Niamey study.

  9. Connective tissue growth factor and bone morphogenetic protein 2 are induced following myocardial ischemia in mice and humans.

    Science.gov (United States)

    Rutkovskiy, Arkady; Sagave, Julia; Czibik, Gabor; Baysa, Anton; Zihlavnikova Enayati, Katarina; Hillestad, Vigdis; Dahl, Christen Peder; Fiane, Arnt; Gullestad, Lars; Gravning, Jørgen; Ahmed, Shakil; Attramadal, Håvard; Valen, Guro; Vaage, Jarle

    2017-09-01

    We aimed to study the cardiac expression of bone morphogenetic protein 2, its receptor 1 b, and connective tissue growth factor, factors implicated in cardiac embryogenesis, following ischemia/hypoxia, heart failure, and in remodeling hearts from humans and mice. Biopsies from the left ventricle of patients with end-stage heart failure due to dilated cardiomyopathy or coronary artery disease were compared with donor hearts and biopsies from patients with normal heart function undergoing coronary artery bypass grafting. Mouse model of post-infarction remodeling was made by permanent ligation of the left coronary artery. Hearts were analyzed by real-time polymerase chain reaction and Western blotting after 24 hours and after 2 and 4 weeks. Patients with dilated cardiomyopathy and mice post-infarction had increased cardiac expression of connective tissue growth factor. Bone morphogenetic protein 2 was increased in human hearts failing due to coronary artery disease and in mice post-infarction. Gene expression of bone morphogenetic protein receptor 1 beta was reduced in hearts of patients with failure, but increased two weeks following permanent ligation of the left coronary artery in mice. In conclusion, connective tissue growth factor is upregulated in hearts of humans with dilated cardiomyopathy, bone morphogenetic protein 2 is upregulated in remodeling due to myocardial infarction while its receptor 1 b in human failing hearts is downregulated. A potential explanation might be an attempt to engage regenerative processes, which should be addressed by further, mechanistic studies.

  10. Transcriptional profile of isoproterenol-induced cardiomyopathy and comparison to exercise-induced cardiac hypertrophy and human cardiac failure

    Directory of Open Access Journals (Sweden)

    McIver Lauren J

    2009-12-01

    Full Text Available Abstract Background Isoproterenol-induced cardiac hypertrophy in mice has been used in a number of studies to model human cardiac disease. In this study, we compared the transcriptional response of the heart in this model to other animal models of heart failure, as well as to the transcriptional response of human hearts suffering heart failure. Results We performed microarray analyses on RNA from mice with isoproterenol-induced cardiac hypertrophy and mice with exercise-induced physiological hypertrophy and identified 865 and 2,534 genes that were significantly altered in pathological and physiological cardiac hypertrophy models, respectively. We compared our results to 18 different microarray data sets (318 individual arrays representing various other animal models and four human cardiac diseases and identified a canonical set of 64 genes that are generally altered in failing hearts. We also produced a pairwise similarity matrix to illustrate relatedness of animal models with human heart disease and identified ischemia as the human condition that most resembles isoproterenol treatment. Conclusion The overall patterns of gene expression are consistent with observed structural and molecular differences between normal and maladaptive cardiac hypertrophy and support a role for the immune system (or immune cell infiltration in the pathology of stress-induced hypertrophy. Cross-study comparisons such as the results presented here provide targets for further research of cardiac disease that might generally apply to maladaptive cardiac stresses and are also a means of identifying which animal models best recapitulate human disease at the transcriptional level.

  11. Takotsubo (Stress Cardiomyopathy

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    Justin J Hourmozdi

    2017-01-01

    Full Text Available History of present illness: A 59-year-old male presented to the emergency department in shock from pneumonia. The patient was initially afebrile, pulse rate 120 beats per minute, blood pressure 117/69 mmHg, respiratory rate 42 breaths per minute, pulse oximetry 94% on a non-rebreather mask and a lactate of 14 mmol/L. He became progressively more hypotensive despite fluid resuscitation and was started on norepinephrine. Shortly after, the patient developed torsades de pointes that was terminated with intravenous push magnesium. His initial ECG had shown sinus tachycardia; however, repeat ECG showed ST-segment elevation in the inferolateral leads and the patient had troponin I elevation that peaked at 16 ng/mL. Significant findings: Bedside echocardiography showed the findings consistent with Takotsubo cardiomyopathy. Echocardiographic images are shown in subxiphoid (A and apical four chamber (B views. Note the apical ballooning appearance (asterisk of the left ventricle (LV. Discussion: Formal echocardiography confirmed features classic for Takotsubo (stress cardiomyopathy, including globally depressed left ventricle (LV ejection fraction, systolic apical ballooning appearance of the LV, mid and apical segments of LV depression, and hyper kinesis of the basal walls. Takotsubo cardiomyopathy is a syndrome known to cause ST-segment elevation on ECG, transient LV dysfunction, and dysrhythmia in the absence of acute obstructive coronary disease. There is no consensus on diagnostic criteria; however, these criteria are commonly used: 1 transient hypokinesis, akinesis, or dyskinesis in the LV mid-segments with or without apical involvement; regional wall motion abnormalities that extend beyond a single epicardial vascular distribution; and frequently, but not always, a stressful trigger 2 the absence of acute coronary disease or angiographic evidence of acute plaque rupture 3 new ECG abnormalities (ST-segment elevation and/or T-wave inversion or modest

  12. Hypertrophic Cardiomyopathy: Clinical Update.

    Science.gov (United States)

    Geske, Jeffrey B; Ommen, Steve R; Gersh, Bernard J

    2018-05-01

    Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy, manifesting as left ventricular hypertrophy in the absence of a secondary cause. The genetic underpinnings of HCM arise largely from mutations of sarcomeric proteins; however, the specific underlying mutation often remains undetermined. Patient presentation is phenotypically diverse, ranging from asymptomatic to heart failure or sudden cardiac death. Left ventricular hypertrophy and abnormal ventricular configuration result in dynamic left ventricular outflow obstruction in most patients. The goal of therapeutic interventions is largely to reduce dynamic obstruction, with treatment modalities spanning lifestyle modifications, pharmacotherapies, and septal reduction therapies. A small subset of patients with HCM will experience sudden cardiac death, and risk stratification remains a clinical challenge. This paper presents a clinical update for diagnosis, family screening, clinical imaging, risk stratification, and management of symptoms in patients with HCM. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  13. Affecting Rhomboid-3 function causes a dilated heart in adult Drosophila.

