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Sample records for hypertrophic cardiomyopathy relation

  1. Hypertrophic cardiomyopathy.

    Science.gov (United States)

    Santos Mateo, Juan José; Sabater Molina, María; Gimeno Blanes, Juan Ramón

    2017-11-14

    Hypertrophic cardiomyopathy is the most common inherited cardiovascular disease. It is characterized by increased ventricular wall thickness and is highly complex due to its heterogeneous clinical presentation, several phenotypes, large number of associated causal mutations and broad spectrum of complications. It is caused by mutations in sarcomeric proteins, which are identified in up to 60% of cases of the disease. Clinical manifestations of Hypertrophic Cardiomyopathy include shortness of breath, chest pain, palpitations and syncope, which are related to the onset of diastolic dysfunction, left ventricular outflow tract obstruction, ischemia, atrial fibrillation and abnormal vascular responses. It is associated with an increased risk of sudden cardiac death, heart failure and thromboembolic events. In this article, we discuss the diagnostic and therapeutic aspects of this disease. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  2. Hypertrophic cardiomyopathy.

    Science.gov (United States)

    Subasic, Kim

    2013-12-01

    Hypertrophic cardiomyopathy (HCM) is an autosomal dominant, cardiovascular disorder that carries the risk of sudden cardiac death. The prevalence of HCM is 1:500 persons. The purpose of this article is to provide an overview of the pathophysiology, symptoms, complications, diagnostic testing, and treatment. The silent presentation of HCM presents unique diagnostic challenges and complicates prompt identification. Diagnostic testing and management strategies for the care of a person with HCM are discussed. HCM has individualized presentation and therefore requires individualized therapy. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Hypertrophic Cardiomyopathy Association

    Science.gov (United States)

    ... organization improving the lives of those with hypertrophic cardiomyopathy, HCM, preventing untimely deaths and advancing global understanding. ... item purchased, 10% will be donated to Hypertrophic Cardiomyopathy Association. iGive.com - Online Shopping Joing iGive.com ...

  4. Decreased coronary flow reserve in hypertrophic cardiomyopathy is related to remodeling of the coronary microcirculation

    NARCIS (Netherlands)

    M.J.M. Kofflard (Marcel); D.J.G.M. Duncker (Dirk); C. von Birgelen (Clemens); S.G. Carlier (Stephan); M. Kliffen (Mike); P.W.J.C. Serruys (Patrick); R. Krams (Rob); F.J. ten Cate (Folkert)

    1998-01-01

    textabstractBACKGROUND: Ischemia occurs frequently in hypertrophic cardiomyopathy (HCM) without evidence of epicardial stenosis. This study evaluates the hypothesis that the occurrence of ischemia in HCM is related to remodeling of the coronary microcirculation. METHODS AND

  5. Echocardiographic evaluation of pre-diagnostic development in young relatives genetically predisposed to hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Jensen, Morten K; Havndrup, Ole; Christiansen, Michael

    2015-01-01

    Identification of the first echocardiographic manifestations of hypertrophic cardiomyopathy may be important for clinical management and our understanding of the pathogenesis. We studied the development of pre-diagnostic echocardiographic changes in young relatives to HCM patients during long...

  6. HYPERTROPHIC CARDIOMYOPATHY IN MULTIMORBIDITY

    Directory of Open Access Journals (Sweden)

    A. I. Lakhonina

    2016-06-01

    Full Text Available Aspects of diagnosis, difficulties in the diagnosis and optimal therapeutic strategies in patient with hypertrophic cardiomyopathy and comorbid conditions such as arterial hypertension, ischemic heart disease, dyslipidemia, diabetes mellitus type 2, stenosis of the left renal artery, obesity are reviewed on the example of clinical case. Hypertrophic cardiomyopathy combined with multimorbidity conditions requires a high-quality medical management, where the main goal is to improve the quality and duration of patient's life. This goal is being achieved by optimizing patient's lifestyle and assigning only the minimum amount of medications. Necessity of careful diagnosis of hypertrophic cardiomyopathy, evaluation of the risk of sudden death and search of optimal treatment in patients with multimorbidity pathology are demonstrated in clinical case.

  7. Hypertrophic cardiomyopathy secondary to hepatitis C virus-related vasculitis.

    Science.gov (United States)

    Cavalli, Giulio; Berti, Alvise; Fragasso, Gabriele; De Cobelli, Francesco

    2016-12-01

    : Almost invariably associated with chronic HCV infection, cryoglobulinemic vasculitis is a small-vessel vasculitis commonly affecting the skin, kidneys, and peripheral nervous system. Cardiac involvement, possibly due to cardiac microcirculation involvement, is an utterly rare and severe complication. We describe a case of hypertrophic cardiomyopathy secondary to cryoglobulinemic vasculitis. Evaluation with transthoracic cardiac ultrasound and cardiac MRI evidenced severe left ventricular hypertrophy and diffuse hypokinesia, a marked decrease in left ventricular ejection fraction, and a subtle late enhancement of inferior and lateral left ventricular walls. Upon clinical stabilization, the patient received treatment with anti-CD20 monoclonal antibody rituximab. Clinical and radiological follow-up with cardiac ultrasound and cardiac MRI documented a dramatic and sustained clinical improvement, with marked reduction of left ventricular hypertrophy, resolution of late enhancement, recovery of left ventricular contractility and function.

  8. Genetics Home Reference: familial hypertrophic cardiomyopathy

    Science.gov (United States)

    ... Home Health Conditions Familial hypertrophic cardiomyopathy Familial hypertrophic cardiomyopathy Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Familial hypertrophic cardiomyopathy is a heart condition characterized by thickening (hypertrophy) ...

  9. HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY

    Directory of Open Access Journals (Sweden)

    A. G. Osiev

    2015-01-01

    Full Text Available Hypertrophic cardiomyopathy (HCMP is a relatively common disease with genetic predisposition, that is widely spread irrespective of gender, race or ethnicity. The cause of this pathology are mutations of genes encoding synthesis of contracting proteins. Degree and type of mutations define clinical manifestation of the disease and its prognosis. HCMP is classified according to four main criteria: depending on morphology, presence of left ventricular outlet obstruction, pressure gradient and hemodynamic parameters. Its prevalence amounts to 1:500, and in the recent years mortality has decreased significantly to 1%. Main symptoms of HCMP include dyspnoea, dizziness, syncope, angina, and heart arrhythmias. HCMP does not manifest obligatorily with all above mentioned signs and symptoms. Presence and severity of any symptoms depend on morphological particulars of the disease. Particular attention should be paid to arrhythmias, with atrial fibrillation among them, that may cause hazardous and occasionally lethal complications. Electrocardiography and echocardiography are recognized as the “golden standard” of HCMP diagnostics, while in the recent years, magnetic resonance imaging has become a highly informative diagnostic tool. Radionuclide diagnostics is used less frequently, while physical examination and assessments have been moving backwards. At present, main strategies in HCMP include medical treatment with β-blockers, calcium antagonists, angiotensin-converting enzyme inhibitors and anti-arrhythmics. There are two techniques for surgical treatment, i.e. myectomy by Morrow and alcohol septal ablation that is becoming increasingly popular. The article reviews literature on state-of-the-art diagnostics and treatment of HCMP patients.

  10. Hypertrophic Cardiomyopathy: A Review

    Science.gov (United States)

    Houston, Brian A; Stevens, Gerin R

    2014-01-01

    Hypertrophic cardiomyopathy (HCM) is a global disease with cases reported in all continents, affecting people of both genders and of various racial and ethnic origins. Widely accepted as a monogenic disease caused by a mutation in 1 of 13 or more sarcomeric genes, HCM can present catastrophically with sudden cardiac death (SCD) or ventricular arrhythmias or insidiously with symptoms of heart failure. Given the velocity of progress in both the fields of heart failure and HCM, we present a review of the approach to patients with HCM, with particular attention to those with HCM and the clinical syndrome of heart failure. PMID:25657602

  11. Misconceptions and Facts About Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Argulian, Edgar; Sherrid, Mark V; Messerli, Franz H

    2016-02-01

    Hypertrophic cardiomyopathy is the most common genetic heart disease. Once considered relentless, untreatable, and deadly, it has become a highly treatable disease with contemporary management. Hypertrophic cardiomyopathy is one of cardiology's "great masqueraders." Mistakes and delays in diagnosis abound. Hypertrophic cardiomyopathy commonly "masquerades" as asthma, anxiety, mitral prolapse, and coronary artery disease. However, once properly diagnosed, patients with hypertrophic cardiomyopathy can be effectively managed to improve both symptoms and survival. This review highlights some of the misconceptions about hypertrophic cardiomyopathy. Providers at all levels should have awareness of hypertrophic cardiomyopathy to promptly diagnose and properly manage these individuals. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Leopard syndrome and hypertrophic cardiomyopathy: an association related to sudden death.

    Science.gov (United States)

    Antunes, Murillo de Oliveira; Arteaga, Edmundo; Matsumoto, Afonso Yoshikiro; Ianni, Barbara Maria

    2009-06-01

    We describe an uncommon association between Leopard syndrome and hypertrophic cardiomyopathy in a 27-year-old woman, who was little symptomatic and came for sudden death risk stratification and prevention. She has a rare syndrome, whose symptoms are maculae over the body and abnormalities in eyes, genital organs, heart and in growth. Association of hypertrophic cardiomyopathy with sudden death risk factors determined the implantation of cardioverter-defibrillator (ICD) for primary prevention.

  13. DIFFERENTIAL DIAGNOSIS OF HYPERTROPHIC CARDIOMYOPATHY

    Directory of Open Access Journals (Sweden)

    I. V. Leontyeva

    2017-01-01

    Full Text Available Hypertrophic cardiomyopathy is the most common form of cardiomyopathy, occurring in childhood, occurring when a gene is mutated that encodes proteins of sarcomeric and non-sarcomeric complexes. The diagnosis of the disease is based on the data of echocardiography, revealing structural changes in the heart muscle according to the type of hypertrophy, while the genesis of these changes remains unclear. The causes of hypertrophic cardiomyopathy in childhood are diverse. Of great importance is the early diagnosis of metabolic forms of hypertrophic cardiomyopathy, so in some cases regress of hypertrophy is possible against the background of enzyme-substitution or other drug therapy. The article presents a clinical (cardiac and extracardiac symptoms and laboratory markers of hypertrophic cardiomyopathy with mutations of genes of proteins of the sarcomeric complex, congenital metabolic disorders (glycogenoses, lysosomal pathology, fatty acid metabolism disorders, and mitochondrial diseases, genetic syndromes (Noonan, LEOPARD, Costello, cardio-fascial-cutaneous, neuromuscular diseases. The criteria for differential diagnosis of genetic forms of hypertrophic cardiomyopathy and myocardial hypertrophy in athletes are presented. 

  14. Multimodality imaging in apical hypertrophic cardiomyopathy

    Science.gov (United States)

    Parisi, Rosario; Mirabella, Francesca; Secco, Gioel Gabrio; Fattori, Rossella

    2014-01-01

    Apical hypertrophic cardiomyopathy (AHCM) is a relatively rare morphologic variant of HCM in which the hypertrophy of myocardium is localized to the left ventricular apex. Symptoms of AHCM might vary from none to others mimic coronary artery disease including acute coronary syndrome, thus resulting in inappropriate hospitalization. Transthoracic echocardiography is the first-line imaging technique for the diagnosis of hypertrophic cardiomyopathies. However, when the hypertrophy of the myocardium is localized in the ventricular apex might results in missed diagnosis. Aim of this paper is to review the different imaging techniques used for the diagnosis of AHCM and their role in the detection and comprehension of this uncommon disease. PMID:25276293

  15. Living with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Subasic, Kim

    2013-12-01

    The purpose of this study is to provide an insider's account of what it is like to live with hypertrophic cardiomyopathy (HCM), a genetic cardiovascular illness that carries the risk for sudden cardiac death. This study aims to reveal how HCM impacts the family and guides the decision whether or not to pursue genetic testing, how the physical limitations associated with HCM alter being-in-the-world, and how HCM alters social relationships. Fifteen adults with HCM were recruited for a longitudinal, phenomenological, qualitative study through purposive sampling and word of mouth. A total of 45 interviews were conducted by the researcher at a time and place designated by the participant between August 2011 and January 2012. The first interview with each participant was conducted in person. While efforts were made to conduct all interviews in person, a total of three interviews were conducted by telephone as requested by three participants due to scheduling conflicts. Through methods of interpretive phenomenology, three audio-recorded, semistructured interviews occurred over the course of 3 months. Detailed narratives were solicited and transcribed verbatim. Methodological and analytical documentation was supported with the identification of key phrases, similar experiences, themes, and documentation of the rationale for decisions throughout the research process. Participation in genetic testing carries a multitude of personal, familial, financial, and emotional implications. The results of a genetic test elicited an emotional response regardless of whether the results were negative, positive, or inconclusive. Living with a potentially life-threatening illness altered identity, disrupted social relationships, and generated chronic fear and uncertainty. A new normal was re-ordered or transformed by the demands and limitations posed by HCM, and by the person's concerns, priorities, and the meaning of the illness. Results from this study underscore the need for healthcare

  16. Psychosocial impact of specialized cardiac genetic clinics for hypertrophic cardiomyopathy.

    Science.gov (United States)

    Ingles, Jodie; Lind, Joanne M; Phongsavan, Philayrath; Semsarian, Christopher

    2008-02-01

    The diagnosis of hypertrophic cardiomyopathy, an autosomal dominant chronic heart disease, can have significant implications, including increased risk of sudden death, exercise limitations, and risk of transmission to offspring. This study sought to describe the psychosocial factors associated with attending a specialty cardiac genetic clinic, and to determine whether these may be predictors of comorbid anxiety and depression in this population. Questionnaires were sent to 184 individuals attending the Royal Prince Alfred Hospital Hypertrophic Cardiomyopathy Clinic. Questionnaires were anonymous and comprised demographics, the Hospital Anxiety and Depression Scale, Patient Experience Scales, and Patient Satisfaction Scales. Completed questionnaires were returned by 109 participants (59.2% response rate), of which 76.9% had a diagnosis of hypertrophic cardiomyopathy, while 23.1% were at-risk relatives attending for clinical screening. Patient satisfaction scores were generally high to very high across all groups, though only 24% of HCM patients showed good adjustment to hypertrophic cardiomyopathy and 10% had low worry about hypertrophic cardiomyopathy scores. Within the disease group, logistic regression analysis adjusting for age, gender, and education revealed adjustment to hypertrophic cardiomyopathy and worry about hypertrophic cardiomyopathy scores to be significantly associated with anxiety, while adjustment scores and location of patient follow-up (i.e., Hypertrophic Cardiomyopathy clinic or another cardiologist) to be significantly associated with depression scores. HCM patients who attend specialized cardiac genetic clinics are better adjusted and worry less, than those who do not attend. An integrated approach, including a genetic counselor, is important in the management of HCM families.

  17. Prevalence of hypertrophic cardiomyopathy in highly trained athletes: relevance to pre-participation screening

    National Research Council Canada - National Science Library

    Basavarajaiah, Sandeep; Wilson, Matthew; Whyte, Gregory; Shah, Ajay; McKenna, William; Sharma, Sanjay

    2008-01-01

    This study sought to determine the prevalence of hypertrophic cardiomyopathy (HCM) in elite athletes. Hypertrophic cardiomyopathy is considered to be the most common cause of exercise-related sudden death in young athletes...

  18. Subendocardial ischemia in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Kawasaki, Tatsuya; Sugihara, Hiroki

    2014-02-01

    Hypertrophic cardiomyopathy (HCM) patients often develop subendocardial ischemia in the left ventricle without atherosclerotic coronary stenosis. Myocardial ischemia plays an important role in the pathophysiology of HCM, but diagnostic techniques for the detection of subendocardial ischemia have not been widely available. We developed specific techniques to quantify subendocardial ischemia on stress scintigraphy, and have compared the results with various clinical features in patients with HCM. This article reviews our understanding of subendocardial ischemia in HCM based on more than 20 years of experience. Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  19. Left Ventricular Systolic Dyssynchrony in Patients with Hypertrophic Cardiomyopathy: The prevalence and its Relation to Syncope

    Directory of Open Access Journals (Sweden)

    N Behzadnia

    2010-12-01

    Full Text Available Background: The distribution and magnitude of left ventricularhypertrophy (LVH are not uniform in patients with hypertrophic cardiomyopathy (HCM , which results in regional heterogeneity of left ventricular ( LVsystolic function. The aim of this study was to evaluate LV regional systolicdyssynchrony in patients with HCM by Tissue Doppler Imaging (TDI and to findany correlation between TDI data and syncope.Methods: A total of 44 consecutive patients with HCM are recruited inthe present study. .All patients, underwent complete clinical andechocardiographic evaluation including TDI . The following were measured in 6different basal and 6 mid-myocardial segments: systolic peak velocity(Sm,early diastolic myocardial velocity (Em, pre-contraction time(Q-Sm frombeginning of Q- wave of ECG to the onset of Sm, total asynchrony index,interventricular mechanical delay(difference in Q-Aortic valve opening andQ-Pulmonic valve opening and maximum difference in time to peak systolicvelocity between 2 of 12 segments(ΔPVI.Results: TDI analysis in HCM subgroup with syncope showed bothsignificant interventricular (36.72±26.26 vs 14.74±11.30 msec, P<0.001 andintraventricular delays(39.40±22.38 vs27.70±17.32 msec, P=0.07. The prevalenceof LV systolic dyssynchrony was from 20.5% to 38.6% based on different methods.Patients with syncope had greater impairment of regional systolic and earlydiastolic function, remarkably lower Sm and Em velocities.Conclusion: The impairment of inter and intraventricular systolicsynchronicity is significantly related to syncope in patients with HCM.TDIanalysis may be able to select subgroups of HCM patients at increasing risk ofsyncope and major cardiac events

  20. Diagnostic yield, interpretation, and clinical utility of mutation screening of sarcomere encoding genes in Danish hypertrophic cardiomyopathy patients and relatives

    DEFF Research Database (Denmark)

    Andersen, Paal Skytt; Havndrup, Ole; Hougs, Lotte

    2008-01-01

    The American Heart Association (AHA) recommends family screening for hypertrophic cardiomyopathy (HCM). We assessed the outcome of family screening combining clinical evaluation and screening for sarcomere gene mutations in a cohort of 90 Danish HCM patients and their close relatives, in all 451......, and in 37.5% of relatives without a mutation, one or more criteria was fulfilled. A total of 60% of family members had no mutation and could be reassured and further follow-up ceased. Genetic diagnosis may be established in approximately 40% of families with the highest yield in familial HCM with clinical...

  1. Hypertrophic cardiomyopathy screening in young athletes

    Energy Technology Data Exchange (ETDEWEB)

    Rappoport, W.J. [Arizona Heart Inst., Phoenix, AZ (United States); Steingard, P.M. [Phoenix Suns, Phoenix, AZ (United States)

    2006-07-01

    Hypertrophic cardiomyopathy is the leading cause of sudden death during vigorous exercise. Early identification of this abnormality by ECG screening of high-school athletes before they participate in competitive sports helps save lives. (orig.)

  2. Diagnosis of apical hypertrophic cardiomyopathy: T-wave inversion and relative but not absolute apical left ventricular hypertrophy.

    Science.gov (United States)

    Flett, Andrew S; Maestrini, Viviana; Milliken, Don; Fontana, Mariana; Treibel, Thomas A; Harb, Rami; Sado, Daniel M; Quarta, Giovanni; Herrey, Anna; Sneddon, James; Elliott, Perry; McKenna, William; Moon, James C

    2015-03-15

    Diagnosis of apical HCM utilizes conventional wall thickness criteria. The normal left ventricular wall thins towards the apex such that normal values are lower in the apical versus the basal segments. The impact of this on the diagnosis of apical hypertrophic cardiomyopathy has not been evaluated. We performed a retrospective review of 2662 consecutive CMR referrals, of which 75 patients were identified in whom there was abnormal T-wave inversion on ECG and a clinical suspicion of hypertrophic cardiomyopathy. These were retrospectively analyzed for imaging features consistent with cardiomyopathy, specifically: relative apical hypertrophy, left atrial dilatation, scar, apical cavity obliteration or apical aneurysm. For comparison, the same evaluation was performed in 60 healthy volunteers and 50 hypertensive patients. Of the 75 patients, 48 met conventional HCM diagnostic criteria and went on to act as another comparator group. Twenty-seven did not meet criteria for HCM and of these 5 had no relative apical hypertrophy and were not analyzed further. The remaining 22 patients had relative apical thickening with an apical:basal wall thickness ratio >1 and a higher prevalence of features consistent with a cardiomyopathy than in the control groups with 54% having 2 or more of the 4 features. No individual in the healthy volunteer group had more than one feature and no hypertension patient had more than 2. A cohort of individuals exist with T wave inversion, relative apical hypertrophy and additional imaging features of HCM suggesting an apical HCM phenotype not captured by existing diagnostic criteria. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Apical Hypertrophic Cardiomyopathy in Association with PulmonaryArtery Hypertension

    Directory of Open Access Journals (Sweden)

    Mehdi Peighambari

    2012-09-01

    Full Text Available Apical Hypertrophic Cardiomyopathy is an uncommon condition constituting 1% -2% of the cases with Hypertrophic Cardiomyopathy (HCM diagnosis. We interestingly report two patients with apical hypertrophic cardiomyopathy in association with significant pulmonary artery hypertension without any other underlying reason for pulmonary hypertension. The patients were assessed by echocardiography, cardiac catheterization and pulmonary function parameters study.

  4. Apical Hypertrophic Cardiomyopathy in Association with Pulmonary Artery Hypertension

    OpenAIRE

    Peighambari, Mehdi; Parsaei, Mozghan; Sadeghpour, Anita; Alizadehasl, Azin

    2012-01-01

    Apical Hypertrophic Cardiomyopathy is an uncommon condition constituting 1% -2% of the cases with Hypertrophic Cardiomyopathy (HCM) diagnosis. We interestingly report two patients with apical hypertrophic cardiomyopathy in association with significant pulmonary artery hypertension without any other underlying reason for pulmonary hypertension. The patients were assessed by echocardiography, cardiac catheterization and pulmonary function parameters study.

  5. Mortality Risk of Untreated Myosin-Binding Protein C-Related Hypertrophic Cardiomyopathy Insight Into the Natural History

    NARCIS (Netherlands)

    Nannenberg, Eline A.; Michels, Michelle; Christiaans, Imke; Majoor-Krakauer, Danielle; Hoedemaekers, Yvonne M.; van Tintelen, J. Peter; Lombardi, M. Paola; ten Cate, Folkert J.; Schinkel, Arend F. L.; Tijssen, Jan G. P.; van Langen, Irene M.; Wilde, Arthur A. M.; Sijbrands, Eric J. G.

    2011-01-01

    Objectives The goal of this study was to assess the mortality of hypertrophic cardiomyopathy (HCM), partly in times when the disease was not elucidated and patients were untreated. Background HCM is feared for the risk of sudden cardiac death (SCD). Insight in the natural history of the disorder is

  6. Left Atrial Performance in the Course of Hypertrophic Cardiomyopathy: Relation to Left Ventricular Hypertrophy and Fibrosis.

    Science.gov (United States)

    Kowallick, Johannes T; Silva Vieira, Miguel; Kutty, Shelby; Lotz, Joachim; Hasenfu, Gerd; Chiribiri, Amedeo; Schuster, Andreas

    2017-03-01

    Hypertrophic cardiomyopathy (HCM) is associated with left atrial (LA) functional abnormalities. The determinants and the degree of LA dysfunction in the course of HCM are not fully understood. We aimed to characterize LA mechanics in HCM, according to the extent of left ventricular (LV) hypertrophy and fibrosis. Seventy-three HCM patients and 23 age- and sex-matched controls underwent cardiovascular magnetic resonance imaging including late gadolinium enhancement (LGE). LA reservoir, conduit, and contractile functions were quantified by fractional volume changes and cardiovascular magnetic resonance feature-tracking-derived strain and strain rate. In multivariable regression, LA mechanics were associated with the extent of LV LGE (P = 0.033 to P < 0.001), but not with the LV mass extent or maximum wall thickness (P = 0.108 to P = 0.964). Left atrial function decreased according to the increase in extent of LV fibrosis (non-LGE; mild LGE ≤ 10%; intermediate LGE 11%-19%; severe LGE ≥ 20%). Compared with healthy controls, LA conduit function was impaired in HCM with no LGE already (LA emptying fraction conduit: 32% ± 7% vs 26 ± 14, P = 0.037). Conversely, LA contractile booster pump function was impaired in HCM with severe LGE only (LA emptying fraction booster: 40% ± 8% vs 20% ± 10%, P < 0.001; for controls vs LGE ≥ 20%, respectively). Left atrial functional abnormalities are associated with LV fibrosis, but not with LV hypertrophy. While LA conduit function is impaired in early HCM stages as represented by mild or absent LV fibrosis, LA contractile function is impaired later in the course of disease progression as demonstrated by the presence of severe LV fibrosis only. These novel markers of LA performance may potentially proof useful for disease staging and early detection of cardiac deterioration.

  7. Contractile Dysfunction in Sarcomeric Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    MacIver, David H; Clark, Andrew L

    2016-09-01

    The pathophysiological mechanisms underlying the clinical phenotype of sarcomeric hypertrophic cardiomyopathy are controversial. The development of cardiac hypertrophy in hypertension and aortic stenosis is usually described as a compensatory mechanism that normalizes wall stress. We suggest that an important abnormality in hypertrophic cardiomyopathy is reduced contractile stress (the force per unit area) generated by myocardial tissue secondary to abnormalities such as cardiomyocyte disarray. In turn, a progressive deterioration in contractile stress provokes worsening hypertrophy and disarray. A maintained or even exaggerated ejection fraction is explained by the increased end-diastolic wall thickness producing augmented thickening. We propose that the nature of the hemodynamic load in an individual with hypertrophic cardiomyopathy could determine its phenotype. Hypertensive patients with hypertrophic cardiomyopathy are more likely to develop exaggerated concentric hypertrophy; athletic individuals an asymmetric pattern; and inactive individuals a more apical hypertrophy. The development of a left ventricular outflow tract gradient and mitral regurgitation may be explained by differential regional strain resulting in mitral annular rotation. Copyright © 2016. Published by Elsevier Inc.

  8. Functional effects of losartan in hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Axelsson, Anna Karin Irene; Iversen, Kasper; Vejlstrup, Niels G.

    2016-01-01

    OBJECTIVE: There is a lack of disease-modifying treatments in hypertrophic cardiomyopathy (HCM). The aim of this randomised, placebo-controlled study was to assess if losartan could improve or ameliorate deterioration of cardiac function and exercise capacity. METHODS: Echocardiography, exercise...

  9. Fabry Disease in Families With Hypertrophic Cardiomyopathy

    DEFF Research Database (Denmark)

    Adalsteinsdottir, Berglind; Palsson, Runolfur; Desnick, Robert J

    2017-01-01

    BACKGROUND: The screening of Icelandic patients clinically diagnosed with hypertrophic cardiomyopathy resulted in identification of 8 individuals from 2 families with X-linked Fabry disease (FD) caused by GLA(α-galactosidase A gene) mutations encoding p.D322E (family A) or p.I232T (family B...

  10. Pregnancy in women with hypertrophic cardiomyopathy

    NARCIS (Netherlands)

    Pieper, P. G.; Walker, F.

    Hypertrophic cardiomyopathy (HCM) is increasingly being diagnosed in pregnant women. Women with HCM generally tolerate pregnancy well. The risk is however higher in women who are symptomatic before pregnancy or in those with severe left ventricular outflow tract obstruction. The incidence of

  11. Alcohol septal ablation for obstructive hypertrophic cardiomyopathy

    NARCIS (Netherlands)

    Steggerda, Robbert

    2015-01-01

    Hypertrophic cardiomyopathy is an inhered heart disease characterised by a thickened heart muscle, common in 1:500 persons. Obstruction of blood flow in the heart due the thickened heart muscle can occur and cause dyspnoea. A heart surgeon can cut away part of the thickened muscle (myectomy). With

  12. Hypertrophic Cardiomyopathy: Pathophysiology, Genetics and Invasive Treatment

    NARCIS (Netherlands)

    M. Michels (Michelle)

    2011-01-01

    textabstractHypertrophic cardiomyopathy (HCM) is the most common inheritable cardiac disorder with a phenotypic prevalence of 1:500. It is defined by the presence of left ventricular hypertrophy (LVH) in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed

  13. Peripheral vascular structure and function in hypertrophic cardiomyopathy

    NARCIS (Netherlands)

    Rowley, N.J.; Green, D.J.; George, K.; Thijssen, D.H.J.; Oxborough, D.; Sharma, S.; Somauroo, J.D.; Jones, J.; Sheikh, N.; Whyte, G.

    2012-01-01

    BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterised by idiopathic cardiac enlargement and represents the most frequent cause of sudden cardiac death in athletes under the age of 35 years. Differentiation between physiological (ie, exercise-related) and pathological (ie, HCM-related)

  14. Penetrance of Hypertrophic Cardiomyopathy in Children and Adolescents

    DEFF Research Database (Denmark)

    Jensen, Morten K; Havndrup, Ole; Christiansen, Michael

    2013-01-01

    The penetrance of hypertrophic cardiomyopathy (HCM) during childhood and adolescence has been only sparsely described. We studied the penetrance of HCM and the short- and long-term outcomes of clinical screening and predictive genetic testing of child relatives of patients with HCM....

  15. Hypertrophic cardiomyopathy in adults: an overview.

    Science.gov (United States)

    Jacobs, Cynthia

    2014-09-01

    To present an overview of clinical issues related to adults with hypertrophic cardiomyopathy (HCM), their presenting symptoms, diagnosis, physical examination findings, treatment, and follow-up care. A comprehensive search of Medline (PubMed) and CINAHL was conducted using the key terms HCM, treatment, diagnosis, sudden cardiac death (SCD), and complications. This search yielded 21 articles used for this article. There were three reference books used for background, diagnosis, and treatment information as well. Although HCM is the most prevalent genetic disorder affecting the heart, it often goes undiagnosed until midlife after patients show symptoms of myocardial remodeling. Adults with cardiomyopathy suffer SCD or adverse events such as stroke and heart failure from HCM. Early diagnosis will prevent SCD, improve quality of life, and slow patient's progression to heart failure. Early recognition of HCM in adults by their primary care providers will improve patients' quality of life and reduce incidence of SCD, heart failure, and stroke. ©2014 American Association of Nurse Practitioners.

  16. Evaluation of left ventricular torsion in children with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Prinz, Christian; Faber, Lothar; Horstkotte, Dieter; Körperich, Hermann; Moysich, Axel; Haas, Nikolaus; Kececioglu, Deniz; Thorsten Laser, Kai

    2014-04-01

    To evaluate the role of torsion in hypertrophic cardiomyopathy in children. A total of 88 children with idiopathic hypertrophic cardiomyopathy (n = 24) and concentric hypertrophy (n = 20) were investigated with speckle-tracking echocardiography and compared with age- and gender-matched healthy controls (n = 44). In hypertrophic cardiomyopathy, we found increased torsion (2.8 ± 1.6 versus 1.9 ± 1.0°/cm [controls], p Hypertrophic cardiomyopathy patients demonstrated a negative correlation between left ventricular muscle mass and torsion (r = -0.7, p hypertrophic cardiomyopathy is characterised by predominantly enhanced systolic basal clockwise rotation. Diastolic untwisting is delayed in both groups. Torsion may be an interesting marker to guide patients with hypertrophic cardiomyopathy.

  17. 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)....

  18. Outcomes of acute myocardial infarction in patients with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Gupta, Tanush; Harikrishnan, Prakash; Kolte, Dhaval; Khera, Sahil; Aronow, Wilbert S; Mujib, Marjan; Palaniswamy, Chandrasekar; Sule, Sachin; Jain, Diwakar; Ahmed, Ali; Lanier, Gregg M; Cooper, Howard A; Frishman, William H; Fonarow, Gregg C; Panza, Julio A

    2015-08-01

    Acute myocardial infarction is a recognized complication in patients with hypertrophic cardiomyopathy. However, limited data are available on outcomes of patients with hypertrophic cardiomyopathy and acute myocardial infarction. We analyzed the 2003-2011 Nationwide Inpatient Sample databases to identify all patients aged ≥18 years with a principal diagnosis of acute myocardial infarction. Patients with a concomitant diagnosis of hypertrophic cardiomyopathy were then identified and analyzed as a separate cohort. Multivariate logistic regression was used to compare outcomes in patients with acute myocardial infarction with and without hypertrophic cardiomyopathy. Of 5,901,827 patients with acute myocardial infarction, 5688 (0.1%) had a diagnosis of hypertrophic cardiomyopathy. Patients with hypertrophic cardiomyopathy were older, more likely to be female, and less likely to have traditional cardiovascular risk factors. Compared with patients without hypertrophic cardiomyopathy, patients with hypertrophic cardiomyopathy were less likely to present with ST-elevation myocardial infarction and more likely to present with non-ST-elevation myocardial infarction. Patients with hypertrophic cardiomyopathy with ST-elevation myocardial infarction or non-ST-elevation myocardial infarction were less likely to receive revascularization. In the overall population with acute myocardial infarction, there was no difference in risk-adjusted in-hospital mortality between patients with and without hypertrophic cardiomyopathy (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.84-1.11; P = .59). In the population with ST-elevation myocardial infarction, patients with hypertrophic cardiomyopathy had lower risk-adjusted in-hospital mortality than those without hypertrophic cardiomyopathy (OR, 0.75; 95% CI, 0.63-0.91; P = .003), whereas in the population with non-ST-elevation myocardial infarction, there was no difference in risk-adjusted in-hospital mortality between patients with

  19. Determination of multidirectional myocardial deformations in cats with hypertrophic cardiomyopathy by using two-dimensional speckle-tracking echocardiography.

    Science.gov (United States)

    Suzuki, Ryohei; Mochizuki, Yohei; Yoshimatsu, Hiroki; Teshima, Takahiro; Matsumoto, Hirotaka; Koyama, Hidekazu

    2017-12-01

    Objectives Hypertrophic cardiomyopathy, a primary disorder of the myocardium, is the most common cardiac disease in cats. However, determination of myocardial deformation with two-dimensional speckle-tracking echocardiography in cats with various stages of hypertrophic cardiomyopathy has not yet been reported. This study was designed to measure quantitatively multidirectional myocardial deformations of cats with hypertrophic cardiomyopathy. Methods Thirty-two client-owned cats with hypertrophic cardiomyopathy and 14 healthy cats serving as controls were enrolled and underwent assessment of myocardial deformation (peak systolic strain and strain rate) in the longitudinal, radial and circumferential directions. Results Longitudinal and radial deformations were reduced in cats with hypertrophic cardiomyopathy, despite normal systolic function determined by conventional echocardiography. Cats with severely symptomatic hypertrophic cardiomyopathy also had lower peak systolic circumferential strain, in addition to longitudinal and radial strain. Conclusions and relevance Longitudinal and radial deformation may be helpful in the diagnosis of hypertrophic cardiomyopathy. Additionally, the lower circumferential deformation in cats with severe hypertrophic cardiomyopathy may contribute to clinical findings of decompensation, and seems to be related to severe cardiac clinical signs. Indices of multidirectional myocardial deformations by two-dimensional speckle-tracking echocardiography may be useful markers and help to distinguish between cats with hypertrophic cardiomyopathy and healthy cats. Additionally, they may provide more detailed assessment of contractile function in cats with hypertrophic cardiomyopathy.

  20. Right ventricular involvement in feline hypertrophic cardiomyopathy.

    Science.gov (United States)

    Schober, K E; Savino, S I; Yildiz, V

    2016-12-01

    To evaluate right ventricular (RV) wall thickness and chamber dimensions in cats with hypertrophic cardiomyopathy (HCM). One hundred fifty-one healthy control cats and 200 cats with HCM. Retrospective, observational, clinical cohort study. Two-dimensional echocardiograms from all cats were analyzed. Right atrial diameter, RV free wall thickness, and RV chamber diameter were quantified using multiple imaging views. Conventional (mean ± 2 standard deviations) and allometrically scaled (Y = a × M b ) reference values were determined in normal cats and compared to values found in cats with HCM. Linear and logistic regression, multivariate regression, and mixed model analysis were performed to identify associations between RV wall thickness and severity of left ventricular (LV) hypertrophy, clinical severity of HCM, and presence of pleural effusion. Mean RV wall thickness was increased in HCM (p0.05) in control cats. Increased RV wall thickness is common in cats with HCM and relates to severity of LV hypertrophy and clinical status. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Septal alcoholization in hypertrophic cardiomyopathy: about 11 cases

    African Journals Online (AJOL)

    Outcomes of septal alcoholization in hypertrophic obstructive cardiomyopathy are not enough studied in all centers. The purpose of this study was to determine the outcomes of septal alcoholization in hypertrophic obstructive cardiomyopathy in our hospital. A retrospective and prospective descriptive study focused on all ...

  2. Clinicopathological profiles of progressive heart failure in hypertrophic cardiomyopathy

    OpenAIRE

    Melacini, Paola; Basso, Cristina; Angelini, Annalisa; Calore, Chiara; Bobbo, Fabiana; Tokajuk, Barbara; Bellini, Nicoletta; Smaniotto, Gessica; Zucchetto, Mauro; Iliceto, Sabino; Thiene, Gaetano; Maron, Barry J.

    2010-01-01

    Aims Hypertrophic cardiomyopathy (HCM) is an important cause of heart failure-related disability over a wide range of ages. Profiles of severe progressive heart failure symptoms and death, or heart transplantation deserve more complete definition within large patient cohorts. Methods and results Clinical and morphological features of heart failure were assessed in 293 consecutive HCM patients over a median follow-up of 6 (inter-quartile range 2?11) years. Gross and histopathological features ...

  3. Hypertrophic cardiomyopathy: Part 1 - Introduction, pathology and pathophysiology

    OpenAIRE

    Praveen Kerala Varma; Praveen Kumar Neema

    2014-01-01

    Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease with many genotype and phenotype variations. Earlier terminologies, hypertrophic obstructive cardiomyopathy and idiopathic hypertrophic sub-aortic stenosis are no longer used to describe this entity. Patients present with or without left ventricular outflow tract (LVOT) obstruction. Resting or provocative LVOT obstruction occurs in 70% of patients and is the most common cause of heart failure. The pathology an...

  4. Myocardial ischemia in hypertrophic cardiomyopathy; Isquemia miocardica na cardiomiopatia hipertrofica

    Energy Technology Data Exchange (ETDEWEB)

    Lima Filho, Moyses de Oliveira; Figueiredo, Geraldo L.; Simoes, Marcus V.; Pyntia, Antonio O.; Marin Neto, Jose Antonio [Sao Paulo Univ., Ribeirao Preto, SP (Brazil). Faculdade de Medicina. Div. de Cardiologia

    2000-08-01

    Myocardial ischemia in hypertrophic cardiomyopathy is multifactorial and explains the occurrence of angina, in about 50% of patients. The pathophysiology of myocardial ischemia may be explained by the increase of the ventricular mass and relative paucity of the coronary microcirculation; the elevated ventricular filling pressures and myocardial stiffness causing a compression of the coronary microvessels; the impaired coronary vasodilator flow reserve caused by anatomic and functional abnormalities; and the systolic compression of epicardial vessel (myocardial bridges). Myocardial ischemia must be investigated by perfusion scintigraphic methods since its presence influences the prognosis and has relevant clinical implications for management of patients. Patients with hypertrophic cardiomyopathy and documented myocardial ischemia usually need to undergo invasive coronary angiography to exclude the presence of concomitant atherosclerotic coronary disease. (author)

  5. The Role of Echocardiography in Hypertrophic Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Jing Ping Sun

    2017-02-01

    Full Text Available Hypertrophic cardiomyopathy (HCM is a common genetic cardiovascular disease and appears in all ethnic groups. HCM is diagnosed on the basis of left ventricular hypertrophy. Echocardiography is a key technique in the diagnosis of HCM, the prognosis of patients with HCM, the management strategy for HCM, and the follow-up of patients with HCM. This review briefly describes and discusses the practical use of established echocardiography techniques and the current and emerging echocardiographic methods that can help physicians in the correct diagnostic and pathophysiological assessment of patients with HCM.

  6. Cardiovascular magnetic resonance in hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Shiozaki, Afonso Akio; Parga, Jose Rodrigues; Arteaga, Edmundo; Rochitte, Carlos Eduardo [Sao Paulo Univ. (USP), SP (Brazil). Instituto do Coracao. Setor de Tomografia Computarizada e Ressonancia Magnetica Cardiovascular]. E-mail: rochitte@incor.usp.br; Kim, Raymond J. [Duke Cardiovascular Magnetic Resonance Center, Durham, NC (United States); Tassi, Eduardo Marinho [Diagnosticos da America S.A., Rio de Janeiro, RJ (Brazil). Sector of Cardiovascular Magnetic Resonance and Computed Tomography

    2007-03-15

    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)

  7. Apical hypertrophic cardiomyopathy: clinical and metabolic studies.

    Science.gov (United States)

    Bertrand, M E; Tilmant, P Y; Lablanche, J M; Thieuleux, F A

    1983-11-01

    Among the hypertrophic non-obstructive cardiomyopathies, a particular group of patients with concentric apical hypertrophy can be described. We studied seven patients (five men and two women) who underwent heart catheterization because they had giant negative T waves in the precordial leads. M-mode and two-dimensional echocardiograms revealed no obstruction within the outflow tract of the ventricle. Coronary angiography was normal in all cases. None of these patients demonstrated any significant peak systolic pressure gradient in the outflow tract. A characteristic spade-like configuration (concentric apical hypertrophy) was observed in the right anterior oblique ventriculogram at end diastole. The apical thickness reached 17.2 +/- 0.85 mm and was significantly greater than mid-anterior wall thickness (9.8 +/- 2.14 mm). In five cases, atrial pacing with coronary arterial and venous lactate sampling revealed abnormalities in myocardial metabolism. With a mean follow up of 43 months, three patients remain asymptomatic and one had heart failure. ECG abnormalities were unchanged and echocardiograms showed an increase of the septal and posterior wall thickness, suggesting a transformation in concentric diffuse hypertrophic cardiomyopathy.

  8. Clinical predictors of genetic testing outcomes in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Ingles, Jodie; Sarina, Tanya; Yeates, Laura; Hunt, Lauren; Macciocca, Ivan; McCormack, Louise; Winship, Ingrid; McGaughran, Julie; Atherton, John; Semsarian, Christopher

    2013-12-01

    Genetic testing for hypertrophic cardiomyopathy has been commercially available for almost a decade; however, low mutation detection rate and cost have hindered uptake. This study sought to identify clinical variables that can predict probands with hypertrophic cardiomyopathy in whom a pathogenic mutation will be identified. Probands attending specialized cardiac genetic clinics across Australia over a 10-year period (2002-2011), who met clinical diagnostic criteria for hypertrophic cardiomyopathy and who underwent genetic testing for hypertrophic cardiomyopathy were included. Clinical, family history, and genotype information were collected. A total of 265 unrelated individuals with hypertrophic cardiomyopathy were included, with 138 (52%) having at least one mutation identified. The mutation detection rate was significantly higher in the probands with hypertrophic cardiomyopathy with an established family history of disease (72 vs. 29%, P < 0.0001), and a positive family history of sudden cardiac death further increased the detection rate (89 vs. 59%, P < 0.0001). Multivariate analysis identified female gender, increased left-ventricular wall thickness, family history of hypertrophic cardiomyopathy, and family history of sudden cardiac death as being associated with greatest chance of identifying a gene mutation. Multiple mutation carriers (n = 16, 6%) were more likely to have suffered an out-of-hospital cardiac arrest or sudden cardiac death (31 vs. 7%, P = 0.012). Family history is a key clinical predictor of a positive genetic diagnosis and has direct clinical relevance, particularly in the pretest genetic counseling setting.

  9. Rupture of mitral valve chordae in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Boissier, Florence; Achkouty, Guy; Bruneval, Patrick; Fabiani, Jean-Noël; Nguyen, Anh Tuan; Riant, Elisabeth; Desnos, Michel; Hagège, Albert

    2015-04-01

    While occasional reports of mitral valve chordal rupture have been described in hypertrophic cardiomyopathy, the exact prevalence and characteristics of this event in a large medical cohort have not been reported. To assess the prevalence of mitral valve chordal rupture in hypertrophic cardiomyopathy and the clinical, echocardiographic, surgical and histological profiles of those patients. We searched for patients with mitral valve chordal rupture diagnosed by echocardiography among all electronic files of patients admitted to our centre for hypertrophic cardiomyopathy between 2000 and 2010. Among 580 patients admitted for hypertrophic cardiomyopathy, six patients (1%, 5 men, age 68-71 years) presented with mitral valve chordal rupture, symptomatic in five cases, always involving the posterior mitral leaflet. In all cases, echocardiography before rupture showed mitral valve systolic anterior motion, with anterior (and not posterior) leaflet elongation compared with a random sample of patients with non-obstructive hypertrophic cardiomyopathy (P=0.006) (and similar to that observed in obstructive hypertrophic cardiomyopathy). Significant resting left ventricular outflow tract obstruction was always present before rupture and disappeared after rupture in the five cases requiring mitral valve surgery for severe mitral regurgitation. Histological findings were consistent with extensive myxomatous degeneration in all cases. Mitral valve chordal rupture is: infrequent in hypertrophic cardiomyopathy; occurs in aged patients with obstructive disease; involves, essentially, the posterior mitral leaflet; and causes, in general, severe mitral regurgitation requiring surgery. Myxomatous degeneration may be the substrate for rupture in these patients. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  10. The embryological basis of subclinical hypertrophic cardiomyopathy.