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    Lin Yu

    2010-05-01

    Full Text Available Drosophila is a well recognized model of several human diseases, and recent investigations have demonstrated that Drosophila can be used as a model of human heart failure. Previously, we described that optical coherence tomography (OCT can be used to rapidly examine the cardiac function in adult, awake flies. This technique provides images that are similar to echocardiography in humans, and therefore we postulated that this approach could be combined with the vast resources that are available in the fly community to identify new mutants that have abnormal heart function, a hallmark of certain cardiovascular diseases. Using OCT to examine the cardiac function in adult Drosophila from a set of molecularly-defined genomic deficiencies from the DrosDel and Exelixis collections, we identified an abnormally enlarged cardiac chamber in a series of deficiency mutants spanning the rhomboid 3 locus. Rhomboid 3 is a member of a highly conserved family of intramembrane serine proteases and processes Spitz, an epidermal growth factor (EGF-like ligand. Using multiple approaches based on the examination of deficiency stocks, a series of mutants in the rhomboid-Spitz-EGF receptor pathway, and cardiac-specific transgenic rescue or dominant-negative repression of EGFR, we demonstrate that rhomboid 3 mediated activation of the EGF receptor pathway is necessary for proper adult cardiac function. The importance of EGF receptor signaling in the adult Drosophila heart underscores the concept that evolutionarily conserved signaling mechanisms are required to maintain normal myocardial function. Interestingly, prior work showing the inhibition of ErbB2, a member of the EGF receptor family, in transgenic knock-out mice or individuals that received herceptin chemotherapy is associated with the development of dilated cardiomyopathy. Our results, in conjunction with the demonstration that altered ErbB2 signaling underlies certain forms of mammalian cardiomyopathy, suggest

  14. Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias

    Science.gov (United States)

    2017-08-10

    Inherited Cardiac Arrythmias; Long QT Syndrome (LQTS); Brugada Syndrome (BrS); Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT); Early Repolarization Syndrome (ERS); Arrhythmogenic Cardiomyopathy (AC, ARVD/C); Hypertrophic Cardiomyopathy (HCM); Dilated Cardiomyopathy (DCM); Muscular Dystrophies (Duchenne, Becker, Myotonic Dystrophy); Normal Control Subjects

  15. The Cardiomyopathy Registry of the EURObservational Research Programme of the European Society of Cardiology: baseline data and contemporary management of adult patients with cardiomyopathies.

    Science.gov (United States)

    Charron, Philippe; Elliott, Perry M; Gimeno, Juan R; Caforio, Alida L P; Kaski, Juan Pablo; Tavazzi, Luigi; Tendera, Michal; Maupain, Carole; Laroche, Cécile; Rubis, Pawel; Jurcut, Ruxandra; Calò, Leonardo; Heliö, Tiina M; Sinagra, Gianfranco; Zdravkovic, Marija; Kavoliuniene, Aušra; Felix, Stephan B; Grzybowski, Jacek; Losi, Maria-Angela; Asselbergs, Folkert W; García-Pinilla, José Manuel; Salazar-Mendiguchia, Joel; Mizia-Stec, Katarzyna; Maggioni, Aldo P

    2018-05-21

    The Cardiomyopathy Registry of the EURObservational Research Programme is a prospective, observational, and multinational registry of consecutive patients with four cardiomyopathy subtypes: hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and restrictive cardiomyopathy (RCM). We report the baseline characteristics and management of adults enrolled in the registry. A total of 3208 patients were enrolled by 69 centres in 18 countries [HCM (n = 1739); DCM (n = 1260); ARVC (n = 143); and RCM (n = 66)]. Differences between cardiomyopathy subtypes (P < 0.001) were observed for age at diagnosis, history of familial disease, history of sustained ventricular arrhythmia, use of magnetic resonance imaging or genetic testing, and implantation of defibrillators. When compared with probands, relatives had a lower age at diagnosis (P < 0.001), but a similar rate of symptoms and defibrillators. When compared with the Long-Term phase, patients of the Pilot phase (enrolled in more expert centres) had a more frequent rate of familial disease (P < 0.001), were more frequently diagnosed with a rare underlying disease (P < 0.001), and more frequently implanted with a defibrillator (P = 0.023). Comparing four geographical areas, patients from Southern Europe had a familial disease more frequently (P < 0.001), were more frequently diagnosed in the context of a family screening (P < 0.001), and more frequently diagnosed with a rare underlying disease (P < 0.001). By providing contemporary observational data on characteristics and management of patients with cardiomyopathies, the registry provides a platform for the evaluation of guideline implementation. Potential gaps with existing recommendations are discussed as well as some suggestions for improvement of health care provision in Europe.

  16. Recommendations for participation in competitive sport and leisure-time physical activity in individuals with cardiomyopathies, myocarditis and pericarditis.

    Science.gov (United States)

    Pelliccia, Antonio; Corrado, Domenico; Bjørnstad, Hans Halvor; Panhuyzen-Goedkoop, Nicole; Urhausen, Axel; Carre, Francois; Anastasakis, Aris; Vanhees, Luc; Arbustini, Eloisa; Priori, Silvia

    2006-12-01

    Several relatively uncommon, but important cardiovascular diseases are associated with increased risk for acute cardiac events during exercise (including sudden death), such as hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC) and myo-pericarditis. Practising cardiologists are frequently asked to advise on exercise programmes and sport participation in young individuals with these cardiovascular diseases. Indeed, many asymptomatic (or mildly symptomatic) patients with cardiomyopathies aspire to a physically active lifestyle to take advantage of the many documented benefits of exercise. While recommendations dictating the participation in competitive sport for athletes with cardiomyopathies and myo-pericarditis have recently been published as a consensus document of the European Society of Cardiology, no European guidelines have addressed the possible participation of patients with cardiomyopathies in recreational and amateur sport activities. The present document is intended to offer a comprehensive overview to practising cardiologists and sport physicians of the recommendations governing safe participation in different types of competitive sport, as well as the participation in a variety of recreational physical activities and amateur sports in individuals with cardiomyopathies and myo-pericarditis. These recommendations, based largely on the experience and insights of the expert panel appointed by the European Society of Cardiology, include the most up-to-date information concerning regular exercise and sports activity in patients with cardiomyopathies and myo-pericarditis.

  17. Dilatations and factorizable equations

    International Nuclear Information System (INIS)

    Humi, Mayer

    2005-01-01

    In this paper, we show that the dilatation operator in one dimension can be used to enlarge the Lie algebra generated by the raising and lowering operators for some classes of special functions. As a result, we are able to derive new recursion relations and addition formulae for these functions. Furthermore, we derive generalized ladder operators for these functions under coordinate stretching and translations

  18. Clinical Features and Echocardiographic Findings in Children with Hypertrophic Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Cristina Blesneac

    2013-12-01

    Full Text Available Background: Hypertrophic cardiomyopathy, one of the most common inherited cardiomyopathies, is a heterogeneous disease resulting from sarcomeric protein mutations, with an incidence in the adult population of 1:500. Current information on the epidemiology and outcomes of this disease in children is limited. Methods: Thirty-four children diagnosed with hypertrophic cardiomyopathy in the Pediatric Cardiology Department from Tîrgu Mureș were evaluated concerning familial and personal history, clinical, paraclinical and therapeutic aspects. Hypertrophic cardiomyopathy was defined by the presence of a hypertrophied, non-dilated ventricle, in the absence of a cardiac or systemic disease that could produce ventricular hypertrophy. Results: The youngest diagnosed child was a neonate, a total of 10 patients being diagnosed until 1 year of age. In 6 cases a positive familial history was found. Noonan syndrome was found in 2 cases. Only 21 patients were symptomatic, the predominant symptoms being shortness of breath on exertion with exercise limitations. Left ventricular outflow tract obstruction was present in 21 cases (61.7%. Twenty-four patients were on β-blocking therapy, while 4 patients underwent septal myectomy. Conclusions: Hypertrophic cardiomyopathy is a heterogeneous disorder in terms of evolution, age of onset, type and extent of hypertrophy, and the risk of sudden death. It can affect children of any age. There is a need for a complex evaluation, including familial and personal anamnesis, clinical examination, electrocardiogram and echocardiography of all patients. It is highly important to develop screening strategies, including genetic testing, for an early diagnosis, especially in asymptomatic patients with a positive familial background

  19. Cardiomyopathy in the pediatric patients

    Directory of Open Access Journals (Sweden)

    Shi-Min Yuan

    2018-04-01

    Full Text Available Pediatric cardiomyopathies are a group of myocardial diseases with complex taxonomies. Cardiomyopathy can occur in children at any age, and it is a common cause of heart failure and heart transplantation in children. The incidence of pediatric cardiomyopathy is increasing with time. They may be associated with variable comorbidities, which are most often arrhythmia, heart failure, and sudden death. Medical imaging technologies, including echocardiography, cardiac magnetic resonance, and nuclear cardiology, are helpful in reaching a diagnosis of cardiomyopathy. Nevertheless, endomyocardial biopsy is the final diagnostic method of diagnosis. Patients warrant surgical operations, such as palliative operations, bridging operations, ventricular septal maneuvers, and heart transplantation, if pharmaceutical therapies are ineffective. Individual therapeutic regimens due to pediatric characteristics, genetic factors, and pathogenesis may improve the effects of treatment and patients' survival. Key Words: cardiomyopathy, classification, pediatrics

  20. Muscle Stem Cell Therapy for the Treatment of DMD Associated Cardiomyopathy

    Science.gov (United States)

    2014-10-01

    cardiomyopathy. Duchenne muscular dystrophy (DMD), one of the progressive muscular dystrophies , is an X-linked muscle disease caused by mutations in the...including Duchenne muscular dystrophy (DMD), develop progressive cardiomyopathy. Cellular cardiomyoplasty, which involves the transplantation of...hepatic failure in a clinically relevant non-human primate model of this process. 15. SUBJECT TERMS Project 1: Duchenne muscular dystrophy

  1. Various manifestations of hypertrophic cardiomyopathy on ultrafast computed tomography

    International Nuclear Information System (INIS)

    Sekiya, Tohru; Karikomi, Masahito; Ohshiro, Masaya; Iwakami, Masayoshi; Takamoto, Toshihiko; Sakamoto, Tsuguya

    1992-01-01

    Ultrafast computed tomography was performed in 30 patients with hypertrophic cardiomyopathy and images were assessed on variability of left ventricular hypertrophy, the pattern of left ventricular contraction, right ventricular hypertrophy, dilatation of the left atrium, and thickening of the mitral valve. Fifteen (50.0%) of 30 patients had asymmetric septal hypertrophy, six (20.0%) had diffuse hypertrophy, and nine (30.0%) had apical hypertrophy. In eleven patients with asymmetric septal hypertrophy and two with apical hypertrophy, non-hypertrophied segments in end-diastole showed vigorous contraction. Sixteen patients showed homogeneous left ventricular contraction and one showed partial apical contraction. Right ventricular hypertrophy was noted in 12 patients (40.0%), dilatation of the left atrium in 13 patients (43.3%), and mitral valve thickening in three (10.0%). Ultrafast computed tomography was useful in the evaluation of apical hypertrophy and right ventricular hypertrophy, which could be difficult to obtain by echocardiography. (author)

  2. [Myocardial regional thickness in patients with and without cardiomyopathy assessed by cardiac magnetic resonance].