    Science.gov (United States)

    Captur, Gabriella; Ho, Carolyn Y; Schlossarek, Saskia; Kerwin, Janet; Mirabel, Mariana; Wilson, Robert; Rosmini, Stefania; Obianyo, Chinwe; Reant, Patricia; Bassett, Paul; Cook, Andrew C; Lindsay, Susan; McKenna, William J; Mills, Kevin; Elliott, Perry M; Mohun, Timothy J; Carrier, Lucie; Moon, James C

    2016-06-21

    Hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomeric proteins, the commonest being MYBPC3 encoding myosin-binding protein C. It is characterised by left ventricular hypertrophy but there is an important pre-hypertrophic phenotype with features including crypts, abnormal mitral leaflets and trabeculae. We investigated these during mouse cardiac development using high-resolution episcopic microscopy. In embryonic hearts from wildtype, homozygous (HO) and heterozygous (HET) Mybpc3-targeted knock-out (KO) mice we show that crypts (one or two) are a normal part of wildtype development but they almost all resolve by birth. By contrast, HO and HET embryos had increased crypt presence, abnormal mitral valve formation and alterations in the compaction process. In scarce normal human embryos, crypts were sometimes present. This study shows that features of the human pre-hypertrophic HCM phenotype occur in the mouse. In an animal model we demonstrate that there is an embryological HCM phenotype. Crypts are a normal part of cardiac development but, along with the mitral valve and trabeculae, their developmental trajectory is altered by the presence of HCM truncating Mybpc3 gene mutation.

  11. [Gene mutation and clinical phenotype analysis of patients with Noonan syndrome and hypertrophic cardiomyopathy].

    Science.gov (United States)

    Liu, X H; Ding, W W; Han, L; Liu, X R; Xiao, Y Y; Yang, J; Mo, Y

    2017-10-02

    Objective: To analyze the gene mutations and clinical features of patients with Noonan syndrome and hypertrophic cardiomyopathy. Method: Determined the mutation domain in five cases diagnosed with Noonan syndrome and hypertrophic cardiomyopathy and identified the relationship between the mutant domain and hypertrophic cardiomyopathy by searching relevant articles in pubmed database. Result: Three mutant genes (PTPN11 gene in chromosome 12, RIT1 gene in chromosome 1 and RAF1 gene in chromosome 3) in five cases all had been reported to be related to hypertrophic cardiomyopathy. The reported hypertrophic cardiomyopathy relevant genes MYPN, MYH6 and MYBP3 had also been found in case 1 and 2. Patients with same gene mutation had different clinical manifestations. Both case 4 and 5 had RAF1 mutation (c.770C>T). However, case 4 had special face, low IQ, mild pulmonary artery stenosis, and only mild ventricular hypertrophy. Conclusion: Noonan syndrome is a genetic heterogeneity disease. Our study identified specific gene mutations that could result in Noonan syndrome with hypertrophic cardiomyopathy through molecular biology methods. The results emphasize the importance of gene detection in the management of Noonan syndrome.

  12. Hypertrophic cardiomyopathy: prognostic factors and survival analysis in 128 Egyptian patients.

    Science.gov (United States)

    El-Saiedi, Sonia A; Seliem, Zeinab S; Esmail, Reem I

    2014-08-01

    Hypertrophic cardiomyopathy is an important cause of disability and death in patients of all ages. Egyptian children may differ from Western and Asian patients in the pattern of hypertrophy distribution, clinical manifestations, and risk factors. The aim of our study was to report the clinical characteristics and outcomes of Egyptian children with hypertrophic cardiomyopathy studied over a 7-year duration and to determine whether the reported adult risk factors for sudden cardiac death are predictive of the outcome in these affected children. This retrospective study included 128 hypertrophic cardiomyopathy children. The data included personal history, family history, physical examination, baseline laboratory measurements, electrocardiogram, and Holter and echocardiographic results. Logistic regression analysis was used for the detection of risk factors of death. Fifty-one out of 128 patients died during the period of the study. Of the 51 deaths, 36 (70.5%) occurred in patients presenting before 1 year of age. Only eight patients had surgical intervention. Extreme left ventricular hypertrophy, that is, interventricular septal wall thickness or posterior wall thickness Z-score >6, sinus tachycardia, and supraventricular tachycardia were found to be independent risk factors for prediction of death in patients with hypertrophic cardiomyopathy. At our Egyptian tertiary care centre, hypertrophic cardiomyopathy has a relatively worse prognosis when compared with reports from Western and Asian series. Infants have a worse outcome than children presenting after the age of 1 year. A poorer prognosis in childhood hypertrophic cardiomyopathy is predicted by an extreme left ventricular hypertrophy, the presence of sinus tachycardia, and supraventricular tachycardia.

  13. Two different cardiomyopathies in a single patient : hypertrophic cardiomyopathy and left ventricular noncompaction.

    Science.gov (United States)

    Sunbul, M; Ozben, B; Mutlu, B

    2013-05-01

    Hypertrophic cardiomyopathy is a complex and relatively common genetic disorder characterized by left ventricular (LV) hypertrophy, usually associated with a nondilated and hyperdynamic chamber with heterogeneous phenotypic expression and clinical course. On the other hand, LV noncompaction is an uncommon cardiomyopathy characterized by the persistence of fetal myocardium with a pattern of prominent trabecular meshwork and deep intertrabecular recesses, systolic dysfunction, and LV dilatation. We report a 29-year-old man with these two different inherent conditions. Our case raises the possibility of a genetic mutation common to these two clinical entities or different gene mutations existing in the same individual.

  14. MT-CYB mutations in hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Hagen, Christian M; Aidt, Frederik H; Havndrup, Ole

    2013-01-01

    Mitochondrial dysfunction is a characteristic of heart failure. Mutations in mitochondrial DNA, particularly in MT-CYB coding for cytochrome B in complex III (CIII), have been associated with isolated hypertrophic cardiomyopathy (HCM). We hypothesized that MT-CYB mutations might play an important...... and m.15482T>C; p.S246P were identified. Modeling showed that the p.C93Y mutation leads to disruption of the tertiary structure of Cytb by helix displacement, interfering with protein-heme interaction. The p.S246P mutation induces a diproline structure, which alters local secondary structure and induces...... of HCM patients. We propose that further patients with HCM should be examined for mutations in MT-CYB in order to clarify the role of these variants....

  15. Hypertrophic cardiomyopathy with mid-ventricular obstruction and apical aneurysm

    Directory of Open Access Journals (Sweden)

    N.D. Oryshchyn

    2016-11-01

    Full Text Available A case report of apical left ventricular aneurysm in patient with hypertrophic cardiomyopathy with mid-ventricular obstruction (diagnosis and surgical treatment is presented. We revealed apical aneurysm and mid-ventricular obstruction during echocardiography and specified anatomical characteristics of aneurysm during computer tomography. There was no evidence of obstructive coronary artery disease during coronary angiography. Taking into consideration multiple cerebral infarcts, aneurysm resection and left ventricular plastics was performed. Electronic microscopy of myocardium confirmed the diagnosis of hypertrophic cardiomyopathy.

  16. The KCNE genes in hypertrophic cardiomyopathy: a candidate gene study

    DEFF Research Database (Denmark)

    Hedley, Paula L; Haundrup, Ole; Andersen, Paal S

    2011-01-01

    as well as the T-tubules of the sarcolemma. It has been suggested that minK forms part of an "electro-mechanical feed-back" which links cardiomyocyte stretching to changes in ion channel function. We examined whether mutations in KCNE genes were associated with hypertrophic cardiomyopathy (HCM), a genetic...... disease associated with an improper hypertrophic response....

  17. [Hypertrophic cardiomyopathy with left ventricular dilatation].

    Science.gov (United States)

    Iwami, G; Miyazaki, Y; Matsuyama, K; Shida, M; Ooga, M; Furuta, Y; Ikeda, H; Toshima, H; Chiba, M; Koga, Y

    1988-06-01

    There is increasing interest in the notion that some patients with hypertrophic cardiomyopathy (HCM) progress to morphological and functional manifestations similar to those of dilated cardiomyopathy (DCM). From 165 consecutive patients with HCM, 20 patients with left ventricular dilatation (left ventricular end-diastolic diameter greater than or equal to 50 mm) were selected and designated as dilated HCM. The diagnosis of HCM was established in these patients either by detection of the classical form of HCM in family members, with 2-dimensional echocardiographic evidence of asymmetric septal hypertrophy (ASH; septal thickness greater than or equal to 15 mm and a ratio of septal to posterior wall thickness greater than or equal to 1.3); or by demonstrating myocardial fiber disarray in autopsy or biopsy samples. The clinical manifestations of these patients with dilated HCM were then compared with those of other forms of HCM without left ventricular dilatation; 1) 40 patients with hypertrophic obstructive cardiomyopathy (HOCM) who had resting intraventricular pressure gradients of 20 mmHg or more, 2) 80 patients with non-obstructive HCM, each of whom had ASH of the entire ventricular septum (typical ASH), and 3) 25 non-obstructive patients whose hypertrophy was localized to the apical region of the ventricular septum (apical ASH). Patients having apical hypertrophy with a spade-like configuration on the left ventriculogram were excluded from the study. Compared with HOCM and typical ASH groups, the patients with dilated HCM had family histories of significantly more frequent HCM and less frequent hypertension. The patients with dilated HCM also had significantly less fractional shortening (FS), decreased interventricular septal thickness, greater left ventricular end-diastolic pressure (LVEDP), and left ventricular dilatation. During the follow-up period (average: 3.5 years), seven patients (35%) with dilated HCM died; five from congestive heart failure (CHF), one

  18. Imaging Phenotype vs. Genotype in Non-Hypertrophic Heritable Cardiomyopathies: Dilated Cardiomyopathy and Arrhythmogenic Right Ventricular Cardiomyopathy

    Science.gov (United States)

    Raman, Subha V.; Basso, Cristina; Tandri, Harikrishna; Taylor, Matthew R. G.

    2011-01-01

    Advances in cardiovascular imaging increasingly afford unique insights into heritable myocardial disease. As clinical presentation of genetic cardiomyopathies may range from nonspecific symptoms to sudden cardiac death, accurate diagnosis has implications for individual patients as well as related family members. The initial consideration of genetic cardiomyopathy may occur in the imaging laboratory, where one must recognize the patient with arrhythmogenic right ventricular cardiomyopathy (ARVC) among the many with ventricular arrhythmia referred to define myocardial substrate. Accurate diagnosis of the patient presenting with dyspnea and palpitations whose first-degree relatives have lamin A/C cardiomyopathy may warrant genetic testing1, 2 plus imaging of diastolic function and myocardial fibrosis3. As advances in cardiac imaging afford detection of subclinical structural and functional changes, the imaging specialist must be attuned to signatures of specific genetic disorders. With increased availability of both advanced imaging as well as genotyping techniques, this review seeks to provide cardiovascular imaging specialists and clinicians with the contemporary information needed for more precise diagnosis and treatment of heritable myocardial disease. A companion paper in this series covers imaging phenotype and genotype considerations in hypertrophic cardiomyopathy (HCM). This review details clinical features, imaging phenotype and current genetic understanding for two of the most common non-HCM conditions that prompt myocardial imaging - dilated cardiomyopathy (DCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC). While all modalities are considered herein, considerable focus is given to CMR with its unique capabilities for myocardial tissue characterization. PMID:21081743

  19. Two cases of apical ballooning syndrome masking apical hypertrophic cardiomyopathy.

    Science.gov (United States)

    Roy, Ranjini Raina; Hakim, Fayaz A; Hurst, R Todd; Simper, David; Appleton, Christopher P

    2014-04-01

    Apical akinesis and dilation in the absence of obstructive coronary artery disease is a typical feature of stress-induced (takotsubo) cardiomyopathy, whereas apical hypertrophy is seen in apical-variant hypertrophic cardiomyopathy. We report the cases of 2 patients who presented with takotsubo cardiomyopathy and were subsequently found to have apical-variant hypertrophic cardiomyopathy, after the apical ballooning from the takotsubo cardiomyopathy had resolved. The first patient, a 43-year-old woman with a history of alcohol abuse, presented with shortness of breath, electrocardiographic and echocardiographic features consistent with takotsubo cardiomyopathy, and no significant coronary artery disease. An echocardiogram 2 weeks later revealed a normal left ventricular ejection fraction and newly apparent apical hypertrophy. The 2nd patient, a 70-year-old woman with pancreatitis, presented with chest pain, apical akinesis, and a left ventricular ejection fraction of 0.39, consistent with takotsubo cardiomyopathy. One month later, her left ventricular ejection fraction was normal; however, hypertrophy of the left ventricular apex was newly noted. To our knowledge, these are the first reported cases in which apical-variant hypertrophic cardiomyopathy was masked by apical ballooning from stress-induced cardiomyopathy.

  20. Cardiac sarcoid: a chameleon masquerading as hypertrophic cardiomyopathy and dilated cardiomyopathy in the same patient.

    Science.gov (United States)

    Agarwal, Anushree; Sulemanjee, Nasir Z; Cheema, Omar; Downey, Francis X; Tajik, A Jamil

    2014-05-01

    Sarcoidosis is a multisystem, granulomatous disease of unknown etiology often seen in young adults, with cardiac involvement in more than one-quarter of sarcoid patients. The clinical presentation of cardiac sarcoid depends upon the location and extent of myocardium involved. Although cardiac sarcoid may produce asymmetrical septal hypertrophy, it is most commonly considered in the differential diagnosis of dilated cardiomyopathy. The hypertrophic stage of cardiac sarcoid is rarely seen. We describe a case of cardiac sarcoid in a young patient wherein a distinctive appearance of the cardiac sarcoid spectrum from "hypertrophic" stage to thinned/scarred stage, masquerading as hypertrophic cardiomyopathy followed by dilated cardiomyopathy, is demonstrated. © 2014, Wiley Periodicals, Inc.

  1. HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY AS A SIDE-EFFECT OF DEXAMETHASONE TREATMENT FOR BRONCHOPULMONARY DYSPLASIA

    NARCIS (Netherlands)

    BRAND, PLP; VANLINGEN, RA; BRUS, F; TALSMA, MD; ELZENGA, NJ

    1993-01-01

    We report three infants who developed hypertrophic obstructive cardiomyopathy during dexamethasone treatment for bronchopulmonary dysplasia. In all three infants, echocardiography had ruled out cardiac abnormalities prior to the dexamethasone course. The hypertrophic obstructive cardiomyopathy

  2. A One Health Approach to Hypertrophic Cardiomyopathy

    Science.gov (United States)

    Ueda, Yu; Stern, Joshua A.

    2017-01-01

    Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease in humans and results in significant morbidity and mortality. Research over the past 25 years has contributed enormous insight into this inherited disease particularly in the areas of genetics, molecular mechanisms, and pathophysiology. Our understanding continues to be limited by the heterogeneity of clinical presentations with various genetic mutations associated with HCM. Transgenic mouse models have been utilized especially studying the genotypic and phenotypic interactions. However, mice possess intrinsic cardiac and hemodynamic differences compared to humans and have limitations preventing their direct translation. Other animal models of HCM have been studied or generated in part to overcome these limitations. HCM in cats shows strikingly similar molecular, histopathological, and genetic similarities to human HCM, and offers an important translational opportunity for the study of this disease. Recently, inherited left ventricular hypertrophy in rhesus macaques was identified and collaborative investigations have been conducted to begin to develop a non-human primate HCM model. These naturally-occurring large-animal models may aid in advancing our understanding of HCM and developing novel therapeutic approaches to this disease. This review will highlight the features of HCM in humans and the relevant available and developing animal models of this condition. PMID:28955182

  3. Pharmacological and non-pharmacological treatment of obstructive hypertrophic cardiomyopathy.

    Science.gov (United States)

    Hidalgo, Luis F; Naidu, Srihari S; Aronow, Wilbert S

    2018-01-01

    Hypertrophic obstructive cardiomyopathy has been rising in prevalence, due to increased awareness and advanced imaging. For the symptomatic patient, pharmacological management remains an effective approach to the majority of patients with obstructive hypertrophic cardiomyopathy. However, a significant subset fails to improve sufficiently with medical therapy initially, or progressively becomes more symptomatic despite augmented medications over time. Most of the advances in the treatment of obstructive hypertrophic cardiomyopathy have therefore been made in the area of non-pharmacologic management, particularly septal reduction therapy. Both surgical myectomy and alcohol septal ablation have undergone iterative modifications that improve outcomes. Current guidelines support these therapies based on large observational studies, with choice of therapy based on a variety of factors but again based primarily on expert consensus opinion. Areas covered: This article reviews both pharmacological and non-pharmacological interventions to improve outflow tract obstruction and symptoms, and provides an algorithm for addressing the symptomatic obstructive patient. Expert commentary: Current options for hypertrophic cardiomyopathy allow the majority of patients to live their lives with no more than NYHA Class 2 heart failure symptoms. Treatment algorithms can add in identification of patients who may benefit from advanced therapies, and should be instituted routinely to improve care for the majority of patients with symptomatic hypertrophic cardiomyopathy.

  4. An unusual ST-segment elevation: apical hypertrophic cardiomyopathy shows the ace up its sleeve.

    Science.gov (United States)

    de Santis, Francesco; Pergolini, Amedeo; Zampi, Giordano; Pero, Gaetano; Pino, Paolo Giuseppe; Minardi, Giovanni

    2013-01-01

    Apical hypertrophic cardiomyopathy is part of the broad clinical and morphologic spectrum of hypertrophic cardiomyopathy. We report a patient with electrocardiographic abnormalities in whom acute coronary syndrome was excluded and apical hypertrophic cardiomyopathy was demonstrated by careful differential diagnosis. Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  5. Family communication in a population at risk for hypertrophic cardiomyopathy.

    Science.gov (United States)

    Batte, Brittany; Sheldon, Jane P; Arscott, Patricia; Huismann, Darcy J; Salberg, Lisa; Day, Sharlene M; Yashar, Beverly M

    2015-04-01

    Encouraging family communication is an integral component of genetic counseling; therefore, we sought to identify factors impacting communication to family members at risk for Hypertrophic Cardiomyopathy (HCM). Participants (N = 383) completed an online survey assessing: 1) demographics (gender, genetic test results, HCM family history, and disease severity); 2) illness representations; 3) family functioning and cohesiveness; 4) coping styles; 5) comprehension of HCM autosomal dominant inheritance; and 6) communication of HCM risk information to at-risk relatives. Participants were a national sample of individuals with HCM, recruited through the Hypertrophic Cardiomyopathy Association. Data from 183 participants were analyzed using a logistic regression analysis, with family communication as a dichotomous dependent variable. We found that female gender and higher comprehension of autosomal dominant inheritance were significant predictors of participants' communication of HCM risk information to all their siblings and children. Our results suggest that utilizing interventions that promote patient comprehension (e.g., a teaching-focused model of genetic counseling) are important and may positively impact family communication within families with HCM.

  6. The 50-Year History, Controversy, and Clinical Implications of Left Ventricular Outflow Tract Obstruction in Hypertrophic Cardiomyopathy: From Idiopathic Hypertrophic Subaortic Stenosis to Hypertrophic Cardiomyopathy

    National Research Council Canada - National Science Library

    Barry J Maron; Martin S Maron; E Douglas Wigle; Eugene Braunwald

    2009-01-01

    ...) clinical descriptions of hypertrophic cardiomyopathy (HCM) and has proved to be a complex phenomenon unique in many respects, as well as arguably the most visible and well-known pathophysiologic component of this heterogeneous disease...

  7. Extent of late gadolinium enhancement at right ventricular insertion points in patients with hypertrophic cardiomyopathy: relation with diastolic dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Yinsu [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); The First Affiliated Hospital of Nanjing Medical University, Department of Radiology, Nanjing, Jiangsu (China); Park, Eun-Ah; Lee, Whal; Chu, Ajung; Chung, Jin Wook; Park, Jae Hyung [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Kim, Hyung-Kwan [Seoul National University Hospital, Division of Cardiology, Department of Internal Medicine, Seoul (Korea, Republic of)

    2015-04-01

    Our aim was to examine the association between the extent of late gadolinium enhancement (LGE) at right ventricular insertion points (RVIP) and left ventricular (LV) functional parameters in patients with hypertrophic cardiomyopathy (HCM). Sixty-one HCM patients underwent echocardiography and cardiovascular magnetic resonance (CMR) within one week. Mitral annular velocities (E/E') were obtained from echocardiography; LV ejection fraction (EF), LV mass index, LV wall maximal thickness, and left atrial volume index (LAVI) were obtained from MR. LGE extent was quantified (proportion of total LV myocardial mass) according to location: % RVIP-LGE and % non-RVIP-LGE. Although LGE was commonly present in both apical (74 %) and non-apical HCMs (88 %) (p = 0.163), RVIP-LGE was more frequent (86 % vs. 47 %, p = 0.002) in non-apical HCMs in which E/E' was significantly higher (19.23 ± 8.40 vs. 13.13 ± 5.06, p = 0.009). In addition, RVIP-LGE extent was associated with LV diastolic dysfunction (r = 0.45, p < 0.001 for E/E'; r = 0.53, p < 0.001 for LAVI) and lower LVEF (r = -0.42, p = 0.001). There was no correlation between non-RVIP-LGE extent and other parameters. Multiple linear regression analysis revealed RVIP-LGE extent as an independent predictor of E/E' (β = 0.45, p < 0.001) and LAVI in HCM patients (β = 0.53, p < 0.001). The extent of LGE at RVIPs in HCM patients is associated with increased estimated LV filling pressure and chronic diastolic burden. (orig.)

  8. Cardiac troponin T and familial hypertrophic cardiomyopathy: an energetic affair

    Science.gov (United States)

    Schwartz, Ketty; Mercadier, Jean-Jacques

    2003-01-01

    It has long been noted that while patients with familial hypertrophic cardiomyopathy due to cardiac troponin T (cTnT) mutations often suffer sudden cardiac death, they do not develop significant ventricular hypertrophy, suggesting that a distinct cellular mechanism apart from alterations in myocardial contractility is responsible. A new study has revealed that a single missense mutation in cTnT causes a striking disruption to energy metabolism, leading to cardiomyopathy. PMID:12952912

  9. Comparison among patients with hypertrophic cardiomyopathy, hypertrophic cardiomyopathy with hypertension and hypertensive heart disease by {sup 123}I-BMIPP myocardial scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Yoneyama, Satoshi; Sugihara, Hiroki; Ito, Kazuki [Kyoto Prefectural Univ. of Medicine (Japan)] [and others

    1997-12-01

    The usefulness of {sup 123}I-BMIPP myocardial SPECT in discriminating hypertrophic cardiomyopathy (46 patients), hypertrophic cardiomyopathy with hypertension (23 patients), and hypertensive hypertrophic heart (20 patients) was studied. SPECT image was divided into 17 domains, and dimension of decreased accumulation was decided visually at each domain as four classes called defect score (DS). Summation of DS (TDS) of each group was used to compare frequency and dimension of decreased accumulation, and characteristic of each site. Frequency of decreased accumulation and TDS in hypertrophic cardiomyopathy were similar in dimension with those in hypertrophic cardiomyopathy with hypertension, and those data in hypertensive hypertrophic heart were lower than those in above-mentioned 2 groups. In the cases of hypertrophic cardiomyopathy and hypertrophic cardiomyopathy with hypertension, decreased accumulation site was similar and was anterior wall-septum junction, septum-posterior wall junction and apex of heart. In the case of hypertensive hypertrophic heart, decreased accumulation site was only the posterior wall. Frequency, dimension and site of decreased accumulation in hypertrophic cardiomyopathy were different from those in hypertensive hypertrophic heart, and BMIPP was thought to be useful in discriminating these diseases. (K.H.)

  10. The prevention of sudden death in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Sachdev, Bhavesh; Hamid, M Shoaib; Elliott, Perry M

    2002-05-01

    Hypertrophic cardiomyopathy (HCM) is a familial myocardial disease caused by mutations in cardiac sarcomeric proteins. HCM is characterised by myocyte disarray and myocardial fibrosis. Most patients are largely asymptomatic but some are prone to a number of disease-related complications, the most problematic of which is sudden cardiac death. Diagnosing patients who are at risk has not been easy because of the clinical heterogeneity of the disease, the frequent absence of symptoms prior to sudden cardiac death and the relatively low disease prevalence and annual mortality rates. To date, both low-dose amiodarone and internal cardioverter/defibrillator implantation have been advocated in high-risk individuals. Further improvements in clinical understanding and risk stratification are necessary to identify HCM patients who are at high risk of sudden death.

  11. Prognosis in hypertrophic cardiomyopathy observed in a large clinic population

    NARCIS (Netherlands)

    M.J.M. Kofflard (Marcel); D.J. Waldstein; J. Vos (Jeroen); F.J. ten Cate (Folkert)

    1993-01-01

    textabstractOverall annual cardiac mortality in hypertrophic cardiomyopathy (HC) has been reported to be between 2 and 4%, although these numbers are primarily from retrospective studies of patients referred to large research institutions. A clinic population of 113 patients with HC was

  12. Hypertrophic cardiomyopathy in South African Blacks | Lewis | South ...

    African Journals Online (AJOL)

    Hypertrophic cardiomyopathy (HCM) has been considered rare among the Black population of southern Africa. We report 7 patients with the disease who presented during a 14-month period. Current concepts in the approach to the diagnosis and treatment of HCM are discussed. It is possible that with greater awareness of ...

  13. Hypertrophic Cardiomyopathy in a Middle Aged Man - A Case Report

    African Journals Online (AJOL)

    Recognition of the condition in our environment is often difficult because of dearth of facilities and expertise for echocardiograghy in most of our hospitals. Objective: To draw attention to the existence of hypertrophic cardiomyopathy in our environment and need to use echocardiography in evaluating patients with cardiac ...

  14. Private mitochondrial DNA variants in danish patients with hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Hagen, Christian M; Aidt, Frederik H; Havndrup, Ole

    2015-01-01

    Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease primarily caused by mutations in genes coding for sarcomeric proteins. A molecular-genetic etiology can be established in ~60% of cases. Evolutionarily conserved mitochondrial DNA (mtDNA) haplogroups are susceptibility factors for HCM...

  15. Founder mutations in hypertrophic cardiomyopathy patients in the Netherlands

    NARCIS (Netherlands)

    Christiaans, I.; Nannenberg, E. A.; Dooijes, D.; Jongbloed, R. J. E.; Michels, M.; Postema, P. G.; Majoor-Krakauer, D.; van den Wijngaard, A.; Mannens, M. M. A. M.; van Tintelen, J. P.; van Langen, I. M.; Wilde, A. A. M.

    In this part of a series on cardiogenetic founder mutations in the Netherlands, we review the Dutch founder mutations in hypertrophic cardiomyopathy (HCM) patients. HCM is a common autosomal dominant genetic disease affecting at least one in 500 persons in the general population. Worldwide, most

  16. Symmetric Dimethylarginine in Cats with Hypertrophic Cardiomyopathy and Diabetes Mellitus

    DEFF Research Database (Denmark)

    Langhorn, R.; Kieler, I. N.; Koch, J.

    2018-01-01

    Background: Symmetric dimethylarginine (SDMA) has been increasingly used as a marker of early chronic kidney disease (CKD) in cats, but little is known about the influence of comorbidities on SDMA in this species. Hypothesis: Hypertrophic cardiomyopathy (HCM) and diabetes mellitus (DM), independe...

  17. Hypertrophic cardiomyopathy and ultra-endurance running - two incompatible entities?

    Directory of Open Access Journals (Sweden)

    Wilson Mathew G

    2011-11-01

    Full Text Available Abstract Regular and prolonged exercise is associated with increased left ventricular wall thickness that can overlap with hypertrophic cardiomyopathy (HCM. Differentiating physiological from pathological hypertrophy has important implications, since HCM is the commonest cause of exercise-related sudden cardiac death in young individuals. Most deaths have been reported in intermittent 'start-stop' sports such as football (soccer and basketball. The theory is that individuals with HCM are unable to augment stroke volume sufficiently to meet the demands of endurance sports and are accordingly 'selected-out' of participation in such events. We report the case of an ultra-endurance athlete with 25 years of > 50 km competitive running experience, with genetically confirmed HCM; thereby demonstrating that these can be two compatible entities.

  18. Hypertrophic cardiomyopathy and ultra-endurance running - two incompatible entities?

    Science.gov (United States)

    Wilson, Mathew G; Chandra, Navin; Papadakis, Michael; O'Hanlon, Rory; Prasad, Sanjay K; Sharma, Sanjay

    2011-11-29

    Regular and prolonged exercise is associated with increased left ventricular wall thickness that can overlap with hypertrophic cardiomyopathy (HCM). Differentiating physiological from pathological hypertrophy has important implications, since HCM is the commonest cause of exercise-related sudden cardiac death in young individuals. Most deaths have been reported in intermittent 'start-stop' sports such as football (soccer) and basketball. The theory is that individuals with HCM are unable to augment stroke volume sufficiently to meet the demands of endurance sports and are accordingly 'selected-out' of participation in such events. We report the case of an ultra-endurance athlete with 25 years of > 50 km competitive running experience, with genetically confirmed HCM; thereby demonstrating that these can be two compatible entities.

  19. Hypertrophic cardiomyopathy: Part 1 - Introduction, pathology and pathophysiology

    Directory of Open Access Journals (Sweden)

    Praveen Kerala Varma

    2014-01-01

    Full Text Available Hypertrophic cardiomyopathy (HCM is the most common genetic cardiovascular disease with many genotype and phenotype variations. Earlier terminologies, hypertrophic obstructive cardiomyopathy and idiopathic hypertrophic sub-aortic stenosis are no longer used to describe this entity. Patients present with or without left ventricular outflow tract (LVOT obstruction. Resting or provocative LVOT obstruction occurs in 70% of patients and is the most common cause of heart failure. The pathology and pathophysiology of HCM includes hypertrophy of the left ventricle with or without right ventricular hypertrophy, systolic anterior motion of mitral valve, dynamic and mechanical LVOT obstruction, mitral regurgitation, diastolic dysfunction, myocardial ischemia, and fibrosis. Thorough understanding of pathology and pathophysiology is important for anesthetic and surgical management.

  20. High T2-weighted signal intensity is associated with elevated troponin T in hypertrophic cardiomyopathy

    NARCIS (Netherlands)

    Gommans, D.H.F.; Cramer, G.E.; Bakker, J.; Michels, M; Dieker, H.J.; Timmermans, J.; Fouraux, M.A.; Marcelis, C.L.M.; Verheugt, F.W.A.; Brouwer, M.A.; Kofflard, M.J.M.

    2017-01-01

    OBJECTIVE: Areas of high signal intensity (HighT2) on T2-weighted cardiovascular magnetic resonance (CMR) imaging have been demonstrated in hypertrophic cardiomyopathy (HCM). It has been hypothesised that HighT2 may indicate active tissue injury in HCM. In this context, we studied HighT2 in relation

  1. Uptake of genetic counselling and predictive DNA testing in hypertrophic cardiomyopathy

    NARCIS (Netherlands)

    Christiaans, Imke; Birnie, Erwin; Bonsel, Gouke J.; Wilde, Arthur A.M.; van Langen, Irene M.

    2008-01-01

    Hypertrophic cardiomyopathy is a common autosomal dominant disease, associated with heart failure and arrhythmias predisposing to sudden cardiac death. After the detection of the causal mutation in the proband predictive DNA testing of relatives is possible (cascade screening). Prevention of sudden

  2. Scintigraphic evaluation of regional myocardial sympathetic activity in patients with hypertrophic cardiomyopathy. Comparison between asymmetrical hypertrophic cardiomyopathy and apical hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Eno, Shin; Takeo, Eiichiro; Sasaki, Satoshi; Matsuda, Keiji; Fujii, Hideaki; Kanazawa, Ikuo [Chugoku Rosai General Hospital, Kure, Hiroshima (Japan)

    1998-02-01

    Using {sup 123}I-MIBG (metaiodobenzylguanidine) and {sup 201}Tl imagings, an examination concerning the relation between the hypertrophic region and its sympathetic nervous function was done. Subjects were 12 normal adults (4 males and 8 females, mean age 61.3 yr), 13 patients with asymmetrical hypertrophic cardiomyopathy (10 males and 3 females, 63.9 yr) and 13 patients with apical hypertrophy (9 males and 4 females, 67.2 yr). The SPECT apparatus was Toshiba two-gated gamma camera GCA 7200A. At 20 min and 3 hr after intravenous injection of 111 MBq of {sup 123}I-MIBG, myocardial SPECT and planar images were obtained with collimator LEHR under following conditions: photoelectric peak 159 KeV, window width 20%, matrix size 64 x 64 (256 x 256 for the planar image), step angle 6deg, 40 sec/step and 180deg for 1 camera. In another day, {sup 201}Tl SPECT and planar imagings were performed 10 min after intravenous injection of 111 MBq of {sup 201}Tl for the photoelectric peak 72 KeV under similar conditions to above. SPECT images were reconstructed using Butterworth filter and Shepp and Logan filter. Images were examined for the defect score, myocardium/mediastinum ratio, whole heart washout rate and regional washout rate. In the asymmetrical hypertrophic myopathy, abnormal sympathetic nerve function was recognized on the regions regardless of their disease severity while in the apical hypertrophy, abnormality was restricted on the apical region. Therefore, the two diseases were found different from each other from the aspect of sympathetic nerve functions. (K.H.)

  3. Relation between left ventricular outflow tract obstruction and left ventricular shape in patients with hypertrophic cardiomyopathy: a cardiac magnetic resonance imaging study.

    Science.gov (United States)

    Martin, Romain; Lairez, Olivier; Boudou, Nicolas; Méjean, Simon; Lhermusier, Thibault; Dumonteil, Nicolas; Berry, Matthieu; Cognet, Thomas; Massabuau, Pierre; Elbaz, Meyer; Rousseau, Hervé; Galinier, Michel; Carrié, Didier

    2013-01-01

    Hypertrophic cardiomyopathies (HCM) are often associated with left ventricular (LV) outflow tract obstruction, which can explain symptoms and impact prognosis. To better understand the mechanisms that link obstruction and LV shape in HCM. Patients with HCM who underwent cardiac magnetic resonance (CMR) imaging were included retrospectively. Obstructive HCM was defined as LV outflow gradient more than 30 mm Hg at rest by transthoracic echocardiography. The LV shape and mitral angle were assessed by CMR. Results were compared with control subjects. Mean LV-mitral angle was smaller in patients with obstructive HCM (n=29) than in patients with non-obstructive HCM (n=15) or control subjects (n=15) (80 ± 5° vs 87 ± 7° [P=0.0002] and 89 ± 2° [P<0.0001]). Mean mitral papillary muscles angle was greater in patients with non-obstructive HCM than in patients with obstructive HCM or control subjects (136 ± 17° vs 123 ± 16° [P=0.007] and 118 ± 10° [P=0.002]). Patients with non-obstructive HCM had a greater mean LV-aortic root angle than patients with obstructive HCM or control subjects (139 ± 6° vs 135 ± 7° [P=0.04] and 133 ± 7° [P=0.03]). There is a relation between morphological and functional parameters in HCM within which the mitral valve is probably part of pathophysiogenesis. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  4. Myocardial metabolic abnormalities in hypertrophic cardiomyopathy assessed by iodine-123-labeled beta-methyl-branched fatty acid myocardial scintigraphy and its relation to exercise-induced ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Matsuo, Shinro; Nakamura, Yasuyuki; Takahashi, Masayuki; Mitsunami, Kenichi; Kinoshita, Masahiko [Shiga Univ. of Medical Science, Otsu (Japan)

    1998-03-01

    Reversible thallium-201 ({sup 201}Tl) abnormalities during exercise stress have been used as markers of myocardial ischemia in hypertrophic cardiomyopathy (HCM) and are most likely to identify relatively underperfused myocardium. Although metabolic abnormalities in HCM were reported, the relationship between impaired energy metabolism and exercise-induced ischemia has not been fully elucidated as yet. To assess the relationship between myocardial perfusion abnormalities and fatty acid metabolic abnormalities, 28 patients with HCM underwent exercise {sup 201}Tl and rest {sup 123}I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP) scintigraphy. Perfusion abnormalities were observed by exercise {sup 201}Tl in 19/28 patients with HCM. {sup 123}I-BMIPP uptake was decreased compared with delayed {sup 201}Tl in 106/364 (29%) of the total myocardial segments (p<0.01, McNemar symmetry test). Such disparity between {sup 123}I-BMIPP and {sup 201}Tl was observed more often in the 49/75 (65%) segments with reversible exercise {sup 201}Tl defects (p<0.001). Our results indicate that exercise-induced myocardial ischemia exists in HCM, resulting in metabolic abnormalities. The combination of {sup 123}I-BMIPP and {sup 201}Tl suggests that myocardial ischemia may play an important role in metabolic abnormalities in HCM. (author)

  5. Atrial myxoma in a patient with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Abdou, Mahmoud; Hayek, Salim; Williams, Byron R

    2013-01-01

    Atrial myxoma is the most common primary cardiac tumor. Patients with atrial myxoma typically present with obstructive, embolic, or systemic symptoms; asymptomatic presentation is very rare. To our knowledge, isolated association of atrial myxoma with hypertrophic cardiomyopathy has been reported only once in the English-language medical literature. We report the case of an asymptomatic 71-year-old woman with known hypertrophic cardiomyopathy in whom a left atrial mass was incidentally identified on cardiac magnetic resonance images. After surgical excision of the mass and partial excision of the left atrial septum, histopathologic analysis confirmed the diagnosis of atrial myxoma. The patient was placed on preventive implantable cardioverter-defibrillator therapy and remained asymptomatic. The management of asymptomatic cardiac myxoma is a topic of debate, because no reports definitively favor either conservative or surgical measures.

  6. The follow-up of progressive hypertrophic cardiomyopathy using magnetic resonance rotating frame relaxation times.

    Science.gov (United States)

    Khan, Muhammad Arsalan; Laakso, Hanne; Laidinen, Svetlana; Kettunen, Sanna; Heikura, Tommi; Ylä-Herttuala, Seppo; Liimatainen, Timo

    2017-12-15

    Magnetic resonance rotating frame relaxation times are an alternative non-contrast agent choice for the diagnosis of chronic myocardial infarct. Fibrosis typically occurs in progressive hypertrophic cardiomyopathy. Fibrosis has been imaged in myocardial infarcted tissue using rotating frame relaxation times, which provides the possibility to follow up progressive cardiomyopathy without contrast agents. Mild and severe left ventricular hypertrophy were induced in mice by transverse aortic constriction, and the longitudinal rotating frame relaxation times (T1ρ ) and relaxation along the fictitious field (TRAFF2 , TRAFF3 ) were measured at 5, 10, 24, 62 and 89 days after transverse aortic constriction in vivo. Myocardial fibrosis was verified using Masson's trichrome staining. Increases in the relative relaxation time differences of T1ρ , together with TRAFF2 and TRAFF3 , between fibrotic and remote tissues over time were observed. Furthermore, TRAFF2 and TRAFF3 showed higher relaxation times overall in fibrotic tissue than T1ρ . Relaxation time differences were highly correlated with an excess of histologically verified fibrosis. We found that TRAFF2 and TRAFF3 are more sensitive than T1ρ to hypertrophic cardiomyopathy-related tissue changes and can serve as non-invasive diagnostic magnetic resonance imaging markers to follow up the mouse model of progressive hypertrophic cardiomyopathy. Copyright © 2017 John Wiley & Sons, Ltd.

  7. T-wave inversions related to left ventricular basal hypertrophy and myocardial fibrosis in non-apical hypertrophic cardiomyopathy: A cardiovascular magnetic resonance imaging study

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Xiuyu, E-mail: cxy0202@126.com [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Zhao, Shihua, E-mail: zhaoshihua0202@126.com [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Zhao, Tao, E-mail: taozhao0202@126.com [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Lu, Minjie, E-mail: lmjkan@126.com [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Yin, Gang, E-mail: gangyin0202@126.com [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Jiang, Shiliang, E-mail: jiangsl-2011@163.com [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037 (China); Prasad, Sanjay, E-mail: s.prasad@rbht.nhs.uk [NIHR Biomedical Research Unit, Royal Brompton Hospital Sydney Street, London, SW3 6NP (United Kingdom)

    2014-02-15

    Objectives: To investigate the relationship between T-wave inversions and left ventricular (LV) segmental hypertrophy and myocardial fibrosis assessed by cardiovascular magnetic resonance (CMR) in patients with non-apical hypertrophic cardiomyopathy (HCM). Methods: 196 consecutive patients with non-apical HCM underwent late gadolinium enhancement (LGE) CMR and 12-lead electrocardiogram. The distribution and magnitude of LV segmental hypertrophy and LGE were assessed according to the AHA 17-segment model and analyzed in relation to T-wave inversions. Results: Of 196 HCM patients, 144 (73%) exhibited T-wave inversions. 144 (73%) patients had evidence of myocardial fibrosis as defined by LGE, and the prevalence of LGE was significantly higher in patients with T-wave inversions compared with those without T-wave inversions (78% vs. 59%, P = 0.008). T-wave inversions were related to basal anterior and basal anteroseptal LGE (20% vs. 10%, P = 0.04 and 68% vs. 46%, P = 0.005, respectively). In addition, T-wave inversions were associated with greater basal anteroseptal and basal inferior wall thickness (19.5 ± 4.7 mm vs. 16.7 ± 4.5 mm, P < 0.001 and 10.9 ± 3.3 mm vs. 9.6 ± 3.0 mm, P = 0.01, respectively). By logistic regression analysis, basal anteroseptal wall thickness and LGE were independent determinants of T-wave inversions (P = 0.005, P = 0.01, respectively). Conclusions: T-wave inversions in HCM are associated with LGE and wall thickness of the left ventricular basal segments. Moreover, basal anteroseptal wall thickness and LGE are independent determinants of T-wave inversions.

  8. The Huntington's disease-related cardiomyopathy prevents a hypertrophic response in the R6/2 mouse model.

    Directory of Open Access Journals (Sweden)

    Michal Mielcarek

    Full Text Available Huntington's disease (HD is neurodegenerative disorder for which the mutation results in an extra-long tract of glutamines that causes the huntingtin protein to aggregate. It is characterized by neurological symptoms and brain pathology that is associated with nuclear and cytoplasmic aggregates and with transcriptional deregulation. Despite the fact that HD has been recognized principally as a neurological disease, there are multiple epidemiological studies showing that HD patients exhibit a high rate of cardiovascular events leading to heart failure. To unravel the mechanistic basis of cardiac dysfunction in HD, we employed a wide range of molecular techniques using the well-established genetic R6/2 mouse model that develop a considerable degree of the cardiac atrophy at end stage disease. We found that chronic treatment with isoproterenol, a potent beta-adrenoreceptor agonist, did not change the overall gross morphology of the HD murine hearts. However, there was a partial response to the beta-adrenergenic stimulation by the further re-expression of foetal genes. In addition we have profiled the expression level of Hdacs in the R6/2 murine hearts and found that the isoproterenol stimulation of Hdac expression was partially blocked. For the first time we established the Hdac transcriptional profile under hypertrophic conditions and found 10 out of 18 Hdacs to be markedly deregulated. Therefore, we conclude that R6/2 murine hearts are not able to respond to the chronic isoproterenol treatment to the same degree as wild type hearts and some of the hypertrophic signals are likely attenuated in the symptomatic HD animals.