    Science.gov (United States)

    de Zan, Macarena; Carrascosa, Patricia; Deviggiano, Alejandro; Capuñay, Carlos; Rodríguez-Granillo, Gastón A

    To explore regional differences in myocardial wall thickness (WT) among the most prevalent cardiomyopathies and in individuals without structural heart disease using cardiac magnetic resonance. Patients older than 18 years referred to cardiac magnetic resonance during the period between January 2014 and September 2014, with a diagnosis of hypertrophic cardiomyopathy, idiopathic dilated cardiomyopathy, ischemic cardiomyopathy, and myocarditis were retrospectively selected from our database. One hundred twenty patients patients were included. The control group had an average WT of 5.9±1.1mm, with a WT index of 2.9±0.8. Significantly lower mean WT in the apical segments were identified in both the control group (basal 6.7±1.3 vs. mid 6.0±1.3 vs. apical 4.6±1.0mm, P<.0001) and in all evaluated cardiomyopathies (hypertrophic cardiomyopathy: basal 10.5±2.4 vs. mid 10.8±2.7 vs. apical 7.3±3.3mm, P<.0001; idiopathic dilated cardiomyopathy: basal 7.7±1.7 vs. mid 7.6±1.3 vs. apical 5.4±1.3mm, P<.0001; ischemic cardiomyopathy: basal 7.4±1.7 vs. mid 7.5±1.9 vs. apical 5.5±1.8mm, P<.0001; myocarditis: basal 7.1±1.5 vs. mid 6.4±1.1 vs. apical 5.1±0.8, P<.0001). Significant gender differences were also evident regarding the mean WT both in the control group (male 6.5±2.1 vs. female 5.2±1.7mm, P<.0001), as in hypertrophic cardiomyopathy (10.5±5.3 vs. 8.5±5.7mm, P<.0001) and myocarditis (6.6±2.0 vs. 5.2±1.6mm, P<.0001). We found a relatively high prevalence of segments commonly deemed thinned among patients without structural heart disease. We also observed a marked asymmetry and longitudinal gradient in wall thickness both in controls and in the various cardiomyopathies evaluated. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

  3. Development of porcine model of chronic tachycardia-induced cardiomyopathy.

    Science.gov (United States)

    Paslawska, Urszula; Gajek, Jacek; Kiczak, Liliana; Noszczyk-Nowak, Agnieszka; Skrzypczak, Piotr; Bania, Jacek; Tomaszek, Alicja; Zacharski, Maciej; Sambor, Izabela; Dziegiel, Piotr; Zysko, Dorota; Banasiak, Waldemar; Jankowska, Ewa A; Ponikowski, Piotr

    2011-11-17

    There are few experimental models of heart failure (HF) in large animals, despite structural and functional similarities to human myocardium. We have developed a porcine model of chronic tachycardia-induced cardiomyopathy. Homogenous siblings of White Large breed swine (n=6) underwent continuous right ventricular (RV) pacing at 170 bpm; 2 subjects served as controls. In the course of RV pacing, animals developed a clinical picture of HF and were presented for euthanasia at subsequent stages: mild, moderate and end-stage HF. Left ventricle (LV) sections were analyzed histologically and relative ANP, BNP, phospholamban and sarcoplasmic reticulum calcium ATPase 2a transcript levels in LV were quantified by real time RT-PCR. In the course of RV pacing, animals demonstrated reduced exercise capacity (time of running until being dyspnoeic: 6.6 ± 0.5 vs. 2.4 ± 1.4 min), LV dilatation (LVEDD: 4.9 ± 0.4 vs. 6.7 ± 0.4 cm), impaired LV systolic function (LVEF: 69 ± 8 vs. 32 ± 7 %), (all baseline vs. before euthanasia, all p<0.001). LV tissues from animals with moderate and end-stage HF demonstrated local foci of interstitial fibrosis, congestion, cardiomyocyte hypertrophy and atrophy, which was not detected in controls and mild HF animals. The up-regulation of ANP and BNP and a reduction in a ratio of sarcoplasmic reticulum calcium ATPase 2a and phospholamban in failing myocardium were observed as compared to controls. In pigs, chronic RV pacing at relatively low rate can be used as an experimental model of HF, as it results in a gradual deterioration of exercise tolerance accompanied by myocardial remodeling confirmed at subcellular level. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  4. Dilation and Curettage (D&C)

    Science.gov (United States)

    ... For Patients About ACOG Dilation and Curettage (D&C) Home For Patients Search FAQs Dilation and Curettage ( ... February 2016 PDF Format Dilation and Curettage (D&C) Special Procedures What is dilation and curettage (D& ...

  5. Catecholamine induced cardiomyopathy in pheochromocytoma

    Directory of Open Access Journals (Sweden)

    Ron Thomas Varghese

    2013-01-01

    Full Text Available Catecholamine induced cardiomyopathy in the setting of pheochromocytoma is an unusual clinical entity. Earlier studies have reported left ventricular dysfunction in around 10% of subjects with pheochromocytoma. [1] Catecholamine induced vasoconstriction, direct toxic effect of byproducts of catecholamine degradation and direct receptor-mediated mechanisms are thought to contribute to cardiomyopathy in subjects with pheochromocytoma. The presentation remains a diagnostic challenge as patients may already have hypertensive heart disease and acute coronary syndrome on account of uncontrolled secondary hypertension. We report a case of a 42-year-old male, who presented with features of pheochromocytoma induced cardiomyopathy.

  6. Microfibrillar cardiomyopathy: A rare case

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    Narender Kumar

    2011-01-01

    Full Text Available Microfibrillar cardiomyopathy is a very rare cause of restrictive cardiomyopathy (RCM. The index case was a male patient who presented with shortness of breath and pedal edema. Further clinical investigations favored a clinical diagnosis of RCM. An endomyocardial biopsy revealed subendocardial and interstitial hyaline eosinophillic material resembling amyloid that did not stain with Congo red. An electron microscopic examination showed that this material was composed of twisted linear and bundles of tangled microfibrils. The etiology of the microfibrillar deposition is currently unknown. The pathologists should entertain the diagnosis of microfibrillar cardiomyopathy in suspected cases of amyloidosis that are negative for Congo red.

  7. The Use of a Novel Heart Failure Agent in the Treatment of Pregnancy-Associated Cardiomyopathy

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    Vamsi C. Gaddipati

    2017-01-01

    Full Text Available Peripartum cardiomyopathy is an uncommon, pregnancy-related form of dilated cardiomyopathy that is associated with development of new-onset left ventricular dysfunction. Its etiology is presently unknown, but current standard of care involves the use of typical drug therapy for the treatment of heart failure. Pregnancy-associated cardiomyopathy (PACM is a similar condition that refers to patients who develop such symptoms prior to the last month of pregnancy. We report the case of a nulliparous Caucasian female who develops early, severe PACM during her first pregnancy with postpartum persistence of New York Heart Association class II-III symptoms despite medical therapy. The use of the novel heart failure agent, sacubitril/valsartan (Entresto, is initiated with near-complete resolution of her symptoms.

  8. Cardiorespiratory and cardiovascular interactions in cardiomyopathy patients using joint symbolic dynamic analysis.

    Science.gov (United States)

    Giraldo, Beatriz F; Rodriguez, Javier; Caminal, Pere; Bayes-Genis, Antonio; Voss, Andreas

    2015-01-01

    Cardiovascular diseases are the first cause of death in developed countries. Using electrocardiographic (ECG), blood pressure (BP) and respiratory flow signals, we obtained parameters for classifying cardiomyopathy patients. 42 patients with ischemic (ICM) and dilated (DCM) cardiomyopathies were studied. The left ventricular ejection fraction (LVEF) was used to stratify patients with low risk (LR: LVEF>35%, 14 patients) and high risk (HR: LVEF≤ 35%, 28 patients) of heart attack. RR, SBP and TTot time series were extracted from the ECG, BP and respiratory flow signals, respectively. The time series were transformed to a binary space and then analyzed using Joint Symbolic Dynamic with a word length of three, characterizing them by the probability of occurrence of the words. Extracted parameters were then reduced using correlation and statistical analysis. Principal component analysis and support vector machines methods were applied to characterize the cardiorespiratory and cardiovascular interactions in ICM and DCM cardiomyopathies, obtaining an accuracy of 85.7%.

  9. VIP Gene Deletion in Mice Causes Cardiomyopathy Associated with Upregulation of Heart Failure Genes

    Energy Technology Data Exchange (ETDEWEB)

    Szema, Anthony M.; Hamidi, Sayyed A.; Smith, S. David; Benveniste, Helene; Katare, Rajesh Gopalrao

    2013-05-20

    Vasoactive Intestinal Peptide (VIP), a pulmonary vasodilator and inhibitor of vascular smooth muscle proliferation, is absent in pulmonary arteries of patients with idiopathic pulmonary arterial hypertension (PAH). We previously determined that targeted deletion of the VIP gene in mice leads to PAH with pulmonary vascular remodeling and right ventricular (RV) dilatation. Whether the left ventricle is also affected by VIP gene deletion is unknown. In the current study, we examined if VIP knockout mice (VIP-/-) develop both right (RV) and left ventricular (LV) cardiomyopathy, manifested by LV dilatation and systolic dysfunction, as well as overexpression of genes conducive to heart failure.

  10. Anabolic steroids abuse-induced cardiomyopathy and ischaemic stroke in a young male patient.

    Science.gov (United States)

    Shamloul, Reham Mohammed; Aborayah, Ahmed Fathy; Hashad, Assem; Abd-Allah, Foad

    2014-02-26

    We report a case of a 37-year-old man presented with acute stroke and hepatorenal impairment which were associated with anabolic-androgenic steroids (AAS) abuse over 2 years. Despite the absence of apparent symptoms and signs of congestive heart failure at presentation, an AAS-induced dilated cardiomyopathy with multiple thrombi in the left ventricle was attributed to be the underlying cause of his condition. Awareness of the complications of AAS led to the prompt treatment of the initially unrecognised dilated cardiomyopathy, and improved the liver and kidney functions. However, the patient was exposed to a second severe ischaemic event, which led to his death. This unique and complex presentation of AAS complications opens for better recognition and treatment of their potentially fatal effects.