  9. Determinants of myocardial energetics and efficiency in symptomatic hypertrophic cardiomyopathy.

    Science.gov (United States)

    Timmer, Stefan A J; Germans, Tjeerd; Götte, Marco J W; Rüssel, Iris K; Dijkmans, Pieter A; Lubberink, Mark; ten Berg, Jurrien M; ten Cate, Folkert J; Lammertsma, Adriaan A; Knaapen, Paul; van Rossum, Albert C

    2010-04-01

    Next to hypertrophy, hypertrophic cardiomyopathy (HCM) is characterized by alterations in myocardial energetics. A small number of studies have shown that myocardial external efficiency (MEE), defined by external work (EW) in relation to myocardial oxidative metabolism (MVO(2)), is reduced. The present study was conducted to identify determinants of MEE in patients with HCM by use of dynamic positron emission tomography (PET) and cardiovascular magnetic resonance imaging (CMR). Twenty patients with HCM (12 men, mean age: 55.2 + or - 13.9 years) and 11 healthy controls (7 men, mean age: 48.1 + or - 10 years) were studied with [(11)C]acetate PET to assess MVO(2). CMR was performed to determine left ventricular (LV) volumes and mass (LVM). Univariate and multivariate analyses were employed to determine independent predictors of myocardial efficiency. Between study groups, MVO(2) (controls: 0.12 + or - 0.04 ml x min(-1) x g(-1), HCM: 0.13 + or - 0.05 ml x min(-1) x g(-1), p = 0.64) and EW (controls: 9,139 + or - 2,484 mmHg x ml, HCM: 9,368 + or - 2,907 mmHg x ml, p = 0.83) were comparable, whereas LVM was significantly higher (controls: 99 + or - 21 g, HCM: 200 + or - 76 g, p efficiency. Mechanical external efficiency could independently be predicted by SV and LVM.

  10. Flow-Induced Mitral Leaflet Motion in Hypertrophic Cardiomyopathy

    Science.gov (United States)

    Meschini, Valentina; Mittal, Rajat; Verzicco, Roberto

    2017-11-01

    Hypertrophic cardiomyopathy (HCM) is considered the cause of sudden cardiac death in developed countries. Clinically it is found to be related to the thickening of the intra-ventricular septum combined with elongated mitral leaflets. During systole the low pressure, induced by the abnormal velocities in the narrowed aortic channel, can attract one or both the mitral leaflets causing the aortic obstruction and sometimes instantaneous death. In this paper a fluid structure interaction model for the flow in the left ventricle with a native mitral valve is employed to investigate the physio-pathology of HCM. The problem is studied using direct numerical simulations of the Navier-Stokes equations with a two-way coupled structural solver based on interaction potential approach for the structure dynamics. Simulations are performed for two different degrees of hypertrophy, and two values of pumping efficiency. The leaflets dynamics and the ventricle deformation resulting from the echocardiography of patients affected by HCM are well captured by the simulations. Moreover, the procedures of leaflets plication and septum myectomy are simulated in order to get insights into the efficiency and reliability of such surgery.

  11. Hypertrophic cardiomyopathy in 2013: Current speculations and future perspectives

    Science.gov (United States)

    Efthimiadis, Georgios K; Pagourelias, Efstathios D; Gossios, Thomas; Zegkos, Thomas

    2014-01-01

    Hypertrophic cardiomyopathy (HCM), the most variable cardiac disease in terms of phenotypic presentation and clinical outcome, represents the most common inherited cardiomyopathic process with an autosomal dominant trait of inheritance. To date, more than 1400 mutations of myofilament proteins associated with the disease have been identified, most of them “private” ones. This striking allelic and locus heterogeneity of the disease certainly complicates the establishment of phenotype-genotype correlations. Additionally, topics pertaining to patients’ everyday lives, such as sudden cardiac death (SCD) risk stratification and prevention, along with disease prognosis, are grossly related to the genetic variation of HCM. This review incorporates contemporary research findings and addresses major aspects of HCM, including preclinical diagnosis, genetic analysis, left ventricular outflow tract obstruction and SCD. More specifically, the spectrum of genetic analysis, the selection of the best method for obstruction alleviation and the need for a unique and accurate factor for SCD risk stratification are only some of the controversial HCM issues discussed. Additionally, future perspectives concerning HCM and myocardial ischemia, as well as atrial fibrillation, are discussed. Rather than enumerating clinical studies and guidelines, challenging problems concerning the disease are critically appraised by this review, highlighting current speculations and recommending future directions. PMID:24575171

  12. Survival and sudden cardiac death after septal ablation for hypertrophic obstructive cardiomyopathy

    DEFF Research Database (Denmark)

    Jensen, Morten Kvistholm; Havndrup, Ole; Hassager, Christian

    2011-01-01

    Reports of long-term survival and the risk of sudden cardiac death (SCD) after percutaneous transluminal septal myocardial ablation (PTSMA) in patients with hypertrophic obstructive cardiomyopathy (HOCM) are sparse.......Reports of long-term survival and the risk of sudden cardiac death (SCD) after percutaneous transluminal septal myocardial ablation (PTSMA) in patients with hypertrophic obstructive cardiomyopathy (HOCM) are sparse....

  13. Influence of Septal Thickness on the Clinical Outcome After Alcohol Septal Alation in Hypertrophic Cardiomyopathy

    DEFF Research Database (Denmark)

    Jensen, Morten K; Jacobsson, Linda; Almaas, Vibeke Marie

    2016-01-01

    BACKGROUND: We assessed the influence of interventricular septal thickness (IVSd) on the clinical outcome and survival after alcohol septal ablation (ASA) in patient with hypertrophic cardiomyopathy. METHODS AND RESULTS: We analyzed 531 patients with hypertrophic cardiomyopathy (age: 56±14 years...

  14. HYPERTROPHIC CARDIOMYOPATHY AS A PART OF INHERITED MALFORMATION SYNDROMES IN INFANTS

    Directory of Open Access Journals (Sweden)

    M.V. Tural'chuk

    2011-01-01

    Full Text Available The data of clinical and instrumental examination of two infantile patients with obstructive hypertrophic cardiomyopathy in association with marked multisystem involvement as a picture of inherited malformation syndromes are given.Key words: infants, hypertrophic cardiomyopathy, LEOPARD syndrome, Noonan syndrome.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (3: 166–169

  15. Collecting, Analyzing, and Publishing Massive Data about the Hypertrophic Cardiomyopathy

    Science.gov (United States)

    Montserrat, Lorenzo; Cotelo-Lema, Jose Antonio; Luaces, Miguel R.; Seco, Diego

    We present in this paper the architecture and some implementation details of a Document Management System and Workflow to help in the diagnosis of the hypertrophic cardiomyopathy, one of the most frequent genetic cardiovascular diseases. The system allows a gradual and collaborative creation of a knowledge base about the mutations associated with this disease. The system manages both the original documents of the scientific papers and the data extracted from these papers by the experts. Furthermore, a semiautomatic report generation module exploits this knowledge base to create high quality reports about the studied mutations.

  16. Histologic Sequelae of Apical Hypertrophic Cardiomyopathy: Dystrophic Calcification

    Directory of Open Access Journals (Sweden)

    Shahryar G Saba

    2017-05-01

    Full Text Available We present cardiac computed tomography (CT findings demonstrating apical hypertrophic cardiomyopathy with dystrophic calcification of the left ventricular apex. The absence of significant epicardial coronary artery disease demonstrated by coronary CT angiography suggests that increased wall tension and decreased microvascular perfusion over time account for the dyskinetic apical myocardium, rather than myocardial infarction secondary to atherosclerotic plaque rupture. These observations support CT as the imaging modality of choice to visualize the deposition of calcium in injured myocardial tissue, a recognized occurrence in chronically infarcted myocardium.

  17. Takotsubo cardiomyopathy in a patient with previously undiagnosed hypertrophic cardiomyopathy with obstruction.

    Science.gov (United States)

    Brabham, William W; Lewis, Geoffrey F; Bonnema, David D; Nielsen, Christopher D; O'Brien, Terrence X

    2011-01-01

    Takotsubo cardiomyopathy (TCM) is usually characterized by left ventricular anteroapical dysfunction in the absence of significant coronary disease commonly precipitated by an emotional or stressful trigger. Hypertrophic cardiomyopathy (HCM) is usually diagnosed on the basis of symptoms, family history, echocardiography, or by the presence of a characteristic murmur. We report a unique case of TCM occurring in a patient with previously undiagnosed HCM with left ventricular outflow tract (LVOT) obstruction who presented with an acute coronary syndrome and ultimately underwent successful alcohol septal ablation. The potential pathophysiologic correlations are discussed. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Social determinants of health in the setting of hypertrophic cardiomyopathy.

    Science.gov (United States)

    Ingles, Jodie; Johnson, Renee; Sarina, Tanya; Yeates, Laura; Burns, Charlotte; Gray, Belinda; Ball, Kylie; Semsarian, Christopher

    2015-04-01

    Social determinants of health play an important role in explaining poor health outcomes across many chronic disease states. The impact of the social gradient in the setting of an inherited heart disease, hypertrophic cardiomyopathy (HCM), has not been investigated. This study sought to profile the socioeconomic status of patients attending a specialized multidisciplinary clinic and to determine the impact on clinical factors, psychosocial wellbeing and adherence to medical advice. Patients with HCM and at-risk relatives attending a specialized multidisciplinary clinic in Sydney Australia between 2011 and 2013 were included. Clinical, socioeconomic, geographic remoteness and adherence data were available. A broader clinic and registry-based group completed a survey including psychological wellbeing, health-related quality of life, Morisky Medication Adherence Scale and individual-level socioeconomic information. Over a 3-year period, 486 patients were seen in the specialized clinic. There was an over-representation of patients from socioeconomically advantaged and the least geographically remote areas. Socioeconomic disadvantage was associated with comorbidities, poor psychological wellbeing and health-related quality of life, lower understanding of HCM and more complex clinical management issues such as NYHA class, atrial fibrillation and left ventricular outflow tract obstruction. Approximately 10% of patients were non-adherent to medical advice, and poor medication adherence was seen in 30% of HCM patients with associated factors being younger age, minority ethnicity, anxiety and poor mental quality of life. Of all the patients attending a specialized cardiac genetic clinic, there is an overrepresentation of patients from very advantaged and major metropolitan areas and suggests that those most in need of a multidisciplinary approach to care are not accessing it. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. N-terminal pro-brain natriuretic peptide is related with coronary flow velocity reserve and diastolic dysfunction in patients with asymmetric hypertrophic cardiomyopathy.

    Science.gov (United States)

    Tesic, Milorad; Seferovic, Jelena; Trifunovic, Danijela; Djordjevic-Dikic, Ana; Giga, Vojislav; Jovanovic, Ivana; Petrovic, Olga; Marinkovic, Jelena; Stankovic, Sanja; Stepanovic, Jelena; Ristic, Arsen; Petrovic, Milan; Mujovic, Nebojsa; Vujisic-Tesic, Bosiljka; Beleslin, Branko; Vukcevic, Vladan; Stankovic, Goran; Seferovic, Petar

    2017-10-01

    The relations of elevated N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and cardiac ischemia in hypertrophic cardiomyopathy (HCM) patients is uncertain. Therefore we designed the study with the following aims: (1) to analyze plasma concentrations of NT-pro-BNP in various subsets of HCM patients; (2) to reveal the correlations of NT-pro-BNP, myocardial ischemia, and diastolic dysfunction; (3) to assess predictors of the elevated plasma levels of NT-pro-BNP. In 61 patients (mean age 48.9±16.3 years; 26 male) with asymmetric HCM plasma levels of NT-pro-BNP were obtained. Standard transthoracic examination, tissue Doppler echocardiography with measurement of transthoracic coronary flow velocity reserve (CFVR) in left anterior descending artery (LAD) was done. Mean natural logarithm value of NT-pro-BNP was 7.11±0.95pg/ml [median value 1133 (interquartile range 561-2442)pg/ml]. NT-pro-BNP was significantly higher in patients with higher NYHA class, in obstructive HCM, more severe mitral regurgitation, increased left atrial volume index (LAVI), presence of calcified mitral annulus, elevated left ventricular (LV) filling pressure and in decreased CFVR. Levels of NT-pro-BNP significantly correlated with the ratio of E/e' (r=0.534, p<0.001), LV outflow tract gradient (r=0.503, p=0.024), LAVI (r=0.443, p<0.001), while inversely correlated with CFVR LAD (r=-0.569, p<0.001). When multivariate analysis was done only CFVR LAD and E/e' emerged as independent predictors of NT-pro-BNP. Plasma levels of NT-pro-BNP were significantly higher in HCM patients with more advanced disease. Elevated NT-pro-BNP not only reflects the diastolic impairment of the LV, but it might also be the result of cardiac ischemia in patients with HCM. Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  20. A Murine Hypertrophic Cardiomyopathy Model: The DBA/2J Strain.

    Directory of Open Access Journals (Sweden)

    Wenyuan Zhao

    Full Text Available Familial hypertrophic cardiomyopathy (HCM is attributed to mutations in genes that encode for the sarcomere proteins, especially Mybpc3 and Myh7. Genotype-phenotype correlation studies show significant variability in HCM phenotypes among affected individuals with identical causal mutations. Morphological changes and clinical expression of HCM are the result of interactions with modifier genes. With the exceptions of angiotensin converting enzyme, these modifiers have not been identified. Although mouse models have been used to investigate the genetics of many complex diseases, natural murine models for HCM are still lacking. In this study we show that the DBA/2J (D2 strain of mouse has sequence variants in Mybpc3 and Myh7, relative to widely used C57BL/6J (B6 reference strain and the key features of human HCM. Four-month-old of male D2 mice exhibit hallmarks of HCM including increased heart weight and cardiomyocyte size relative to B6 mice, as well as elevated markers for cardiac hypertrophy including β-myosin heavy chain (MHC, atrial natriuretic peptide (ANP, brain natriuretic peptide (BNP, and skeletal muscle alpha actin (α1-actin. Furthermore, cardiac interstitial fibrosis, another feature of HCM, is also evident in the D2 strain, and is accompanied by up-regulation of type I collagen and α-smooth muscle actin (SMA-markers of fibrosis. Of great interest, blood pressure and cardiac function are within the normal range in the D2 strain, demonstrating that cardiac hypertrophy and fibrosis are not secondary to hypertension, myocardial infarction, or heart failure. Because D2 and B6 strains have been used to generate a large family of recombinant inbred strains, the BXD cohort, the D2 model can be effectively exploited for in-depth genetic analysis of HCM susceptibility and modifier screens.

  1. High sensitivity of late gadolinium enhancement for predicting microscopic myocardial scarring in biopsied specimens in hypertrophic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Tetsuo Konno

    Full Text Available BACKGROUND: Myocardial scarring can be assessed by cardiac magnetic resonance imaging with late gadolinium enhancement and by endomyocardial biopsy. However, accuracy of late gadolinium enhancement for predicting microscopic myocardial scarring in biopsied specimens remains unknown in hypertrophic cardiomyopathy. We investigated whether late gadolinium enhancement in the whole heart reflects microscopic myocardial scarring in the small biopsied specimens in hypertrophic cardiomyopathy. METHODS AND RESULTS: Twenty-one consecutive patients with hypertrophic cardiomyopathy who were examined both by cardiac magnetic resonance imaging and by endomyocardial biopsy were retrospectively studied. The right interventricular septum was the target site for endomyocardial biopsy in all patients. Late gadolinium enhancement in the ventricular septum had an excellent sensitivity (100% with a low specificity (40% for predicting microscopic myocardial scarring in biopsied specimens. The sensitivity of late gadolinium enhancement in the whole heart remained 100% with a specificity of 27% for predicting microscopic myocardial scarring in biopsied specimens. Quantitative assessments of fibrosis revealed that the extent of late gadolinium enhancement in the whole heart was the only independent variable related to the microscopic collagen fraction in biopsied specimens (β  =  0.59, 95% confident interval: 0.15 - 1.0, p  =  0.012. CONCLUSIONS: Although there was a compromise in the specificity, the sensitivity of late gadolinium enhancement was excellent for prediction of microscopic myocardial scarring in hypertrophic cardiomyopathy. Moreover, the severity of late gadolinium enhancement was independently associated with the quantitative collagen fraction in biopsied specimens in hypertrophic cardiomyopathy. These findings indicate that late gadolinium enhancement can reflect both the presence and the extent of microscopic myocardial scarring in the small

  2. Subaortic and midventricular obstructive hypertrophic cardiomyopathy with extreme segmental hypertrophy

    Directory of Open Access Journals (Sweden)

    Karoulas Takis

    2007-03-01

    Full Text Available Abstract Background Subaortic and midventricular hypertrophic cardiomyopathy in a patient with extreme segmental hypertrophy exceeding the usual maximum wall thickness reported in the literature is a rare phenomenon. Case Presentation A 19-year-old man with recently diagnosed hypertrophic cardiomyopathy (HCM was referred for sudden death risk assessment. The patient had mild exertional dyspnea (New York Heart Association functional class II, but without syncope or chest pain. There was no family history of HCM or sudden death. A two dimensional echocardiogram revealed an asymmetric type of LV hypertrophy; anterior ventricular septum = 49 mm; posterior ventricular septum = 20 mm; anterolateral free wall = 12 mm; and posterior free wall = 6 mm. The patient had 2 types of obstruction; a LV outflow obstruction due to systolic anterior motion of both mitral leaflets (Doppler-estimated 38 mm Hg gradient at rest; and a midventricular obstruction (Doppler-estimated 43 mm Hg gradient, but without apical aneurysm or dyskinesia. The patient had a normal blood pressure response on exercise test and no episodes of non-sustained ventricular tachycardia in 24-h ECG recording. Cardiac MRI showed a gross late enhancement at the hypertrophied septum. Based on the extreme degree of LV hypertrophy and the myocardial hyperenhancement, an implantation of a cardioverter-defibrillator was recommended prophylactically for primary prevention of sudden death. Conclusion Midventricular HCM is an infrequent phenotype, but may be associated with an apical aneurysm and progression to systolic dysfunction (end-stage HCM.

  3. Nonfamilial Hypertrophic Cardiomyopathy: Prevalence, Natural History, and Clinical Implications.

    Science.gov (United States)

    Ingles, Jodie; Burns, Charlotte; Bagnall, Richard D; Lam, Lien; Yeates, Laura; Sarina, Tanya; Puranik, Rajesh; Briffa, Tom; Atherton, John J; Driscoll, Tim; Semsarian, Christopher

    2017-04-01

    Yield of causative variants in hypertrophic cardiomyopathy (HCM) is increased in some probands, suggesting different clinical subgroups of disease occur. We hypothesized that a negative family history and no sarcomere mutations represent a nonfamilial subgroup of HCM. We sought to determine the prevalence, natural history, and potential clinical implications of this nonfamilial subgroup of HCM. Four hundred and thirteen unrelated probands with HCM seen in a specialized HCM center between 2002 and 2015 and genetic testing performed were included in this retrospective cohort study. There were 251 (61%) probands with no reported family history of HCM, including 166 (40% of total) probands with no sarcomere mutation, that is, nonfamilial HCM. Quantified family pedigree data revealed no difference in mean number of first-degree relatives screened between nonfamilial and sarcomere-positive groups. Adjusted predictors of nonfamilial status were older age (odds ratio, 1.04; 95% confidence interval, 1.02-1.06; P =0.0001), male sex (odds ratio, 1.96; 95% confidence interval, 1.11-3.45; P =0.02), hypertension (odds ratio, 2.80; 95% confidence interval, 1.57-5.00; P =0.0005), and nonasymmetric septal morphology (odds ratio, 3.41; 95% confidence interval, 1.64-7.08; P =0.001). They had a less severe clinical course with greater event-free survival from major cardiac events ( P =0.04) compared with sarcomere-positive HCM probands. Genotype prediction scores showed good performance in identifying genotype-positive patients (area under the curve, 0.71-0.75) and, in combination with pedigree characteristics, were further improved. Approximately 40% of HCM probands have a nonfamilial subtype, with later onset and less severe clinical course. We propose a revised clinical pathway for management, highlighting the role of genetic testing, a detailed pedigree, and refined clinical surveillance recommendations for family members. © 2017 American Heart Association, Inc.

  4. Clinical Characteristics and Prognosis of End-stage Hypertrophic Cardiomyopathy

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    Yan Xiao

    2015-01-01

    Full Text Available Background: End-stage hypertrophic cardiomyopathy (HCM is complicated by substantial adverse events. However, few studies have focused on electrocardiographic features and their prognostic values in HCM. This study aimed to evaluate the clinical manifestations and prognostic value of electrocardiography in patients with end-stage HCM. Methods: End-stage HCM patients were enrolled from a total of 1844 consecutive HCM patients from April 2002 to November 2013 at Fuwai Hospital. Clinical data, including medical history, electrocardiography, and echocardiography, were analyzed. Cox hazards regression analysis was used to assess the risk factors for cardiovascular mortality. Results: End-stage HCM was identified in 99 (5.4% patients, averaged at 52 ± 16 years old at entry. Atrial fibrillation was observed in 53 patients and mural thrombus in 19 patients. During 3.9 ± 3.0 years of follow-up, embolic stroke, refractory heart failure, and death or transplantation were observed in 20, 39, and 51 patients, respectively. The incidence of annual mortality was 13.2%. Multivariate Cox hazards regression analysis identified New York Heart Association Class (NYHA III/IV at entry (hazard ratio [HR]: 1.99; 95% confidence interval [CI]: 1.05-3.80; P = 0.036, left bundle branch block (LBBB (HR: 2.80; 95% CI: 1.47-5.31; P = 0.002, and an abnormal Q wave (HR: 2.21; 95% CI: 1.16-4.23; P = 0.016 as independent predictors of cardiovascular death, in accordance with all-cause death and heart failure-related death. Conclusions: LBBB and an abnormal Q wave are risk factors of cardiovascular mortality in end-stage HCM and provide new evidence for early intervention. Susceptibility of end-stage HCM patients to mural thrombus and embolic events warrants further attention.

  5. Biventricular / Left Ventricular Pacing in Hypertrophic Obstructive Cardiomyopathy: An Overview

    Directory of Open Access Journals (Sweden)

    Radu Vatasescu, MD

    2012-05-01

    Full Text Available Hypertrophic cardiomyopathy (HCM is an autosomal dominant inherited genetic disease characterized by compensatory pathological left ventricle (LV hypertrophy due to sarcomere dysfunction. In an important proportion of patients with HCM, the site and extent of cardiac hypertrophy results in severe obstruction to LV outflow tract (LVOT, contributing to disabling symptoms and increasing the risk of sudden cardiac death (SCD. In patients with progressive and/or refractory symptoms despite optimal pharmacological treatment, invasive therapies that diminish or abolish LVOT obstruction relieve heart failure-related symptoms, improve quality of life and could be associated with long-term survival similar to that observed in the general population. The gold standard in this respect is surgical septal myectomy, which might be supplementary associated with a reduction in SCD. Percutaneous techniques, particularly alcohol septal ablation (ASA and more recently radiofrequency (RF septal ablation, can achieve LVOT gradient reduction and symptomatic benefit in a large proportion of HOCM patients at the cost of a supposedly limited septal myocardial necrosis and a 10-20% risk of chronic atrioventricular block. After an initial period of enthusiasm, standard DDD pacing failed to show in randomized trials significant LVOT gradient reductions and objective improvement in exercise capacity. However, case reports and recent small pilot studies suggested that atrial synchronous LV or biventricular (biV pacing significantly reduce LVOT obstruction and improve symptoms (acutely as well as long-term in a large proportion of severely symptomatic HOCM patients not suitable to other gradient reduction therapies. Moreover, biV/LV pacing in HOCM seems to be associated with significant LV reverse remodelling.

  6. Clinicopathological profiles of progressive heart failure in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Melacini, Paola; Basso, Cristina; Angelini, Annalisa; Calore, Chiara; Bobbo, Fabiana; Tokajuk, Barbara; Bellini, Nicoletta; Smaniotto, Gessica; Zucchetto, Mauro; Iliceto, Sabino; Thiene, Gaetano; Maron, Barry J

    2010-09-01

    Hypertrophic cardiomyopathy (HCM) is an important cause of heart failure-related disability over a wide range of ages. Profiles of severe progressive heart failure symptoms and death, or heart transplantation deserve more complete definition within large patient cohorts. Clinical and morphological features of heart failure were assessed in 293 consecutive HCM patients over a median follow-up of 6 (inter-quartile range 2-11) years. Gross and histopathological features were analysed in 12 patients for whom the heart was available for inspection. Of the 293 patients, 50 (17%) developed severe progressive heart failure, including 18 who died or were transplanted. Three profiles of heart failure were identified predominantly associated with: (i) end-stage systolic dysfunction (ejection fraction heart failure in 32 patients (64%) among the three profiles. Compared with other patients, those non-obstructive with preserved systolic function had earlier onset of heart failure symptoms mainly due to diastolic dysfunction, and the most accelerated progression to advanced heart failure and adverse outcome (P = 0.04). Thrombi were identified in the left atrial appendage of five gross heart specimens all belonging to patients with AF, including three of which were unrecognized clinically and had previously embolized. Extensive myocardial scarring with LV remodelling was evident in all end-stage patients; no or only focal scars were present in other patients. Profiles of advanced heart failure in HCM are due to diverse pathophysiological mechanisms, including LV outflow obstruction and diastolic or global systolic ventricular dysfunction. Atrial fibrillation proved to be the most common disease variable associated with progressive heart failure. Recognition of the heterogeneous pathophysiology of heart failure in HCM is relevant, given the targeted management strategies necessary in this disease.

  7. Down Syndrome with Complete Atrioventricular Septal Defect, Hypertrophic Cardiomyopathy, and Pulmonary Vein Stenosis.

    Science.gov (United States)

    Mahadevaiah, Guruprasad; Gupta, Manoj; Ashwath, Ravi

    2015-10-01

    The prevalence of congenital heart disease in infants with Down syndrome is 40%, compared with 0.3% in children who have normal chromosomes. Atrioventricular and ventricular septal defects are often associated with chromosomal aberrations, such as in trisomy 21, whereas hypertrophic cardiomyopathy is chiefly thought to be secondary to specific gene mutations. We found only one reported case of congenital hypertrophic cardiomyopathy and atrioventricular septal defect in an infant with Down syndrome. Here, we report atrioventricular septal defect, hypertrophic cardiomyopathy, and pulmonary vein stenosis in a neonate with Down syndrome-an apparently unique combination. In addition, we discuss the relevant medical literature.

  8. Perioperative anesthetic management of patients with hypertrophic cardiomyopathy for noncardiac surgery: A case series

    Directory of Open Access Journals (Sweden)

    Sahoo Rajendra

    2010-01-01

    Full Text Available Hypertrophic cardiomyopathy with or without left ventricular outflow tract obstruction is characterized by asymmetric hypertrophy of the interventricular septum causing intermittent obstruction of the left ventricular outflow tract. Because Hypertrophic cardiomyopathy is the most common genetic cardiovascular disease, it may present to the anesthesiologist more often than anticipated, sometimes in undiagnosed form during routine preoperative visit. Surgery and anesthesia often complicate the perioperative outcome if adequate monitoring and proper care are not taken. Therefore, a complete understanding of the pathophysiology, hemodynamic changes and anesthetic implications is needed for successful perioperative outcome. We hereby describe the perioperative management of three patients with Hypertrophic cardiomyopathy for different surgical procedures.

  9. Hypertrophic cardiomyopathy: an autopsy analysis of 14 cases.

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    Phadke R

    2001-07-01

    Full Text Available BACKGROUND: Hypertrophic cardiomyopathy (HCM is one of the less common forms of primary cardiomyopathies. There is little data available on HCM in Indian literature. AIMS: To assess the incidence and analyse the clinicopathological features of HCM. SETTINGS: Analysis of data of 15 years from a tertiary care centre. METHODS AND MATERIAL: The clinical and pathological data in fourteen cases of HCM with respect to their gross and microscopic features and clinical presentation were reviewed. RESULTS: Incidence of HCM amongst the autopsied primary cardiomyopathies (N = 101 was 13.9% (n=14. Males were affected more. Common presenting symptoms were exertional dyspnoea, angina and palpitations. Concentric and asymmetric hypertrophy was equally seen. Obliterative small vessel disease was noted in 50% of the cases. Although significant myofibre disarray (>5% was seen in all fourteen cases, it could be demonstrated in only 40- 50% of an average of twenty sections studied. Type IA myofibre disarray was the commonest. Six of the fourteen patients died suddenly. Cardiac failure was the commonest cause of death. CONCLUSIONS: Myofibre disarray is a highly sensitive and specific marker for HCM only when considered in a quantitative rather than a qualitative fashion. In this context, the rationale for performing endomyocardial biopsy is to rule out mimics of HCM.

  10. Concomitant ablation for atrial fibrillation during septal myectomy in patients with hypertrophic obstructive cardiomyopathy.

    Science.gov (United States)

    Bogachev-Prokophiev, Alexander V; Afanasyev, Alexander V; Zheleznev, Sergei I; Pivkin, Alexei N; Fomenko, Michael S; Sharifulin, Ravil M; Karaskov, Alexander M

    2017-09-01

    The appearance of atrial fibrillation is associated with significant clinical deterioration in patients with obstructive hypertrophic cardiomyopathy; therefore, maintenance of sinus rhythm is desirable. Guidelines and most articles have reported the results of catheter ablation and pharmacologic atrial fibrillation treatment; nevertheless, data regarding concomitant procedures during septal myectomy are limited. The aim of this study was to assess the outcomes of concomitant atrial fibrillation treatment in patients with obstructive hypertrophic cardiomyopathy. Between 2010 and 2013 in our clinic, 187 patients with obstructive hypertrophic cardiomyopathy underwent extended myectomy. In 45 cases, concomitant Cox-Maze IV procedure was performed; however, obstructive hypertrophic cardiomyopathy was the primary indication for surgery. Atrial fibrillation was paroxysmal in 26 patients (58%) and nonparoxysmal in 19 patients (42%). The mean age of patients was 52.8 ± 14.2 years (range, 22-74 years). Mean peak gradient was 90.7 ± 24.2 mm Hg, and interventricular septum thickness was 26.1 ± 4.3 mm. Mean atrial fibrillation duration was 17.3 ± 8.5 months. There were no early deaths. No procedure-related complications occurred with regard to ablation procedure. Complete atrioventricular block was achieved in 2 patients (4.0%). Mean crossclamping time was 61 ± 36 minutes. Peak left ventricular outflow tract gradient was 12.6 ± 5.5 mm Hg based on transesophageal echocardiography. The Maze IV procedure was used for ablation in all patients (radiofrequency ablation with bipolar clamp + cryolesion for mitral and tricuspid lines). Because of the atrial wall thickness (5-6 mm), applications were performed 8 to 10 times on each line. There were no cases of pacemaker implantation due to sinus node dysfunction. All patients were discharged in stable sinus rhythm. Mean follow-up was 23.7 ± 1.3 months. The rate of atrial fibrillation freedom was 100% (45

  11. Burden of Recurrent and Ancestral Mutations in Families With Hypertrophic Cardiomyopathy

    NARCIS (Netherlands)

    Ross, Samantha Barratt; Bagnall, Richard D.; Ingles, Jodie; van Tintelen, J. Peter; Semsarian, Christopher

    2017-01-01

    Hypertrophic cardiomyopathy is a genetically heterogeneous myocardial disease with >1000 causal variants identified. Nonunique variants account for disease in many families. We sought to characterize nonunique variants in Australian families and determine whether they arise from common ancestral

  12. Hypertrophic cardiomyopathy family with double-heterozygous mutations; does disease severity suggest doubleheterozygosity?

    OpenAIRE

    van Rijsingen, I.A.W.; Hermans-van Ast, J.F.; Arens, Y.H.J.M.; Schalla, S.M.; de Die-Smulders, C.E.M.; van den Wijngaard, A.; Pinto, Y.M.

    2009-01-01

    Background. With the improvement in genetic testing over time, double-heterozygous mutations are more often found by coincidence in families with hypertrophic cardiomyopathy (HCM). Double heterozygosity can be a cause of the wellknown clinical diversity within HCM families.

  13. Angiotensin II type 2 receptors and cardiac hypertrophy in women with hypertrophic cardiomyopathy

    NARCIS (Netherlands)

    J. Deinum (Jacob); J.M. van Gool (Jeanette); M.J.M. Kofflard (Marcel); A.H.J. Danser (Jan); F.J. ten Cate (Folkert)

    2001-01-01

    textabstractThe development of left ventricular hypertrophy in subjects with hypertrophic cardiomyopathy (HCM) is variable, suggesting a role for modifying factors such as angiotensin II. Angiotensin II mediates both trophic and antitrophic effects, via angiotensin II type 1

  14. Extent of hypertrophy in hypertrophic cardiomyopathy: two-dimensional echocardiographic and angiographic correlation

    NARCIS (Netherlands)

    S. Domenicucci; S.K. Das (Swadesh); P.W.J.C. Serruys (Patrick); W.B. Vletter (Wim); J.R.T.C. Roelandt (Jos); F.J. ten Cate (Folkert)

    1983-01-01

    textabstractSince the first anatomical and functional descriptions of hypertrophic cardiomyopathy (HCM) there have been convincing attempts at better understanding and definition of the controversial aspects of this complex disease.

  15. Impaired cardiac mitochondrial oxidative phosphorylation and enhanced mitochondrial oxidative stress in feline hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Christiansen, Liselotte Bruun; Dela, Flemming; Koch, Jørgen

    2015-01-01

    Mitochondrial dysfunction and oxidative stress are important players in the development of various cardiovascular diseases, but their roles in hypertrophic cardiomyopathy (HCM) remain unknown. We examined whether mitochondrial oxidative phosphorylation (OXPHOS) capacity was impaired with enhanced...

  16. Ultrastructural myocardial changes in seven cats with spontaneous hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Christiansen, Liselotte Bruun; Prats Gavalda, Clara; Hyttel, Poul

    2015-01-01

    OBJECTIVES: Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats and shares clinical and pathological characteristics with human HCM. Little is known about the pathogenic mechanisms underlying development of spontaneous feline HCM. ANIMALS: The study population consisted...... of seven cats diagnosed with HCM and eight age-matched cats with no evidence of cardiac disease. METHODS: Fresh myocardial biopsies taken from the middle of the left ventricular posterior free wall were obtained and examined with transmission electron microscopy. RESULTS: Electron microscopic examination...... showed ultrastructural aberrations of the myocardial cytoarchitecture and of the interstitium in the seven cats with HCM. In the most severely affected cats the myofibrils were disorganized and subsarcolemmal mitochondria were depleted. In control cats, contraction band artifacts were commonly seen...

  17. Cardiac symptoms before sudden cardiac death caused by hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Lynge, Thomas Hadberg; Risgaard, Bjarke; Jabbari, Reza

    2016-01-01

    AIMS: Hypertrophic cardiomyopathy (HCM) is a frequent cause of sudden cardiac death (SCD) among the young (SCDY). The aim of this study was to characterize symptoms before SCDY due to HCM. METHODS AND RESULTS: Through review of all death certificates, we identified all SCDs in Danes aged 1-35 years...... in 2000-2009. Nationwide we included all deaths (n = 8756) and identified 431 autopsied SCDYs. All available records from hospitals and general practitioners were retrieved. To compare symptoms, we included a control groups consisting of traffic accident victims (n = 74). In the 10-year study period, 431...... autopsied SCDY cases were reviewed and 38 cases (9%) were included, of which 22 (58%) had morphologic findings diagnostic of HCM and 16 (42%) had findings suggestive, but not diagnostic, of HCM ('possible HCM'). Cardiac symptoms >1 h prior to death were reported in 21 (55%) of cases, and 16 (42%) sought...

  18. Serious arrhythmias in patients with apical hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Okishige, Kaoru; Sasano, Tetsuo; Yano, Kei; Azegami, Kouji; Suzuki, Kou; Itoh, Kuniyasu [Yokohama Red Cross Hospital (Japan)

    2001-05-01

    We report cases of serious arrhythmias associated with apical hypertrophic cardiomyopathy (AHCM). Thirty-one patients were referred to our institute to undergo further assessment of their AHCM from 1988 to 1999. Three patients with nonsustained ventricular tachycardia demonstrated an {sup 123}I-MIBG regional reduction in the tracer uptake. In two patients with ventricular fibrillation (VF), the findings from {sup 123}I-MIBG imaging revealed regional sympathetic denervation in the inferior and lateral regions. Electrophysiologic study demonstrated reproducible induction of VF in aborted sudden death and presyncopal patients, resulting in the need for an implantable defibrillator device and amiodarone in each patient. Patients with refractory atrial fibrillation with a rapid ventricular response suffered from serious congestive heart failure. A prudent assessment and strategy in patients with this disease would be indispensable in avoiding a disastrous outcome. (author)

  19. Hypertrophic Cardiomyopathy: How do Mutations Lead to Disease?

    Energy Technology Data Exchange (ETDEWEB)

    Marsiglia, Júlia Daher Carneiro, E-mail: julia.marsiglia@usp.br; Pereira, Alexandre Costa [Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2014-03-15

    Hypertrophic cardiomyopathy (HCM) is the most common monogenic genetic cardiac disease, with an estimated prevalence of 1:500 in the general population. Clinically, HCM is characterized by hypertrophy of the left ventricle (LV) walls, especially the septum, usually asymmetric, in the absence of any cardiac or systemic disease that leads to a secondary hypertrophy. The clinical course of the disease has a large inter- and intrafamilial heterogeneity, ranging from mild symptoms of heart failure late in life to the onset of sudden cardiac death at a young age and is caused by a mutation in one of the genes that encode a protein from the sarcomere, Z-disc or intracellular calcium modulators. Although many genes and mutations are already known to cause HCM, the molecular pathways that lead to the phenotype are still unclear. This review focus on the molecular mechanisms of HCM, the pathways from mutation to clinical phenotype and how the disease's genotype correlates with phenotype.

  20. Contemporary Natural History and Management of Nonobstructive Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Maron, Martin S; Rowin, Ethan J; Olivotto, Iacopo; Casey, Susan A; Arretini, Anna; Tomberli, Benedetta; Garberich, Ross F; Link, Mark S; Chan, Raymond H M; Lesser, John R; Maron, Barry J

    2016-03-29

    Left ventricular outflow tract gradients are absent in an important proportion of patients with hypertrophic cardiomyopathy (HCM). However, the natural course of this important patient subgroup remains largely unresolved. The authors systematically employed exercise (stress) echocardiography to define those patients without obstruction to left ventricular outflow at rest and/or under physiological exercise and to examine their natural history and clinical course to create a more robust understanding of this complex disease. We prospectively studied 573 consecutive HCM patients in 3 centers (44 ± 17 years; 66% male) with New York Heart Association functional class I/II symptoms at study entry, including 249 in whom left ventricular outflow tract obstruction was absent both at rest and following physiological exercise (<30 mm Hg; nonobstructive HCM) and retrospectively assembled clinical follow-up data. Over a median follow-up of 6.5 years, 225 of 249 nonobstructive patients (90%) remained in classes I/II, whereas 24 (10%) developed progressive heart failure to New York Heart Association functional classes III/IV. Nonobstructive HCM patients were less likely to experience advanced limiting class III/IV symptoms than the 324 patients with outflow obstruction (1.6%/year vs. 7.4%/year rest obstruction vs. 3.2%/year provocable obstruction; p < 0.001). However, 7 nonobstructive patients (2.8%) did require heart transplantation for progression to end stage versus none of the obstructive patients. HCM-related mortality among nonobstructive patients was low (n = 8; 0.5%/year), with 5- and 10-year survival rates of 99% and 97%, respectively, which is not different from expected all-cause mortality in an age- and sex-matched U.S. population (p = 0.15). HCM patients with nonobstructive disease appear to experience a relatively benign clinical course, associated with a low risk for advanced heart failure symptoms, other disease complications, and HCM-related mortality, and

  1. Determinants of myocardial energetics and efficiency in symptomatic hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Timmer, Stefan A.J.; Germans, Tjeerd; Goette, Marco J.W.; Ruessel, Iris K.; Dijkmans, Pieter A.; Knaapen, Paul; Rossum, Albert C. van [VU University Medical Center, Department of Cardiology, 5F, Amsterdam (Netherlands); Lubberink, Mark; Lammertsma, Adriaan A. [VU University Medical Center, Department of Nuclear Medicine and PET Research, Amsterdam (Netherlands); Berg, Jurrien M. ten [St. Antonius Hospital, Department of Cardiology, Nieuwegein (Netherlands); Cate, Folkert J. ten [Thoraxcenter Erasmus Medical Center, Department of Cardiology, Rotterdam (Netherlands)

    2010-04-15

    Next to hypertrophy, hypertrophic cardiomyopathy (HCM) is characterized by alterations in myocardial energetics. A small number of studies have shown that myocardial external efficiency (MEE), defined by external work (EW) in relation to myocardial oxidative metabolism (MVO{sub 2}), is reduced. The present study was conducted to identify determinants of MEE in patients with HCM by use of dynamic positron emission tomography (PET) and cardiovascular magnetic resonance imaging (CMR). Twenty patients with HCM (12 men, mean age: 55.2 {+-} 13.9 years) and 11 healthy controls (7 men, mean age: 48.1 {+-} 10 years) were studied with [{sup 11}C]acetate PET to assess MVO{sub 2}. CMR was performed to determine left ventricular (LV) volumes and mass (LVM). Univariate and multivariate analyses were employed to determine independent predictors of myocardial efficiency. Between study groups, MVO{sub 2} (controls: 0.12 {+-} 0.04 ml.min{sup -1}.g{sup -1}, HCM: 0.13 {+-} 0.05 ml.min{sup -1}.g{sup -1}, p = 0.64) and EW (controls: 9,139 {+-} 2,484 mmHg.ml, HCM: 9,368 {+-} 2,907 mmHg.ml, p = 0.83) were comparable, whereas LVM was significantly higher (controls: 99 {+-} 21 g, HCM: 200 {+-} 76 g, p < 0.001) and MEE was decreased in HCM patients (controls: 35 {+-} 8%, HCM: 21 {+-} 10%, p < 0.001). MEE was related to stroke volume (SV), LV outflow tract gradient, NH{sub 2}-terminal pro-brain natriuretic peptide (NT-proBNP) and serum free fatty acid levels (all p < 0.05). Multivariate analysis revealed that SV (ss = 0.74, p < 0.001) and LVM (ss = -0.43, p = 0.013) were independently related to MEE. HCM is characterized by unaltered MVO{sub 2}, impaired EW generation per gram of myocardial tissue and subsequent deteriorated myocardial efficiency. Mechanical external efficiency could independently be predicted by SV and LVM. (orig.)

  2. Comparison Between Clinical and Echocardiographic Findings in Infants and Children Diagnosed with Hypertrophic Cardiomyopathy

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    Cristina Blesneac

    2015-06-01

    Full Text Available Background: Hypertrophic cardiomyopathy is a rather common hereditary disease with an autozomal dominant character, caused by mutations of genes that code for proteins of the cardiac sarcomere. The observed prevalence of this disease is much lower in pediatric patients compared to adults, because it’s late gene expression. Hypertrophic cardiomyopathy presenting in infancy has been shown to have a very high mortality.

  3. The Comparision of Left Atrial Functions Between Hypertrophic Cardiomyopathy and Hypertension

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    Ahmet Akdi

    2016-12-01

    Full Text Available INTRODUCTION: The presence of left ventricule hypertrophy (LVH due to arterial hypertension may impair atrial function. Also, hypertrophic cardiomyopathy (HCM represents a generalized myopathic process affecting both ventricular and atrial myocardium. In this study we aimed to evaluate left atrial volumes, phasic functions in hypertrophic cardiomyopathy and hypertensive heart disease. METHODS: The study consisted of 42 patients (25 men, 17 women; mean age 51.2 years with hypertrophic cardiomyopathy (n = 20 or hypertensive heart disease (n = 22. Two-dimensional echocardiographic left atrial volumes (maximal, minimal and pre-contraction volumes were obtained and left atrial phasic functions (reservoir, conduit, and pumping functions were calculated. The findings were compared with those of age- and sex-matched 20 controls (9 men, 11 women; mean age 44.2 years without structural heart disease. RESULTS: Left atrial volumes were found to be significantly increased in patients with hypertrophic cardiomyopathy and hypertensive heart disease compared with control groups. Left atrial reservoir and conduit functions were significantly lower in patients with hypertrophic cardiomyopathy than in those with hypertensive heart disease and control groups (p < 0.01 and p < 0.01, respectively. There was no significant difference of left atrial pumping functions between study groups (p = 0.2. DISCUSSION AND CONCLUSION: This study showed that left atrial minimal, maximal and pre-contraction volume indexes are increased in hypertensive and hypertrophic cardiomyopathy groups compared with control group, but there was no significant difference between hypertrophic cardiomyopathy and hypertensive patients. In hypertrophic cardiomyopathy group left atrial phasic functions, including conduit, reservoir and pump, were decreased significantly more than hypertensive and control group. In hypertensive patients left atrial phasic functions were decreased but compared with

  4. Outcome of Alcohol Septal Ablation in Mildly Symptomatic Patients With Hypertrophic Obstructive Cardiomyopathy

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    Veselka, Josef; Faber, Lothar; Liebregts, Max

    2017-01-01

    BACKGROUND: The long-term efficacy and safety of alcohol septal ablation (ASA) in patients with highly symptomatic hypertrophic obstructive cardiomyopathy has been demonstrated. The aim of this study was to evaluate the long-term outcomes of mildly symptomatic patients with hypertrophic obstructive...

  5. Lack of Phenotypic Differences by Cardiovascular Magnetic Resonance Imaging in MYH7 (β-Myosin Heavy Chain)- Versus MYBPC3 (Myosin-Binding Protein C)-Related Hypertrophic Cardiomyopathy.

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    Weissler-Snir, Adaya; Hindieh, Waseem; Gruner, Christiane; Fourey, Dana; Appelbaum, Evan; Rowin, Ethan; Care, Melanie; Lesser, John R; Haas, Tammy S; Udelson, James E; Manning, Warren J; Olivotto, Iacopo; Tomberli, Benedetta; Maron, Barry J; Maron, Martin S; Crean, Andrew M; Rakowski, Harry; Chan, Raymond H

    2017-02-01

    The 2 most commonly affected genes in hypertrophic cardiomyopathy (HCM) are MYH7 (β-myosin heavy chain) and MYBPC3 (β-myosin-binding protein C). Phenotypic differences between patients with mutations in these 2 genes have been inconsistent. Scarce data exist on the genotype-phenotype association as assessed by tomographic imaging using cardiac magnetic resonance imaging. Cardiac magnetic resonance imaging was performed on 358 consecutive genotyped hypertrophic cardiomyopathy probands at 5 tertiary hypertrophic cardiomyopathy centers. Genetic testing revealed a pathogenic mutation in 159 patients (44.4%). The most common genes identified were MYH7 (n=53) and MYBPC3 (n=75); 33.1% and 47% of genopositive patients, respectively. Phenotypic characteristics by cardiac magnetic resonance imaging of these 2 groups were similar, including left ventricular volumes, mass, maximal wall thickness, morphology, left atrial volume, and mitral valve leaflet lengths (all P=non-significant). The presence of late gadolinium enhancement (65% versus 64%; P=0.99) and the proportion of total left ventricular mass (%late gadolinium enhancement; 10.4±13.2% versus 8.5±8.5%; P=0.44) were also similar. This multicenter multinational study shows lack of phenotypic differences between MYH7- and MYBPC3-associated hypertrophic cardiomyopathy when assessed by cardiac magnetic resonance imaging. Postmutational mechanisms appear more relevant to thick-filament disease expression and outcome than the disease-causing variant per se. © 2017 American Heart Association, Inc.

  6. Investigation of global and regional myocardial mechanics with 3-dimensional speckle tracking echocardiography and relations to hypertrophy and fibrosis in hypertrophic cardiomyopathy.

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    Urbano-Moral, Jose Angel; Rowin, Ethan J; Maron, Martin S; Crean, Andrew; Pandian, Natesa G

    2014-01-01

    In hypertrophic cardiomyopathy (HCM), heterogeneous myocardial hypertrophy and fibrosis are responsible for abnormalities of left ventricular (LV) function. We aimed to characterize LV global and regional myocardial mechanics in HCM, according to segmental hypertrophy and fibrosis. Fifty-nine patients with HCM underwent standard echocardiography, 3-dimensional speckle tracking echocardiography, and cardiac magnetic resonance with late gadolinium enhancement (LGE); all 3 tests were <24 hours apart. Longitudinal, circumferential, and area strains were investigated according to the extent of LGE (no LGE, LGE<10%, and LGE≥10%), segmental thickness (≥15 versus <15 mm), and segmental LGE (LGE versus non-LGE). Attenuated global longitudinal strain showed association with extent of hypertrophy (indexed LV mass, r=0.32, P=0.01; maximum LV wall thickness, r=0.34, P=0.009; number of segments≥15 mm, r=0.44, P<0.001), whereas enhanced global circumferential strain was correlated to LV global functional parameters (indexed end-systolic volume, r=0.47, P<0.001; ejection fraction, r=-0.75, P<0.001). Parameters of global myocardial mechanics showed no association with the extent of LGE; in contrast, the extent of LGE was associated with the extent of hypertrophy. All 3 deformation parameters were attenuated both in segments≥15 mm in thickness and in those with LGE; adjusted analysis demonstrated that segmental presence of LGE was associated with additional attenuation in myocardial deformation. Both hypertrophy and fibrosis contribute to regional impairment of myocardial shortening in HCM. The extent of hypertrophy is the primary factor altering global myocardial mechanics. Circumferential myocardial shortening seems to be directly involved in preservation of LV systolic performance in HCM.

  7. Diastolic filling in a physical model of obstructive hypertrophic cardiomyopathy

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    Schovanec, Joseph; Samaee, Milad; Lai, Hong Kuan; Santhanakrishnan, Arvind

    2015-11-01

    Hypertrophic Cardiomyopathy (HCM) is an inherited heart disease that affects as much as one in 500 individuals, and is the most common cause of sudden death in young athletes. The myocardium becomes abnormally thick in HCM and deforms the internal geometry of the left ventricle (LV). Previous studies have shown that a vortex is formed during diastolic filling, and further that the dilated LV morphology seen in systolic heart failure results in altering the filling vortex from elliptical to spherical shape. We have also previously shown that increasing LV wall stiffness decreases the filling vortex circulation. However, alterations to intraventricular filling fluid dynamics due to an obstructive LV morphology and locally elevated wall stiffness (in the hypertrophied region) have not been previously examined from a mechanistic standpoint. We conducted an experimental study using an idealized HCM physical model and compared the intraventricular flow fields obtained from 2D PIV to a baseline LV physical model with lower wall stiffness and anatomical geometry. The obstruction in the HCM model leads to earlier breakdown of the filling vortex as compared to the anatomical LV. Intraventricular filling in both models under increased heart rates will be discussed.

  8. The diagnosis of hypertrophic cardiomyopathy by cardiovascular magnetic resonance

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    2012-01-01

    Hypertrophic cardiomyopathy (HCM) is the most common genetic disease of the heart. HCM is characterized by a wide range of clinical expression, ranging from asymptomatic mutation carriers to sudden cardiac death as the first manifestation of the disease. Over 1000 mutations have been identified, classically in genes encoding sarcomeric proteins. Noninvasive imaging is central to the diagnosis of HCM and cardiovascular magnetic resonance (CMR) is increasingly used to characterize morphologic, functional and tissue abnormalities associated with HCM. The purpose of this review is to provide an overview of the clinical, pathological and imaging features relevant to understanding the diagnosis of HCM. The early and overt phenotypic expression of disease that may be identified by CMR is reviewed. Diastolic dysfunction may be an early marker of the disease, present in mutation carriers prior to the development of left ventricular hypertrophy (LVH). Late gadolinium enhancement by CMR is present in approximately 60% of HCM patients with LVH and may provide novel information regarding risk stratification in HCM. It is likely that integrating genetic advances with enhanced phenotypic characterization of HCM with novel CMR techniques will importantly improve our understanding of this complex disease. PMID:22348519

  9. Hypertrophic Obstructive Cardiomyopathy: Surgical Myectomy and Septal Ablation.

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    Nishimura, Rick A; Seggewiss, Hubert; Schaff, Hartzell V

    2017-09-15

    Hypertrophic cardiomyopathy is a genetic disorder characterized by marked hypertrophy of the myocardium. It is frequently accompanied by dynamic left ventricular outflow tract obstruction and symptoms of dyspnea, angina, and syncope. The initial therapy for symptomatic patients with obstruction is medical therapy with β-blockers and calcium antagonists. However, there remain a subset of patients who have continued severe symptoms, which are unresponsive to medical therapy. These patients can be treated with septal reduction therapy, either surgical septal myectomy or alcohol septal ablation. When performed by experienced operators working in high-volume centers, septal myectomy is highly effective with a >90% relief of obstruction and improvement in symptoms. The perioperative mortality rate for isolated septal myectomy in most centers is <1%. Alcohol septal ablation is a less invasive treatment. In many patients, the hemodynamic and clinical results are comparable to that of septal myectomy. However, the results of alcohol septal ablation are dependent on the septal perforator artery supplying the area of the contact between the hypertrophied septum and the anterior leaflet of the mitral valve. There are some patients, particularly younger patients with severe hypertrophy, who do not uniformly experience complete relief of obstruction and symptoms. Both techniques of septal reduction therapy are highly operator dependent. The final decision as to which approach should be selected in any given patient is dependent up patient preference and the availability and experience of the operator and institution at which the patient is being treated. © 2017 American Heart Association, Inc.

  10. Cardiac troponin C-L29Q, related to hypertrophic cardiomyopathy, hinders the transduction of the protein kinase A dependent phosphorylation signal from cardiac troponin I to C.

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    Schmidtmann, Anja; Lindow, Christopher; Villard, Sylvie; Heuser, Arnd; Mügge, Andreas; Gessner, Reinhard; Granier, Claude; Jaquet, Kornelia

    2005-12-01

    We investigated structural and functional aspects of the first mutation in TNNC1, coding for the calcium-binding subunit (cTnC) of cardiac troponin, which was detected in a patient with hypertrophic cardiomyopathy [ Hoffmann B, Schmidt-Traub H, Perrot A, Osterziel KJ & Gessner R (2001) Hum Mut17, 524]. This mutation leads to a leucine-glutamine exchange at position 29 in the nonfunctional calcium-binding site of cTnC. Interestingly, the mutation is located in a putative interaction site for the nonphosphorylated N-terminal arm of cardiac troponin I (cTnI) [ Finley NL, Abbott MB, Abusamhadneh E, Gaponenko V, Dong W, Seabrook G, Howarth JW, Rana M, Solaro RJ, Cheung HC et al. (1999) EJB Lett453, 107-112]. According to peptide array experiments, the nonphosphorylated cTnI arm interacts with cTnC around L29. This interaction is almost abolished by L29Q, as observed upon protein kinase A-dependent phosphorylation of cTnI at serine 22 and serine 23 in wild-type troponin. With CD spectroscopy, minor changes are observed in the backbone of Ca2+-free and Ca2+-saturated cTnC upon the L29Q replacement. A small, but significant, reduction in calcium sensitivity was detected upon measuring the Ca2+-dependent actomyosin subfragment 1 (actoS1)-ATPase activity and the sliding velocity of thin filaments. The maximum actoS1-ATPase activity, but not the maximum sliding velocity, was significantly enhanced. In addition, we performed our investigations at different levels of protein kinase A-dependent phosphorylation of cTnI. The in vitro assays mainly showed that the Ca2+ sensitivity of the actoS1-ATPase activity, and the mean sliding velocity of thin filaments, were no longer affected by protein kinase A-dependent phosphorylation of cTnI owing to the L29Q exchange in cTnC. The findings imply a hindered transduction of the phosphorylation signal from cTnI to cTnC.

  11. Determining pathogenicity of genetic variants in hypertrophic cardiomyopathy: importance of periodic reassessment.

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    Das K, Jipin; Ingles, Jodie; Bagnall, Richard D; Semsarian, Christopher

    2014-04-01

    Major advances have been made in our understanding and clinical application of genetic testing in hypertrophic cardiomyopathy. Determining pathogenicity of a single-nucleotide variant remains a major clinical challenge. This study sought to reassess single-nucleotide variant classification in hypertrophic cardiomyopathy probands. Consecutive probands with hypertrophic cardiomyopathy with a reported pathogenic mutation or variation of uncertain significance were included. Family and medical history were obtained. Each single-nucleotide variant was reassessed by a panel of four reviewers for pathogenicity based on established criteria together with updated cosegregation data and current population-based allele frequencies. From 2000 to 2012, a total of 136 unrelated hypertrophic cardiomyopathy probands had genetic testing, of which 63 (46%) carried at least one pathogenic mutation. MYBPC3 (n = 34; 47%) and MYH7 (n = 23; 32%) gene variants together accounted for 79%. Five variants in six probands (10%) were reclassified: two variation of uncertain significance were upgraded to pathogenic, one variation of uncertain significance and one pathogenic variant were downgraded to benign, and one pathogenic variant (found in two families) was downgraded to variation of uncertain significance. None of the reclassifications had any adverse clinical consequences. Given the rapid growth of genetic information available in both disease and normal populations, periodic reassessment of single-nucleotide variant data is essential in hypertrophic cardiomyopathy.

  12. Hypertrophic cardiomyopathy in pompe disease is not limited to the classic infantile-onset phenotype.

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    Lee, Dong-Hwan; Qiu, Wen-Juan; Lee, Jeongho; Chien, Yin-Hsiu; Hwu, Wuh-Liang

    2014-01-01

    Pompe disease is a genetic disorder caused by a deficiency of acid α-glucosidase (GAA). Patients with classic infantile-onset Pompe disease usually present with hypertrophic cardiomyopathy and die before 1 year of age, if not treated with enzyme replacement therapy (ERT). In comparison, patients with late-onset Pompe disease typically do not have hypertrophic cardiomyopathy. However, here we describe five patients who presented with hypertrophic cardiomyopathy but did not fit the criteria of classic infantile-onset Pompe disease. Their ages at diagnosis of cardiomyopathy were 1 month in two patients following detection of an audible cardiac murmur and 2-3 years in the three remaining patients. All patients survived for 5-8 years without ERT. Three patients died before the advent of ERT from causes other than congestive heart failure. One patient had a good response to ERT starting at 5 years of age. The sibling of one patient, who did not receive ERT and died at age seven, was diagnosed prenatally. At 3 months of age, the sibling had hypertrophic cardiomyopathy, and a muscle biopsy at that time revealed glycogen accumulation.This case series demonstrates that Pompe disease is a continuum of disease, and the development of cardiomyopathy is not limited to classic infantile-onset Pompe disease. These patients do not fit into the discrete phenotypes of infantile- or late-onset Pompe disease, which may suggest reconsidering the nomenclature of Pompe disease.

  13. Exercise Tl-201 myocardial scintigraphy and coronary blood flow velocity in patients with hypertrophic cardiomyopathy

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    Sugihara, Hiroki; Umamoto, Ikuo; Harada, Yoshiaki (Kyoto Prefectural Univ. of Medicine (Japan)) (and others)

    1992-03-01

    In 22 patients with hypertrophic cardiomyopathy not associated with coronary stenosis, findings of exercise Tl-201 myocardial scintigraphy were reviewed in relation to coronary blood flow velocity. Blood flow velocity of the left antero-inferior segment was recorded by using a Doppler catheter. From time velocity integration in systolic and diastolic phases, both % systolic fraction (%SF) and %diastolic 1st third fraction (%d1F) were obtained. A decreased perfusion was visually assessed on exercise Tl-201 myocardial images. In addition, transient dilation of the left ventricular cavity was quantitatively assessed by expressing it as a transient dilation index (TDI) for subendocardial ischemia. Coronary blood flow velocity was characterized by a decrease in both %SF and %d1F and negative systolic flow. Both %SF and %d1F were inversely correlated with TDI. Coronary negative systolic flow was frequently associated with a decreased perfusion. These results suggest factors such as left ventricular relaxation impairment, other than coronary small vessel lesions, may also be involved in the occurrence of myocardial ischemia in hypertrophic cardiomyopathy. (N.K.).

  14. Long-term outcome of percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy: a Scandinavian multicenter study

    DEFF Research Database (Denmark)

    Jensen, Morten Kvistholm; Almaas, Vibeke Marie; Jacobsson, Linda

    2011-01-01

    Single-center reports on percutaneous transluminal septal myocardial ablation (PTSMA) in patients with hypertrophic obstructive cardiomyopathy have shown considerable differences in outcome.......Single-center reports on percutaneous transluminal septal myocardial ablation (PTSMA) in patients with hypertrophic obstructive cardiomyopathy have shown considerable differences in outcome....

  15. The clinical features, outcomes and genetic characteristics of hypertrophic cardiomyopathy patients with severe right ventricular hypertrophy.

    Directory of Open Access Journals (Sweden)

    Xiying Guo

    Full Text Available Severe right ventricular hypertrophy (SRVH is a rare phenotype in hypertrophic cardiomyopathy (HCM for which limited information is available. This study was undertaken to investigate the clinical, prognostic and genetic characteristics of HCM patients with SRVH.HCM with SRVH was defined as HCM with a maximum right ventricular wall thickness ≥10 mm. Whole-genome sequencing (WGS was performed in HCM patients with SRVH. Multivariate Cox proportional hazards regression models were used to identify risk factors for cardiac death and events in HCM with SRVH. Patients with apical hypertrophic cardiomyopathy (ApHCM were selected as a comparison group. The clinical features and outcomes of 34 HCM patients with SRVH and 273 ApHCM patients were compared.Compared with the ApHCM group, the HCM with SRVH group included younger patients and a higher proportion of female patients and also displayed higher cardiovascular morbidity and mortality. The multivariate Cox proportional hazards regression models identified 2 independent predictors of cardiovascular death in HCM patients with SRVH, a New York Heart Association class ≥III (hazard ratio [HR] = 8.7, 95% confidence interval (CI: 1.43-52.87, p = 0.019 and an age at the time of HCM diagnosis ≤18 (HR = 5.5, 95% CI: 1.24-28.36, p = 0.026. Among the 11 HCM patients with SRVH who underwent WGS, 10 (90.9% were identified as carriers of at least one specific sarcomere gene mutation. MYH7 and TTN mutations were the most common sarcomere mutations noted in this study. Two or more HCM-related gene mutations were observed in 9 (82% patients, and mutations in either other cardiomyopathy-related genes or ion-channel disease-related genes were found in 8 (73% patients.HCM patients with SRVH were characterized by poor clinical outcomes and the presentation of multiple gene mutations.

  16. Epidemiology of cardiomyopathy - A clinical and genetic study of hypertrophic cardiomyopathy: The EPOCH-H study

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    Amitabh Biswas

    2015-01-01

    Full Text Available Background: Hypertrophic cardiomyopathy (HCM is a genetic disorder with the prevalence of 1 in 500 globally. HCM is clinically characterized by thickening of the wall of the heart, predominantly left ventricle (LV, and interventricular septum (IVS. Our study aims to report the demographical, clinical and genetic profile of Indian HCM patients. Methods: HCM patients were recruited on the basis of WHO criteria. The clinical phenotypes were analyzed using electrocardiography, two-dimensional electrocardiography, and hotspot region of the MYH7 gene was sequenced for all patients as well as for controls. Results: There were 59 patients with a clinical diagnosis of HCM with a preponderance of disease in males with a ratio (men, women of 5.5:1. Average age of onset of the disease was late 30 s (39.2 ± 14.5 with familial HCM accounting for 18% (n = 9 for total HCM families (n = 50. Nonobstructive kind of HCM was more prevalent as compared to obstructive HCM (66.1% vs. 33.9%. Average posterior wall LV thickness of the HCM patients was 16 ± 4.8 mm and IVS thickness was 21 ± 8.3 mm with familial patients having greater wall thickness as compared to sporadic patients. Sequencing of hotspot region of MYH7 identified three mutations in three different patients. Two mutations were found to be segregating in familial cases. Conclusion: HCM is more prevalent in males with a predominance of hypertrophic nonobstructive cardiomyopathy form. Eighteen percent of cases were familial and showed an early onset of the disease and worse prognosis as compared to sporadic cases. Hotspot sequencing of MYH7 only explains 6% of its genetic basis. More of the candidate genes need to be screened through advanced techniques like next generation sequencing to identify the causal genes which could make us understand the mechanistic pathways.

  17. Successful management of hypertrophic cardiomyopathy in a Matschie's tree kangaroo (Dendrolagus matschiei).

    Science.gov (United States)

    Fredholm, Daniel V; Jones, Ashley E; Hall, Natalie H; Russell, Kathleen; Heard, Darryl J

    2015-03-01

    A 3-yr-old, intact male Matschie's tree kangaroo (Dendrolagus matschiei) was examined for a 1-wk history of intermittent lethargy and tachypnea. An echocardiogram revealed concentric hypertrophy of the left ventricular free wall and interventricular septum. These findings were compared to measurements from healthy Matschie's tree kangaroos, supporting a diagnosis of hypertrophic cardiomyopathy. At the time of publication, the patient has been managed for over 11.5 yr, using a combination of enalapril, furosemide, diltiazem, and diet modifications. Hypertrophic cardiomyopathy should be considered as a differential diagnosis in tree kangaroos exhibiting signs of cardiovascular or respiratory distress. This case represents the first report of antemortem diagnosis and successful management of hypertrophic cardiomyopathy in a Matschie's tree kangaroo.

  18. Outcome of alcohol septal ablation in mildly symptomatic patients with hypertrophic obstructive cardiomyopathy

    DEFF Research Database (Denmark)

    Veselka, Josef; Faber, Lothar; Liebregts, Max

    2017-01-01

    Background- The long-term efficacy and safety of alcohol septal ablation (ASA) in patients with highly symptomatic hypertrophic obstructive cardiomyopathy has been demonstrated. The aim of this study was to evaluate the long-term outcomes of mildly symptomatic patients with hypertrophic obstructive......, and III at the last clinical checkup, respectively. Conclusions- Mildly symptomatic hypertrophic obstructive cardiomyopathy patients treated with ASA had sustained symptomatic and hemodynamic relief with a low risk of developing severe heart failure. Their survival is comparable to the general population....... cardiomyopathy treated with ASA. Methods and Results- We retrospectively evaluated consecutive patients enrolled in the Euro-ASA registry (1427 patients) and identified 161 patients (53±13 years; 27% women) who were mildly symptomatic (New York Heart Association [NYHA] class II) pre-ASA. The median...

  19. Ventricular arrhythmias and left ventricular hypertrophy in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Piva e Mattos, Beatriz; Torres, Marco Antonio Rodrigues; Freitas, Valéria Centeno de; Scolari, Fernando Luís; Loreto, Melina Silva de

    2013-05-01

    In hypertrophic cardiomyopathy (HCM), the degree of left ventricular hypertrophy (LVH) could influence the development of ventricular arrhythmias. In HCM, analyze the association between the occurrence of ventricular arrhythmias determined by Holter electrocardiogram (ECG-Holter) and the degree of LVH determined by maximum wall thickness (MWT) in echocardiography and body mass index (BMI). Fifty-four consecutive patients with HCM underwent 24-hour ECG-Holter and echocardiography for assessment of level of LVH through MWT and BMI. Two levels were established for the occurrence of Ventricular Arrhythmias: I - alone or paired extrasystoles and II - Non- Sustained Ventricular Tachycardia (NSVT). In 13 patients (24%) with NSVT (level II), there was a higher frequency of MWT of the left ventricle (LV) > 21 mm (n = 10, 77%, 25 ± 4 mm) and LLLV = 144 g/m² (n = 10, 77%, 200 ± 30 g/m²), in comparison with those presenting with extrasystole arrhythmias (level I) (n = 41, 76%), in which these measures were identified in, respectively, 37 % (n= 15, 23 ± 1 mm), p = 0.023, and 39% (n = 16, 192 ± 53 g / m²) of the cases (p = 0.026). The cut-off values mentioned were determined by the ROC curve with a confidence interval of 95%. NSVT was more common in patients with MWTLV > 21 mm and LLLV > 144 g/m² (8 of 13, 62%) than in those with (4 of 13, 31%) or without (1 of 13; 8%) echocardiographic variables above cut-off values (p = 0.04). In HCM, occurrence of ventricular arrhythmias by Holter was associated with the degree of LVH assessed by echocardiography through MWT and BMI.

  20. Sudden death during empiric amiodarone therapy in symptomatic hypertrophic cardiomyopathy.

    Science.gov (United States)

    Fananapazir, L; Leon, M B; Bonow, R O; Tracy, C M; Cannon, R O; Epstein, S E

    1991-01-15

    Amiodarone is reported to improve symptoms and to prevent sudden death in patients with hypertrophic cardiomyopathy (HC). Amiodarone treatment (loading dose 30 g given over 6 weeks; maintenance dose 400 mg/day) was prospectively evaluated in 50 patients with HC in whom the drug was initiated because of symptoms refractory to conventional drug therapy (calcium antagonists and beta blockers). Twenty-one (42%) patients had ventricular tachycardia (VT) during Holter monitoring. Amiodarone significantly and often markedly improved the patients' New York Heart Association functional class status (from 3.3 to 2.7 at 2 months, p less than 0.001) and treadmill exercise duration (p less than 0.001). Eight patients, however, died (7 suddenly) during a mean follow-up period of 2.2 +/- 1.8 years. Of the 7 sudden deaths, 6 occurred within 5 months of initiation of treatment. The 6-month and 1- and 2-year survival rates were 87, 85 and 80%, respectively. The survival rate of patients with VT was significantly worse than that of patients without VT (61 vs 97% at 2 years; p less than 0.01). Sudden death occurred despite abolition of VT on Holter monitoring. Amiodarone increased left ventricular peak filling rate by radionuclide angiography in 20 of 33 patients (61%) (p less than 0.01). Decrease in peak left ventricular filling rate within 10 days of amiodarone therapy (8 of 33 patients) was associated with subsequent sudden death (p less than 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Hypertrophic cardiomyopathy with aortic dilation: a novel observation.

    Science.gov (United States)

    Yousefzai, Rayan; Agarwal, Anushree; Fuad Jan, M; Cho, Chi; Anigbogu, Michael; Shetabi, Kambiz; Singh, Maharaj; Bush, Michelle; Treiber, Shannon; Port, Steven; Ammar, Khawaja Afzal; Paterick, Timothy E; Jain, Renuka; Khandheria, Bijoy K; Jamil Tajik, A

    2017-12-01

    Our goal was to identify the prevalence of aortic dilation in patients with hypertrophic cardiomyopathy (HCM), the most prevalent (0.2%) heritable, genetic cardiovascular disease. Aortic dilation also represents a spectrum of familial inheritance. However, data regarding the prevalence of aortic dilation in HCM patients is lacking. This is an observational retrospective study of all patients referred to our HCM centre. Aortic dilation was defined based on recent American Society of Echocardiography and European Association of Cardiovascular Imaging published guidelines. Of the 201 HCM patients seen between Jan. 1, 2011 and March 31, 2014, 18 (9.0%) met the definition of aortic dilation. Mean age was 56.3 ± 9.3 years, 77.8% were male, mean ascending aorta diameter was 4.0 ± 0.4 cm in males and 3.8 ± 0.2 cm in females, mean sinuses of Valsalva diameter was 4.2 ± 0.2 cm in males and 3.8 ± 0.4 cm in females, and 13 (72.2%) had left ventricular outflow tract obstruction. HCM patients with dilated aorta were more likely males, less likely hypertensive and had larger left ventricle diameter and more aortic valve regurgitation; remaining characteristics were similar. We report a novel observation with 9.0% prevalance of dilated aorta in HCM patients. Further studies are needed to help define the genetic and pathophysiologic basis as well as the clinical implications of this association in a larger group of HCM patients.

  2. [Sigmoid septum: A variant of the ventricular hypertrophy or of the hypertrophic cardiomyopathy?].

    Science.gov (United States)

    Gentille-Lorente, Delicia; Salvadó-Usach, Teresa

    2016-01-01

    Sigmoid septum and hypertrophic cardiomyopathy presenting with left ventricular hypertrophy and, although they appear to be different entities, often involve problems in the differential diagnosis. This study was carried out to assess the prevalence and characteristics of the echocardiographic sigmoid septum and its differential findings regarding hypertrophic cardiomyopathy. Descriptive, observational and prospective study. A total of 1,770 patients were studied by echocardiography. Sigmoid septum (focal and isolated hypertrophy of the basal interventricular septum≥13mm in men and ≥12mm in women, exceeding ≥50% of the median septum thickness) was classified as «Type 1» (≤14mm) and «Type 2» (≥15mm). There were 59 cases of sigmoid septum (prevalence of 3.3%): 26 (1.5%) patients with type 1 (50% male) and 33 (1.9%) patients with type 2 (72.7% male); there were 25 (1.4%) cases of hypertrophic cardiomyopathy (76% male). The group with type 2 sigmoid septum differed from hypertrophic cardiomyopathy in: was older (73±10.5years; Phypertrophic cardiomyopathy, patients with type 2 sigmoid septum are older and generally hypertensive; otherwise, often they have no clear differences in their clinical, electrocardiographic or echocardiographic characteristics. Therefore, cardiac resonance is helpful in the differential diagnosis. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  3. Asymmetric left ventricular hypertrophy associated with morbid obesity mimicking familial hypertrophic cardiomyopathy.

    Science.gov (United States)

    Wong, Raymond Ching-Chiew; Tan, Kong Bing

    2014-12-01

    Asymmetric septal hypertrophy with systolic anterior motion of the mitral valve is frequently a phenotypic, but not pathognomonic, expression of genetic hypertrophic cardiomyopathy (HCM) with or without obstruction. It can, however, be associated nonspecifically with other forms of increased left ventricular (LV) afterload. We herein report the case of a young man with obesity cardiomyopathy and heart failure who presented with asymmetric septal hypertrophy and marked LV hypertrophy, and endomyocardial biopsy ruled out genetic HCM.

  4. Late enhancement of the left ventricular myocardium in young patients with hypertrophic cardiomyopathy by electron beam computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kurosaki, Kenichi; Yoshibayashi, Muneo; Tsukano, Shinya; Ono, Yasuo; Arakaki, Yoshio; Naito, Hiroaki; Echigo, Shigeyuki [National Cardiovascular Center, Suita, Osaka (Japan)

    2001-05-01

    In the assessment of myocardial characteristics with computed tomography, late enhancement (intense stain in delayed phase image of contrast enhancement) is an abnormal finding and thought to represent fibrotic change. The purpose of this study was to investigate the clinical importance of late enhancement in young patients with hypertrophic cardiomyopathy. Forty-five patients with hypertrophic cardiomyopathy, aged 1 to 24 years, were examined by electron beam computed tomography. We also assessed the clinical data on these patients. Late enhancement was found in 29 (64%) patients, usually as a patchy, stained area in the myocardium. In 29 patients with late enhancement, seven (24%) has syncopal episode and seven (24%) had a family history of sudden death. In contrast, none (0%) of 16 patients without late enhancement had syncopal episode nor a family history of sudden death (p<0.05). Twenty-four hour electrocardiographic monitoring was performed for 31 patients. Al patients with ventricular tachycardia were in the group with late enhancement [10/23 (43%) vs 0/8 (0%), p<0.05]. Thirty-seven patients were examined by thallium scintigraphy. The perfusion defect was more frequently found in patients with late enhancement than in patients without [14/26 (54%) vs 2/11 (18%), p<0.05]. These data suggest that late enhancement shown with electron beam computed tomography is related to syncopal episode, family history of sudden death, ventricular tachycardia, and myocardial damage in young patients with hypertrophic cardiomyopathy. (author)

  5. The effects of candesartan on left ventricular hypertrophy and function in nonobstructive hypertrophic cardiomyopathy: a pilot, randomized study.

    Science.gov (United States)

    Penicka, Martin; Gregor, Pavel; Kerekes, Roman; Marek, Dan; Curila, Karol; Krupicka, Jiri

    2009-01-01

    Hypertrophic cardiomyopathy is caused by mutations in the genes that encode sarcomeric proteins and is primarily characterized by unexplained left ventricular hypertrophy, impaired cardiac function, reduced exercise tolerance, and a relatively high incidence of sudden cardiac death, especially in the young. The extent of left ventricular hypertrophy is one of the major determinants of disease prognosis. Angiotensin II has trophic effects on the heart and plays an important role in the development of myocardial hypertrophy. Here in a double-blind, placebo-controlled, randomized study, we show that the long-term administration of the angiotensin II type 1 receptor antagonist candesartan in patients with hypertrophic cardiomyopathy was associated with the significant regression of left ventricular hypertrophy, improvement of left ventricular function, and exercise tolerance. The magnitude of the treatment effect was dependent on specific sarcomeric protein gene mutations that had the greatest responses on the carriers of ss-myosin heavy chain and cardiac myosin binding protein C gene mutations. These data indicate that modulating the role of angiotensin II in the development of hypertrophy is specific with respect to both the affected sarcomeric protein gene and the affected codon within that gene. Thus, angiotensin II type 1 receptor blockade has the potential to attenuate myocardial hypertrophy and may, therefore, provide a new treatment option to prevent sudden cardiac death in patients with hypertrophic cardiomyopathy.

  6. Myocardial glucose metabolism in patients with hypertrophic cardiomyopathy. Assessment by F-18-FDG PET study

    Energy Technology Data Exchange (ETDEWEB)

    Uehara, Toshiisa [Osaka Univ., Suita (Japan). Medical School; Ishida, Yoshio; Hayashida, Kohei [and others

    1998-04-01

    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)

  7. Psychosocial adjustment and quality of life in children undergoing screening in a specialist paediatric hypertrophic cardiomyopathy clinic.

    Science.gov (United States)

    Spanaki, Adriani; O'Curry, Sara; Winter-Beatty, Jasmine; Mead-Regan, Sarah; Hawkins, Kate; English, Jennifer; Head, Catherine; Ridout, Deborah; Tome-Esteban, Maria T; Elliott, Perry; Kaski, Juan P

    2016-06-01

    This study aimed to assess the psychological well-being and quality of life in children with hypertrophic cardiomyopathy and the potential psychosocial impact of screening. A total of 152 children (aged 3-18 years) attending a specialist paediatric hypertrophic cardiomyopathy clinic, and their parents completed the Generic Core Scales and Cardiac Module of the Paediatric Quality of Life Inventory (PedsQL) questionnaire as well as the Strengths and Difficulties Questionnaire; 21 patients (14%) had hypertrophic cardiomyopathy (group A); 23 children (15%) harboured hypertrophic cardiomyopathy-causing sarcomeric mutations with normal echocardiograms (group G); and 108 children (71%) had a family history of hypertrophic cardiomyopathy with normal investigations and attended for clinical cardiological screening (group S). In group A, mean PedsQLTM total scores reported by children and parents were lower than those reported by unaffected children (pchildren and parents were lower in children with hypertrophic cardiomyopathy compared with unaffected patients [mean child-reported total score 86.4 in group S versus 72.3 in group A (pChildren with hypertrophic cardiomyopathy have a significantly reduced quality of life. Importantly, Quality-of-Life scores among unaffected children attending for screening were not different compared with scores from a normative UK population.

  8. Echocardiographic strain imaging to assess early and late consequences of sarcomere mutations in hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Ho, Carolyn Y; Carlsen, Christian; Thune, Jens Jakob

    2009-01-01

    BACKGROUND: Genetic testing identifies sarcomere mutation carriers (G+) before clinical diagnosis of hypertrophic cardiomyopathy (HCM), allowing characterization of initial disease manifestations. Previous studies demonstrated that impaired relaxation develops before left ventricular hypertrophy...... to reshape the clinical paradigm for treatment, based on early diagnosis and disease prevention....

  9. Assessment of quantitative hypertrophy scores in hypertrophic cardiomyopathy : Magnetic resonance imaging versus echocardiography

    NARCIS (Netherlands)

    Posma, JL; Blanksma, PK; vanderWall, EE; Hamer, HPM; Mooyaart, EL; Lie, KI

    1996-01-01

    To compare the diagnostic value of spin-echo magnetic resonance (MR) imaging and transthoracic echocardiography in quantitative assessment of the extent of hypertrophy in patients with hypertrophic cardiomyopathy (HCM), we examined 52 consecutive patients with HCM. The Spirito-Maron and Wigle

  10. Hypertrophic cardiomyopathy family with double-heterozygous mutations; does disease severity suggest doubleheterozygosity?

    NARCIS (Netherlands)

    van Rijsingen, I. A. W.; Hermans-van Ast, J. F.; Arens, Y. H. J. M.; Schalla, S. M.; de Die-Smulders, C. E. M.; van den Wijngaard, A.; Pinto, Y. M.

    2009-01-01

    Background. With the improvement in genetic testing over time, double-heterozygous mutations are more often found by coincidence in families with hypertrophic cardiomyopathy (HCM). Double heterozygosity can be a cause of the wellknown clinical diversity within HCM families.Methods and results. We

  11. Heterogeneity of myocardial fluoro-18 2-deoxyglucose uptake in patients with apical hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Shiba, Nobuyuki; Kagaya, Yutaka; Ishide, Nobumasa [Tohoku Univ., Sendai (Japan). School of Medicine] [and others

    1997-03-01

    We have shown that myocardial glucose metabolism is heterogeneous in patients with hypertrophic cardiomyopathy. It is not known, however, whether glucose metabolism is impaired in patients with apical hypertrophic cardiomyopathy, which is fairly common in Japan. We studied 7 patients with apical hypertrophic cardiomyopathy and 5 normal subjects using fluoro-18 2-deoxyglucose (FDG) and positron emission tomography (PET). We calculated regional FDG fractional uptake and the inter-regional coefficient of variation (CV) of FDG fractional uptake in the interventricular septal, anteroapical, and posterolateral regions. The regional FDG fractional uptake was similar in the 2 groups and among the 3 different segments within each group. However, the inter-regional CV of FDG fractional uptake was increased in the anteroapical wall segment of the patient group compared with the control group and also with the other 2 regions in the patient group. The results did not differ when we studied another 5 patients and 6 normal control subjects with a PET scanner with higher spatial resolution. These data suggest that myocardial glucose metabolism may be impaired in the anteroapical wall segment of patients with apical hypertrophic cardiomyopathy. (author)

  12. Regression of outflow tract obstruction subsequent to treatment with verapamil in hypertrophic obstructive cardiomyopathy

    DEFF Research Database (Denmark)

    Frandsen, F; Mickley, H

    1990-01-01

    A 29-year-old man suffering from hypertrophic obstructive cardiomyopathy was treated with verapamil 240 mg daily for 4.5 years. During this period the symptoms were reduced, and an intraventricular gradient diminished from 80 to 20 mm Hg, possibly due to a decrease in left ventricular ejection fr...

  13. Systolic anterior motion of the tricuspid valve in a patient with hypertrophic obstructive cardiomyopathy

    NARCIS (Netherlands)

    Farag, Emile S.; Planken, R. Nils; Boekholdt, S. Matthijs; Kluin, Jolanda

    2017-01-01

    Hypertrophic cardiomyopathy is a heterogeneous myocardial disease and is characterized by increased left ventricular wall thickness. Left ventricular outflow tract obstruction occurs in up to 70% of patients and is often caused by systolic anterior motion of the mitral valve, a paradoxical

  14. Long-term clinical outcome after alcohol septal ablation for obstructive hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Veselka, Josef; Jensen, Morten Kvistholm; Liebregts, Max

    2016-01-01

    AIMS: The first cases of alcohol septal ablation (ASA) for obstructive hypertrophic cardiomyopathy (HCM) were published two decades ago. Although the outcomes of single-centre and national ASA registries have been published, the long-term survival and clinical outcome of the procedure are still...

  15. Cardiac troponin I degradation in serum of patients with hypertrophic obstructive cardiomyopathy undergoing percutaneous septal ablation

    DEFF Research Database (Denmark)

    Madsen, Lene H; Lund, Terje; Grieg, Zanina

    2009-01-01

    : percutaneous transluminal septal myocardial ablation (PTSMA) of hypertrophic obstructive cardiomyopathy (HOCM). Here the iatrogenic induction of myocardial necrosis occurs in vivo, allowing us to investigate degradation of cTnI by the second. METHODS: Blood samples were obtained from 8 patients with HOCM just...

  16. Electrocardiographic features of sarcomere mutation carriers with and without clinically overt hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Lakdawala, Neal K; Thune, Jens Jakob; Maron, Barry J

    2011-01-01

    In hypertrophic cardiomyopathy (HC), electrocardiographic (ECG) changes have been postulated to be an early marker of disease, detectable in sarcomere mutation carriers when left ventricular (LV) wall thickness is still normal. However, the ECG features of mutation carriers have not been fully...

  17. Familial hypertrophic cardiomyopathy: Functional effects of myosin mutation R723G in cardiomyocytes

    NARCIS (Netherlands)

    Kraft, T.; Witjas-Paalberends, E.R.; Boontje, N.; Tripathi, S.; Brandis, A.; Montag, J.; Hodgkinson, J.L.; Francino, A.; Navarro-Lopez, F.; Brenner, B.; Stienen, G.J.M.; van der Velden, J.

    2013-01-01

    Familial Hypertrophic Cardiomyopathy (FHC) is frequently caused by mutations in the β-cardiac myosin heavy chain (β-MyHC). To identify changes in sarcomeric function triggered by such mutations, distinguishing mutation effects from other functional alterations of the myocardium is essential. We

  18. Obtaining insurance after DNA diagnostics : A survey among hypertrophic cardiomyopathy mutation carriers

    NARCIS (Netherlands)

    Christiaans, Imke; Kok, Tjitske M.; Van Langen, Irene M.; Birnie, Erwin; Bonsel, Gouke J.; Wilde, Arthur A. M.; Smets, Ellen M. A.

    2010-01-01

    Hypertrophic cardiomyopathy (HCM) is a common hereditary heart disease associated with increased mortality. Disclosure of DNA test results may have social implications such as low access to insurance. In the Netherlands, insurance companies are restricted in the use of genetic information of their

  19. Obtaining insurance after DNA diagnostics: a survey among hypertrophic cardiomyopathy mutation carriers

    NARCIS (Netherlands)

    Christiaans, Imke; Kok, Tjitske M.; van Langen, Irene M.; Birnie, Erwin; Bonsel, Gouke J.; Wilde, Arthur A. M.; Smets, Ellen M. A.

    2010-01-01

    Hypertrophic cardiomyopathy (HCM) is a common hereditary heart disease associated with increased mortality. Disclosure of DNA test results may have social implications such as low access to insurance. In the Netherlands, insurance companies are restricted in the use of genetic information of their

  20. Genetic counseling and cardiac care in predictively tested hypertrophic cardiomyopathy mutation carriers: The patients' perspective

    NARCIS (Netherlands)

    Christiaans, Imke; Van Langen, Irene M.; Birnie, Erwin; Bonsel, Gouke J.; Wilde, Arthur A. M.; Smets, Ellen M. A.

    2009-01-01

    Hypertrophic cardiomyopathy (HCM) is a common hereditary heart disease associated with sudden cardiac death. Predictive genetic counseling and testing are performed using adapted Huntington guidelines, that is, psychosocial care and time for reflection are not obligatory and the test result can be

  1. Risk stratification for sudden cardiac death in hypertrophic cardiomyopathy : Systematic review of clinical risk markers

    NARCIS (Netherlands)

    Christiaans, Imke; Van Engelen, Klaartje; Van Langen, Irene M.; Birnie, Erwin; Bonsel, Gouke J.; Elliott, Perry M.; Wilde, Arthur A.M.

    2010-01-01

    We performed a systematic literature review of recommended 'major' and 'possible' clinical risk markers for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). We searched the Medline, Embase and Cochrane databases for articles published between 1971 and 2007. We included English

  2. Risk stratification for sudden cardiac death in hypertrophic cardiomyopathy: systematic review of clinical risk markers

    NARCIS (Netherlands)

    Christiaans, Imke; van Engelen, Klaartje; van Langen, Irene M.; Birnie, Erwin; Bonsel, Gouke J.; Elliott, Perry M.; Wilde, Arthur A. M.

    2010-01-01

    We performed a systematic literature review of recommended 'major' and 'possible' clinical risk markers for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). We searched the Medline, Embase and Cochrane databases for articles published between 1971 and 2007. We included English

  3. Electrocardiographic features of sarcomere mutation carriers with and without clinically overt hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Lakdawala, Neal K; Thune, Jens Jakob; Maron, Barry J

    2011-01-01

    In hypertrophic cardiomyopathy (HC), electrocardiographic (ECG) changes have been postulated to be an early marker of disease, detectable in sarcomere mutation carriers when left ventricular (LV) wall thickness is still normal. However, the ECG features of mutation carriers have not been fully ch...

  4. Three patients presenting with severe macrosomia and congenital hypertrophic cardiomyopathy: a case series.

    Science.gov (United States)

    Vincent, Marie; Benbrik, Nadir; Romefort, Bénédicte; Colombel, Agnès; Bézieau, Stéphane; Isidor, Bertrand

    2017-03-24

    Macrosomia and hypertrophic cardiomyopathy are two features often associated in neonates of diabetic mothers. We report the cases of three patients with severe macrosomia and critical hypertrophic cardiomyopathy without severely unbalanced maternal diabetes. Only three patients with those two features and no uncontrolled maternal diabetes have been previously reported. The first patient was a 39-week-old girl, the second patient was a 39-week-old girl, and the third patient was a 41-week-old boy. The two French girls and the French boy had severe macrosomia and hypertrophic cardiomyopathy, leading to the death of the boy. The outcome of the two girls was favorable, with a standardization of growth curves and ventricular hypertrophy. Their mothers presented with high body mass index but no severe documented maternal diabetes; glycemic imbalance was only suspected on postnatal analyses. There was no hydramnios during pregnancy and no other environmental factor, especially toxic exposure. Their parents are from Mayotte, Guadeloupe, and Guinea-Conakry. The usual genetics causes, Beckwith-Wiedemann syndrome, and chromosomal copy number variation, were also excluded. This report suggests the implication of other factors in addition to glycemic disorders, including genetic factors, in the occurrence of macrosomia and severe hypertrophic cardiomyopathy in neonates. These three original observations indicate that gynecologists and neonatologists should pay attention to neonates from mothers with a high body mass index and when maternal diabetes is not documented.