  11. Myocardial glucose metabolism in patients with hypertrophic cardiomyopathy. Assessment by F-18-FDG PET study

    International Nuclear Information System (INIS)

    Uehara, Toshiisa; Ishida, Yoshio; Hayashida, Kohei

    1998-01-01

    In an investigation of myocardial metabolic abnormalities in hypertrophic myocardium, the myocardial glucose metabolism was evaluated with F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in 32 patients with hypertrophic cardiomyopathy, and the results were compared with those in 9 patients with hypertensive heart disease. F-18-FDG PET study was performed in the fasting and glucose-loading states. The myocardial regional %dose uptake was calculated quantitatively. The average regional %dose uptake in the fasting state in the patients with asymmetric septal hypertrophy and dilated-phase hypertrophic cardiomyopathy was significantly higher than that in the patients with hypertensive heart disease (0.75±0.34%, 0.65±0.25%, and 0.43±0.22%/100 g myocardium, respectively). In contrast, the average %dose uptake in the glucose-loading state in the patients with asymmetric septal hypertrophy and dilated-phase hypertrophic cardiomyopathy was not significantly different from that in patients with hypertensive heart disease (1.17±0.49%, 0.80±0.44% and 0.99±0.45%, respectively). The patients with apical hypertrophy had also low %dose uptake in the fasting state (0.38±0.21%) as in the hypertensive heart disease patients, so that the characteristics of asymmetric septal hypertrophy and dilated-phase hypertrophic cardiomyopathy are considered to be high FDG uptake throughout the myocardium in the fasting state. Patients with apical hypertrophy are considered to belong to other disease categories metabolically. F-18-FDG PET study is useful in the evaluation of the pathophysiologic diagnosis of patients with hypertrophic cardiomyopathy. (author)

  12. Clinical and Prognostic Profiles of Cardiomyopathies Caused by Mutations in the Troponin T Gene.

    Science.gov (United States)

    Ripoll-Vera, Tomás; Gámez, José María; Govea, Nancy; Gómez, Yolanda; Núñez, Juana; Socías, Lorenzo; Escandell, Ángela; Rosell, Jorge

    2016-02-01

    Mutations in the troponin T gene (TTNT2) have been associated in small studies with the development of hypertrophic cardiomyopathy characterized by a high risk of sudden death and mild hypertrophy. We describe the clinical course of patients carrying mutations in this gene. We analyzed the clinical characteristics and prognosis of patients with mutations in the TNNT2 gene who were seen in an inherited cardiac disease unit. Of 180 families with genetically studied cardiomyopathies, 21 families (11.7%) were identified as having mutations in TNNT2: 10 families had Arg92Gln, 5 had Arg286His, 3 had Arg278Cys, 1 had Arg92Trp, 1 had Arg94His, and 1 had Ile221Thr. Thirty-three additional genetic carriers were identified through family assessment. The study included 54 genetic carriers: 56% were male, and the mean average age was 41 ± 17 years. There were 33 cases of hypertrophic cardiomyopathy, 9 of dilated cardiomyopathy, and 1 of noncompaction cardiomyopathy, and maximal myocardial thickness was 18.5 ± 6mm. Ventricular dysfunction was present in 30% of individuals and a history of sudden death in 62%. During follow-up, 4 patients died and 14 (33%) received a defibrillator (8 probands, 6 relatives). Mean survival was 54 years. Carriers of Arg92Gln had early disease development, high penetrance, a high risk of sudden death, a high rate of defibrillator implantation, and a high frequency of mixed phenotype. Mutations in the TNNT2 gene were more common in this series than in previous studies. The clinical and prognostic profiles depended on the mutation present. Carriers of the Arg92Gln mutation developed hypertrophic or dilated cardiomyopathy and had a significantly worse prognosis than those with other mutations in TNNT2 or other sarcomeric genes. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  13. Responsiveness of cardiodynamics to exercise loading in normal subjects and in patients with idiopathic cardiomyopathy

    International Nuclear Information System (INIS)

    Fukuoka, Yukie; Matsuda, Takeshi

    1996-01-01

    In the present study, we examined the responses of the left ventricular systolic function and diastolic function to exertion by cardiac blood pool scintigraphy using 99mTc in reference to changes with aging and changes in the cases of idiopathic cardiomyopathy. In order to study the functional response with aging to exertion, 38 normal subjects were divided by age. Subsequently, 28 hypertrophic cardiomyopathy cases (Group H), 13 dilated cardiomyopathy cases (Group D) and 14 normal cases (Group N) were studied. Ejection Fraction (EF) and Peak Ejection Rate (PER) were used as the indicators for the systolic function. Peak Filling Rate (PER), 1/3 Filling Rate (1/3FR) and Time to Peak Filling (TPF) were used as the indicators for the diastolic function. When comparison was made among the normal subjects by age, the systolic function and diastolic function at rest, varied as they were, showed no significant change with aging. The %delta EF and %delta PER tended to decrease linearly with aging (Y=-4E-X+28, p<0.0001; Y=-X+57, p<0.0001). As to the %delta PFR, %delta 1/3FR and %delta TPF, however, correlation with aging was not found. In comparing hypertrophic cardiomyopathy and dilated cardiomyopathy, Group D showed significantly lower values before exertion and after maximum exertion than the other two groups. A difference in the response of the systolic function and diastolic function to exertion was noted in both the comparative study on aging of the normal subjects and the study of cases of cardiomyopathy. The presence of the compensatory mechanism due to elevation of the left atrial pressure and an increase in the left atrial contractile power may be mentioned as a reservoir of blood and also as a booster pump. Particularly, the effect of the latter compensates for the decline in the left ventricular compliance, which may lead to the maintenance of the diastolic function. (K.H.)

  14. Genetics of cardiomyopathies in children

    Directory of Open Access Journals (Sweden)

    Matteo Vatta

    2011-08-01

    Full Text Available Cardiomyopathies are diseases of the heart muscle leading to heart failure and/or an increased risk of arrhythmogenic sudden cardiac death. These disorders represent a major cause of morbidity and mortality in children. In childhood forms of cardiomyopathy, genetic etiologies are frequent, but non-genetic or acquired causes, such viral infection, also play a significant role. In the last twenty years, the genetic causes of cardiomyopathies have been increasingly identified and clinical correlations are beginning to be defined. Here we present an overview of the recent advances in our understanding of the genetics of cardiomyopathies in children and what is known about the pathophysiological mechanisms underlying these gene-related forms of disease.