  5. Left Atrial Mechanical Function and Global Strain in Hypertrophic Cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Kyung-Jin Kim

    Full Text Available Atrial fibrillation is the most common arrhythmia and is associated with adverse outcomes in hypertrophic cardiomyopathy (HCM. Although left atrial (LA remodeling and dysfunction are known to associate with the development of atrial fibrillation in HCM, the changes of the LA in HCM patients remain unclear. This study aimed to evaluate the changes in LA size and mechanical function in HCM patients compared to control subjects and to determine the characteristics of HCM associated with LA remodeling and dysfunction.Seventy-nine HCM patients (mean age, 54 ± 11 years; 76% were men were compared to 79 age- and sex-matched controls (mean age, 54 ± 11 years; 76% were men and 20 young healthy controls (mean age, 33 ± 5 years; 45% were men. The LA diameter, volume, and mechanical function, including global strain (ε, were evaluated by 2D-speckle tracking echocardiography. The phenotype of HCM, maximal left ventricular (LV wall thickness, LV mass, and presence and extent of late gadolinium enhancement (LGE were evaluated with cardiac magnetic resonance imaging.HCM patients showed increased LA volume index, impaired reservoir function, and decreased LA ε compared to the control subjects. When we divided the HCM group according to a maximal LA volume index (LAVImax of 38.7 ml/m2 or LA ε of 21%, no significant differences in the HCM phenotype and maximal LV wall thickness were observed for patients with LAVImax >38.7 ml/m2 or LA ε ≤21%. Conversely, the LV mass index was significantly higher both in patients with maximal LA volume index >38.7 ml/m2 and with LA ε ≤21% and was independently associated with LAVImax and LA ε. Although the LGE extent was increased in patients with LA ε ≤21%, it was not independently associated with either LAVImax or LA ε.HCM patients showed progressed LA remodeling and dysfunction; the determinant of LA remodeling and dysfunction was LV mass index rather than LV myocardial fibrosis by LGE-magnetic resonance

  6. Clinical Utility of Cardiovascular Magnetic Resonance in Hypertrophic Cardiomyopathy

    Science.gov (United States)

    2012-01-01

    Hypertrophic cardiomyopathy (HCM) is characterized by substantial genetic and phenotypic heterogeneity, leading to considerable diversity in clinical course including the most common cause of sudden death in young people and a determinant of heart failure symptoms in patients of any age. Traditionally, two-dimensional echocardiography has been the most reliable method for establishing a clinical diagnosis of HCM. However, cardiovascular magnetic resonance (CMR), with its high spatial resolution and tomographic imaging capability, has emerged as a technique particularly well suited to characterize the diverse phenotypic expression of this complex disease. For example, CMR is often superior to echocardiography for HCM diagnosis, by identifying areas of segmental hypertrophy (ie., anterolateral wall or apex) not reliably visualized by echocardiography (or underestimated in terms of extent). High-risk HCM patient subgroups identified with CMR include those with thin-walled scarred LV apical aneurysms (which prior to CMR imaging in HCM remained largely undetected), end-stage systolic dysfunction, and massive LV hypertrophy. CMR observations also suggest that the cardiomyopathic process in HCM is more diffuse than previously regarded, extending beyond the LV myocardium to include thickening of the right ventricular wall as well as substantial morphologic diversity with regard to papillary muscles and mitral valve. These findings have implications for management strategies in patients undergoing invasive septal reduction therapy. Among HCM family members, CMR has identified unique phenotypic markers of affected genetic status in the absence of LV hypertrophy including: myocardial crypts, elongated mitral valve leaflets and late gadolinium enhancement. The unique capability of contrast-enhanced CMR with late gadolinium enhancement to identify myocardial fibrosis has raised the expectation that this may represent a novel marker, which may enhance risk stratification. At

  7. Genetic variations of β-MYH7 in hypertrophic cardiomyopathy and dilated cardiomyopathy.

    Science.gov (United States)

    Tanjore, Reena; Rangaraju, Advithi; Vadapalli, Shivani; Remersu, Sushant; Narsimhan, Calambur; Nallari, Pratibha

    2010-05-01

    Hypertrophic cardiomyopathy (HCM) is known to be manifested by mutations in 12 sarcomeric genes and dilated cardiomyopathy (DCM) is known to manifest due to cytoskeletal mutations. Studies have revealed that sarcomeric mutations can also lead to DCM. Therefore, in the present study, we have made an attempt to compare and analyze the genetic variations of beta-myosin heavy chain gene (β-MYH7), which are interestingly found to be common in both HCM and DCM. The underlying pathophysiological mechanism leading to two different phenotypes has been discussed in this study. Till date, about 186 and 73 different mutations have been reported in HCM and DCM, respectively, with respect to this gene. The screening of β-MYH7 gene in both HCM and DCM has revealed some common genetic variations. The aim of the present study is to understand the pathophysiological mechanism underlying the manifestation of two different phenotypes. 100 controls, 95 HCM and 97 DCM samples were collected. Genomic DNA was extracted following rapid nonenzymatic method as described by Lahiri and Nurnberger (1991), and the extracted DNA was later subjected to polymerase chain reaction (PCR) based single stranded conformation polymorphism (SSCP) analysis to identify single nucleotide polymorphism (SNP)s/mutations associated with the diseased phenotypes. Similar variations were observed in β-MYH7 exons 7, 12, 19 and 20 in both HCM and DCM. This could be attributed to impaired energy compromise, or to dose effect of the mutant protein, or to even environmental factors/modifier gene effects wherein an HCM could progress to a DCM phenotype affecting both right and left ventricles, leading to heart failure.

  8. Isolated papillary muscle hypertrophy: A gap in our knowledge of hypertrophic cardiomyopathy?

    Science.gov (United States)

    Ferreira, Catarina; Delgado, Carlos; Vázquez, María; Trinidad, Carmen; Vilar, Manuel

    2014-06-01

    Increased thickness of left ventricular walls is the predominant characteristic and one of the diagnostic criteria of hypertrophic cardiomyopathy (HCM). This case illustrates an uncommon but important finding of isolated hypertrophy of the papillary muscles (PMs), observed in a young woman in whom an abnormal electrocardiogram was initially detected. During the investigation isolated PM hypertrophy was identified. The structural characteristics of the PMs have received scant attention in this setting and there is little information in the literature on this entity, whose real prevalence and clinical significance remain to be determined. The available information relates solitary PM hypertrophy with an early form or a different pattern of HCM. In this case PM hypertrophy was only detected due to the finding of an abnormal electrocardiogram, which prompted further diagnostic tests and a search for possible etiologies. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  9. Changes in gadolinium-DTPA enhanced magnetic resonance signal intensity ratio in hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Tsukihashi, Hironori; Ishibashi, Yutaka; Shimada, Toshio; Hatano, Jun; Tanabe, Kazuaki; Ooyake, Nobuyuki; Morioka, Shigefumi; Moriyama, Katsutoshi (Shimane Medical Univ., Izumo (Japan))

    Serial gadolinium-diethylene-triamine-pentaacetic acid (Gd-DTPA) enhanced magnetic resonance (MR) signal intensity ratios were measured in 6 normal subjects and 20 hypertrophic cardiomyopathy (HCM) patients to try to differentiate normal from disorganized myocardial tissue. Images were obtained at 10-minute intervals 5-60 minutes after Gd-DTPA (0.1 mmol/kg) injection. The signal intensity ratio (myocardial signal intensity/skeletal muscle signal intensity) was measured at both hypertrophic and non-hypertrophic regions in each image at the apex and mid-ventricular levels. The signal intensity ratio was standardized to compare each case. Hypertrophic myocardium was classified into two types. Type I in 11 of 20 patients was visualized as a homogeneous image, while type II in the other 9 patients was revealed as a mixed isointensity and high intensity area. The peak value of the standardized signal intensity ratio at the apex level was 1.28[+-]0.09 in HCM patients and 1.23[+-]0.06 in normal subjects, and at the mid ventricular level was 1.26[+-]0.07 in hypertrophic regions, 1.17[+-]0.12 in non-hypertrophic regions, and 1.16[+-]0.07 in normal subjects. Thirty minutes after Gd injection, the standardized signal intensity ratio at the apex level was 1.21[+-]0.08 in HCM patients and 1.07[+-]0.08 in normal subjects, and those at the mid ventricular level was 1.20[+-]0.09 in hypertrophic regions, 1.11[+-]0.11 in non-hypertrophic regions, and 1.04[+-]0.06 in normal subjects. The delayed decay of the signal intensity ratio and high signal intensity ratio in Gd-DTPA enhanced MR images are useful in myocardial tissue characterization in hypertrophic cardiomyopathy. (author).

  10. Pathogenesis of depression- and anxiety-like behavior in an animal model of hypertrophic cardiomyopathy.

    Science.gov (United States)

    Dossat, Amanda M; Sanchez-Gonzalez, Marcos A; Koutnik, Andrew P; Leitner, Stefano; Ruiz, Edda L; Griffin, Brittany; Rosenberg, Jens T; Grant, Samuel C; Fincham, Francis D; Pinto, Jose R; Kabbaj, Mohamed

    2017-06-01

    Cardiovascular dysfunction is highly comorbid with mood disorders, such as anxiety and depression. However, the mechanisms linking cardiovascular dysfunction with the core behavioral features of mood disorder remain poorly understood. In this study, we used mice bearing a knock-in sarcomeric mutation, which is exhibited in human hypertrophic cardiomyopathy (HCM), to investigate the influence of HCM over the development of anxiety and depression. We employed behavioral, MRI, and biochemical techniques in young (3-4 mo) and aged adult (7-8 mo) female mice to examine the effects of HCM on the development of anxiety- and depression-like behaviors. We focused on females because in both humans and rodents, they experience a 2-fold increase in mood disorder prevalence vs. males. Our results showed that young and aged HCM mice displayed echocardiographic characteristics of the heart disease condition, yet only aged HCM females displayed anxiety- and depression-like behaviors. Electrocardiographic parameters of sympathetic nervous system activation were increased in aged HCM females vs. controls and correlated with mood disorder-related symptoms. In addition, when compared with controls, aged HCM females exhibited adrenal gland hypertrophy, reduced volume in mood-related brain regions, and reduced hippocampal signaling proteins, such as brain-derived neurotrophic factor and its downstream targets vs. controls. In conclusion, prolonged systemic HCM stress can lead to development of mood disorders, possibly through inducing structural and functional brain changes, and thus, mood disorders in patients with heart disease should not be considered solely a psychologic or situational condition.-Dossat, A. M., Sanchez-Gonzalez, M. A., Koutnik, A. P., Leitner, S., Ruiz, E. L., Griffin, B., Rosenberg, J. T., Grant, S. C., Fincham, F. D., Pinto, J. R. Kabbaj, M. Pathogenesis of depression- and anxiety-like behavior in an animal model of hypertrophic cardiomyopathy. © FASEB.

  11. A new 4D trajectory-based approach unveils abnormal LV revolution dynamics in hypertrophic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Andrea Madeo

    Full Text Available The assessment of left ventricular shape changes during cardiac revolution may be a new step in clinical cardiology to ease early diagnosis and treatment. To quantify these changes, only point registration was adopted and neither Generalized Procrustes Analysis nor Principal Component Analysis were applied as we did previously to study a group of healthy subjects. Here, we extend to patients affected by hypertrophic cardiomyopathy the original approach and preliminarily include genotype positive/phenotype negative individuals to explore the potential that incumbent pathology might also be detected. Using 3D Speckle Tracking Echocardiography, we recorded left ventricular shape of 48 healthy subjects, 24 patients affected by hypertrophic cardiomyopathy and 3 genotype positive/phenotype negative individuals. We then applied Generalized Procrustes Analysis and Principal Component Analysis and inter-individual differences were cleaned by Parallel Transport performed on the tangent space, along the horizontal geodesic, between the per-subject consensuses and the grand mean. Endocardial and epicardial layers were evaluated separately, different from many ecocardiographic applications. Under a common Principal Component Analysis, we then evaluated left ventricle morphological changes (at both layers explained by first Principal Component scores. Trajectories' shape and orientation were investigated and contrasted. Logistic regression and Receiver Operating Characteristic curves were used to compare these morphometric indicators with traditional 3D Speckle Tracking Echocardiography global parameters. Geometric morphometrics indicators performed better than 3D Speckle Tracking Echocardiography global parameters in recognizing pathology both in systole and diastole. Genotype positive/phenotype negative individuals clustered with patients affected by hypertrophic cardiomyopathy during diastole, suggesting that incumbent pathology may indeed be foreseen by

  12. Cheating the CHA2DS2-VASc Score: Thromboembolism in Apical Hypertrophic Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Robin A. P. Weir

    2014-01-01

    Full Text Available Atrial fibrillation increases the risk of systemic thromboembolism in general and stroke in particular. Not all patients who develop atrial fibrillation are at significantly heightened risk of thromboembolic complications, however, with the development of risk scoring systems aiding clinicians in determining whether formal anticoagulation is mandated. The most commonly used contemporary scoring systems—CHADS2 and CHA2DS2-VASc—provide a reliable means of assessing stroke risk, but certain cardiac conditions are associated with an increased incidence of thromboembolism without impacting on these risk scores. Hypertrophic cardiomyopathy, with its apical variant, is such a condition. We present a case of a patient with apical hypertrophic cardiomyopathy and atrial fibrillation who suffered dire thromboembolic consequences despite a reassuringly low CHA2DS2-VASc score and suggest that this scoring system is modified to incorporate the thromboembolic risk inherent to certain cardiomyopathies irrespective of impairment of left ventricular systolic dysfunction or clinical heart failure.

  13. The influence of Angiotensin converting enzyme and angiotensinogen gene polymorphisms on hypertrophic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Rong Luo

    Full Text Available Some studies have reported that angiotensin converting enzyme (ACE and angiotensinogen (AGT genes have been associated with hypertrophic cardiomyopathy (HCM. However, there have been inconsonant results among different studies. To clarify the influence of ACE and AGT on HCM, a systemic review and meta-analysis of case-control studies were performed. The following databases were searched to indentify related studies: PubMed database, the Embase database, the Cochrane Central Register of Controlled Trials database, China National Knowledge Information database, and Chinese Scientific and Technological Journal database. Search terms included "hypertrophic cardiomyopathy", "angiotensin converting enzyme" (ACE or "ACE" and "polymorphism or mutation". For the association of AGT M235T polymorphism and HCM, "angiotensin converting enzyme" or "ACE" was replaced with "angiotensinogen". A total of seventeen studies were included in our review. For the association of ACE I/D polymorphism and HCM, eleven literatures were included in the meta-analysis on association of penetrance and genotype. Similarly, six case-control studies were included in the meta-analysis for AGT M235T. For ACE I/D polymorphism, the comparison of DI/II genotype vs DD genotype was performed in the present meta-analysis. The OR was 0.73 (95% CI: 0.527, 0.998, P = 0.049, power = 94%, alpha = 0.05 after the study which deviated from Hardy-Weinberg Equilibrium was excluded, indicating that the ACE I/D gene polymorphism might be associated with HCM. The AGT M235T polymorphism did not significantly affect the risk of HCM. In addition, ACE I/D gene polymorphism did not significantly influence the interventricular septal thickness in HCM patients. In conclusion, the ACE I/D polymorphism might be associated with the risk of HCM.

  14. Hypertrophic Cardiomyopathy from A to Z: Genetics, Pathophysiology, Imaging, and Management.

    Science.gov (United States)

    Baxi, Ameya Jagdish; Restrepo, Carlos S; Vargas, Daniel; Marmol-Velez, Alejandro; Ocazionez, Daniel; Murillo, Horacio

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is a heterogeneous group of diseases related to sarcomere gene mutations exhibiting heterogeneous phenotypes with an autosomal dominant mendelian pattern of inheritance. The disorder is characterized by diverse phenotypic expressions and variable natural progression, which may range from dyspnea and/or syncope to sudden cardiac death. It is found across all racial groups and is associated with left ventricular hypertrophy in the absence of another systemic or cardiac disease. The management of HCM is based on a thorough understanding of the underlying morphology, pathophysiology, and clinical course. Imaging findings of HCM mirror the variable expressivity and penetrance heterogeneity, with the added advantage of diagnosis even in cases where a specific mutation may not yet be found. The diagnostic information obtained from imaging varies depending on the specific stage of HCM-phenotype manifestation, including the prehypertrophic, hypertrophic, and later stages of adverse remodeling into the burned-out phase of overt heart failure. However, subtle or obvious, these imaging findings become critical components in diagnosis, management, and follow-up of HCM patients. Although diagnosis of HCM traditionally relies on clinical assessment and transthoracic echocardiography, recent studies have demonstrated increased utility of multidetector computed tomography (CT) and particularly cardiac magnetic resonance (MR) imaging in diagnosis, phenotype differentiation, therapeutic planning, and prognostication. In this article, we provide an overview of the genetics, pathophysiology, and clinical manifestations of HCM, with the spectrum of imaging findings at MR imaging and CT and their contribution in diagnosis, risk stratification, and therapy. (©)RSNA, 2016.

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

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    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.

  16. Comparison of Valsalva manoeuvre and exercise in echocardiographic evaluation of left ventricular outflow tract obstruction in hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Jensen, Morten Krogh; Havndrup, Ole; Pecini, Redi

    2010-01-01

    Several methods are used to induce latent left ventricular outflow tract (LVOT) gradients in patients with hypertrophic cardiomyopathy (HCM). We compared LVOT gradients induced by Valsalva manoeuvre (VM) and exercise echocardiography (EE) in patients with HCM treated with percutaneous translumina...

  17. Comparison of Valsalva manoeuvre and exercise in echocardiographic evaluation of left ventricular outflow tract obstruction in hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Jensen, Morten Krogh; Havndrup, Ole; Pecini, Redi

    2010-01-01

    Several methods are used to induce latent left ventricular outflow tract (LVOT) gradients in patients with hypertrophic cardiomyopathy (HCM). We compared LVOT gradients induced by Valsalva manoeuvre (VM) and exercise echocardiography (EE) in patients with HCM treated with percutaneous transluminal...

  18. In vivo cardiovascular magnetic resonance diffusion tensor imaging shows evidence of abnormal myocardial laminar orientations and mobility in hypertrophic cardiomyopathy

    National Research Council Canada - National Science Library

    Ferreira, Pedro F; Kilner, Philip J; McGill, Laura-Ann; Nielles-Vallespin, Sonia; Scott, Andrew D; Ho, Siew Y; McCarthy, Karen P; Haba, Margarita M; Ismail, Tevfik F; Gatehouse, Peter D; de Silva, Ranil; Lyon, Alexander R; Prasad, Sanjay K; Firmin, David N; Pennell, Dudley J

    2014-01-01

    ... orientation and mobility in hypertrophic cardiomyopathy (HCM). We performed cDTI in vivo at 3 Tesla at end-systole and late diastole in 11 healthy controls and 11 patients with HCM, as well as late gadolinium enhancement (LGE...

  19. Unravelling the grey zone : Cardiac MRI volume to wall mass ratio to differentiate hypertrophic cardiomyopathy and the athlete's heart

    NARCIS (Netherlands)

    Luijkx, Tim; Cramer, Maarten J.; Buckens, Stan; Zaidi, Abbas; Rienks, R; Mosterd, Arend; Prakken, Niek H J; Dijkman, Barbara; Mali, W.P.; Velthuis, BK

    2015-01-01

    Background Differentiating physiological left ventricular hypertrophy (LVH) in athletes from pathological hypertrophic cardiomyopathy (HCM) can be challenging. This study assesses the ability of cardiac MRI (CMR) to distinguish between physiological LVH (so-called athlete's heart) and HCM. Methods

  20. Morphological and Tissue Alterations in one Papillary Muscle: an Early Sign of Hypertrophic Cardiomyopathy?

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    Alberto Cresti

    2016-12-01

    Full Text Available Isolated Papillary Muscle (PM hypertrophy has been supposed to be a phenotypic variant of hypertrophic cardiomyopathy. Whether this finding may explain an electrocardiographic pattern of left ventricular hypertrophy has to be demonstrated. A cardiac magnetic resonance imaging may add additional crucial information. Our case was a 26-year-old asymptomatic male cyclist who underwent routine sport medicine screening. His cousin had suddenly died during a bicycle race at 40 years of age, and autopsy had revealed a hypertrophic cardiomyopathy. Screening revealed an electrocardiographic pattern of left ventricular hypertrophy. A multimodal imaging examination was also performed and the only abnormal finding was a hypertrophic anterolateral PM and cardiac magnetic resonance imaging showed fibrotic substitution of its head. An otherwise unexplained electrocardiographic pattern of left ventricular hypertrophy can be justified by an isolated PM hypertrophy. Cardiac magnetic resonance imaging is crucial for precise ventricular wall and papillary thickness measurement. In the presence of an isolated PM hypertrophy, postgadolinium T1 mapping can demonstrate the presence of abnormal tissue and probably fibrosis of the papillary head, which can confirm the presence of a strictly localized form of hypertrophic cardiomyopathy.

  1. Risk stratification at the time of diagnosis for children with hypertrophic cardiomyopathy: a report from the Pediatric Cardiomyopathy Registry Study Group

    Science.gov (United States)

    Lipshultz, Steven E; Orav, E John; Wilkinson, James D; Towbin, Jeffrey A; Messere, Jane E; Lowe, April M; Sleeper, Lynn A; Cox, Gerald F; Hsu, Daphne T; Canter, Charles E; Hunter, Juanita A; Colan, Steven D

    2014-01-01

    Summary Background Treatment of children with hypertrophic cardiomyopathy might be improved if the risk of death or heart transplantation could be predicted by risk factors present at the time of diagnosis. Methods The Pediatric Cardiomyopathy Registry collected longitudinal data on 1085 children with hypertrophic cardiomyopathy from 1990 to 2006. The primary outcome was death or heart transplantation. Our goal is to understand how patient factors measured at the time of diagnosis will predict the subsequent risk of death or heart transplantation. The Kaplan-Meier method was used to calculate time-to-event rates from the time of diagnosis to the earlier of heart transplantation or death for children in each subgroup. Cox proportional-hazards regression was used to identify both univariable and multivariable predictors of death or heart transplantation within each aetiologic subgroup. Findings The poorest outcomes (death or transplant) were observed among children with inborn errors of metabolism, for whom the estimated rate of death or heart transplantation was 57% (95% CI: 45%, 69%) at 2 years. Children with mixed functional phenotypes also did poorly, with rates of death or heart transplantation of 45% (95% CI: 33%, 57%) at 2 years for children with mixed hypertrophic and dilated cardiomyopathy, and 38% (95% CI: 24%, 52%) at 2 years for children with mixed hypertrophic and restrictive cardiomyopathy. Excellent outcomes were observed among the 407 children who received a diagnosis of idiopathic hypertrophic cardiomyopathy at 1 year of age or older, with rates of death or heart transplantation of 3% (95% CI: 1%, 5·0%) at 2 years. The risk factors for poor outcomes varied according to hypertrophic cardiomyopathy subgroup, but they generally included age, weight, congestive heart failure, lower left ventricular (LV) fractional shortening, or higher LV end-diastolic posterior wall thickness or end-diastolic ventricular septal thickness at the time of cardiomyopathy

  2. Genetics of hypertrophic cardiomyopathy: advances and pitfalls in molecular diagnosis and therapy

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    Roma-Rodrigues C

    2014-10-01

    Full Text Available Catarina Roma-Rodrigues,1 Alexandra R Fernandes1,2 1UCIBIO, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, Campus de Caparica, Caparica, Portugal; 2Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal Abstract: Hypertrophic cardiomyopathy (HCM is a primary disease of the cardiac muscle that occurs mainly due to mutations (>1,400 variants in genes encoding for the cardiac sarcomere. HCM, the most common familial form of cardiomyopathy, affecting one in every 500 people in the general population, is typically inherited in an autosomal dominant pattern, and presents variable expressivity and age-related penetrance. Due to the morphological and pathological heterogeneity of the disease, the appearance and progression of symptoms is not straightforward. Most HCM patients are asymptomatic, but up to 25% develop significant symptoms, including chest pain and sudden cardiac death. Sudden cardiac death is a dramatic event, since it occurs without warning and mainly in younger people, including trained athletes. Molecular diagnosis of HCM is of the outmost importance, since it may allow detection of subjects carrying mutations on HCM-associated genes before development of clinical symptoms of HCM. However, due to the genetic heterogeneity of HCM, molecular diagnosis is difficult. Currently, there are mainly four techniques used for molecular diagnosis of HCM, including Sanger sequencing, high resolution melting, mutation detection using DNA arrays, and next-generation sequencing techniques. Application of these methods has proven successful for identification of mutations on HCM-related genes. This review summarizes the features of these technologies, highlighting their strengths and weaknesses. Furthermore, current therapeutics for HCM patients are correlated with clinically observed phenotypes and are based on the alleviation of symptoms. This is

  3. Multiple Gene Variants in Hypertrophic Cardiomyopathy in the Era of Next-Generation Sequencing.

    Science.gov (United States)

    Burns, Charlotte; Bagnall, Richard D; Lam, Lien; Semsarian, Christopher; Ingles, Jodie

    2017-08-01

    Multiple likely pathogenic/pathogenic (LP/P; ≥2) variants in patients with hypertrophic cardiomyopathy were described 10 years ago with a prevalence of 5%. We sought to re-examine the significance of multiple rare variants in patients with hypertrophic cardiomyopathy in the setting of comprehensive and targeted panels. Of 758 hypertrophic cardiomyopathy probands, we included 382 with ≥45 cardiomyopathy genes screened. There were 224 (59%) with ≥1 rare variant (allele frequency ≤0.02%). Variants were analyzed using varying sized gene panels to represent comprehensive or targeted testing. Based on a 45-gene panel, 127 (33%) had a LP/P variant, 139 (36%) had variants of uncertain significance, and 66 (17%) had multiple rare variants. A targeted 8-gene panel yielded 125 (32%) LP/P variants, 52 (14%) variants of uncertain significance, and 14 (4%) had multiple rare variants. No proband had 2 LP/P variants. Including affected family members (total n=412), cluster-adjusted analyses identified a phenotype effect, with younger age (odds ratio, 0.95; 95% confidence interval, 0.92-0.98; P =0.004) and family history of sudden cardiac death (odds ratio, 3.5; 95% confidence interval, 1.3-9.9; P =0.02) significantly more likely in multiple versus single variant patients when considering an 8-gene panel but not larger panels. Those with multiple variants had worse event-free survival from all-cause death, cardiac transplantation, and cardiac arrest (log-rank P =0.008). No proband had multiple LP/P variants in contrast to previous reports. However, multiple rare variants regardless of classification were seen in 4% and contributed to earlier disease onset and cardiac events. Our findings support a cumulative variant hypothesis in hypertrophic cardiomyopathy. © 2017 American Heart Association, Inc.

  4. Cardiac MRI in a Patient with Coincident Left Ventricular Non-Compaction and Hypertrophic Cardiomyopathy

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    Zahra Alizadeh-Sani

    2011-12-01

    Full Text Available Left ventricular non-compaction cardiomyopathy is a rare congenital cardiomyopathy that affects both children and adults. Since the clinical manifestations are not sufficient to establish diagnosis, echocardiography is the diagnostic tool that makes it possible to document ventricular non-compaction and establish prognostic factors. We report a 47-year-old woman with a history of dilated cardiomyopathy with unknown etiology. Echocardiography showed mild left ventricular enlargement with severe systolic dysfunction (EF = 20-25%. According to cardiac magnetic resonance imaging findings non-compaction left ventricle with hypertrophic cardiomyopathy was considered, and right ventricular septal biopsy was recommended. Right ventricular endomyocardial biopsy showed moderate hypertrophy of cardiac myocytes with foci of myocytolysis and moderate interstitial fibrosis. No evidence of infiltrative deposition was seen.

  5. Cardiac MRI in a Patient with Coincident Left Ventricular Non-Compaction and Hypertrophic Cardiomyopathy

    Science.gov (United States)

    Alizadeh-Sani, Zahra; Madadi, Shabnam; Sadeghpour, Anita; Khajali, Zahra; Golnari, Pedram; Kiavar, Majid

    2011-01-01

    Left ventricular non-compaction cardiomyopathy is a rare congenital cardiomyopathy that affects both children and adults. Since the clinical manifestations are not sufficient to establish diagnosis, echocardiography is the diagnostic tool that makes it possible to document ventricular non-compaction and establish prognostic factors. We report a 47-year-old woman with a history of dilated cardiomyopathy with unknown etiology. Echocardiography showed mild left ventricular enlargement with severe systolic dysfunction (EF = 20–25%). According to cardiac magnetic resonance imaging findings non-compaction left ventricle with hypertrophic cardiomyopathy was considered, and right ventricular septal biopsy was recommended. Right ventricular endomyocardial biopsy showed moderate hypertrophy of cardiac myocytes with foci of myocytolysis and moderate interstitial fibrosis. No evidence of infiltrative deposition was seen. PMID:23074372

  6. Percutaneous septal ablation for left mid-ventricular obstructive hypertrophic cardiomyopathy: a case report

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    Alioglu Emin

    2006-04-01

    Full Text Available Abstract Background Mid-ventricular obstructive hypertrophic cardiomyopathy (MVOHC is a rare type of cardiomyopathy. The diagnosis is based on the hourglass appearance on the left ventriculogram and the presence of pressure gradient between apical and basal chamber of the ventriculum on the hemodynamic assessment. Case presentation The present case represents successful percutaneous treatment with septal ablation to patient with MVOHC associated with systolic anterior motion of the mitral valve and obstruction at both the mid-ventricular and outflow levels. Conclusion Alcohol septal ablation has been proposed as less invasive alternatives to surgery in patients with MVOHC.

  7. Renin-angiotensin system gene polymorphisms as potential modifiers of hypertrophic and dilated cardiomyopathy phenotypes.

    Science.gov (United States)

    Rani, Bindu; Kumar, Amit; Bahl, Ajay; Sharma, Rajni; Prasad, Rishikesh; Khullar, Madhu

    2017-03-01

    The renin-angiotensin (RAS) pathway has an important role in the etiology of heart failure and given the importance of RAS as a therapeutic target in various cardiomyopathies, genetic polymorphisms in the RAS genes may modulate the risk and severity of disease in cardiomyopathy patients. In the present study, we examined the association of RAS pathway gene polymorphisms, angiotensin converting enzyme (ACE), angiotensinogen (AGT), and angiotensin receptor type 1 (AGTR1) with risk and disease severity in Asian Indian idiopathic cardiomyopathy patients. The case-control study was conducted in 400 cardiomyopathy patients diagnosed with HCM, DCM, or restrictive cardiomyopathy (RCM) and 235 healthy controls. Genotyping of patients and controls was done by PCR-RFLP assays. Left ventricular wall thickness and left ventricular ejection fraction were measured by means of M-mode echocardiography. We observed significantly higher prevalence of ACE DD and AGTR1 1166CC genotypes in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) patients. Also, 235TT genotype of AGT (M235T) was significantly associated with enhanced risk of the disease phenotype in HCM, DCM, and RCM.

  8. Q wave T wave vector discordance in hypertrophic cardiomyopathy: septal hypertrophy and strain pattern.

    Science.gov (United States)

    Goldberger, A L

    1979-08-01

    Hypertrophic cardiomyopathy is a common cause of prominent non-infarctional Q waves. A retrospective analysis of previously published cases confirmed a characteristic Q wave T wave vector discordance in hypertrophic cardiomyopathy. In 41 of 44 cases with predominant Q waves (as part of QS or Qr complexes where Q wave amplitude exceeded R wave height), the T wave was positive, and in all cases with QS type complexes the T wave was positive. This characteristic electrocardiographic sign probably represents a pattern of septal hypertrophy and strain (Q waves with positive T waves and ST segment elevation) which is the inverse of the classical pattern of left ventricular hypertrophy and strain (tall R waves with inverted T waves and ST segment depression).

  9. Apical hypertrophic cardiomyopathy with hemodynamically unstable ventricular arrhythmia – Atypical presentation

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    Hemant Chaturvedi

    2016-09-01

    Full Text Available We present a patient with asymptomatic apical hypertrophic cardiomyopathy (AHCM who recently developed cardiac arrhythmias, and shortly discuss the diagnostic modalities, differential diagnosis, and treatment strategy for this condition. AHCM is a rare form of hypertrophic cardiomyopathy, which usually involves the apex of the left ventricle. AHCM can occur with varied presentations such as chest pain, palpitations, dyspnea, syncope, atrial fibrillation, myocardial infarction, embolic events, ventricular fibrillation, and congestive heart failure. The most peculiar electrocardiogram findings are giant T-waves inversion in the precordial leads with left ventricular (LV hypertrophy. A transthoracic echocardiogram is the initial diagnostic modality in the evaluation of AHCM and shows hypertrophy of the LV apex. Other diagnostic modalities, including left ventriculography, multislice spiral computed tomography, and cardiac magnetic resonance imagings, are also valuable tools. Medications used to manage include verapamil, beta-blockers, and antiarrhythmic agents. An implantable cardioverter defibrillator (ICD is recommended for high-risk patients.

  10. Hypertrophic Cardiomyopathy Mimicking Acute Anterior Myocardial Infarction Associated with Sudden Cardiac Death

    Directory of Open Access Journals (Sweden)

    Y. Daralammouri

    2012-01-01

    Full Text Available Hypertrophic cardiomyopathy is the most common genetic disease of the heart. We report a rare case of hypertrophic obstructive cardiomyopathy mimicking an acute anterior myocardial infarction associated with sudden cardiac death. The patient presented with acute ST elevation myocardial infarction and significant elevation of cardiac enzymes. Cardiac catheterization showed some atherosclerotic coronary artery disease, without significant stenosis. Echocardiography showed left ventricular hypertrophy with a left ventricular outflow tract obstruction; the pressure gradient at rest was 20 mmHg and became severe with the Valsalva maneuver (100 mmHg. There was no family history of sudden cardiac death. Six days later, the patient suffered a syncope on his way to magnetic resonance imaging. He was successfully resuscitated by ventricular fibrillation.

  11. Hypertrophic Cardiomyopathy (HCM): How Flow Analysis May Drive Medical Management and Surgical Approach

    Science.gov (United States)

    Abraham, Theodore P.

    2011-11-01

    Hypertrophic Cardiomyopathy (HCM) is the most common inherited heart disease and occurs in 1 in 500 persons worldwide regardless of race, age and gender. It is the most common cause of sudden death in the young and also causes heart failure and cardiac arrhythmias. The primary anatomic abnormality is thickening of certain walls, or sometimes global thickening of the left or right ventricle. The patterns of thickening along with increased ventricular stiffness lead to suboptimal ventricular filling and inefficient ejection of blood from the ventricle. Treatment for HCM can be medical or surgical. The choice of therapy is driven by the presence and severity of outflow obstruction. Flow analysis could provide sophisticated information about outflow and inflow ventricular dynamics. These flow dynamics features may enable better medical choices and provide information that would allow superior surgical planning. Associate Professor of Medicine & Director, Hypertrophic Cardiomyopathy Clinic

  12. Efficacy and safety of the angiotensin II receptor blocker losartan for hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Axelsson, Anna; Iversen, Kasper; Vejlstrup, Niels

    2015-01-01

    . Treatment was well tolerated by patients with left ventricular outflow obstruction at baseline. INTERPRETATION: Our findings challenge the generally held view that angiotensin II receptor blockers reduce cardiac hypertrophy. Treatment with losartan was safe, suggesting that it can be used for other......BACKGROUND: No medical treatment has been reliably shown to halt or reverse disease progression in hypertrophic cardiomyopathy, but the results of several pilot studies have suggested beneficial effects of angiotensin II receptor blockers on left ventricular hypertrophy and fibrosis, which...... are predictive of an adverse outcome. We aimed to assess the effect of the angiotensin II receptor blocker losartan on left ventricular hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy. METHODS: In this single-centre, randomised, double-blind, placebo-controlled trial, adult patients (aged...

  13. Effect of Institutional Experience on Outcomes of Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy

    DEFF Research Database (Denmark)

    Veselka, Josef; Faber, Lothar; Jensen, Morten Kvistholm

    2018-01-01

    BACKGROUND: The current American College of Cardiology Foundation/American Heart Association guidelines on hypertrophic cardiomyopathy state that institutional experience is a key determinant of successful outcomes and lower complication rates of alcohol septal ablation (ASA). The aim of this study...... was to evaluate the safety and efficacy of ASA according to institutional experience with the procedure. METHODS: We retrospectively evaluated 1310 patients with symptomatic obstructive hypertrophic cardiomyopathy who underwent ASA and were divided into 2 groups. The first-50 group consisted of the first......), and a probability of repeated septal reduction therapy (P = 0.03). CONCLUSIONS: An institutional experience of > 50 ASA procedures was associated with a lower occurrence of ASA complications, better cardiovascular survival, better hemodynamic and clinical effect, and less need for repeated septal reduction therapy....

  14. Targeted sequence capture and GS-FLX Titanium sequencing of 23 hypertrophic and dilated cardiomyopathy genes: implementation into diagnostics

    NARCIS (Netherlands)

    Mook, Olaf R. F.; Haagmans, Martin A.; Soucy, Jean-François; van de Meerakker, Judith B. A.; Baas, Frank; Jakobs, Marja E.; Hofman, Nynke; Christiaans, Imke; Lekanne Deprez, Ronald H.; Mannens, Marcel M. A. M.

    2013-01-01

    Genetic evaluation of cardiomyopathies poses a challenge. Multiple genes are involved but no clear genotype-phenotype correlations have been found so far. In the past, genetic evaluation for hypertrophic (HCM) and dilated (DCM) cardiomyopathies was performed by sequential screening of a very limited

  15. [Utility of cardiovascular magnetic resonance in hypertrophic cardiomyopathy: when is it superior to echocardiography?].

    Science.gov (United States)

    Kammoun, I; Marrakchi, S; Zidi, A; Ibn ElHaj, Z; Naccache, S; Ben Amara, W; Jebri, F; Bennour, E; Kachboura, S

    2015-02-01

    The diagnosis of hypertrophic cardiomyopathy is usually established by echocardiography. Recently, there has been greatly increased use of cardiac magnetic resonance (CMR) because of its precise determination of myocardial anatomy and the depiction of myocardial fibrosis. In this review, we describe the role of echocardiography and magnetic resonance in the assessment of this complex disease. In conclusion, there is a complementarity between cardiovascular magnetic resonance imaging and echocardiography for the diagnosis and the management of HCM. Copyright © 2014. Published by Elsevier SAS.

  16. Lack of reliable clinical predictors to identify obstructive sleep apnea in patients with hypertrophic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Flávia B. Nerbass

    2013-07-01

    Full Text Available OBJECTIVE: Obstructive sleep apnea is common among patients with hypertrophic cardiomyopathy and may contribute to poor cardiovascular outcomes. However, obstructive sleep apnea is largely unrecognized in this population. We sought to identify the clinical predictors of obstructive sleep apnea among patients with hypertrophic cardiomyopathy. METHODS: Consecutive patients with hypertrophic cardiomyopathy were recruited from a tertiary University Hospital and were evaluated using validated sleep questionnaires (Berlin and Epworth and overnight portable monitoring. Ninety patients (males, 51%; age, 46±15 years; body mass index, 26.6±4.9 kg/m2 were included, and obstructive sleep apnea (respiratory disturbance index ≥15 events/h was present in 37 patients (41%. RESULTS: Compared with the patients without obstructive sleep apnea, patients with obstructive sleep apnea were older and had higher body mass index, larger waist circumference, larger neck circumference, and higher prevalence of atrial fibrillation. Excessive daytime sleepiness (Epworth scale was low and similar in the patients with and without obstructive sleep apnea, respectively. The only predictors of obstructive sleep apnea (using a logistic regression analysis were age ≥45 years (odds ratio [OR], 4.46; 95% confidence interval [CI 95%], 1.47-13.54; p = 0.008 and the presence of atrial fibrillation [OR, 5.37; CI 95%, 1.43-20.12; p = 0.013]. CONCLUSION: Consistent clinical predictors of obstructive sleep apnea are lacking for patients with hypertrophic cardiomyopathy, which suggests that objective sleep evaluations should be considered in this population, particularly among elderly patients with atrial fibrillation.

  17. Pattern and degree of left ventricular remodeling following a tailored surgical approach for hypertrophic obstructive cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Ismail El-Hamamsy

    2012-07-01

    Full Text Available Background The role of a tailored surgical approach for hypertrophic cardiomyopathy (HCM on regional ventricular remodelling remains unknown. The aims of this study were to evaluate the pattern, extent and functional impact of regional ventricular remodelling after a tailored surgical approach. Conclusion Following a tailored surgical relief of outflow obstruction for HCM, there is a marked regional reverse LV remodelling. These changes could have a significant impact on overall ventricular dynamics and function.

  18. Papillary thyroid carcinoma treated with radiofrequency ablation in a patient with hypertrophic cardiomyopathy: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jian Yi; Liu, Xiao Sun; Zhang, Qing; Hong, Yan Yun; Song, Bin; Teng, Xiao Dong; Yu, Ji Ren [The First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou (China)

    2016-07-15

    Standard therapy has not been established for thyroid cancer when a thyroidectomy is contraindicated due to systemic disease. Herein, we reported a patient who had hypertrophic cardiomyopathy and papillary thyroid carcinoma treated by radiofrequency ablation because of inability to tolerate a thyroidectomy. Radiofrequency ablation can be used to treat thyroid cancer when surgery is not feasible, although the long-term outcome needs further observation.

  19. Lack of reliable clinical predictors to identify obstructive sleep apnea in patients with hypertrophic cardiomyopathy

    Science.gov (United States)

    Nerbass, Flávia B.; Pedrosa, Rodrigo P.; Genta, Pedro R.; Antunes, Murillo O.; Arteaga-Fernández, Edmundo; Drager, Luciano F.; Lorenzi-Filho, Geraldo

    2013-01-01

    OBJECTIVE: Obstructive sleep apnea is common among patients with hypertrophic cardiomyopathy and may contribute to poor cardiovascular outcomes. However, obstructive sleep apnea is largely unrecognized in this population. We sought to identify the clinical predictors of obstructive sleep apnea among patients with hypertrophic cardiomyopathy. METHODS: Consecutive patients with hypertrophic cardiomyopathy were recruited from a tertiary University Hospital and were evaluated using validated sleep questionnaires (Berlin and Epworth) and overnight portable monitoring. Ninety patients (males, 51%; age, 46±15 years; body mass index, 26.6±4.9 kg/m2) were included, and obstructive sleep apnea (respiratory disturbance index ≥15 events/h) was present in 37 patients (41%). RESULTS: Compared with the patients without obstructive sleep apnea, patients with obstructive sleep apnea were older and had higher body mass index, larger waist circumference, larger neck circumference, and higher prevalence of atrial fibrillation. Excessive daytime sleepiness (Epworth scale) was low and similar in the patients with and without obstructive sleep apnea, respectively. The only predictors of obstructive sleep apnea (using a logistic regression analysis) were age ≥45 years (odds ratio [OR], 4.46; 95% confidence interval [CI 95%], 1.47–13.54; p = 0.008) and the presence of atrial fibrillation [OR, 5.37; CI 95%, 1.43–20.12; p = 0.013]. CONCLUSION: Consistent clinical predictors of obstructive sleep apnea are lacking for patients with hypertrophic cardiomyopathy, which suggests that objective sleep evaluations should be considered in this population, particularly among elderly patients with atrial fibrillation. PMID:23917665

  20. Papillary Thyroid Carcinoma Treated with Radiofrequency Ablation in a Patient with Hypertrophic Cardiomyopathy: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jianyi; Liu, Xiaosun; Zhang, Qing; Hong, Yanyun; Song, Bin [Department of Gastrointestinal and Thyroid Surgery, The First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou 310003 (China); Teng, Xiaodong [Department of Pathology, The First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou 310003 (China); Yu, Jiren [Department of Gastrointestinal and Thyroid Surgery, The First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou 310003 (China)

    2016-11-01

    Standard therapy has not been established for thyroid cancer when a thyroidectomy is contraindicated due to systemic disease. Herein, we reported a patient who had hypertrophic cardiomyopathy and papillary thyroid carcinoma treated by radiofrequency ablation because of inability to tolerate a thyroidectomy. Radiofrequency ablation can be used to treat thyroid cancer when surgery is not feasible, although the long-term outcome needs further observation.

  1. Intrauterine Treatment of a Fetus with Familial Hypertrophic Cardiomyopathy Secondary to MYH7 Mutation.

    Science.gov (United States)

    Hill, Meghan G; Sekhon, Mehtab K; Reed, Kathryn L; Anderson, Caroline F; Borjon, Nydia D; Tardiff, Jil C; Barber, Brent J

    2015-12-01

    There is no clear consensus on optimal management of fetuses affected by familial hypertrophic cardiomyopathy (HCM). Intrauterine treatment of the condition has not been attempted in any standardized fashion. We report the case of a fetus treated by maternal propranolol during the third trimester after septal hypertrophy and diastolic dysfunction was diagnosed on fetal echocardiogram. The pregnancy went successfully to term, and fetal septal hypertrophy was noted to improve prior to delivery.

  2. A Case Report of Percutaneous Transluminal Septal Myocardial Ablation in Patients with Hypertrophic Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    M.H. Namazi

    2004-10-01

    Full Text Available A number of patients with severe obstruction due to hypertrophic cardiomyopathy have derived benefit at least over the short-term from inventional infarction of a portion of the interventricular septum by the infusion of alcohol into a selectively catheterized septal artery , with reduction of the outflow gradient and improvement in symptoms .This paper contains successful TASH on a symptomatic patient with high LVOT gradient and methods and complications.

  3. Burden of Recurrent and Ancestral Mutations in Families With Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Ross, Samantha Barratt; Bagnall, Richard D; Ingles, Jodie; Van Tintelen, J Peter; Semsarian, Christopher

    2017-06-01

    Hypertrophic cardiomyopathy is a genetically heterogeneous myocardial disease with >1000 causal variants identified. Nonunique variants account for disease in many families. We sought to characterize nonunique variants in Australian families and determine whether they arise from common ancestral mutations or recurrent mutation events. Genetic test results of 467 index patients from apparently unrelated families with hypertrophic cardiomyopathy were evaluated. Causal variants were found in 185 of 467 (40%) families. Nonunique variants accounted for 122 of 185 (66%) families. The most common single genetic cause of hypertrophic cardiomyopathy is the recurrent MYBPC3 (myosin-binding protein-C) variant c.1504C>T, p.Arg502Trp, which was found in 13 of 185 (7%) families with a causal variant identified. Thirteen variants in MYBPC3 and MYH7 (myosin heavy chain 7) were each identified >3 times and accounted for 78 of 185 (42%) hypertrophic cardiomyopathy families with a causal variant. Haplotype analysis of these 13 variants was performed on 126 individuals from 70 Australian families, and 11 variants arose through recurrent mutation events. Two variants, MYBPC3 c.1928-2A>G and MYH7 c.2681A>G, p.Glu894Gly, were found on 1 haplotype in 6 families each, supportive of a single mutation event inherited from a common ancestor. The majority of families with a causal variant identified have a nonunique variant. Discovery of the genetic origins of human disease forms a fundamental basis for improved understanding of disease pathogenesis and phenotype development. © 2017 American Heart Association, Inc.

  4. Improved survival with amiodarone in patients with hypertrophic cardiomyopathy and ventricular tachycardia.

    OpenAIRE

    McKenna, W. J.; Oakley, C M; Krikler, D. M.; Goodwin, J. F.

    1985-01-01

    The effect of amiodarone on survival was assessed in patients with hypertrophic cardiomyopathy and ventricular tachycardia in a drug trial with historical controls. During 1976 and 1977, 24 hour (seven) or 48 hour (79) electrocardiographic monitoring was performed in 86 consecutive patients; 24 had ventricular tachycardia and received conventional antiarrhythmic agents. Nineteen clinical, echocardiographic, and haemodynamic features were assessed. Seven patients died suddenly during follow up...

  5. Bilateral brachial plexus blocks in a patient of hypertrophic obstructive cardiomyopathy with hypertensive crisis

    OpenAIRE

    Bhat Pai, Rohini V; Hegde, Harihar V.; MCB, Santhosh; S Roopa; Shrinivas S Deshpande; P Raghavendra Rao

    2013-01-01

    Hypertrophic obstructive cardiomyopathy (HOCM) is a challenge to anesthesiologists due to the complex pathophysiology involved and various perioperative complications associated with it. We present a 50-year-old man, a known case of HOCM, who successfully underwent emergency haemostasis, and debridement of the traumatically amputated right upper limb and the contused lacerated wound on the left forearm under bilateral brachial plexus blocks. His co-morbidities included hypertension (in hypert...

  6. Differentiation of infiltrative cardiomyopathy from hypertrophic cardiomyopathy using high-sensitivity cardiac troponin T: a case-control study.

    Science.gov (United States)

    Kubo, Toru; Baba, Yuichi; Hirota, Takayoshi; Tanioka, Katsutoshi; Yamasaki, Naohito; Yamanaka, Shigeo; Iiyama, Tatsuo; Kumagai, Naoko; Furuno, Takashi; Sugiura, Tetsuro; Kitaoka, Hiroaki

    2015-06-16

    Because infiltrative cardiomyopathy and hypertrophic cardiomyopathy (HCM) share clinical and hemodynamic features of left ventricular (LV) hypertrophy and abnormal diastolic function, it is often difficult to distinguish these entities. We investigated the potential role of high-sensitivity cardiac troponin T (hs-cTnT) for differentiation of infiltrative cardiomyopathy from HCM. The study group consisted of 46 consecutive patients with infiltrative cardiomyopathies or HCM in whom sarcomere protein gene mutations were identified at Kochi Medical School Hospital; of these, there were 11 patients with infiltrative cardiomyopathy (cardiac amyloidosis in 8 patients and Fabry disease in 3 patients) and 35 HCM patients. Serum hs-cTnT level was significantly higher in patients who had infiltrative cardiomyopathy than in those who had HCM (0.083 ± 0.057 ng/ml versus 0.027 ± 0.034 ng/ml, p  40 years at age), hs-cTnT level, maximum LV wall thickness, posterior wall thickness, peak early (E) transmitral filling velocity, peak early diastolic (Ea) velocity of tissue Doppler imaging at the lateral corner and E/Ea ratios at both the septal and lateral corners were significantly different between the two groups. As for diagnostic accuracy to differentiate the two groups by using receiver operating characteristic analysis, hs-cTnT was the highest value of area under the curve (0.939) and E/Ea (lateral) was second highest value (0.914). Serum hs-cTnT is a helpful diagnostic indicator for accurate differentiation between infiltrative cardiomyopathy and HCM.

  7. Evaluation of hypertrophic obstructive cardiomyopathy by exercise stress echocardiography. New methodology.

    Science.gov (United States)

    Cotrim, Carlos; Loureiro, Maria José; Simões, Otília; Miranda, Rita; Cordeiro, Pedro; Ialá, Mário; Matias, Carla; João, Isabel; Carrageta, Manuel

    2005-11-01

    Exercise echocardiography with image acquisition during treadmill exercise is the most common form of stress testing used in our department. The usual evaluation of patients with hypertrophic obstructive cardiomyopathy consists of serial echocardiographic studies at rest. The purpose of this study was to evaluate intraventricular gradients during exercise echocardiography in patients with a diagnosis of hypertrophic obstructive cardiomyopathy. We studied 13 patients, 8 male, mean age 56 +/- 9 years Intraventricular gradients were measured using continuous wave Doppler; two evaluations were performed at rest: one in left lateral decubitus and the other in orthostatic position after one minute in this position. The patients then underwent a treadmill exercise test using the modified Bruce protocol, during which intraventricular gradients were measured at peak exercise. Finally, a further measurement was taken in the first 90 seconds of the recovery period in left lateral decubitus. The intraventricular gradient in left lateral decubitus was 54 +/- 29 mmHg; in orthostatic position 69 +/- 30 mmHg (p happens during effort or therefore during these patients' daily activities. This type of evaluation can help us to better understand the pathophysiology of patients with a diagnosis of hypertrophic obstructive cardiomyopathy and to optimize treatment.

  8. Ranolazine Prevents Phenotype Development in a Mouse Model of Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Coppini, Raffaele; Mazzoni, Luca; Ferrantini, Cecilia; Gentile, Francesca; Pioner, Josè Manuel; Laurino, Annunziatina; Santini, Lorenzo; Bargelli, Valentina; Rotellini, Matteo; Bartolucci, Gianluca; Crocini, Claudia; Sacconi, Leonardo; Tesi, Chiara; Belardinelli, Luiz; Tardiff, Jil; Mugelli, Alessandro; Olivotto, Iacopo; Cerbai, Elisabetta; Poggesi, Corrado

    2017-03-01

    Current therapies are ineffective in preventing the development of cardiac phenotype in young carriers of mutations associated with hypertrophic cardiomyopathy (HCM). Ranolazine, a late Na + current blocker, reduced the electromechanical dysfunction of human HCM myocardium in vitro. To test whether long-term treatment prevents cardiomyopathy in vivo, transgenic mice harboring the R92Q troponin-T mutation and wild-type littermates received an oral lifelong treatment with ranolazine and were compared with age-matched vehicle-treated animals. In 12-months-old male R92Q mice, ranolazine at therapeutic plasma concentrations prevented the development of HCM-related cardiac phenotype, including thickening of the interventricular septum, left ventricular volume reduction, left ventricular hypercontractility, diastolic dysfunction, left-atrial enlargement and left ventricular fibrosis, as evaluated in vivo using echocardiography and magnetic resonance. Left ventricular cardiomyocytes from vehicle-treated R92Q mice showed marked excitation-contraction coupling abnormalities, including increased diastolic [Ca 2+ ] and Ca 2+ waves, whereas cells from treated mutants were undistinguishable from those from wild-type mice. Intact trabeculae from vehicle-treated mutants displayed inotropic insufficiency, increased diastolic tension, and premature contractions; ranolazine treatment counteracted the development of myocardial mechanical abnormalities. In mutant myocytes, ranolazine inhibited the enhanced late Na + current and reduced intracellular [Na + ] and diastolic [Ca 2+ ], ultimately preventing the pathological increase of calmodulin kinase activity in treated mice. Owing to the sustained reduction of intracellular Ca 2+ and calmodulin kinase activity, ranolazine prevented the development of morphological and functional cardiac phenotype in mice carrying a clinically relevant HCM-related mutation. Pharmacological inhibitors of late Na + current are promising candidates for an

  9. Mitochondrial haplogroups modify the risk of developing hypertrophic cardiomyopathy in a Danish population

    DEFF Research Database (Denmark)

    Hagen, Christian M; Aidt, Frederik H; Hedley, Paula L

    2013-01-01

    Hypertrophic cardiomyopathy (HCM) is a genetic disorder caused by mutations in genes coding for proteins involved in sarcomere function. The disease is associated with mitochondrial dysfunction. Evolutionarily developed variation in mitochondrial DNA (mtDNA), defining mtDNA haplogroups...... and haplogroup clusters, is associated with functional differences in mitochondrial function and susceptibility to various diseases, including ischemic cardiomyopathy. We hypothesized that mtDNA haplogroups, in particular H, J and K, might modify disease susceptibility to HCM. Mitochondrial DNA, isolated from...... factors in the development of HCM. Thus, constitutive differences in mitochondrial function may influence the occurrence and clinical presentation of HCM. This could explain some of the phenotypic variability in HCM. The fact that haplogroup H and J are also modifying factors in ischemic cardiomyopathy...

  10. Attitudes, knowledge and consequences of uncertain genetic findings in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Burns, Charlotte; Yeates, Laura; Spinks, Catherine; Semsarian, Christopher; Ingles, Jodie

    2017-06-01

    With the surge of next-generation sequencing (NGS) technologies making almost all genetic tests more affordable and available, cardiac genetic testing now routinely encompasses a large number of genes within a panel setting. The additional sensitivity of this practice is limited and has the potential to inflict a spectrum of uncertainty. We sought to explore attitudes, preferences, recall and psychological consequences of informative and uninformative genetic results amongst probands diagnosed with hypertrophic cardiomyopathy (HCM). We conducted semi-structured interviews and analysed the qualitative data using a framework analysis process. In general, we found probands were more concerned with their clinical diagnosis than gene result and in some, recall and understanding of genetic diagnosis was poor. Several participants expected genetic testing would alleviate uncertainty, often holding an altruistic view of participation in testing, removing their sense of self and failing to appreciate fully the familial implications. With the key utility of HCM genetic testing and counselling being for greater risk prediction for at-risk relatives, effective communication within the family is critical. While communication appeared adequate, further questioning found it was often vague, failing to translate into meaningful action by relatives. Based on these findings, a framework of key outcomes to assist multidisciplinary teams in genetic counselling of probands receiving an HCM gene result was developed.

  11. Serial Observations and Mutational Analysis of an Adoptee with Family History of Hypertrophic Cardiomyopathy

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    Bronwyn Harris

    2010-01-01

    Full Text Available Hypertrophic cardiomyopathy (HCM is an inherited cardiac disease with an autosomal dominant mode of transmission. Comprehensive genetic screening of several genes frequently found mutated in HCM is recommended for first-degree relatives of HCM patients. Genetic testing provides the means to identify those at risk of developing HCM and to institute measures to prevent sudden cardiac death (SCD. Here, we present an adoptee whose natural mother and maternal relatives were known be afflicted with HCM and SCD. The proband was followed closely from age 6 to 17 years, revealing a natural history of the progression of clinical findings associated with HCM. Genetic testing of the proband and her natural mother, who is affected by HCM, revealed that they were heterozygous for both the R719Q and T1513S variants in the cardiac beta-myosin heavy chain (MYH7 gene. The proband's ominous family history indicates that the combination of the R719Q and T1513S variants in cis may be a “malignant” variant that imparts a poor prognosis in terms of the disease progression and SCD risk.

  12. Occurrence and Natural History of Clinically Silent Episodes of Atrial Fibrillation in Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Rowin, Ethan J; Orfanos, Alexander; Estes, N A Mark; Wang, Wendy; Link, Mark S; Maron, Martin S; Maron, Barry J

    2017-06-01

    Overt symptomatic atrial fibrillation (AF) occurs in over 20% of patients with hypertrophic cardiomyopathy (HC) leading to impaired quality of life, loss of productivity, and the risk for embolic stroke. However, the overall burden presented by AF in the HC population is unresolved due to the unknown frequency of silent asymptomatic episodes that do not necessarily achieve clinical recognition but nevertheless may have important disease-related implications. Therefore, stored electrograms were analyzed retrospectively for AF in 75 consecutive patients with HC (without AF history) implanted with dual-chamber cardioverter-defibrillators. Patients were followed for 5.0 ± 4.1 years at the Tufts Medical Center HCM Institute; ages were 50 ± 15 years, and 55% were male. Implantable cardioverter-defibrillator interrogation in the 75 patients showed AF to be absent in 54 (72%), 18 (24%) had clinically silent AF episodes, and the remaining 3 (4%) without previous asymptomatic episodes developed symptomatic and clinically overt paroxysmal AF. Of the 18 patients with clinically silent AF, 8 developed symptomatic AF, 4.1 ± 1.5 years later. Nonfatal embolic stroke occurred in 1 patient associated with asymptomatic AF and without other risk factors. In conclusion, clinically silent AF appears to be common in HC, occurring in almost 25% of patients. Such asymptomatic episodes of AF have important future implications, including potential thromboembolic risk, and development of symptomatic and clinically overt AF requiring prophylactic anticoagulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Changes in left atrial deformation in hypertrophic cardiomyopathy: Evaluation by vector velocity imaging

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    Hala Mahfouz Badran

    2012-12-01

    Full Text Available Objectives: Hypertrophic cardiomyopathy (HCM represents a generalized myopathic process affecting both ventricular and atrial myocardium. We assessed the global and regional left atrial (LA function and its relation to left ventricular (LV mechanics and clinical status in patients with HCM using Vector Velocity Imaging (VVI. Methods: VVI of the LA and LV was acquired from apical four- and two-chamber views of 108 HCM patients (age 40±19years, 56.5% men and 33 healthy subjects, all had normal LV systolic function. The LA subendocardium was traced to obtain atrial volumes, ejection fraction, velocities, and strain (ɛ/strain rate (SR measurements. Results: Left atrial reservoir (ɛsys,SRsys and conduit (early diastolic SRe function were significantly reduced in HCM compared to controls (P-1.8s-1 was 81% sensitive and 30% specific, SRa>-1.5s-1 was 73% sensitive and 40% specific. By multivariate analysis global LVɛsys and LV septal thickness are independent predictors for LAɛsys, while end systolic diameter is the only independent predictor for SRsys, P<.001. Conclusion: Left atrial reservoir and conduit function as measured by VVI were significantly impaired while contractile function was preserved among HCM patients. Left atrial deformation was greatly influenced by LV mechanics and correlated to severity of phenotype.

  14. Extent of Late Gadolinium Enhancement on Cardiac Magnetic Resonance Imaging in Japanese Hypertrophic Cardiomyopathy Patients.

    Science.gov (United States)

    Hen, Yasuki; Iguchi, Nobuo; Utanohara, Yuko; Takada, Kaori; Machida, Haruhiko; Takara, Ayako; Teraoka, Kunihiko; Sumiyoshi, Tetsuya; Takamisawa, Itaru; Takayama, Morimasa; Yoshikawa, Tsutomu

    2016-01-01

    In addition to the presence of late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR), the extent of LGE is considered clinically important in hypertrophic cardiomyopathy (HCM). We evaluated the extent of LGE on CMR in a large series of Japanese HCM patients. CMR was performed in 317 HCM patients (147 male). The extent of LGE was scored as the sum of LGE-positive segments in a left ventricle (LV) 17-segment model. LGE was present in 246 patients (77.6%). LGE was detected in 3.5±3.1 segments on average. When the patients were divided according to maximum wall thickness (mild, 65%), median LGE score increased as EF decreased (reduced, 7 vs. low-normal, 4 vs. normal, 2; P=0.000). On multivariate analysis, reduced EF (OR, 0.947, P=0.015), pressure gradient <30 mmHg (OR, 0.359, P=0.000) and increased maximum wall thickness (OR, 1.236, P=0.000) were independent factors associated with extensive LGE. Progression of LGE was related to increased wall thickness, decreased contractility, and reduced intraventricular pressure gradient.

  15. Myosin-binding Protein C Compound Heterozygous Variant Effect on the Phenotypic Expression of Hypertrophic Cardiomyopathy

    Science.gov (United States)

    Rafael, Julianny Freitas; Cruz Filho, Fernando Eugênio dos Santos; de Carvalho, Antônio Carlos Campos; Gottlieb, Ilan; Cazelli, José Guilherme; Siciliano, Ana Paula; Dias, Glauber Monteiro

    2017-01-01

    Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disease caused by mutations in genes encoding sarcomere proteins. It is the major cause of sudden cardiac death in young high-level athletes. Studies have demonstrated a poorer prognosis when associated with specific mutations. The association between HCM genotype and phenotype has been the subject of several studies since the discovery of the genetic nature of the disease. This study shows the effect of a MYBPC3 compound variant on the phenotypic HCM expression. A family in which a young man had a clinical diagnosis of HCM underwent clinical and genetic investigations. The coding regions of the MYH7, MYBPC3 and TNNT2 genes were sequenced and analyzed. The proband present a malignant manifestation of the disease, and is the only one to express HCM in his family. The genetic analysis through direct sequencing of the three main genes related to this disease identified a compound heterozygous variant (p.E542Q and p.D610H) in MYBPC3. A family analysis indicated that the p.E542Q and p.D610H alleles have paternal and maternal origin, respectively. No family member carrier of one of the variant alleles manifested clinical signs of HCM. We suggest that the MYBPC3-biallelic heterozygous expression of p.E542Q and p.D610H may cause the severe disease phenotype seen in the proband. PMID:28538763

  16. Myosin-binding Protein C Compound Heterozygous Variant Effect on the Phenotypic Expression of Hypertrophic Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Julianny Freitas Rafael

    Full Text Available Abstract Hypertrophic cardiomyopathy (HCM is an autosomal dominant genetic disease caused by mutations in genes encoding sarcomere proteins. It is the major cause of sudden cardiac death in young high-level athletes. Studies have demonstrated a poorer prognosis when associated with specific mutations. The association between HCM genotype and phenotype has been the subject of several studies since the discovery of the genetic nature of the disease. This study shows the effect of a MYBPC3 compound variant on the phenotypic HCM expression. A family in which a young man had a clinical diagnosis of HCM underwent clinical and genetic investigations. The coding regions of the MYH7, MYBPC3 and TNNT2 genes were sequenced and analyzed. The proband present a malignant manifestation of the disease, and is the only one to express HCM in his family. The genetic analysis through direct sequencing of the three main genes related to this disease identified a compound heterozygous variant (p.E542Q and p.D610H in MYBPC3. A family analysis indicated that the p.E542Q and p.D610H alleles have paternal and maternal origin, respectively. No family member carrier of one of the variant alleles manifested clinical signs of HCM. We suggest that the MYBPC3-biallelic heterozygous expression of p.E542Q and p.D610H may cause the severe disease phenotype seen in the proband.

  17. Autosomal recessive transmission of MYBPC3 mutation results in malignant phenotype of hypertrophic cardiomyopathy.

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    Yilu Wang

    Full Text Available BACKGROUND: Hypertrophic cardiomyopathy (HCM due to mutations in genes encoding sarcomere proteins is most commonly inherited as an autosomal dominant trait. Since nearly 50% of HCM cases occur in the absence of a family history, a recessive inheritance pattern may be involved. METHODS: A pedigree was identified with suspected autosomal recessive transmission of HCM. Twenty-six HCM-related genes were comprehensively screened for mutations in the proband with targeted second generation sequencing, and the identified mutation was confirmed with bi-directional Sanger sequencing in all family members and 376 healthy controls. RESULTS: A novel missense mutation (c.1469G>T, p.Gly490Val in exon 17 of MYBPC3 was identified. Two siblings with HCM were homozygous for this mutation, whereas other family members were either heterozygous or wild type. Clinical evaluation showed that both homozygotes manifested a typical HCM presentation, but none of others, including 5 adult heterozygous mutation carriers up to 71 years of age, had any clinical evidence of HCM. CONCLUSIONS: Our data identified a MYBPC3 mutation in HCM, which appeared autosomal recessively inherited in this family. The absence of a family history of clinical HCM may be due to not only a de novo mutation, but also recessive mutations that failed to produce a clinical phenotype in heterozygous family members. Therefore, consideration of recessive mutations leading to HCM is essential for risk stratification and genetic counseling.

  18. Multiple sclerosis presents with psychotic symptoms and coexists with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Ozcan, Muhammed Emin; Ince, Bahri; Karadeli, Hasan Hüseyin; Asil, Talip

    2014-01-01

    Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. Psychiatric symptoms are not infrequent during MS, yet onset of MS with psychosis is rarely encountered. A 27-year-old Caucasian male was admitted due to numbness in his right arm and difficulty in walking. His clinical and laboratorial exams lead to the MS diagnosis. Nine months earlier, he also developed psychotic disorder, not otherwise specified (PD-NOS). His sudden onset of PD-NOS, his rapid and complete response to antipsychotics, and a relatively short interval between psychiatric and neurological signs indicate a high likelihood that PD-NOS was a manifestation of underlying MS. He also suffers from hypertrophic obstructive cardiomyopathy (HOCM). The patient's neurological complaints were recovered with methylprednisolone (1 g/day, i.v.) given for five days. Glatiramer acetate (1 × 1 tb.s.c.) was prescribed for consolidation and, after nine months of his admission, the patient fully recovered from neurological and psychiatric complaints. Interestingly, very recent studies indicate specific alpha-actinin antibodies in MS and alpha-actinin mutations cause HOCM. Thus, concurrence of MS with HOCM can be even a new syndrome, if further genetic studies prove.

  19. Outcomes of Alcohol Septal Ablation in Younger Patients With Obstructive Hypertrophic Cardiomyopathy

    DEFF Research Database (Denmark)

    Liebregts, Max; Faber, Lothar; Jensen, Morten K.

    2017-01-01

    Objectives The aim of this study was to describe the safety and outcomes of alcohol septal ablation (ASA) in younger patients with obstructive hypertrophic cardiomyopathy. Background The American College of Cardiology Foundation/American Heart Association guidelines reserve ASA for older patients...... and patients with serious comorbidities. Data on long-term age-specific outcomes after ASA are scarce. Methods A total of 1,197 patients (mean age 58 ± 14 years) underwent ASA for obstructive hypertrophic cardiomyopathy. Patients were divided into young (≤50 years), middle-age (51 to 64 years), and older (≥65...... patients with obstructive hypertrophic cardiomyopathy was safe and effective for relief of symptoms at long-term follow-up. The authors propose that the indication for ASA can be broadened to younger patients....

  20. Mechanism of Progressive Heart Failure and Significance of Pulmonary Hypertension in Obstructive Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Covella, Michele; Rowin, Ethan J; Hill, Nicholas S; Preston, Ioana R; Milan, Alberto; Opotowsky, Alexander R; Maron, Barry J; Maron, Martin S; Maron, Bradley A

    2017-04-01

    There are limited data on the prevalence, pathophysiology, and management implications of pulmonary hypertension in patients with obstructive hypertrophic cardiomyopathy and advanced heart failure. To assess the clinical significance of measured cardiopulmonary hemodynamics in hypertrophic cardiomyopathy patients with heart failure, we retrospectively assessed right heart catheterization data in 162 consecutive patients with outflow tract gradients (median [interquartile range], 90 mm Hg [70-110 mm Hg]), 59±11 years old, and 49% men, predominately New York Heart Association class III/IV status. Pulmonary hypertension (mean pulmonary artery pressure, ≥25 mm Hg) was present in 82 patients (51%), including 29 (18%) regarded as moderate-severe (mean pulmonary artery pressure, ≥35 mm Hg) and 28 (34%) also had increased pulmonary vascular resistance >3.0 WU. The pulmonary artery wedge pressure was ≤15 mm Hg in 54%, indicating that left atrial hypertension was absent in a majority of patients. Notably, 9 patients (11%) met hemodynamic criteria for precapillary pulmonary hypertension (mean pulmonary artery pressure, ≥25 mm Hg; pulmonary vascular resistance, >3.0 WU; pulmonary artery wedge pressure, ≤15 mm Hg). Over a median follow-up of 327 days (90-743 days) after surgical myectomy (or alcohol septal ablation), 92% and 95% of patients with or without preoperative pulmonary hypertension, respectively, were asymptomatic or mildly symptomatic. One postoperative death occurred in a 59-year-old woman with acute respiratory failure and mean pulmonary artery pressure of 65 mm Hg. Pulmonary hypertension was common in obstructive hypertrophic cardiomyopathy patients with advanced heart failure. Although possibly a contributor to preoperative heart failure, pulmonary hypertension did not significantly influence clinical and surgical outcome. Notably, a novel patient subgroup was identified with resting invasive hemodynamics consistent with pulmonary

  1. Hypertrophic Cardiomyopathy After a Single Dose of Dexamethasone in a Preterm Infant

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    Yusuf Kale

    2015-08-01

    Full Text Available Dexamethasone is widely used in preterm infants with severe pulmonary disease. Hypertrophic cardiomyopathy (HCM is a transient side effect observed after multiple doses of dexamethasone. We report a preterm infant with myocardial hypertrophy after a single dose of dexamethasone (0.5 mg/kg used to treat laryngeal edema secondary to prolonged intubation. A benign course was observed without left ventricular outflow tract obstruction and with recovery within 4 weeks. Myocardial effects of dexamethasone may be independent of dose and duration of treatment. The risk/benefit ratio must be carefully considered before using even a single dose of dexamethasone in preterm infants.

  2. Vagal enhancement linking abnormal blood pressure response and subendocardial ischemia in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Kawasaki, Tatsuya; Sugihara, Hiroki

    2014-01-01

    An abnormal blood pressure response to exercise has been reported to be associated with left ventricular subendocardial ischemia in patients with hypertrophic cardiomyopathy (HCM), but the underlying mechanism remains unclear. We report a case of HCM with an abnormal blood pressure response and subendocardial ischemia, in which the analysis of heart rate variability revealed exercise-induced vagal enhancement. The present case highlights the possible mechanism linking abnormal blood pressure response and left ventricular subendocardial ischemia in patients with HCM. ©2013 Wiley Periodicals, Inc.

  3. Increased left ventricular torsion in hypertrophic cardiomyopathy mutation carriers with normal wall thickness

    Science.gov (United States)

    2011-01-01

    Background Increased left ventricular (LV) torsion has been observed in patients with manifest familial hypertrophic cardiomyopathy (HCM), and is thought to be caused by subendocardial dysfunction. We hypothesize that increased LV torsion is already present in healthy mutation carriers with normal wall thickness. Methods Seventeen carriers with an LV wall thickness subendocardial myocardial dysfunction. As similar abnormalities are observed in patients with manifest HCM, the changes in healthy carriers may be target for clinical intervention to delay or prevent the onset of hypertrophy. PMID:21219655

  4. Hypertrophic Cardiomyopathy due to Mitochondrial Disease: Prenatal Diagnosis, Management, and Outcome

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    Lutgardo García-Díaz

    2013-01-01

    Full Text Available A case of prenatally diagnosed fetal hypertrophic cardiomyopathy is reported. The mother was referred to our department at 37 weeks' gestation because of suspected congenital heart disease. Prenatal echocardiography showed biventricular hypertrophy and pericardial effusion, without additional abnormalities. Postnatal echocardiography confirmed prenatal diagnosis. Neonatal EKG showed biventricular hypertrophy and Wolff-Parkinson-White syndrome. Skeletal muscle biopsy was consistent with mitochondrial oxidative phosphorylation defect involving a combined defect of respiratory complexes I and IV. Echocardiographic followup during the first year of life showed progressive regression of hypertrophy and evolution to left ventricular myocardial noncompaction.

  5. Hypertrophic obstructive cardiomyopathy in rheumatoid arthtritis - coincidence or association? A case report.

    Science.gov (United States)

    Moyssakis, I; Lionakis, N; Votteas, V

    2009-01-01

    A 60-year-old woman with a history of rheumatoid arthritis was admitted to the hospital for investigation of dyspnea on exertion (New York Heart Association class II), polyarthralgias and mild fever. An echocardiogram revealed asymmetric hypertrophy of the interventricular septum with signs of subaortic obstruction.The coexistence of rheumatoid arthritis and hypertrophic cardiomyopathy could be connected with the human lymphocyte antigen DR4, which is common in both conditions. Further studies are necessary to assess whether a true association of the above diseases exists.

  6. Hypertrophic obstructive cardiomyopathy in rheumatoid arthtritis – coincidence or association? A case report

    Science.gov (United States)

    Moyssakis, I; Lionakis, N; Votteas, V

    2009-01-01

    A 60-year-old woman with a history of rheumatoid arthritis was admitted to the hospital for investigation of dyspnea on exertion (New York Heart Association class II), polyarthralgias and mild fever. An echocardiogram revealed asymmetric hypertrophy of the interventricular septum with signs of subaortic obstruction. The coexistence of rheumatoid arthritis and hypertrophic cardiomyopathy could be connected with the human lymphocyte antigen DR4, which is common in both conditions. Further studies are necessary to assess whether a true association of the above diseases exists. PMID:19492031

  7. The role of imaging in the diagnosis and management of hypertrophic cardiomyopathy.

    Science.gov (United States)

    Weissler-Snir, Adaya; Crean, Andrew; Rakowski, Harry

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy, affecting approximately 1:500 people. As the yield of genetic testing is only about 35-60%, the diagnosis of HCM is still clinical and based on the demonstration of unexplained and usually asymmetric left ventricular (LV) hypertrophy by imaging modalities. In the past, echocardiography was the sole imaging modality used for the diagnosis and management of HCM. However, in recent years other imaging modalities such as cardiac magnetic resonance have played a major role in the diagnosis, management and risk stratification of HCM, particularly when the location of left ventricular hypertrophy is atypical (apex, lateral wall) and when the echocardiographic imaging is sub-optimal. However, the most unique contribution of cardiac magnetic resonance is the quantification of myocardial fibrosis. Exercise stress echocardiography is the preferred provocative test for the assessment of LV outflow tract obstruction, which is detected only on provocation in one-third of the patients.

  8. Pathogenesis of Hypertrophic Cardiomyopathy is Mutation Rather Than Disease Specific: A Comparison of the Cardiac Troponin T E163R and R92Q Mouse Models.

    Science.gov (United States)

    Ferrantini, Cecilia; Coppini, Raffaele; Pioner, Josè Manuel; Gentile, Francesca; Tosi, Benedetta; Mazzoni, Luca; Scellini, Beatrice; Piroddi, Nicoletta; Laurino, Annunziatina; Santini, Lorenzo; Spinelli, Valentina; Sacconi, Leonardo; De Tombe, Pieter; Moore, Rachel; Tardiff, Jil; Mugelli, Alessandro; Olivotto, Iacopo; Cerbai, Elisabetta; Tesi, Chiara; Poggesi, Corrado

    2017-07-22

    In cardiomyocytes from patients with hypertrophic cardiomyopathy, mechanical dysfunction and arrhythmogenicity are caused by mutation-driven changes in myofilament function combined with excitation-contraction (E-C) coupling abnormalities related to adverse remodeling. Whether myofilament or E-C coupling alterations are more relevant in disease development is unknown. Here, we aim to investigate whether the relative roles of myofilament dysfunction and E-C coupling remodeling in determining the hypertrophic cardiomyopathy phenotype are mutation specific. Two hypertrophic cardiomyopathy mouse models carrying the R92Q and the E163R TNNT2 mutations were investigated. Echocardiography showed left ventricular hypertrophy, enhanced contractility, and diastolic dysfunction in both models; however, these phenotypes were more pronounced in the R92Q mice. Both E163R and R92Q trabeculae showed prolonged twitch relaxation and increased occurrence of premature beats. In E163R ventricular myofibrils or skinned trabeculae, relaxation following Ca(2+) removal was prolonged; resting tension and resting ATPase were higher; and isometric ATPase at maximal Ca(2+) activation, the energy cost of tension generation, and myofilament Ca(2+) sensitivity were increased compared with that in wild-type mice. No sarcomeric changes were observed in R92Q versus wild-type mice, except for a large increase in myofilament Ca(2+) sensitivity. In R92Q myocardium, we found a blunted response to inotropic interventions, slower decay of Ca(2+) transients, reduced SERCA function, and increased Ca(2+)/calmodulin kinase II activity. Contrarily, secondary alterations of E-C coupling and signaling were minimal in E163R myocardium. In E163R models, mutation-driven myofilament abnormalities directly cause myocardial dysfunction. In R92Q, diastolic dysfunction and arrhythmogenicity are mediated by profound cardiomyocyte signaling and E-C coupling changes. Similar hypertrophic cardiomyopathy phenotypes can be

  9. Identification of established arrhythmogenic right ventricular cardiomyopathy mutation in a patient with the contrasting phenotype of hypertrophic cardiomyopathy.

    Science.gov (United States)

    Bainbridge, Matthew Neil; Li, Lili; Tan, Yanli; Cheong, Benjamin Y; Marian, Ali J

    2017-03-03

    Advances in the nucleic acid sequencing technologies have ushered in the era of genetic-based "precision medicine". Applications of the genetic discoveries to practice of medicine, however, are hindered by phenotypic variability of the genetic variants. The report illustrates extreme pleiotropic phenotypes associated with an established causal mutation for hereditary cardiomyopathy. We report a 61-year old white female who presented with syncope and echocardiographic and cardiac magnetic resonance (CMR) imaging findings consistent with the diagnosis of hypertrophic cardiomyopathy (HCM). The electrocardiogram, however, showed a QRS pattern resembling an Epsilon wave, a feature of arrhythmogenic right ventricular cardiomyopathy (ARVC). Whole exome sequencing (mean depth of coverage of exons 178X) analysis did not identify a pathogenic variant in the known HCM genes but identified an established causal mutation for ARVC. The mutation involves a canonical splice accepter site (c.2146-1G > C) in the PKP2 gene, which encodes plakophillin 2. Sanger sequencing confirmed the mutation. PKP2 is the most common causal gene for ARVC but has not been implicated in HCM. Findings on echocardiography and CMR during the course of 4-year follow up showed septal hypertrophy and a hyperdynamic left ventricle, consistent with the diagnosis of HCM. However, neither baseline nor follow up echocardiography and CMR studies showed evidence of ARVC. The right ventricle was normal in size, thickness, and function and there was no evidence of fibro-fatty infiltration in the myocardium. The patient carries an established pathogenic mutation for ARVC and a subtle finding of ARVC but exhibits the classic phenotype of HCM, a contrasting phenotype to ARVC. The case illustrates the need for detailed phenotypic characterization for patients with hereditary cardiomyopathies as well as the challenges physicians face in applying the genetic discoveries in practicing genetic-based "precision medicine".

  10. Furthering the link between the sarcomere and primary cardiomyopathies: restrictive cardiomyopathy associated with multiple mutations in genes previously associated with hypertrophic or dilated cardiomyopathy.

    Science.gov (United States)

    Caleshu, Colleen; Sakhuja, Rahul; Nussbaum, Robert L; Schiller, Nelson B; Ursell, Philip C; Eng, Celeste; De Marco, Teresa; McGlothlin, Dana; Burchard, Esteban González; Rame, J Eduardo

    2011-09-01

    Mutations in genes that encode components of the sarcomere are well established as the cause of hypertrophic and dilated cardiomyopathies. Sarcomere genes, however, are increasingly being associated with other cardiomyopathies. One phenotype more recently recognized as a disease of the sarcomere is restrictive cardiomyopathy (RCM). We report on two patients with RCM associated with multiple mutations in sarcomere genes not previously associated with RCM. Patient 1 presented with NYHA Class III/IV heart failure at 22 years of age. She was diagnosed with RCM and advanced heart failure requiring heart transplantation. Sequencing of sarcomere genes revealed previously reported homozygous p.Glu143Lys mutations in MYL3, and a novel heterozygous p.Gly57Glu mutation in MYL2. The patient's mother is a double heterozygote for these mutations, with no evidence of cardiomyopathy. Patient 2 presented at 35 years of age with volume overload while hospitalized for oophorectomy. She was diagnosed with RCM and is being evaluated for heart transplantation. Sarcomere gene sequencing identified homozygous p.Asn279His mutations in TPM1. The patient's parents are consanguineous and confirmed heterozygotes. Her father was diagnosed with HCM at 42 years of age. This is the first report of mutations in TPM1, MYL3, and MYL2 associated with primary, non-hypertrophied RCM. The association of more sarcomere genes with RCM provides further evidence that mutations in the various sarcomere genes can cause different cardiomyopathy phenotypes. These cases also contribute to the growing body of evidence that multiple mutations have an additive effect on the severity of cardiomyopathies. Copyright © 2011 Wiley-Liss, Inc.

  11. Late sodium current inhibition reverses electromechanical dysfunction in human hypertrophic cardiomyopathy.

    Science.gov (United States)

    Coppini, Raffaele; Ferrantini, Cecilia; Yao, Lina; Fan, Peidong; Del Lungo, Martina; Stillitano, Francesca; Sartiani, Laura; Tosi, Benedetta; Suffredini, Silvia; Tesi, Chiara; Yacoub, Magdi; Olivotto, Iacopo; Belardinelli, Luiz; Poggesi, Corrado; Cerbai, Elisabetta; Mugelli, Alessandro

    2013-02-05

    Hypertrophic cardiomyopathy (HCM), the most common mendelian heart disorder, remains an orphan of disease-specific pharmacological treatment because of the limited understanding of cellular mechanisms underlying arrhythmogenicity and diastolic dysfunction. We assessed the electromechanical profile of cardiomyocytes from 26 HCM patients undergoing myectomy compared with those from nonfailing nonhypertrophic surgical patients by performing patch-clamp and intracellular Ca(2+) (Ca(2+)(i)) studies. Compared with controls, HCM cardiomyocytes showed prolonged action potential related to increased late Na(+) (I(NaL)) and Ca(2+) (I(CaL)) currents and decreased repolarizing K(+) currents, increased occurrence of cellular arrhythmias, prolonged Ca(2+)(i) transients, and higher diastolic Ca(2+)(i). Such changes were related to enhanced Ca(2+)/calmodulin kinase II (CaMKII) activity and increased phosphorylation of its targets. Ranolazine at therapeutic concentrations partially reversed the HCM-related cellular abnormalities via I(NaL) inhibition, with negligible effects in controls. By shortening the action potential duration in HCM cardiomyocytes, ranolazine reduced the occurrence of early and delayed afterdepolarizations. Finally, as a result of the faster kinetics of Ca(2+)(i) transients and the lower diastolic Ca(2+)(i), ranolazine accelerated the contraction-relaxation cycle of HCM trabeculae, ameliorating diastolic function. We highlighted a specific set of functional changes in human HCM myocardium that stem from a complex remodeling process involving alterations of CaMKII-dependent signaling, rather than being a direct consequence of the causal sarcomeric mutations. Among the several ion channel and Ca(2+)(i) handling proteins changes identified, an enhanced I(NaL) seems to be a major contributor to the electrophysiological and Ca(2+)(i) dynamic abnormalities of ventricular myocytes and trabeculae from patients with HCM, suggesting potential therapeutic implications of

  12. Unequal allelic expression of wild-type and mutated β-myosin in familial hypertrophic cardiomyopathy.

    Science.gov (United States)

    Tripathi, Snigdha; Schultz, Imke; Becker, Edgar; Montag, Judith; Borchert, Bianca; Francino, Antonio; Navarro-Lopez, Francisco; Perrot, Andreas; Özcelik, Cemil; Osterziel, Karl-Josef; McKenna, William J; Brenner, Bernhard; Kraft, Theresia

    2011-11-01

    Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease, which in about 30% of the patients is caused by missense mutations in one allele of the β-myosin heavy chain (β-MHC) gene (MYH7). To address potential molecular mechanisms underlying the family-specific prognosis, we determined the relative expression of mutant versus wild-type MYH7-mRNA. We found a hitherto unknown mutation-dependent unequal expression of mutant to wild-type MYH7-mRNA, which is paralleled by similar unequal expression of β-MHC at the protein level. Relative abundance of mutated versus wild-type MYH7-mRNA was determined by a specific restriction digest approach and by real-time PCR (RT-qPCR). Fourteen samples from M. soleus and myocardium of 12 genotyped and clinically well-characterized FHC patients were analyzed. The fraction of mutated MYH7-mRNA in five patients with mutation R723G averaged to 66 and 68% of total MYH7-mRNA in soleus and myocardium, respectively. For mutations I736T, R719W and V606M, fractions of mutated MYH7-mRNA in M. soleus were 39, 57 and 29%, respectively. For all mutations, unequal abundance was similar at the protein level. Importantly, fractions of mutated transcripts were comparable among siblings, in younger relatives and unrelated carriers of the same mutation. Hence, the extent of unequal expression of mutated versus wild-type transcript and protein is characteristic for each mutation, implying cis-acting regulatory mechanisms. Bioinformatics suggest mRNA stability or splicing effectors to be affected by certain mutations. Intriguingly, we observed a correlation between disease expression and fraction of mutated mRNA and protein. This strongly suggests that mutation-specific allelic imbalance represents a new pathogenic factor for FHC.

  13. Visual evaluation of I-123-betamethyliodophenylpentadecanoic acid (BMIPP) myocardial SPECT findings in hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Bunko, Hisashi; Tonami, Norihisa; Hisada, Kinichi (Kanazawa Univ. (Japan). School of Medicine)

    1993-03-01

    I-123-betamethyliodophenylpentadecanoic acid (BMIPP) is a branched fatty acid analogue for the imaging of myocardial metabolism. Seventeen patients with hypertrophic cardiomyopathy (HCM) and 17 patients with ischemic or valvular heart diseases (non-HCMs) were studied to evaluate the characteristic findings of the BMIPP myocardial images in HCM. Early (20 min) and delayed (3 hr) images were obtained after intravenous injection of 111 MBq of BMIPP with 3-headed SPECT. Tl-201 myocardial SPECT was also obtained within a week of BMIPP SPECT. Regional myocardial uptake of BMIPP relative to Tl-201 and its serial change from early to delayed images were visually evaluated in patient basis as well as segmental basis. Decreased uptake of BMIPP in HCM was frequently seen in anterior, septal, apical and inferior wall. Relatively decreased myocardial uptake of BMIPP (type H+B) was seen in 14 patients (82%) of HCM which was significantly higher than non-HCMs (12%, p<0.001). Number of segments with type H+B was higher in HCM than non-HCMs (mean: 4.59 vs 0.53, p<0.001). This relative decrease of BMIPP uptake was frequently seen in hypertrophied segments of HCM (71%, p<0.01). Serial decrease of regional BMIPP uptake was also frequently seen in HCM especially in hypertrophied myocardium than non-HCMs (76% vs 41%, p<0.01). This was concordant with segmental analysis (mean: 3.41 vs 1.06, p<0.01). Significant decrease in BMIPP image quality in HCM was concordant with higher frequency of serial decrease of BMIPP in HCM. In conclusion, HCM patients frequently showed abnormality of BMIPP uptake and retention which indicated the presence of metabolic abnormality in hypertrophied myocardium. (author).