  15. Efficacy of Gd-DTPA-enhanced MRI in hypertrophic cardiomyopathy

    International Nuclear Information System (INIS)

    Okamoto, Shinya; Aoki, Toshikazu; Konishi, Tokuji; Nakano, Takeshi; Yamakado, Kyoichiro; Sakuma, Hajime; Takeda, Kann; Nakagawa, Takashi

    1991-01-01

    The cabability of magnetic resonance (MR) imaging to detect tissue characterization or myocardial degeneration process of the hypertrophied myocardium was evaluated in 15 patients with hypertrophic cardiomyopathy. T1-weighted MR images were obtained with a 1.5 T MR unit by using ECG-gated spin-echo techniques. MR images were visually reviewed before and after enhancement of Gd-DTPA. Four patients had an increase in signal intensity mainly in the endocardium of the left ventricular septum on non-enhanced MR images, 3 of whom had widespread high intensity in addition to two-thirds of the wall. Gd-DTPA enhanced-MR images showed high intensity over the whole septum in 5 patients and also in the antero-lateral endocardium in 4 patients. Decreased intensity on non-enhanced MR images, as shown in 4 patients, became clear on enhanced-MR images. According to findings on enhanced-MR images, signal intensity was defined as normal (N), septum (S), and diffuse (D). Patients in Group D tended to be younger and have more frequently family history. Regarding both interventricular septum thickness and left ventricular posterior wall thickness, there was no significant difference among the three groups. Both left ventricular diastolic diameter and left ventricular systolic diameter were significantly larger in Group D than the other two groups. Left ventricular ejection fraction was significantly lower in both Group S and Group D. Widespread abnormal intensity on Gd-DTPA enhanced MR images was associated with findings similar to dilated cardiomyopathy, such as dilated left ventricular lumen and decreased ejection fraction. Gd-DTPA enhanced MR imaging seemed to be useful for visualizing myocardial degeneration in hypertrophic cardiomyopathy.(N.K.)

  16. Diabetic Cardiomyopathy: Bench to Bedside

    Science.gov (United States)

    Schilling, Joel D.; Mann, Douglas L.

    2012-01-01

    The study of diabetic cardiomyopathy (diabetic CM) is an area of significant interest given the strong association between diabetes and the risk of heart failure. Many unanswered questions remain regarding the clinical definition and pathogenesis of this metabolic cardiomyopathy. This article reviews the current understanding of diabetic CM with a particular emphasis on the unresolved issues that have limited translation of scientific discovery to patient bedside. PMID:22999244

  17. Brain Abscess after Esophageal Dilatation

    DEFF Research Database (Denmark)

    Gaïni, S; Grand, M; Michelsen, J

    2007-01-01

    Brain abscess formation is a serious disease often seen as a complication to other diseases and to procedures. A rare predisposing condition is dilatation therapy of esophageal strictures. A case of brain abscess formation after esophageal dilatations is presented. A 59-year-old woman was admitted...... with malaise, progressive lethargy, fever, aphasia and hemiparesis. Six days before she had been treated with esophageal dilatation for a stricture caused by accidental ingestion of caustic soda. The brain abscess was treated with surgery and antibiotics. She recovered completely. This clinical case...... illustrates the possible association between therapeutic esophageal dilatation and the risk of brain abscess formation....

  18. NGS testing for cardiomyopathy: Utility of adding RASopathy-associated genes.

    Science.gov (United States)

    Ceyhan-Birsoy, Ozge; Miatkowski, Maya M; Hynes, Elizabeth; Funke, Birgit H; Mason-Suares, Heather

    2018-04-25

    RASopathies include a group of syndromes caused by pathogenic germline variants in RAS-MAPK pathway genes and typically present with facial dysmorphology, cardiovascular disease, and musculoskeletal anomalies. Recently, variants in RASopathy-associated genes have been reported in individuals with apparently nonsyndromic cardiomyopathy, suggesting that subtle features may be overlooked. To determine the utility and burden of adding RASopathy-associated genes to cardiomyopathy panels, we tested 11 RASopathy-associated genes by next-generation sequencing (NGS), including NGS-based copy number variant assessment, in 1,111 individuals referred for genetic testing for hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM). Disease-causing variants were identified in 0.6% (four of 692) of individuals with HCM, including three missense variants in the PTPN11, SOS1, and BRAF genes. Overall, 36 variants of uncertain significance (VUSs) were identified, averaging ∼3VUSs/100 cases. This study demonstrates that adding a subset of the RASopathy-associated genes to cardiomyopathy panels will increase clinical diagnoses without significantly increasing the number of VUSs/case. © 2018 Wiley Periodicals, Inc.

  19. Tachycardia-Induced Cardiomyopathy in a 12-Year-Old Child With Long QT Syndrome

    Directory of Open Access Journals (Sweden)

    Ghandi

    2016-05-01

    Full Text Available Introduction Tachycardia-induced cardiomyopathy (TIC is a ventricular dysfunction secondary to chronic and persistent tachycardia that can regress partially or completely following heart rate normalization. Paroxysmal atrial tachycardia and permanent junctional reciprocating tachycardia are two types of frequent arrhythmias that can cause cardiomyopathy in children. Case Presentation A 12-year-old child with obesity (body mass index > 26.8 was admitted with fatigue, pallor and tachypnea to the clinic. He had palpitation for the past 24 hours. On the cardiac auscultation, holosystolic 2/6 murmur was heard in the apex as well as gallop rhythm. Electrocardiogram revealed heart rate of 150 - 160 bpm and negative P waves in II, III and AVF leads. The echocardiography revealed dilated cardiomyopathy with an ejection fraction of 30%. Conclusions Diagnosis of tachycardia-induced cardiomyopathy in children is important, since appropriate treatment improves the prognosis. Every child with recurrent and persistent palpitation with the first episode of congestive heart failure should be evaluated for tachycardia- induced cardiomyopathy.