  14. Familial Hypertrophic Cardiomyopathy: Functional variance among individual cardiomyocytes as a trigger of FHC-phenotype development

    Directory of Open Access Journals (Sweden)

    Bernhard eBrenner

    2014-10-01

    Full Text Available Familial hypertrophic cardiomyopathy (FHC is the most frequent inherited cardiac disease. It has been related to numerous mutations in many sarcomeric and even some non-sarcomeric proteins. So far, however, no common mechanism has been identified by which the many different mutations in different sarcomeric and non-sarcomeric proteins trigger development of the FHC phenotype. Here we show for different MYH7 mutations variance in force pCa-relations from normal to highly abnormal as a feature common to all mutations we studied, while direct functional effects of the different FHC-mutations, e.g., on force generation, ATPase or calcium sensitivity of the contractile system, can be quite different. The functional variation among individual M. soleus fibers of FHC-patients is accompanied by large variation in mutant vs. wildtype β-MyHC-mRNA. Preliminary results show a similar variation in mutant vs. wildtype β-MyHC-mRNA among individual cardiomyocytes. We discuss our previously proposed concept as to how different mutations in the β-MyHC and possibly other sarcomeric and non-sarcomeric proteins may initiate an FHC-phenotype by functional variation among individual cardiomyocytes that results in structural distortions within the myocardium, leading to cellular and myofibrillar disarray. In addition, distortions can activate stretch-sensitive signalling in cardiomyocytes and non-myocyte cells which is known to induce cardiac remodelling with interstitial fibrosis and hypertrophy. Such a mechanism will have major implications for therapeutic strategies to prevent FHC-development, e.g., by reducing functional imbalances among individual cardiomyocytes or by inhibition of their triggering of signalling paths initiating remodelling. Targeting increased or decreased contractile function would require selective targeting of mutant or wildtype protein to reduce functional imbalances.

  15. Pattern of left ventricular hypertrophy seen on transthoracic echo in patients with hypertensive cardiomyopathy when compared with idiopathic hypertrophic cardiomyopathy.

    Science.gov (United States)

    Mirza, Sumbul Javed; Radaideh, Ghazi Ahmad

    2013-01-01

    To explore the pattern of left ventricular hypertrophy caused by hypertension and to compare it with idiopathic hypertrophiccardiomyopathy. The retrospective study was conducted at the echocardiography lab of Rashid Hospital, Dubai, from January 2009 to January 2010. Cases of 11 patients with significant left ventricular hypertrophy (septum > 15 mm) due to underlying hypertension were analysed and compared with 11 cases of idiopathic hypertrophic cardiography (septum >15mm) to assess the two groups with similar baseline echocardiographic features. Minitab software was used for statistical analysis. Although the pattern of hypertrophy in hypertensive patients was more concentric (n = 5; 45%), there was also asymmetrical septal hypertrophy in 4 (36%) cases, particularly the elderly with sigmoid shape septum. There was evidence of resting mid-cavity gradient due to reduced left ventricular end-systolic diametre in 4 (36%) cases. Although the equation between hypertension and left ventricular hypertrophy is more concentric, but it can be associated with left ventricular outflow tract obstruction and significant mid-cavity gradients similar to that seen in idiopathic hypertrophic cardiomyopathy.

  16. Percutaneous Septal Ablation in Hypertrophic Obstructive Cardiomyopathy: From Experiment to Standard of Care

    Directory of Open Access Journals (Sweden)

    Lothar Faber

    2014-01-01

    Full Text Available Hypertrophic cardiomyopathy (HCM is one of the more common hereditary cardiac conditions. According to presence or absence of outflow obstruction at rest or with provocation, a more common (about 60–70% obstructive type of the disease (HOCM has to be distinguished from the less common (30–40% nonobstructive phenotype (HNCM. Symptoms include exercise limitation due to dyspnea, angina pectoris, palpitations, or dizziness; occasionally syncope or sudden cardiac death occurs. Correct diagnosis and risk stratification with respect to prophylactic ICD implantation are essential in HCM patient management. Drug therapy in symptomatic patients can be characterized as treatment of heart failure with preserved ejection fraction (HFpEF in HNCM, while symptoms and the obstructive gradient in HOCM can be addressed with beta-blockers, disopyramide, or verapamil. After a short overview on etiology, natural history, and diagnostics in hypertrophic cardiomyopathy, this paper reviews the current treatment options for HOCM with a special focus on percutaneous septal ablation. Literature data and the own series of about 600 cases are discussed, suggesting a largely comparable outcome with respect to procedural mortality, clinical efficacy, and long-term outcome.

  17. Higher copeptin levels are associated with worse outcome in patients with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Sahin, Irfan; Gungor, Baris; Ozkaynak, Berk; Uzun, Fatih; Küçük, Suat Hayri; Avci, Ilhan Iker; Ozal, Ender; Ayça, Burak; Cetın, Sukru; Okuyan, Ertugrul; Dinckal, Mustafa Hakan

    2017-01-01

    Correlation of increased copeptin levels with various cardiovascular diseases has been described. The clinical use of copeptin levels in patients with hypertrophic cardiomyopathy (HCM) has not been investigated before. In this study, we aimed to investigate the prognostic value of copeptin levels in patients with hypertrophic cardiomyopathy (HCM). HCM was defined as presence of left ventricular wall thickness ≥15 mm in a subject without any concomitant disease that may cause left ventricular hypertrophy. Levels of copeptin and plasma N-terminal probrain natriuretic peptide (NT-proBNP) were evaluated prospectively in 24 obstructive HCM patients, 36 nonobstructive HCM patients, and 36 age- and sex-matched control subjects. Blood samples were collected in the morning between 7 and 9 am after overnight fasting. Patients were followed for 24 months. Hospitalization with diagnosis of heart failure/arrhythmia, implantable cardioverter-defibrillator implantation, and cardiac mortality were accepted as adverse cardiac events. Copeptin and NT-proBNP levels were higher in the HCM group compared with controls (14.1 vs 8.4 pmol/L, P Copeptin and NT-proBNP levels were higher in the obstructive HCM subgroup compared with the nonobstructive HCM subgroup (18.3 vs 13.1 pmol/L, P copeptin and NT-proBNP levels remained as independent predictors of heart failure (P Copeptin and NT-proBNP levels were significantly higher in patients with obstructive HCM, and higher levels were associated with worse outcome. © 2016 Wiley Periodicals, Inc.

  18. Alcohol Septal Ablation for Obstructive Hypertrophic Cardiomyopathy: A Word of Endorsement.

    Science.gov (United States)

    Liebregts, Max; Vriesendorp, Pieter A; Ten Berg, Jurrien M

    2017-07-25

    Twenty years after the introduction of alcohol septal ablation (ASA) for the treatment of obstructive hypertrophic cardiomyopathy, the arrhythmogenicity of the ablation scar appears to be overemphasized. When systematically reviewing all studies comparing ASA with myectomy with long-term follow-up, (aborted) sudden cardiac death and mortality rates were found to be similarly low. The focus should instead shift toward lowering the rate of reinterventions and pacemaker implantations following ASA because, in this area, ASA still seems inferior to myectomy. Part of the reason for this difference is that ASA is limited by the route of the septal perforators, whereas myectomy is not. Improvement may be achieved by: 1) confining ASA to hypertrophic cardiomyopathy centers of excellence with high operator volumes; 2) improving patient selection using multidisciplinary heart teams; 3) use of (3-dimensional) myocardial contrast echocardiography for selecting the correct septal (sub)branch; and 4) use of appropriate amounts of alcohol for ASA. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  19. Invasive assessment of coronary microvascular dysfunction in hypertrophic cardiomyopathy: the index of microvascular resistance

    Energy Technology Data Exchange (ETDEWEB)

    Gutiérrez-Barrios, Alejandro, E-mail: aleklos@hotmail.com [Cardiology Department, Jerez Hospital, Jerez (Spain); Camacho-Jurado, Francisco [Cardiology Department, Punta Europa Hospital, Algeciras (Spain); Díaz-Retamino, Enrique; Gamaza-Chulián, Sergio; Agarrado-Luna, Antonio; Oneto-Otero, Jesús; Del Rio-Lechuga, Ana; Benezet-Mazuecos, Javier [Cardiology Department, Jerez Hospital, Jerez (Spain)

    2015-10-15

    Summary: We present a review of microvascular dysfunction in hypertrophic cardiomyopathy (HCM) and an interesting case of a symptomatic familial HCM patient with inducible ischemia by single photon emission computed tomography. Coronary angiography revealed normal epicardial arteries. Pressure wire measurements of fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microvascular resistance (IMR) demonstrated a significant microcirculatory dysfunction. This is the first such case that documents this abnormality invasively using the IMR. The measurement of IMR, a novel marker of microcirculatory dysfunction, provides novel insights into the pathophysiology of this condition. - Highlights: • Microvascular dysfunction is a common feature in hypertrophic cardiomyopathy (HCM) and represents a strong predictor of unfavorable outcome and cardiovascular mortality. • The index of microvascular resistance (IMR) is a new method for invasively assessing the state of the coronary microcirculation using a single pressure-temperature sensor-tipped coronary wire. • However assessment of IMR in HCM has not been previously reported. We report a case in which microvascular dysfunction is assessed by IMR. This index may be useful in future researches of HCM.

  20. Continuous rhythm monitoring for ventricular arrhythmias after alcohol septal ablation for hypertrophic cardiomyopathy.

    Science.gov (United States)

    Balt, Jippe C; Wijffels, Maurits C E F; Boersma, Lucas V A; Wever, Eric F D; ten Berg, Jurriën M

    2014-12-01

    The purpose of the present study was to determine the incidence of ventricular arrhythmias before and after alcohol septal ablation (ASA). In patients with hypertrophic obstructive cardiomyopathy (HOCM), gradient reduction by ASA is an alternative for surgical myectomy. However, concerns exist about whether the induction of a myocardial scar during ASA may create substrate for ventricular arrhythmias. The study group consisted of 44 patients in whom ASA was performed for symptomatic, drug-refractory hypertrophic cardiomyopathy. Continuous rhythm monitoring was obtained by implantable loop recorder (n=30) or pacemaker (n=14). Occurrence of ventricular and supraventricular arrhythmias before and after ASA was noted, retrospectively. The ASA procedure was considered successful (resting gradient 30 days after ASA. No cardiac deaths occurred during follow-up. In a low-risk cohort of patients who underwent ASA, in which continuous rhythm monitoring was performed, sustained VT or VF within 30 days occurred in 3 patients (7%) while no VT/VF was observed before ASA. During long-term follow-up, no sustained VT or VF was observed >30 days after ASA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  1. Plasma level of big endothelin-1 predicts the prognosis in patients with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Wang, Yilu; Tang, Yida; Zou, Yubao; Wang, Dong; Zhu, Ling; Tian, Tao; Wang, Jizheng; Bao, Jingru; Hui, Rutai; Kang, Lianming; Song, Lei; Wang, Ji

    2017-09-15

    Cardiac remodeling is one of major pathological process in hypertrophic cardiomyopathy (HCM). Endothelin-1 has been linked to cardiac remodeling. Big endothelin-1 is the precursor of endothelin-1. A total of 245 patients with HCM were enrolled from 1999 to 2011 and partitioned to low, middle and high level groups according to their plasma big endothelin-1 levels. At baseline, significant associations were found between high level of big endothelin-1 and left atrium size, heart function and atrial fibrillation. Big endothelin-1 was positively correlated with N-terminal B-type natriuretic peptide (r=0.291, pbig endothelin-1 level was positively associated with the risks of all-cause mortality, cardiovascular death and progression to NYHA class 3 or 4 (p=0.020, 0.044 and 0.032, respectively). The rate of above events in the highest tertile were 18.1%, 15.7%, 24.2%, respectively. After adjusting for multiple factors related to survival and cardiac function, the significance remained in the association of big endothelin-1 with the risk of all-cause mortality (hazard ratio (HR)=4.94, 95% confidence interval (CI) 1.07-22.88; p=0.041) and progression to NYHA class 3 or 4 (HR=4.10, 95%CI 1.32-12.75, p=0.015). Our study showed that high level of plasma big endothelin-1 predicted prognosis for patients with HCM and it can be added to the marker panel in stratifying HCM patients for giving treatment priority to those at high risk. Copyright © 2017. Published by Elsevier B.V.

  2. Myocardial tissue characterization using magnetic resonance noncontrast t1 mapping in hypertrophic and dilated cardiomyopathy.

    Science.gov (United States)

    Dass, Sairia; Suttie, Joseph J; Piechnik, Stefan K; Ferreira, Vanessa M; Holloway, Cameron J; Banerjee, Rajarshi; Mahmod, Masliza; Cochlin, Lowri; Karamitsos, Theodoros D; Robson, Matthew D; Watkins, Hugh; Neubauer, Stefan

    2012-11-01

    Noncontrast magnetic resonance T1 mapping reflects a composite of both intra- and extracellular signal. We hypothesized that noncontrast T1 mapping can characterize the myocardium beyond that achieved by the well-established late gadolinium enhancement (LGE) technique (which detects focal fibrosis) in both hypertrophic (HCM) and dilated (DCM) cardiomyopathy, by detecting both diffuse and focal fibrosis. Subjects underwent Cardiovascular Magnetic Resonance imaging at 3T (28 HCM, 18 DCM, and 12 normals). Matching short-axis slices were acquired for cine, T1 mapping, and LGE imaging (0.1 mmol/kg). Circumferential strain was measured in the midventricular slice, and (31)P magnetic resonance spectroscopy was acquired for the septum of the midventricular slice. Mean T1 relaxation time was increased in HCM and DCM (HCM 1209±28 ms, DCM 1225±42 ms, normal 1178±13 ms, PT1 and LGE (r=0.32, PT1 values were higher in segments with LGE than in those without (HCM with LGE 1228±41 ms versus no LGE 1192±79 ms, PT1 values were significantly higher than normal (PT1 values correlated with disease severity, being increased as wall thickness increased in HCM; conversely, in DCM, T1 values were highest in the thinnest myocardial segments. T1 values also correlated significantly with circumferential strain (r=0.42, PT1 values and phosphocreatine/adenosine triphosphate ratios (r=-0.59, PT1 mapping detects underlying disease processes beyond those assessed by LGE in relatively low-risk individuals.

  3. Physical activity in hypertrophic cardiomyopathy: prevalence of inactivity and perceived barriers

    Science.gov (United States)

    Sweeting, Joanna; Ingles, Jodie; Timperio, Anna; Patterson, Jillian; Ball, Kylie; Semsarian, Christopher

    2016-01-01

    Objectives This study aimed to determine the prevalence of physical inactivity and perceived barriers to physical activity among individuals with hypertrophic cardiomyopathy (HCM), and to determine potential demographic, clinical and health-related factors influencing likelihood of meeting physical activity guidelines. Methods This was a cross-sectional study of consecutive patients (n=198) with HCM attending a specialist HCM centre from July 2014 to November 2015. The primary outcome measure was physical activity (minutes per day), as measured by self-report (International Physical Activity Questionnaire (IPAQ)) and objective means (ActiGraph accelerometer). For both, participants were classified as meeting guidelines if they did at least 150 min per week of physical activity. Quality of life (Short Form-36 V.2, SF-36v2), barriers to exercise and clinical–demographic data were also collected. Results In total, 54.8% of participants did not meet physical activity recommendations based on IPAQ, and 12.7% did not meet guidelines based on accelerometer data. The most commonly identified barriers to exercise were ‘pain interferes with my exercise’ (33%) and ‘I have an injury/disability that stops me’ (29%). Independent factors associated with meeting guidelines included older age (OR 0.66, 95% CI 0.51 to 0.85, p=0.002), higher education level (OR 2.31, 95% CI 1.08 to 4.93, p=0.03), better physical quality of life (OR 1.05, 95% CI 1.0 to 1.09, p=0.05) and more reported barriers (OR 0.71, 95% CI 0.56 to 0.91, p=0.01). Conclusions More than half of the patients with HCM did not meet minimum physical activity recommendations. Several barriers to exercise among individuals with HCM exist, and provide the basis for targeted interventions to promote physical activity and improve overall health in patients with HCM. PMID:27547438

  4. Intracoronary electrocardiogram during alcohol septal ablation for hypertrophic obstructive cardiomyopathy predicts myocardial injury size.

    Science.gov (United States)

    Meng, Jing; Qu, Xiaolong; Huang, Haiyun; Zhang, Shanwen; Zhao, Weibo; He, Guoxiang; Song, Zhiyuan; Hu, Houyuan

    2016-01-01

    Alcohol septal ablation (ASA) has been used widely to treat patients with hypertrophic obstructive cardiomyopathy (HOCM). During the routine ASA procedure, it is difficult to detect the septal injury in real-time. The aim of the present study is to assess myocardial injury during ASA by recording intracoronary electrocardiogram (IC-ECG). From 2012 to 2015, 31 HOCM patients were treated with ASA, and IC-ECG was recorded in 21 patients successfully before and after ethanol injection. The elevation of ST-segment on IC-ECG after ethanol injection was expressed as its ratio to the level before injection or the absolute increasing value. Blood samples were collected before and after ASA for measuring changes in cardiac biomarkers. The ratio value of ST-segment elevation was positively correlated with both the amount of ethanol injected (r = 0.645, P = 0.001) and the myocardial injury size (creatine kinase-MB area under the curve (AUC) of CK-MB) (r = 0.466, P = 0.017). The absolute increment of ST-segment was also positively associated with both the amount of ethanol (r = 0.665, P = 0.001) and AUC of CK-MB (0.685, P = 0.001). However, there was no statistical correlation between the reduction of left ventricular outflow tract gradient and ST-segment elevation. Additionally no severe ASA procedure-related complications were observed in our patients. In conclusion, myocardial injury induced by ethanol injection can be assessed immediately by ST-segment elevation on IC-ECG. This study is the first to show that IC-ECG is a useful method for predicting myocardial injury during ASA in real-time. © 2015 Wiley Publishing Asia Pty Ltd.

  5. Physical activity in hypertrophic cardiomyopathy: prevalence of inactivity and perceived barriers.

    Science.gov (United States)

    Sweeting, Joanna; Ingles, Jodie; Timperio, Anna; Patterson, Jillian; Ball, Kylie; Semsarian, Christopher

    2016-01-01

    This study aimed to determine the prevalence of physical inactivity and perceived barriers to physical activity among individuals with hypertrophic cardiomyopathy (HCM), and to determine potential demographic, clinical and health-related factors influencing likelihood of meeting physical activity guidelines. This was a cross-sectional study of consecutive patients (n=198) with HCM attending a specialist HCM centre from July 2014 to November 2015. The primary outcome measure was physical activity (minutes per day), as measured by self-report (International Physical Activity Questionnaire (IPAQ)) and objective means (ActiGraph accelerometer). For both, participants were classified as meeting guidelines if they did at least 150 min per week of physical activity. Quality of life (Short Form-36 V.2, SF-36v2), barriers to exercise and clinical-demographic data were also collected. In total, 54.8% of participants did not meet physical activity recommendations based on IPAQ, and 12.7% did not meet guidelines based on accelerometer data. The most commonly identified barriers to exercise were 'pain interferes with my exercise' (33%) and 'I have an injury/disability that stops me' (29%). Independent factors associated with meeting guidelines included older age (OR 0.66, 95% CI 0.51 to 0.85, p=0.002), higher education level (OR 2.31, 95% CI 1.08 to 4.93, p=0.03), better physical quality of life (OR 1.05, 95% CI 1.0 to 1.09, p=0.05) and more reported barriers (OR 0.71, 95% CI 0.56 to 0.91, p=0.01). More than half of the patients with HCM did not meet minimum physical activity recommendations. Several barriers to exercise among individuals with HCM exist, and provide the basis for targeted interventions to promote physical activity and improve overall health in patients with HCM.

  6. N-acetylcysteine reverses diastolic dysfunction and hypertrophy in familial hypertrophic cardiomyopathy.

    Science.gov (United States)

    Wilder, Tanganyika; Ryba, David M; Wieczorek, David F; Wolska, Beata M; Solaro, R John

    2015-11-15

    S-glutathionylation of cardiac myosin-binding protein C (cMyBP-C) induces Ca(2+) sensitization and a slowing of cross-bridge kinetics as a result of increased oxidative signaling. Although there is evidence for a role of oxidative stress in disorders associated with hypertrophic cardiomyopathy (HCM), this mechanism is not well understood. We investigated whether oxidative myofilament modifications may be in part responsible for diastolic dysfunction in HCM. We administered N-acetylcysteine (NAC) for 30 days to 1-mo-old wild-type mice and to transgenic mice expressing a mutant tropomyosin (Tm-E180G) and nontransgenic littermates. Tm-E180G hearts demonstrate a phenotype similar to human HCM. After NAC administration, the morphology and diastolic function of Tm-E180G mice was not significantly different from controls, indicating that NAC had reversed baseline diastolic dysfunction and hypertrophy in our model. NAC administration also increased sarco(endo)plasmic reticulum Ca(2+) ATPase protein expression, reduced extracellular signal-related kinase 1/2 phosphorylation, and normalized phosphorylation of phospholamban, as assessed by Western blot. Detergent-extracted fiber bundles from NAC-administered Tm-E180G mice showed nearly nontransgenic (NTG) myofilament Ca(2+) sensitivity. Additionally, we found that NAC increased tension cost and rate of cross-bridge reattachment. Tm-E180G myofilaments were found to have a significant increase in S-glutathionylation of cMyBP-C, which was returned to NTG levels upon NAC administration. Taken together, our results indicate that oxidative myofilament modifications are an important mediator in diastolic function, and by relieving this modification we were able to reverse established diastolic dysfunction and hypertrophy in HCM. Copyright © 2015 the American Physiological Society.

  7. Factors Influencing the Phenotypic Expression of Hypertrophic Cardiomyopathy in Genetic Carriers.

    Science.gov (United States)

    Pérez-Sánchez, Inmaculada; Romero-Puche, Antonio José; García-Molina Sáez, Esperanza; Sabater-Molina, María; López-Ayala, José María; Muñoz-Esparza, Carmen; López-Cuenca, David; de la Morena, Gonzalo; Castro-García, Francisco José; Gimeno-Blanes, Juan Ramón

    2017-07-04

    Hypertrophic cardiomyopathy (HCM) is a disorder with variable expression. It is mainly caused by mutations in sarcomeric genes but the phenotype could be modulated by other factors. The aim of this study was to determine whether factors such as sex, systemic hypertension, or physical activity are modifiers of disease severity and to establish their role in age-related penetrance of HCM. We evaluated 272 individuals (mean age 49 ± 17 years, 57% males) from 72 families with causative mutations. The relationship between sex, hypertension, physical activity, and left ventricular hypertrophy was studied. The proportion of affected individuals increased with age. Men developed the disease 12.5 years earlier than women (adjusted median, 95%CI, -17.52 to -6.48; P < .001). Hypertensive patients were diagnosed with HCM later (10.8 years of delay) than normotensive patients (adjusted median, 95%CI, 6.28-17.09; P < .001). Individuals who performed physical activity were diagnosed with HCM significantly earlier (7.3 years, adjusted median, 95%CI, -14.49 to -1.51; P = .016). Sex, hypertension, and the degree of physical activity were not significantly associated with the severity of left ventricular hypertrophy. Adjusted survival both free from sudden death and from the combined event were not influenced by any of the exploratory variables. Men and athletes who are carriers of sarcomeric mutations are diagnosed earlier than women and sedentary individuals. Hypertensive carriers of sarcomeric mutations have a delayed diagnosis. Sex, hypertension, and physical activity are not associated with disease severity in carriers of HCM causative mutations. Copyright © 2017 Sociedad Española de Cardiología. All rights reserved.

  8. Screening of MYH7, MYBPC3, and TNNT2 genes in Brazilian patients with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Marsiglia, Julia Daher Carneiro; Credidio, Flávia Laghi; de Oliveira, Théo Gremen Mimary; Reis, Rafael Ferreira; Antunes, Murillo de Oliveira; de Araujo, Aloir Queiroz; Pedrosa, Rodrigo Pinto; Barbosa-Ferreira, João Marcos Bemfica; Mady, Charles; Krieger, José Eduardo; Arteaga-Fernandez, Edmundo; Pereira, Alexandre da Costa

    2013-10-01

    Hypertrophic cardiomyopathy (HC) is the most prevalent genetic cardiac disease caused by a mutation in sarcomeres, Z-disks, or calcium-handling genes and is characterized by unexplained left ventricular hypertrophy. The aim of this study was to determine the genetic profile of Brazilian patients with HC and correlate the genotype with the phenotype. We included 268 index patients from São Paulo city and 3 other cities in Brazil and extracted their DNA from whole blood. We amplified the coding sequencing of MYH7, MYBPC3, and TNNT2 genes and sequenced them with an automatic sequencer. We identified causal mutations in 131 patients (48.8%). Seventy-eight (59.5%) were in the MYH7 gene, 50 (38.2%) in the MYBPC3 gene, and 3 (2.3%) in the TNNT2 gene. We identified 69 mutations, 24 not previously described. Patients with an identified mutation were younger at diagnosis and at current age, had a higher mean heart rate and higher nonsustained ventricular tachycardia frequency compared with those without a mutation. Patients with MYH7 gene mutations had a larger left atrium and higher frequency of atrial fibrillation than did patients with MYBPC3 gene mutations. The presence of a mutation in one of the genes suggests a worse prognosis. Mutations in the MYH7 gene, rather than in the MYBPC3 gene, were also related to a worse prognosis. This is the first work characterizing HC molecular epidemiology in the Brazilian population for the 3 most important genes. © 2013.

  9. Late enhanced computed tomography in Hypertrophic Cardiomyopathy enables accurate left-ventricular volumetry

    Energy Technology Data Exchange (ETDEWEB)

    Langer, Christoph; Lutz, M.; Kuehl, C.; Frey, N. [Christian-Albrechts-Universitaet Kiel, Department of Cardiology, Angiology and Critical Care Medicine, University Medical Center Schleswig-Holstein (Germany); Partner Site Hamburg/Kiel/Luebeck, DZHK (German Centre for Cardiovascular Research), Kiel (Germany); Both, M.; Sattler, B.; Jansen, O; Schaefer, P. [Christian-Albrechts-Universitaet Kiel, Department of Diagnostic Radiology, University Medical Center Schleswig-Holstein (Germany); Harders, H.; Eden, M. [Christian-Albrechts-Universitaet Kiel, Department of Cardiology, Angiology and Critical Care Medicine, University Medical Center Schleswig-Holstein (Germany)

    2014-10-15

    Late enhancement (LE) multi-slice computed tomography (leMDCT) was introduced for the visualization of (intra-) myocardial fibrosis in Hypertrophic Cardiomyopathy (HCM). LE is associated with adverse cardiac events. This analysis focuses on leMDCT derived LV muscle mass (LV-MM) which may be related to LE resulting in LE proportion for potential risk stratification in HCM. N=26 HCM-patients underwent leMDCT (64-slice-CT) and cardiovascular magnetic resonance (CMR). In leMDCT iodine contrast (Iopromid, 350 mg/mL; 150mL) was injected 7 minutes before imaging. Reconstructed short cardiac axis views served for planimetry. The study group was divided into three groups of varying LV-contrast. LeMDCT was correlated with CMR. The mean age was 64.2 ± 14 years. The groups of varying contrast differed in weight and body mass index (p < 0.05). In the group with good LV-contrast assessment of LV-MM resulted in 147.4 ± 64.8 g in leMDCT vs. 147.1 ± 65.9 in CMR (p > 0.05). In the group with sufficient contrast LV-MM appeared with 172 ± 30.8 g in leMDCT vs. 165.9 ± 37.8 in CMR (p > 0.05). Overall intra-/inter-observer variability of semiautomatic assessment of LV-MM showed an accuracy of 0.9 ± 8.6 g and 0.8 ± 9.2 g in leMDCT. All leMDCT-measures correlated well with CMR (r > 0.9). LeMDCT primarily performed for LE-visualization in HCM allows for accurate LV-volumetry including LV-MM in > 90 % of the cases. (orig.)

  10. Tissue Doppler-derived indices predict exercise capacity in patients with apical hypertrophic cardiomyopathy.

    Science.gov (United States)

    Ha, Jong-Won; Cho, Jung-Rae; Kim, Jin-Mi; Ahn, Jeong-Ah; Choi, Eui-Young; Kang, Seok-Min; Rim, Se-Joong; Chung, Namsik

    2005-11-01

    Although impaired left ventricular (LV) diastolic function is a prominent feature of hypertrophic cardiomyopathy (HCM), diastolic function and its relation to exercise capacity in apical HCM (ApHCM) has not been explored previously. This study was sought to determine the relationship between diastolic mitral annular velocities combined with conventional Doppler indexes and exercise capacity in patients with ApHCM. Twenty-nine patients with ApHCM (24 men; mean age +/- SD, 57 +/- 10 years) underwent supine bicycle exercise with simultaneous respiratory gas analysis and two-dimensional and Doppler echocardiographic study. The mitral inflow velocities (early filling [E], late filling, and deceleration time) were traced and measured. Early diastolic mitral annular velocity (E') was measured at the septal corner of mitral annulus by Doppler tissue imaging (DTI) from the apical four-chamber view. Pro-brain natriuretic peptide (proBNP) was measured at the time of echocardiography using a quantitative electrochemiluminescence immunoassay. E/E' ratio correlated inversely with maximal oxygen uptake (Vo(2)max) [r = - 0.47, p = 0.0106]. There was a significant positive correlation between E' and Vo(2)max (r = 0.41, p = 0.024). However, no correlation was found between conventional two-dimensional, Doppler indices, and proBNP and Vo(2)max). Of all the echocardiographic and clinical parameters assessed, E/E' ratio had the best correlation with exercise capacity (r - 0.47) and was the strongest independent predictor of Vo(2)max by multivariate analysis (p = 0.0106). DTI-derived indexes (E', E/E' ratio), an estimate of myocardial relaxation and LV filling pressures, correlate with exercise capacity in patients with ApHCM, suggesting that abnormal diastolic function may be a factor limiting exercise capacity.

  11. Implantable Cardioverter-defibrillator Therapy for Hypertrophic Cardiomyopathy: Usefulness in Primary and Secondary Prevention.

    Science.gov (United States)

    Sarrias, Axel; Galve, Enrique; Sabaté, Xavier; Moya, Àngel; Anguera, Ignacio; Núñez, Elaine; Villuendas, Roger; Alcalde, Óscar; García-Dorado, David

    2015-06-01

    Hypertrophic cardiomyopathy is a frequent cause of sudden death. Clinical practice guidelines indicate defibrillator implantation for primary prevention in patients with 1 or more risk factors and for secondary prevention in patients with a history of aborted sudden death or sustained ventricular arrhythmias. The aim of the present study was to analyze the follow-up of patients who received an implantable defibrillator following the current guidelines in nonreferral centers for this disease. This retrospective observational study included all patients who underwent defibrillator implantation between January 1996 and December 2012 in 3 centers in the province of Barcelona. The study included 69 patients (mean age [standard deviation], 44.8 [17] years; 79.3% men), 48 in primary prevention and 21 in secondary prevention. The mean number of risk factors per patient was 1.8 in the primary prevention group and 0.5 in the secondary prevention group (P=.029). The median follow-up duration was 40.5 months. The appropriate therapy rate was 32.7/100 patient-years in secondary prevention and 1.7/100 patient-years in primary prevention (P<.001). Overall mortality was 10.1%. Implant-related complications were experienced by 8.7% of patients, and 13% had inappropriate defibrillator discharges. In patients with a defibrillator for primary prevention, the appropriate therapy rate is extremely low, indicating the low predictive power of the current risk stratification criteria. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  12. Diagnostic performance of ultrasonic tissue characterization for subendocardial ischaemia in patients with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Kawasaki, Tatsuya; Yamano, Michiyo; Sakai, Chieko; Harimoto, Kuniyasu; Miki, Shigeyuki; Kamitani, Tadaaki; Sugihara, Hiroki

    2013-08-01

    Hypertrophic cardiomyopathy (HCM) patients often develop left--ventricular subendocardial ischaemia, a cause of chest symptoms, despite normal epicardial coronary arteries. The aim of this study was to examine whether ultrasonic tissue characterization or late gadolinium enhancement on cardiac magnetic resonance imaging can detect subendocardial ischaemia in patients with HCM. Subendocardial ischaemia was quantified on exercise Tc-99m tetrofosmin myocardial scintigraphy in 29 non-obstructive HCM patients with asymmetric septal hypertrophy. Ultrasonic tissue characterization using cyclic variation of integrated backscatter (CV-IB) and late gadolinium enhancement on cardiac magnetic resonance imaging were analysed separately in the right halves and the left halves of the ventricular septum in relation to subendocardial ischaemia. Subendocardial ischaemia was identified in 17 (59%) patients. The ratio of CV-IB in the right-to-left halves of the ventricular septum was significantly higher in patients with subendocardial ischaemia (1.19 ± 0.10) than those without (0.84 ± 0.10, P = 0.04). The optimal cutoff for the detection of subendocardial ischaemia was the ratio of CV-IB >1.0, with a sensitivity of 80%, specificity of 71%, and accuracy of 76%. On the other hand, late gadolinium enhancement was not associated with subendocardial ischaemia in our cohort. Ultrasonic tissue characterization using CV-IB separately in the right and left halves of the ventricular septum, but not late gadolinium enhancement on magnetic resonance imaging, provided useful information in detecting subendocardial ischaemia in patients with HCM. Ultrasonic tissue characterization may be useful in selecting patients who will benefit from medications to relieve chest symptoms.

  13. Prevalence of exercise-induced left ventricular outflow tract obstruction in symptomatic patients with non-obstructive hypertrophic cardiomyopathy.

    LENUS (Irish Health Repository)

    Shah, J S

    2008-10-01

    Resting left ventricular outflow tract obstruction (LVOTO) occurs in 25% of patients with hypertrophic cardiomyopathy (HCM) and is an important cause of symptoms and disease progression. The prevalence and clinical significance of exercise induced LVOTO in patients with symptomatic non-obstructive HCM is uncertain.

  14. Validation of the HCM Risk-SCD model in patients with hypertrophic cardiomyopathy following alcohol septal ablation

    DEFF Research Database (Denmark)

    Liebregts, Max; Faber, Lothar; Jensen, Morten K

    2018-01-01

    Aims: The HCM Risk-SCD model for prediction of sudden cardiac death (SCD) in hypertrophic cardiomyopathy recommended by the 2014 European Society of Cardiology (ESC) guidelines has not been validated after septal reduction therapy. The aim of this study was to validate the HCM Risk-SCD model...

  15. One third of Danish hypertrophic cardiomyopathy patients with MYH7 mutations have mutations [corrected] in MYH7 rod region

    DEFF Research Database (Denmark)

    Hougs, Lotte; Havndrup, Ole; Bundgaard, Henning

    2005-01-01

    Familial hypertrophic cardiomyopathy (FHC) is, in most cases, a disease of the sarcomere, caused by a mutation in one of 10 known sarcomere disease genes. More than 266 mutations have been identified since 1989. The FHC disease gene first characterized MYH7, encodes the cardiac beta-myosin heavy...

  16. Life-long tailoring of management for patients with hypertrophic cardiomyopathy: Awareness and decision-making in changing scenarios

    NARCIS (Netherlands)

    M. Michels (Michelle); I. Olivotto (Iacopo); F.W. Asselbergs (Folkert); J. van der Velden (Jolanda)

    2017-01-01

    textabstractHypertrophic cardiomyopathy (HCM) is the most common genetic heart disease, characterised by complex pathophysiology and extensive genetic and clinical heterogeneity. In most patients, HCM is caused by mutations in cardiac sarcomere protein genes and inherited as an autosomal dominant

  17. Life-long tailoring of management for patients with hypertrophic cardiomyopathy : Awareness and decision-making in changing scenarios

    NARCIS (Netherlands)

    Michels, M.; Olivotto, I; Asselbergs, F. W.|info:eu-repo/dai/nl/270752137; van der Velden, J.

    2017-01-01

    Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease, characterised by complex pathophysiology and extensive genetic and clinical heterogeneity. In most patients, HCM is caused by mutations in cardiac sarcomere protein genes and inherited as an autosomal dominant trait. The

  18. Complex phenotype linked to a mutation in exon 11 of the lamin A/C gene: Hypertrophic cardiomyopathy, atrioventricular block, severe dyslipidemia and diabetes.

    Science.gov (United States)

    Francisco, Ana Rita G; Santos Gonçalves, Inês; Veiga, Fátima; Mendes Pedro, Mónica; Pinto, Fausto J; Brito, Dulce

    2017-09-01

    The lamin A/C (LMNA) gene encodes lamins A and C, which have an important role in nuclear cohesion and chromatin organization. Mutations in this gene usually lead to the so-called laminopathies, the primary cardiac manifestations of which are dilated cardiomyopathy and intracardiac conduction defects. Some mutations, associated with lipodystrophy but not cardiomyopathy, have been linked to metabolic abnormalities such as diabetes and severe dyslipidemia. Herein we describe a new phenotype associated with a mutation in exon 11 of the LMNA gene: hypertrophic cardiomyopathy, atrioventricular block, severe dyslipidemia and diabetes. A 64-year-old woman with hypertrophic cardiomyopathy and a point mutation in exon 11 of the LMNA gene (c.1718C>T, Ser573Leu) presented with severe symptomatic ventricular hypertrophy and left ventricular outflow tract obstruction. She underwent septal alcohol ablation, followed by Morrow myectomy. The patient was also diagnosed with severe dyslipidemia, diabetes and obesity, and fulfilled diagnostic criteria for metabolic syndrome. No other characteristics of LMNA mutation-related phenotypes were identified. The development of type III atrioventricular block with no apparent cause, and mildly depressed systolic function, prompted referral for cardiac resynchronization therapy. In conclusion, the association between LMNA mutations and different phenotypes is complex and not fully understood, and can present with a broad spectrum of severity. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. A Comparison of Whole Genome Sequencing to Multigene Panel Testing in Hypertrophic Cardiomyopathy Patients.

    Science.gov (United States)

    Cirino, Allison L; Lakdawala, Neal K; McDonough, Barbara; Conner, Lauren; Adler, Dale; Weinfeld, Mark; O'Gara, Patrick; Rehm, Heidi L; Machini, Kalotina; Lebo, Matthew; Blout, Carrie; Green, Robert C; MacRae, Calum A; Seidman, Christine E; Ho, Carolyn Y

    2017-10-01

    As DNA sequencing costs decline, genetic testing options have expanded. Whole exome sequencing and whole genome sequencing (WGS) are entering clinical use, posing questions about their incremental value compared with disease-specific multigene panels that have been the cornerstone of genetic testing. Forty-one patients with hypertrophic cardiomyopathy who had undergone targeted hypertrophic cardiomyopathy genetic testing (either multigene panel or familial variant test) were recruited into the MedSeq Project, a clinical trial of WGS. Results from panel genetic testing and WGS were compared. In 20 of 41 participants, panel genetic testing identified variants classified as pathogenic, likely pathogenic, or uncertain significance. WGS identified 19 of these 20 variants, but the variant detection algorithm missed a pathogenic 18 bp duplication in myosin binding protein C (MYBPC3) because of low coverage. In 3 individuals, WGS identified variants in genes implicated in cardiomyopathy but not included in prior panel testing: a pathogenic protein tyrosine phosphatase, non-receptor type 11 (PTPN11) variant and variants of uncertain significance in integrin-linked kinase (ILK) and filamin-C (FLNC). WGS also identified 84 secondary findings (mean=2 per person, range=0-6), which mostly defined carrier status for recessive conditions. WGS detected nearly all variants identified on panel testing, provided 1 new diagnostic finding, and allowed interrogation of posited disease genes. Several variants of uncertain clinical use and numerous secondary genetic findings were also identified. Whereas panel testing and WGS provided similar diagnostic yield, WGS offers the advantage of reanalysis over time to incorporate advances in knowledge, but requires expertise in genomic interpretation to appropriately incorporate WGS into clinical care. URL: https://clinicaltrials.gov. Unique identifier: NCT01736566. © 2017 American Heart Association, Inc.

  20. [Hypertrophic cardiomyopathy with ventricular septal hypertrophy localized to the apical region of the left ventricle (apical ASH)].

    Science.gov (United States)

    Koga, Y; Takahashi, H; Ifuku, M; Itaya, M; Adachi, K; Toshima, H

    1984-08-01

    Clinical and morphologic features are described in a subgroup of 22 patients with hypertrophic cardiomyopathy, who showed ventricular septal hypertrophy localized to the apical region (apical asymmetric septal hypertrophy: apical ASH). All patients had ventricular septal thickness of 17 mm or less with an average of 13 +/- 3 mm in the M-mode echocardiograms. In contrast, the two-dimensional echocardiograms demonstrated septal hypertrophy localized to the apical region, with an average septal thickness of 20 +/- 3 mm at the mitral valve and papillary muscle levels. On the left ventriculogram, 82% of patients with apical ASH showed inward concavity of the right-inferior wall of the left ventricle, indicating hypertrophy of the ventricular septum. However, no patient showed spade-like appearance of the left ventricle and only two showed giant T wave inversion exceeding 10 mm. Echocardiographic examination performed in eight affected relatives revealed typical asymmetric septal hypertrophy (ASH) in four relatives, one of them showing a resting pressure gradient of 30 mmHg in the left ventricle. The remaining four relatives showed similar apical ASH. When compared with patients of typical ASH, patients with apical ASH demonstrated significantly greater cardiac size, left ventricular end-diastolic pressure, left atrial and left ventricular diameters and significantly lower percent fractional shortening. Atrial fibrillation, B bump of the mitral echogram and heart failure were more frequent in this subgroup of patients. Thus, apical ASH appeared to be a part of the morphologic spectrum of hypertrophic cardiomyopathy with ASH and to be a separate disease entity from apical hypertrophy previously described in Japan. Severely impaired diastolic performances associated with mild to moderately depressed systolic function of the left ventricle were the characteristic clinical features of the subgroup of patients with apical ASH.

  1. Inappropriate Shock Due to T-Wave Oversensing by a Subcutaneous ICD after Alcohol Septal Ablation for Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Van Dijk, Vincent F; Liebregts, Max; Luermans, Justin G L M; Balt, Jippe C

    2016-03-01

    A 53-year-old female patient with hypertrophic obstructive cardiomyopathy (HOCM) was admitted for alcohol septal ablation (ASA). A subcutaneous internal cardioverter defibrillator (S-ICD) was implanted for primary prevention. After ASA, the patient developed a right bundle branch block, and the S-ICD delivered a total of five inappropriate shocks due to T-wave oversensing (TWOS). TWOS is a relatively frequent cause of inappropriate shocks in S-ICD patients. After invasive treatment for HOCM, there is a risk of developing intraventricular conduction delay and subsequent changes in QRS and T-wave morphology. This should be taken into consideration when ICD indication is evaluated in HOCM patients. ©2015 Wiley Periodicals, Inc.

  2. A case of mid-apical obstructive hypertrophic cardiomyopathy treated with a transapical myectomy approach: a case report.

    Science.gov (United States)

    Scudeler, Thiago Luis; Rezende, Paulo Cury; Oikawa, Fernando Teiichi Costa; da Costa, Leandro Menezes Alves; Hueb, Alexandre Ciappina; Hueb, Whady

    2014-11-11

    Hypertrophic cardiomyopathy is a genetic cardiac disease characterized by marked variability in morphological expression and natural history. The hypertrophic myocardium is often confined to the septum or lateral wall of the left ventricle, but it can also be encountered in the middle or apical segments of the myocardium. Treatment is based on medical therapy. Others therapies, such as embolization of the septal artery or ventriculomyectomy, are indicated in special situations. Surgery is the standard treatment, and it is classically done via a transaortic approach; however, in cases in which the hypertrophic myocardium is confined to mid-apical segments, a transapical approach is an option. Only a few cases of mid-apical obstructive hypertrophic cardiomyopathy treated with a myectomy using a transapical approach have been reported in the English-language literature. In this report, we present a case of a patient with mid-apical obstructive hypertrophic cardiomyopathy treated using this new approach. A 63-year-old Caucasian woman presented with a history of chest pain and shortness of breath causing significant limitations on her daily life activities. She had a history of coronary artery disease. Her physical examination was unremarkable. Transthoracic echocardiography revealed normal systolic function and significant concentric left ventricular hypertrophy that was greater in the mid-apical region. Nuclear magnetic resonance imaging confirmed significant hypertrophy of the median segments of the left ventricle. The patient had persistent symptoms despite receiving optimized medical treatment, and a surgical approach was indicated. As a myectomy using transaortic technique was thought to be difficult to perform in her case, a transapical approach was used. No complications occurred, and her symptoms resolved. A transapical myectomy should be taken into consideration for patients with mid-apical obstructive hypertrophic cardiomyopathy that is refractory to medical

  3. A Meta-analysis on the correlation between the polymorphism of angiotensin converting enzyme gene and hypertrophic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Ling CHEN

    2014-01-01

    Full Text Available Objective To systematically investigate the correlation between the polymorphism of angiotensin converting enzyme (ACE gene I/D and hypertrophic cardiomyopathy. Methods The databases, such as PubMed, Embase, OVID, Web of Science, Cochrane library, CNKI, WanFang Data and VIP, were searched to collect the studies on the correlation between ACE I/D polymorphism and hypertrophic cardiomyopathy susceptibility. Studies that met the inclusion criteria were Meta-analyzed using Stata 11.0 software. Results Fifteen articles were collected including 1114 cases and 1648 controls. The Meta-analysis indicated that there was significant correlation between the 4 models of ACE I/D polymorphism and hypertrophic cardiomyopathy susceptibility [D vs I: OR=1.49, 95%CI (1.20, 1.84; DD vs (ID+II: OR=1.56, 95%CI (1.17, 2.08; (DD+ID vs II: OR=1.76, 95%CI (1.30, 2.38; DD vs II: OR=2.20, 95%CI (1.44, 3.37]. In subgroup analysis, the significant difference existed in Asian population, but no significance was found in European population (P<0.05. Conclusions There is a positive correlation between hypertrophic cardiomyopathy and ACE I/D polymorphism in population, and D allele and DD genotype are likely to be the risk factors of hypertrophic cardiomyopathy. But such correlation does not exist in European population. DOI: 10.11855/j.issn.0577-7402.2013.12.07

  4. Myocardial tissue characterization in hypertrophic cardiomyopathy. Comparison between Gd-DTPA enhanced MR signal intensity ratio and myocardial biopsy

    Energy Technology Data Exchange (ETDEWEB)

    Tsukihashi, Hironori; Shimada, Toshio; Ishibashi, Yutaka [Shimane Medical Univ., Izumo (Japan)] [and others

    1995-09-01

    The aim of this study is to demonstrate whether Gd-DTPA enhanced magnetic resonance imaging (Gd-EMRI) can be used to evaluate myocardial tissue characterization. We performed Gd-EMRI in 20 patients with hypertrophic cardiomyopathy (HCM) and 6 normal controls. Ventricular myocardial biopsy was performed in 7 patients. Gd-EMRI was obtained every 10 minutes from 5 to 50 minutes after intravenous Gd-DTPA (0.1 mmol/kg) injection. Signal intensity (SI) in hypertrophic region of myocardium was measured from LV short axis image. We standardized the data according to following equations. IR (intensity ratio) =SI (myocardium) /SI (skeletal muscle). SIR=IR (in time course) /IR (before Gd-DTPA injection). SIR in HCM was delayed in time course compared with that in normal controls. Interstitial fibrosis was prominent when SIR (peak) minus SIR (40min. after) /SIR (peak) was small. The delayed decay of IR in HCM was closely related to the grade of interstitial fibrosis rather than the edema of interstitial tissue or the myocardial cell diameter. We conclude that the decay analysis with Gd-EMRI is useful to evaluate myocardial tissue characterization closely related to myocardial fibrosis in comparison with cardiac histology. (author).