  20. MELAS syndrome and cardiomyopathy: linking mitochondrial function to heart failure pathogenesis.

    Science.gov (United States)

    Hsu, Ying-Han R; Yogasundaram, Haran; Parajuli, Nirmal; Valtuille, Lucas; Sergi, Consolato; Oudit, Gavin Y

    2016-01-01

    Heart failure remains an important clinical burden, and mitochondrial dysfunction plays a key role in its pathogenesis. The heart has a high metabolic demand, and mitochondrial function is a key determinant of myocardial performance. In mitochondrial disorders, hypertrophic remodeling is the early pattern of cardiomyopathy with progression to dilated cardiomyopathy, conduction defects and ventricular pre-excitation occurring in a significant proportion of patients. Cardiac dysfunction occurs in approximately a third of patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, a stereotypical example of a mitochondrial disorder leading to a cardiomyopathy. We performed unique comparative ultrastructural and gene expression in a MELAS heart compared with non-failing controls. Our results showed a remarkable increase in mitochondrial inclusions and increased abnormal mitochondria in MELAS cardiomyopathy coupled with variable sarcomere thickening, heterogeneous distribution of affected cardiomyocytes and a greater elevation in the expression of disease markers. Investigation and management of patients with mitochondrial cardiomyopathy should follow the well-described contemporary heart failure clinical practice guidelines and include an important role of medical and device therapies. Directed metabolic therapy is lacking, but current research strategies are dedicated toward improving mitochondrial function in patients with mitochondrial disorders.

  1. Selective decrease of components of the creatine kinase system and ATP synthase complex in chronic Chagas disease cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Priscila Camillo Teixeira

    2011-06-01

    Full Text Available BACKGROUND: Chronic Chagas disease cardiomyopathy (CCC is an inflammatory dilated cardiomyopathy with a worse prognosis than other cardiomyopathies. CCC occurs in 30 % of individuals infected with Trypanosoma cruzi, endemic in Latin America. Heart failure is associated with impaired energy metabolism, which may be correlated to contractile dysfunction. We thus analyzed the myocardial gene and protein expression, as well as activity, of key mitochondrial enzymes related to ATP production, in myocardial samples of end-stage CCC, idiopathic dilated (IDC and ischemic (IC cardiomyopathies. METHODOLOGY/PRINCIPAL FINDINGS: Myocardium homogenates from CCC (N=5, IC (N=5 and IDC (N=5 patients, as well as from heart donors (N=5 were analyzed for protein and mRNA expression of mitochondrial creatine kinase (CKMit and muscular creatine kinase (CKM and ATP synthase subunits aplha and beta by immunoblotting and by real-time RT-PCR. Total myocardial CK activity was also assessed. Protein levels of CKM and CK activity were reduced in all three cardiomyopathy groups. However, total CK activity, as well as ATP synthase alpha chain protein levels, were significantly lower in CCC samples than IC and IDC samples. CCC myocardium displayed selective reduction of protein levels and activity of enzymes crucial for maintaining cytoplasmic ATP levels. CONCLUSIONS/SIGNIFICANCE: The selective impairment of the CK system may be associated to the loss of inotropic reserve observed in CCC. Reduction of ATP synthase alpha levels is consistent with a decrease in myocardial ATP generation through oxidative phosphorylation. Together, these results suggest that the energetic deficit is more intense in the myocardium of CCC patients than in the other tested dilated cardiomyopathies.

  2. Molecular screening by polymerase chain reaction detects panleukopenia virus DNA in formalin-fixed hearts from cats with idiopathic cardiomyopathy and myocarditis.

    Science.gov (United States)

    Meurs, K M; Fox, P R; Magnon, A L; Liu, S; Towbin, J A

    2000-01-01

    Viral myocarditis has been suggested as an etiology for cardiomyopathy in several mammalian species. Myocarditis and idiopathic cardiomyopathy have been reported in the domestic cat, although a viral etiology has not been demonstrated. Because of the continuing interest in the potential relationship between viral myocarditis and cardiomyopathy, we evaluated hearts from cats with spontaneous, idiopathic cardiomyopathy for viral genomic material within myocytes by polymerase chain reaction, and for the presence of myocarditis by light microscopy. Thirty-one (31) formalin-fixed hearts from domestic cats who died of idiopathic cardiomyopathy were randomly selected from pathology archives. Seventeen (17) formalin-fixed hearts from healthy cats were similarly selected as normal controls. The polymerase chain reaction (PCR) was used to evaluate myocardial tissue for the presence of viral genome from feline panleukopenia virus, herpes virus, calici virus, and corona virus. Hearts were examined using light microscopy for histologic evidence of myocarditis according to the Dallas criteria. Panleukopenia virus was identified by PCR in 10 of 31 cats with cardiomyopathy but in none of the controls. Neither cardiomyopathic or control cats tested positive by PCR for herpes virus, calici virus, and corona virus. Myocarditis was detected by histologic examination in 18 of 31 cardiomyopathic cats and in none of 17 control cats. Myocarditis and or feline panleukopenia virus genome was detected in felines with idiopathic hypertrophic, dilated, and restrictive cardiomyopathy, suggesting a possible role of viral infection and inflammation in the pathogenesis of cardiomyopathy in this species.

  3. Cardiomyopathy in Patients With Hereditary Bullous Epidermolysis.

    Science.gov (United States)

    Batalla, A; Vicente, A; Bartrons, J; Prada, F; Fortuny, C; González-Enseñat, M A

    In recent decades, an association has been reported between epidermolysis bullosa (EB) and dilated cardiomyopathy (DC). DC is typically in an advanced phase when detected, le