  5. Atrioventricular conduction after alcohol septal ablation for obstructive hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Axelsson, Anna; Weibring, Kristina; Havndrup, Ole

    2014-01-01

    .1-9.4) after ASA. Patients with high-grade atrioventricular block at follow-up had longer PR intervals at baseline [205 ms (200-230)] than the rest of the cohort [180 ms (140-200), P = 0.004] and a higher incidence of acute complete heart block (63 vs. 15%; P = 0.007) during ASA. A PR interval of at least 200...... ms at baseline was associated with higher prevalence of high-grade atrioventricular block at follow-up (30 vs. 2%; P = 0.0013). The incidence of late-onset complete heart block was 1.5% per year after ASA. CONCLUSION: We found normalized atrioventricular conduction at long-term follow-up, suggesting...... recovery in 6 of 14 patients with a pacemaker implanted in relation to ASA. Permanent atrioventricular conduction abnormalities were associated with baseline PR intervals of at least 200 ms and acute persistent complete heart block during ASA....

  6. Carriers of the hypertrophic cardiomyopathy MYBPC3 mutation are characterized by reduced myocardial efficiency in the absence of hypertrophy and microvascular dysfunction

    NARCIS (Netherlands)

    Timmer, Stefan A. J.; Germans, Tjeerd; Brouwer, Wessel P.; Lubberink, Mark; van der Velden, Jolanda; Wilde, Arthur A. M.; Christiaans, Imke; Lammertsma, Adriaan A.; Knaapen, Paul; van Rossum, Albert C.

    2011-01-01

    Next to left ventricular (LV) hypertrophy, hypertrophic cardiomyopathy (HCM) is characterized by microvascular dysfunction and reduced myocardial external efficiency (MEE). Insights into the presence of these abnormalities as early markers of disease are of clinical importance in risk

  7. Redistribution of myocardial perfusion during permanent dual chamber pacing in symptomatic non-obstructive hypertrophic cardiomyopathy : A quantitative positron emission tomography study

    NARCIS (Netherlands)

    Posma, JL; Blanksma, PK; vanderWall, EE

    Dual chamber pacing causes significant symptomatic improvement in many patients with hypertrophic cardiomyopathy. The mechanism behind this beneficial response is not fully understood. Positron emission tomography showed a redistribution of myocardial flow during pacing in a patient with

  8. Periprocedural Complications and Long-Term Outcome After Alcohol Septal Ablation Versus Surgical Myectomy in Hypertrophic Obstructive Cardiomyopathy A Single-Center Experience

    NARCIS (Netherlands)

    Steggerda, Robbert C.; Damman, Kevin; Balt, Jippe C.; Liebregts, Max; ten Berg, Jurrien M.; van den Berg, Maarten P.

    2014-01-01

    OBJECTIVES This study compared alcohol septal ablation (ASA) and surgical myectomy for periprocedural complications and long-term clinical outcome in patients with symptomatic hypertrophic obstructive cardiomyopathy. BACKGROUND Debate remains whether ASA is equally effective and safe compared with

  9. An International External Validation Study of the 2014 European Society of Cardiology Guideline on Sudden Cardiac Death Prevention in Hypertrophic Cardiomyopathy (Evidence from HCM)

    DEFF Research Database (Denmark)

    O'Mahony, Constantinos; Jichi, Fatima; Ommen, Steve R

    2018-01-01

    Background -Identification of people with hypertrophic cardiomyopathy (HCM) who are at risk of sudden cardiac death (SCD) and require prophylactic implantable cardioverter defibrillator (ICD) is challenging. In 2014, the European Society of Cardiology (ESC) proposed a new risk stratification meth...

  10. Assessment of atrial diastolic function in patients with hypertrophic cardiomyopathy by cine magnetic resonance imaging.

    Science.gov (United States)

    Grassedonio, Emanuele; Todiere, Giancarlo; La Grutta, Ludovico; Toia, Patrizia; Gentile, Giovanni D; Galia, Massimo; Midiri, Federico; Pepe, Alessia; Midiri, Massimo; Aquaro, Giovanni Donato

    2015-08-01

    This study was conducted to assess the role of atrial function by cardiac magnetic resonance (CMR) for the evaluation of diastolic physiology in patients with hypertrophic cardiomyopathy (HCM) compared to healthy controls. We enrolled 23 consecutive patients affected by HCM and 43 healthy subjects as age-matched control cases (CC). CMR was performed through acquisition of cine steady-state free precession sequences using a 1.5-T scanner. Image postprocessing was carried out using Tracking Tool software. Atrial volumes were significantly higher in patients with HCM compared to CC: maximum atrial volume (p = 0.007) and minimum atrial volume (p = 0.01). A statistically significant difference was also observed in atrial ejection fraction in patients with HCM (p study demonstrated that in HCM patients with early diastolic dysfunction the parameters of left atrial function assessed by CMR are impaired before the ventricular diastolic indexes such as the early peak filling rate and the active peak filling rate.

  11. Effects of alcohol septal ablation on coronary microvascular function and myocardial energetics in hypertrophic obstructive cardiomyopathy.

    Science.gov (United States)

    Timmer, Stefan A J; Knaapen, Paul; Germans, Tjeerd; Dijkmans, Pieter A; Lubberink, Mark; Ten Berg, Jurrien M; Ten Cate, Folkert J; Rüssel, Iris K; Götte, Marco J W; Lammertsma, Adriaan A; van Rossum, Albert C

    2011-07-01

    This study investigated the effects of alcohol septal ablation (ASA) on microcirculatory function and myocardial energetics in patients with hypertrophic cardiomyopathy (HCM) and left ventricular outflow tract (LVOT) obstruction. In 15 HCM patients who underwent ASA, echocardiography was performed before and 6 mo after the procedure to assess the LVOT gradient (LVOTG). Additionally, [(15)O]water PET was performed to obtain resting myocardial blood flow (MBF) and coronary vasodilator reserve (CVR). Changes in LV mass (LVM) and volumes were assessed by cardiovascular magnetic resonance imaging. Myocardial oxygen consumption (MVo(2)) was evaluated by [(11)C]acetate PET in a subset of seven patients to calculate myocardial external efficiency (MEE). After ASA, peak LVOTG decreased from 41 ± 32 to 23 ± 19 mmHg (P = 0.04), as well as LVM (215 ± 74 to 169 ± 63 g; P energetics.

  12. [Athlete's heart and hypertrophic cardiomyopathy: contribution on clinical and morphologic differentiation].

    Science.gov (United States)

    Bahlmann, Edda; Kuck, Karl Heinz; Nienaber, Christoph A

    2015-07-01

    Hypertrophic cardiomyopathy (HCM) is a complex genetic disorder usually diagnosed in a young adult population. The diagnosis is based on echocardiographic identification of left ventricular hypertrophy, associated with a non-dilated hyperdynamic chamber in the absence of another cardiac or systemic disorder. The differentiation between HCM and physiological left ventricular hypertrophy (athlete`s heart) is essential: HCM is the main cause of exercise-induced sudden cardiac death in the young and especially in young athletes with overlapping features in Athlete's Heart or HCM. Differentiation between physiological left ventricular hypertrophy and HCM is challenging. Echocardiography allows detailed assessment of left ventricular structure and function which is fundamental. Additional genetic studies for identification of the broad HCM phenotype can be necessary to differentiate between Athlete's Heart and HCM. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Supraventricular arrhythmia as the cause of sudden death in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Madariaga, I; Carmona, J R; Mateas, F R; Lezaun, R; de los Arcos, E

    1994-01-01

    Electrophysiological studies with simultaneous echocardiographic control and invasive measurement of intravascular pressures were carried out in a 13-year-old boy with hypertrophic cardiomyopathy who was hospitalized after an episode of aborted sudden death. Ventricular stimulation did not induce ventricular tachycardia, but atrial stimulation induced atrial fibrillation, atrial flutter and non-sustained ventricular tachycardia. Atrial stimulation (S1) at 200 beats.min-1 (10-15 s) also induced significant repolarization abnormalities in the 5-10 post-stimulation beats. Akinesia of the ventricular septum and posterior wall without opening of the mitral valve was documented by echocardiography. A complete anterior systolic motion, not observed under basal conditions, was detected in the first post-stimulation beat. Atrial stimulation at rates over 120 beats.min-1 caused a drop in systolic blood pressure, a rise in pulmonary artery pressure, and a decrease in cardiac output. Despite therapy with propranolol and amiodarone, the patient died suddenly.

  14. Safety profile and utility of treadmill exercise in patients with high-gradient hypertrophic cardiomyopathy

    DEFF Research Database (Denmark)

    Sorensen, Lars Lindholm; Liang, Hsin-Yueh; Pinheiro, Aurelio

    2017-01-01

    BACKGROUND: Exercise echocardiography in the evaluation of hypertrophic cardiomyopathy (HCM) provides valuable information for risk stratification, selection of optimal treatment, and prognostication. However, HCM patients with left ventricular outflow tract gradients ≥30mm Hg are often excluded....... Patients were divided based on peak left ventricular outflow tract gradients using a 30-mm Hg threshold into the following: obstructive (n=152), labile-obstructive (n=178), and nonobstructive (n=169) groups. RESULTS: There were no deaths during exercise testing. We noted 20 complications (2.1% of tests......) including 3 serious ventricular arrhythmias (0.3% of tests). There was no difference in complication rate between groups. Patients with obstructive HCM had a higher frequency of abnormal blood pressure response (obstructive: 53% vs labile: obstructive: 41% and nonobstructive: 37%; P=.008). Obstructive...

  15. MicroRNAs Based Therapy of Hypertrophic Cardiomyopathy: The Road Traveled So Far

    Directory of Open Access Journals (Sweden)

    Catarina Roma-Rodrigues

    2015-01-01

    Full Text Available Hypertrophic cardiomyopathy (HCM is an autosomal dominant disease characterized by variable expressivity, age penetrance, and a high heterogeneity. The transcriptional profile (miRNAs, mRNAs, epigenetic modifications, and posttranslational modifications seem to be highly relevant for the onset of the disease. miRNAs, small noncoding RNAs with 22 nucleotides, have been implicated in the regulation of cardiomyocyte function, being differentially expressed in several heart diseases, including HCM. Moreover, a different miRNA expression profile in the various stages of HCM development is also observed. This review summarizes the current knowledge of the profile of miRNAs characteristic of asymptomatic to overt HCM patients, discussing alongside their potential use for diagnosis and therapy. Indeed, the stability and specificity of miRNAs make them suitable targets for use as biomarkers for diagnosis and prognosis and as therapeutical targets.

  16. Hypertrophic cardiomyopathy

    Science.gov (United States)

    ... arteries that feed the thickened part of the heart (alcohol septal ablation). People who have this procedure often show much improvement. You may need surgery to repair the heart's mitral valve if it is leaking.

  17. Pathophysiology and meaning of washout rate in hypertrophic heart. Comparison between hypertensive cardiac hypertrophy and hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Nitta, Yutaka (Kanazawa Univ. (Japan). School of Medicine)

    1989-02-01

    The present study was attempted to clarify clinically the pathogenesis of hypertensive cardiac hypertrophy (HT) and hypertrophic cardiomyopathy (HCM). The exercise thallium-201 (Tl-201) myocardial scintigraphy by bicycle ergometer was performed in three groups: control, HT and HCM. The scintigrams were evaluated by circumferential profile analysis. Furthermore, the change of Tl-201 dynamics of exercise Tl-201 scintigraphy with verapamil injection was compared with the change of coronary sinus flow after verapamil injection at cardiac catheterization. The analysis of exercise Tl-201 scintigraphy without verapamil injection showed that initial uptake was not different among the three groups, but washout rate at three hours after Tl-201 injection (WR{sub 3}) was different among the three groups. Although WR{sub 3} of HT was not different from that of control, WR{sub 3} of HCM was lower than that of control. Comparison of WR{sub 3} with and without verapamil was performed. Although WR{sub 3} with verapamil injection was equal to that without verapamil injection in control and HT, WR{sub 3} with verapamil injection decreased compared to that without verapamil injection in HCM. As an index at the time that circulation changes rapidly and on a large scale, washout rate at one hour after Tl-201 injection (WR{sub 1}) was calculated. WR{sub 1} without verapamil injection was not different in the three groups and did not differ from that with verapamil injection in each group. By intravenous administration of verapamil, coronary sinus flow (CSF) increased to the same extent in the three groups. And the increment of CSF was not different in the three groups. (J.P.N.).

  18. Daily Step Count as a Simple Marker of Disease Severity in Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Sweeting, Joanna; Ingles, Jodie; Ball, Kylie; Semsarian, Christopher

    2018-01-31

    Individuals with hypertrophic cardiomyopathy (HCM) may be asymptomatic or display activity-limiting symptoms. A common cause of symptoms is left ventricular outflow tract obstruction (LVOTO), which may impact the individuals' ability to undertake physical activity. This study sought to examine daily step count as a potential marker of exercise capacity, which may represent a proxy marker of disease severity in HCM. A cross-sectional study of 63 HCM patients was conducted from March to November 2015. Participants wore an ActiGraph GT3X+ (Pensacola, Florida, USA) accelerometer for 7 days. Minutes per day of light, moderate and vigorous physical activity and step count were calculated, and those with LVOTO were compared to those without. Similarly, those with good functional capacity (New York Heart Association; NYHA class I) were compared to those with NYHA class II-IV. The majority of HCM patients were male (n=45, 71%) with mean age of 48.8±14.9years. Hypertrophic cardiomyopathy patients with history of LVOTO and those NYHA class II-IV took significantly fewer steps per day (LV obstruction: 5527±2370 versus 7027±2095, p=0.01 and NYHA: 5346±1898 versus 6801±2339, p=0.03). No differences were observed across the different intensities of physical activity. Measurement of daily step count may be a useful and simple tool to determine exercise capacity and provide an indicator of disease severity in individuals with HCM. Copyright © 2018 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. Effects of losartan on left ventricular hypertrophy and fibrosis in patients with nonobstructive hypertrophic cardiomyopathy.

    Science.gov (United States)

    Shimada, Yuichi J; Passeri, Jonathan J; Baggish, Aaron L; O'Callaghan, Caitlin; Lowry, Patricia A; Yannekis, Gia; Abbara, Suhny; Ghoshhajra, Brian B; Rothman, Richard D; Ho, Carolyn Y; Januzzi, James L; Seidman, Christine E; Fifer, Michael A

    2013-12-01

    The aim of this study was to evaluate the effects of losartan on left ventricular (LV) hypertrophy and fibrosis in patients with nonobstructive hypertrophic cardiomyopathy (HCM). Despite evidence that myocardial hypertrophy and fibrosis are mediated by angiotensin II and are important determinants of morbidity and mortality in patients with HCM, no prior studies have evaluated the effects of angiotensin receptor blockers on LV hypertrophy and fibrosis with cardiac magnetic resonance imaging. In double-blind fashion, 20 patients (3 women, 17 men; age: 51 ± 13 years) with HCM were randomly assigned to receive placebo (n = 9) or losartan 50 mg twice a day (n = 11) for 1 year. Cardiac magnetic resonance imaging was performed at baseline and 1 year to measure LV mass and extent of fibrosis as assessed by late gadolinium enhancement. There was a trend toward a significant difference in the percent change in LV mass (median [interquartile range]: +5% [-4% to +21%] with placebo vs. -5% [-11% to -0.9%] with losartan; p = 0.06). There was a significant difference in the percent change in extent of late gadolinium enhancement, with the placebo group experiencing a larger increase (+31% ± 26% with placebo vs. -23% ± 45% with losartan; p = 0.03). This pilot study suggests attenuation of progression of myocardial hypertrophy and fibrosis with losartan in patients with nonobstructive HCM. Confirmation of these results in a larger trial is required to confirm a place for angiotensin receptor blockers in the management of patients with HCM. (Effect of Losartan in Patients With Nonobstructive Hypertrophic Cardiomyopathy; NCT01150461). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  20. Influence of dynamic obstruction and hypertrophy location on diastolic function in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Avegliano, Gustavo; Costabel, J Pablo; Huguet, Marina; Thierer, Jorge; Trivi, Marcelo; Catalina, Tobon-Gomez; Petit, Mario; Bijnens, Bart; Frangi, Alejandro; Ronderos, Ricardo

    2014-03-01

    Hypertrophic cardiomyopathy (HCM) is a disease with marked genetic and phenotypic heterogeneity. It is well known that obstructive septal forms of this disease entail worse clinical outcome compared with nonobstructive septal and apical forms. The objective of this study was to analyze the differences in left ventricular diastolic function in different subgroups of HCMs and to assess the influence of the location of myocardial hypertrophy and the presence of dynamic obstruction on impairment of diastolic function and its correlation with the clinical status. We studied 86 patients with HCM; 27 with the obstructive asymmetric septal type (OAS), 37 with the nonobstructive asymmetric septal type (NOAS) and 22 with apical hypertrophic cardiomyopathy (ApHCM). Patients underwent conventional and tissue Doppler echocardiography and were assessed applying the latest recommendations regarding diastolic dysfunction. Cardiac magnetic resonance was used to study the various morphologic subtypes and quantify left ventricular mass (LVM). The early diastolic annular velocity (e') was significantly lower in OAS with a median of 5 cm/s compared with NOAS with 7 cm/s and ApHCM with 7.5 cm/s (P = 0.0002), and the E/e' ratio was 8.5 in ApHCM, 10 in NOAS and 14 in OAS (P = 0.0001); no significant differences were found in LVM or maximal wall thickness. In HCM, the location of left ventricular hypertrophy and the presence of dynamic obstruction affect the degree of diastolic dysfunction; impairment is greater in patients with the OAS type, and markedly less in patients with apical involvement.

  1. Virtual Cardiac Surgery Using CFD: Application to Septal Myectomy in Obstructive Hypertrophic Cardiomyopathy

    Science.gov (United States)

    Vedula, Vijay; Mittal, Rajat; Abraham, Theodore

    2011-11-01

    Obstructive hypertrophic cardiomyopathy (HOCM) is characterized by ventricular wall thickening, diastolic dysfunction, and dynamic outflow tract obstruction, all of which strongly influence the vortex dynamics and pressure distribution in the left ventricle (LV). Severe cases of HCM are usually managed through septal myectomy where the surgeon resects the hypertrophic mass. Surgeons currently try to remove as much tissue as possible in order to optimize the post surgical result. However, excessive debulking increases the chance of ventricular septal defects, bundle branch block or complete heart block, and aneurysmal septal thinning. On the other hand, insufficient tissue removal also leads to unsatisfactory outcomes in terms of reduction of outflow tract pressure gradient. Knowing how much muscle to remove and where to remove it from could reduce the likelihood of complications and suboptimal outcomes. In the present study, we employ an immersed boundary solver to model the effect of septal myectomy for ventricles with HOCM and demonstrate the potential of such an approach for surgical planning. Computational resources were provided by the National Institute of Computational Science under Tergrid grant number TG-CTS100002.

  2. Relationship between electrocardiographic features and distribution of hypertrophy in patients with hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Tetsuya; Nakamura, Kazufumi; Yamanari, Hiroshi; Ohe, Tohru [Okayama Univ. (Japan). School of Medicine; Yoshinouchi, Takeo

    1998-07-01

    To evaluate the relationship between the distribution of hypertrophy and the electrocardiographic findings in patients with hypertrophic cardiomyopathy (HCM), 54 HCM patients were studied using magnetic resonance imaging. The patients were divided into 4 groups according to hypertrophic patterns: hypertrophy only at the apex (group I, n=12); hypertrophy in both the apex and base (group II, n=20); hypertrophy only at the base with asymmetric septal hypertrophy (ASH) (group IIIa, n=17); and hypertrophy only at the base without ASH (group IIIb, n=5). Abnormal Q waves in leads II, III and aV{sub F} were found in 1/12, 3/20, 10/17 and 0/5, respectively, and in leads I and aV{sub L} they were found in 1/12, 8/20, 4/17 and 1/5, respectively. The largest negative T waves (mm) were found in group I (group I vs group II vs group IIIa vs group IIIb: 15.2{+-}5.3, 8.2{+-}6.1, 1.6{+-}2.0, 0.8{+-}1.3, respectively). The largest positive T waves (mm) were identified in group IIIb (3.8{+-}3.0, 6.8{+-}3.2, 5.8{+-}3.6, 9.3{+-}2.1, respectively). The presence of abnormal Q waves reflected regional hypertrophy in HCM patients but the configuration of T waves represented the difference in the localization of hypertrophy between the basal and apical segments. (author)

  3. Myocardial Fibrosis in Hypertrophic Cardiomyopathy Demonstrated by Integrated Cardiac F-18 FDG PET/MR

    Energy Technology Data Exchange (ETDEWEB)

    Kong, Eunjung; Lee, Sanghee; Cho, Ihnho [Yeungnam Univ., Daegu (Korea, Republic of)

    2013-09-15

    Hypertrophic cardiomyopathy (HCM) is a common condition defined as a diffuse or segmental left ventricular (LV) hypertrophy with a nondilated and hyperdynamic chamber as well as cardiac arrhythmias. Cardiac MR (CMR) imaging is a key modality for evaluation of HCM. In addition to the assessment of LV wall thickness, LV function and aortic flow, CMR is capable of estimation of late gadolinium enhancement (LGE) in affected myocardium which has been shown to have a direct correlation with incidence and severity of arrhythmias in HCM. In patients with HCM, LGE on CMR is presumed to represent intramyocardial fibrosis. Meanwhile, F-18 FDG myocardial PET has been sporadically studied in HCM, mostly for evaluation of the metabolic status of a hypertrophic myocardial segment, especially after interventions or to demonstrate partial myocardial fibrosis. We presented here the case of a 25-year-old male patient referred for simultaneous F-18 FDG cardiac PET/MR for the evaluation of septal hypertrophy. The PET/MR revealed myocardial fibrosis in the septum associated with FDG-defect and LGE.

  4. Ventricular hypertrophy in cardiomyopathy.

    Science.gov (United States)

    Oakley, C

    1971-01-01

    Semantic difficulties arise when hypertrophic obstructive cardiomyopathy is seen without obstruction and with congestive failure, and also when congestive cardiomyopathy is seen with gross hypertrophy but without heart failure. Retention of a small left ventricular cavity and a normal ejection fraction characterizes hypertrophic cardiomyopathy at all stages of the disorder. Congestive cardiomyopathy is recognized by the presence of a dilated left ventricular cavity and reduced ejection fraction regardless of the amount of hypertrophy and the presence or not of heart failure. Longevity in congestive cardiomyopathy seems to be promoted when hypertrophy is great relative to the amount of pump failure as measured by increase in cavity size. Conversely, death in hypertrophic cardiomyopathy is most likely when hypertrophy is greatest at a time when outflow tract obstruction has been replaced by inflow restriction caused by diminishing ventricular distensibility. Hypertrophy is thus beneficial and compensatory in congestive cardiomyopathy, whereas it may be the primary disorder and eventual cause of death in hypertrophic cardiomyopathy. Reasons are given for believing that hypertension may have been the original cause of left ventricular dilatation in some case of congestive cardiomyopathy in which loss of stroke output thenceforward is followed by normotension. Development of severe hypertension in these patients after recovery from a prolonged period of left ventricular failure with normotension lends weight to this hypothesis. No fault has been found in the large or small coronary arteries in either hypertrophic cardiomyopathy or congestive cardiomyopathy when they have been examined in life by selective coronary angiography, or by histological methods in biopsy or post-mortem material. Coronary blood supply may be a limiting factor in the compensatory hypertrophy of congestive cardiomyopathy, and the ability to hypertrophy may explain the better prognosis of some

  5. Metabolic crosstalk between the heart and liver impacts familial hypertrophic cardiomyopathy.

    Science.gov (United States)

    Magida, Jason A; Leinwand, Leslie A

    2014-04-01

    Familial hypertrophic cardiomyopathy (HCM) is largely caused by dominant mutations in genes encoding cardiac sarcomeric proteins, and it is etiologically distinct from secondary cardiomyopathies resulting from pressure/volume overload and neurohormonal or inflammatory stimuli. Here, we demonstrate that decreased left ventricular contractile function in male, but not female, HCM mice is associated with reduced fatty acid translocase (CD36) and AMP-activated protein kinase (AMPK) activity. As a result, the levels of myocardial ATP and triglyceride (TG) content are reduced, while the levels of oleic acid and TG in circulating very low density lipoproteins (VLDLs) and liver are increased. With time, these metabolic changes culminate in enhanced glucose production in male HCM mice. Remarkably, restoration of ventricular TG and ATP deficits via AMPK agonism as well as inhibition of gluconeogenesis improves ventricular architecture and function. These data underscore the importance of the systemic effects of a primary genetic heart disease to other organs and provide insight into potentially novel therapeutic interventions for HCM.

  6. The Role of Cardiac MRI in the Diagnosis and Risk Stratification of Hypertrophic Cardiomyopathy

    Science.gov (United States)

    Maron, Martin S

    2016-01-01

    Hypertrophic cardiomyopathy (HCM), the most common genetic cardiomyopathy, is a disease characterised by substantial heterogeneity. Although the majority of patients with HCM remain asymptomatic with near-normal longevity, a small, but important, subset remain at risk for a wide range of clinical outcomes including sudden death. Cardiovascular magnetic resonance (CMR), with its high spatial resolution and tomographic imaging capability, has emerged as an imaging modality particularly well suited to characterise the phenotypic expression of HCM. CMR helps in the diagnosis of HCM by identifying areas of hypertrophy not well visualised by echocardiography, providing more accurate wall thickness measurements and differentiating HCM from other causes of left ventricular (LV) hypertrophy. CMR has led to the identification of novel subgroups of patients with HCM, including those with LV apical aneurysms (a subgroup at increased risk for ventricular arrhythmias and thromboembolic stroke), as well as abnormalities that contribute to LV outflow obstruction. Additionally, contrast-enhanced CMR with late-gadolinium enhancement (LGE) has recognised patients with extensive LGE (≥15 % LV myocardium) as individuals who may be at increased risk of sudden death, independent of other high-risk features, with implications on management strategies including consideration for primary prevention implantable cardioverter defibrillator therapy. These observations justify an expanded role of CMR in the routine clinical assessment of patients with HCM. PMID:28116085

  7. Significant regional heterogeneity of coronary flow reserve in paediatric hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Tadamura, E.; Kudoh, T.; Kubo, S.; Konishi, J. [Kyoto Univ. (Japan). School of Medicine; Yoshibayashi, M.; Yonemura, T. [Dept. of Pediatrics, Kyoto Univ. Graduate School of Medicine, Kyoto (Japan); Motooka, M.; Nohara, R.; Matsumori, A.; Sasayama, S. [Third Div., Dept. of Internal Medicine, Kyoto Univ. Graduate School of Medicine, Kyoto (Japan); Matsuda, T. [Dept. of Medical Informatics, Kyoto Univ. Graduate School of Medicine, Kyoto (Japan); Tamaki, N. [Dept. of Nuclear Medicine, Hokkaido Univ. School of Medicine, Sapporo (Japan)

    2000-09-01

    Previous studies have indicated that cardiac events in young patients with hypertrophic cardiomyopathy (HCM) are related to ischaemia rather than to arrhythmia. We measured coronary flow reserve in paediatric HCM and compared the values with those in adult HCM. We studied 12 patients with HCM including six paediatric (<20 years old; mean 13 years) and six adult patients (>20 years old: mean 62 years), and six healthy young adults (mean 29 years) as controls. Every patient underwent magnetic resonance imaging (MRI) for anatomical assessment. Myocardial blood flow at rest and after dipyridamole infusion was measured with dynamic nitrogen-13 ammonia positron emission tomography (PET). Partial volume effect was corrected for using the anatomical data obtained with MRI. In adult patients with HCM, coronary flow reserve in the hypertrophied septal region was not significantly different from that in the non-hypertrophied lateral wall (1.38{+-}0.29 vs 1.77{+-}0.39, respectively). In the paediatric patients, coronary flow reserve in the hypertrophied septal region was significantly lower than in the non-hypertrophied lateral wall (0.84{+-}0.33 vs 2.74{+-}0.90, respectively, P<0.01). In addition, coronary flow reserve in adult patients was lower than in control subjects both in the septal wall (1.38{+-}0.29 vs 2.94{+-}0.35, respectively, P<0.0001) and in the lateral wall (1.77{+-}0.39 vs 2.85{+-}0.69, respectively, P<0.05). In contrast, coronary flow reserve in paediatric patients was not significantly different from that in control subjects in the lateral wall (2.74{+-}0.90 vs 2.85{+-}0.69, respectively), while absolute reduction of myocardial blood flow was noted after pharmacological vasodilatation in the hypertrophied septal region. In conclusion, significant regional differences of coronary flow reserve were present in the paediatric patients with HCM. These results suggest that paediatric patients with HCM intrinsically have the potential to experience significant

  8. [Advanced sequelae of apical hypertrophic cardiomyopathy: report of two cases with wall motion abnormalities].

    Science.gov (United States)

    Kusukawa, J; Suwa, M; Nakayama, Y; Hirota, Y; Kawamura, K; Adachi, I; Akagi, H

    1988-03-01

    In view of the paucity of reports describing symptoms of increased degree, and deterioration of left ventricular systolic function in patients with apical hypertrophic cardiomyopathy (apical HCM), two cases with congestive heart failure and progressive thinning of previously hypertrophied apical portions of the left ventricle are reported. These were among 13 patients observed from eight to 10 years. Case 1: A 56-year-old man was diagnosed as having apical HCM at the age of 49 years. Severe left ventricular hypertrophy and prominent ST-T changes were observed on ECG during his first admission. His left ventricular end-diastolic pressure (LVEDP) was 24 mmHg and a left ventriculo-gram revealed a decrease in the left ventricular cavity in the apex and marked hypertrophy of the apical wall. Moderate interstitial fibrosis without hypertrophy or disarray of myocytes was observed in a left ventricular endomyocardial biopsy specimen. In two episodes of cardiac arrest he was successfully resuscitated at the age of 50 years. At the age of 55 years, two-dimensional echocardiography revealed thinning and abnormal motion in the apical wall, and a defect in 201T1 accumulation was observed in the same region by perfusion scintigraphy. This patient was readmitted with a diagnosis of cerebral embolism at the age of 56 years. Cardiac catheterization revealed normal LVEDP (8 mmHg), and a left ventriculogram revealed an aneurysm in the left ventricular apex with normal major epicardial coronary arteries. He has been under treatment with antiarrhythmic medications, calcium antagonists and anticoagulants, and has become relatively asymptomatic. Case 2: A 69-year-old-man was diagnosed as having apical HCM after a complete evaluation, including cardiac catheterization, at the age of 59 years. His LVEDP was elevated (17 mmHg), and a left ventricular angiogram revealed marked hypertrophy localized to the apex. Ejection fraction was 64%. A left ventricular endomyocardial biopsy revealed

  9. Cardiomyopathies and anaesthesia

    Directory of Open Access Journals (Sweden)

    Rajiv Juneja

    2017-01-01

    Full Text Available Cardiomyopathy is considered as a heart muscle disease of multiple aetiologies, unlike other cardiac diseases related to a definitive pathophysiology. With more and more research and with the advent of genetic analysis pin pointing the disease causing mutations, causative factors have been defined and classifications and definitions have changed over time. Patients with these conditions present to anaesthesiologists in elective and emergency situations, placement of automated internal cardioverter defibrillator (AICD devices or biventricular pacing but may also be diagnosed at anaesthetic pre-assessment. We describe cardiomyopathies such as dilated cardiomyopathy, hypertrophic cardiomyopathy, post-partum cardiomyopathy and Takotsubo cardiomyopathy in brief and their anaesthetic management.

  10. Ablation of plasma membrane Ca(2+)-ATPase isoform 4 prevents development of hypertrophy in a model of hypertrophic cardiomyopathy.

    Science.gov (United States)

    Prasad, Vikram; Lorenz, John N; Lasko, Valerie M; Nieman, Michelle L; Jiang, Min; Gao, Xu; Rubinstein, Jack; Wieczorek, David F; Shull, Gary E

    2014-12-01

    The mechanisms linking the expression of sarcomeric mutant proteins to the development of pathological hypertrophy in hypertrophic cardiomyopathy (HCM) remain poorly understood. We investigated the role of the plasma membrane Ca(2+)-ATPase PMCA4 in the HCM phenotype using a transgenic model that expresses mutant (Glu180Gly) α-tropomyosin (Tm180) in heart. Immunoblot analysis revealed that cardiac PMCA4 expression was upregulated early in Tm180 disease pathogenesis. This was accompanied by an increase in levels of the L-type Ca(2+)-channel, which is implicated in pathological hypertrophy. When Tm180 mice were crossed with a PMCA4-null line, loss of PMCA4 caused the abrogation of hypertrophy in Tm180/PMCA4-null double mutant mice. RT-PCR analysis of Tm180/PMCA4-null hearts revealed blunting of the fetal program and reversion of pro-fibrotic Col1a1 and Col3a1 gene expression to wild-type levels. This was accompanied by evidence of reduced L-type Ca(2+)-channel expression, and diminished calcineurin activity. Expression of the metabolic substrate transporters glucose transporter 4 and carnitine palmitoyltransferase 1b was preserved and Tm180-related changes in mRNA levels of various contractile stress-related proteins including the cardiac ankyrin protein CARP and the N2B isoform of titin were reversed in Tm180/PMCA4-null hearts. cGMP levels were increased and phosphorylation of vasodilator-stimulated phosphoprotein was elevated in Tm180/PMCA4-null hearts. These changes were associated with a sharp reduction in left ventricular end-diastolic pressure in Tm180/PMCA4-null hearts, which occurred despite persistence of Tm180-related impairment of relaxation dynamics. These results reveal a novel and specific role for PMCA4 in the Tm180 hypertrophic phenotype, with the "protective" effects of PMCA4 deficiency encompassing multiple determinants of HCM-related hypertrophy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Disease Stage-Dependent Changes in Cardiac Contractile Performance and Oxygen Utilization Underlie Reduced Myocardial Efficiency in Human Inherited Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Güçlü, Ahmet; Knaapen, Paul; Harms, Hendrik J; Parbhudayal, Rahana Y; Michels, Michelle; Lammertsma, Adriaan A; van Rossum, Albert C; Germans, Tjeerd; van der Velden, Jolanda

    2017-05-01

    Reduced myocardial efficiency represents a target for therapy in hypertrophic cardiomyopathy although therapeutic benefit may depend on disease stage. Here, we determined disease stage-dependent changes in myocardial efficiency and effects of myectomy surgery. Myocardial external efficiency (MEE) was determined in 27 asymptomatic mutation carriers (genotype positive/phenotype negative), 10 patients with hypertrophic obstructive cardiomyopathy (HOCM), 10 patients with aortic valve stenosis, and 14 healthy individuals using [ 11 C]-acetate positron emission tomography and cardiovascular magnetic resonance imaging. Follow-up measurements were performed in HOCM and aortic valve stenosis patients 4 months after surgery. External work did not differ in HOCM compared with controls, whereas myocardial oxygen consumption was lower in HOCM. Because of a higher cardiac mass, total cardiac oxygen consumption was significantly higher in HOCM than in controls and genotype positive/phenotype negative. MEE was significantly lower in genotype positive/phenotype negative than in controls (28±6% versus 42±6%) and was further decreased in HOCM (22±5%). In contrast to patients with aortic valve stenosis, MEE was not improved in patients with HOCM after surgery, which was explained by opposite changes in the septum (decrease) and lateral (increase) wall. Different mechanisms underlie reduced MEE at the early and advanced stage of hypertrophic cardiomyopathy. The initial increase and subsequent reduction in myocardial oxygen consumption during disease progression indicates that energy deficiency is a primary mutation-related event, whereas mechanisms secondary to disease remodeling underlie low MEE in HOCM. Our data highlight that the benefit of therapies to improve energetic status of the heart may vary depending on the disease stage and that treatment should be initiated before cardiac remodeling. © 2017 American Heart Association, Inc.

  12. Canopy 2 attenuates the transition from compensatory hypertrophy to dilated heart failure in hypertrophic cardiomyopathy.

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    Guo, Jian; Mihic, Anton; Wu, Jun; Zhang, Yuemei; Singh, Kaustabh; Dhingra, Sanjiv; Weisel, Richard D; Li, Ren-Ke

    2015-10-01

    A mismatch between adequate angiogenesis and overgrowth of myocytes may be a critical mechanism controlling the transition from adaptive hypertrophy to heart failure. Canopy 2 (CNPY2) was recently identified as a secreted, HIF-1α-regulated angiogenic growth factor. As angiogenic factors play important roles in the development of myocardial hypertrophy, we investigated the role of CNPY2 in molecular and functional changes during development of chronic heart failure using cardiac-specific transgenic (TG) mice that overexpress human CNPY2. We generated TG mice that constitutively express CNPY2 in the myocardium. Cardiomyopathy was induced in TG and wild-type (WT) mice by transverse aortic constriction (TAC). WT mice developed significant ventricular hypertrophy at 4 weeks and severe dilatation and heart failure at 12 weeks after TAC. However, TG mice preserved much better cardiac structure and function, with less severe ventricular dilatation and markedly reduced cardiac apoptosis and fibrosis following TAC. Excess CNPY2 in TG mice prevented significant loss of vasculature up to 12 weeks after TAC injury, resulting in a better local myocardial environment that facilitated myocyte survival and prevented excessive matrix remodelling compared with WT mice. TG mice had less accumulation of endogenous tumor suppressor p53 after TAC, indicating intrinsic activation of the p53-mediated repression of HIF-1α, and Cnpy2 was diminished in TG mice compared with WT controls. Our study showed a correlation between downregulation of endogenous mouse Cnpy2 and p53-mediated HIF-1α inhibition during late-stage hypertrophic development. Additional CNPY2 attenuated the transition from compensatory hypertrophic response to maladaptive ventricular dilatation and heart failure. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  13. Doppler echocardiographic evaluation of midventricular obstruction in cats with hypertrophic cardiomyopathy.

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    MacLea, H B; Boon, J A; Bright, J M

    2013-01-01

    Hypertrophic cardiomyopathy (HCM) is heterogeneous in both people and cats, with variability in the distribution of hypertrophy, hemodynamic characteristics, and Doppler echocardiographic findings. To document the Doppler echocardiographic characteristics of midventricular obstruction in some cats with HCM. Eight cats with hypertrophic cardiomyopathy. Retrospective case series. The medical records of cats presenting to the cardiology service at Colorado State University between February 2009 and January 2012 were reviewed. All cats had a physical examination; Doppler systolic blood pressure measurement; and transthoracic two-dimensional (2D), M-mode, and Doppler echocardiography were performed. A more thorough evaluation of the echocardiographic images and measurements was performed. Cats included in this study had echocardiograms of adequate quality to confirm the diagnosis of midventricular obstruction by documentation of left midventricular concentric hypertrophy; a midventricular turbulent Doppler color flow pattern; and high velocity, late-peaking flow at the area of turbulence. Cats with evidence of systemic hypertension defined as a systolic Doppler blood pressure of greater than 170 mmHg were excluded. All 8 cats had left ventricular hypertrophy at the level of the papillary muscles; left, midventricular hypertrophy; and in 4/8 cats there was apical hypertrophy or basilar hypertrophy of the interventricular septum. Color flow Doppler revealed turbulent flow in 8/8 cats and spectral Doppler (continuous and pulsed wave) revealed increased flow velocities and late-peaking flow profiles at the level of the left midventricle. Two of 8 cats had a bifid midventricular flow profile in which there was a midsystolic decline in left ventricular velocities with elevated velocities extending into early diastole. The peak left ventricular outflow velocity in all 8 cats was normal. A variant of HCM characterized by hypertrophy at the level of the papillary muscles with

  14. Mitral valve replacement or repair: choosing optimal surgical treatment of hypertrophic obstructive cardiomyopathy

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    Богачев-Прокофьев А. В.

    2016-01-01

    Full Text Available Objective. The purpose of this study was to compare clinical and hemodynamic efficacy of different surgical approaches to correct outflow tract obstruction and mitral insufficiency in patients with hypertrophic cardiomyopathy.Methods. Over a period from November 2010 to August 2013, 146 patients with hypertrophic obstructive cardiomyopathy (HOCM underwent surgical treatment. 88 patients met the inclusion criteria and were randomized in two groups: Group I – extended myomectomy and MV replacement; Group II – extended myomectomy and MV repair. Mean age in Group I and Group II was 51.4±14.4 and 47.9±14.1 years respectively (p = 0.262. Mean peak gradient in Group I and Group II was 89.9±27.2 mm Hg. and 96.6±28.1 mm Hg. (p = 0.168. Pronounced MR was observed in 24 (58.5% and 23 (56.1% cases, moderate one in 17 (41.5% and 18 (43.9% cases in Group I and Group II respectively (p = 0.823. All patients demonstrated SAM syndrome. Results. There was one (2.4% early death in Group I (p = 0.314. In both groups such complications as AV block, ventricular septal defect and rupture of the left ventricle (p = 1.0 didn’t differ significantly. Average follow-up was 23.2 months for Group 1 and 25.8 months for Group 2. The survival rate in group I and group II was 78.9% and 96.6% respectively (Log-rank test = 0.034. Freedom from thromboembolic events was 83.2% and 100% respectively (Log-rank test = 0.026.Conclusion. MV replacement and MV repair during extended septal myomectomy in patients with HOCM can be an effective method to eliminate MR and outflow tract obstruction. MV repair in patients with HOCM reduces thromboembolic events and provides better mid-term survival.

  15. Novel deletions in MYH7 and MYBPC3 identified in Indian families with familial hypertrophic cardiomyopathy.

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    Waldmüller, Stephan; Sakthivel, Sadayappan; Saadi, Abdul Vahab; Selignow, Carmen; Rakesh, Pareppally Gopal; Golubenko, Maria; Joseph, Pulavelli Kurian; Padmakumar, Ramachandran; Richard, Pascale; Schwartz, Ketty; Tharakan, Jagan Mohan; Rajamanickam, Chellam; Vosberg, Hans Peter

    2003-06-01

    Mutations causing familial hypertrophic cardiomyopathy (HCM) have been described in at least 11 genes encoding cardiac sarcomeric proteins. In this study, three previously unknown deletions have been identified in the human cardiac genes coding for beta-myosin heavy chain (MYH7 on chromosome 14) and myosin-binding protein-C (MYBPC3 on chromosome 11). In family MM, a 3-bp deletion in MYH7 was detected to be associated with loss of glutamic acid in position 927 (DeltaE927) of the myosin rod. In two other families (HH and NP, related by a common founder) a 2-bp loss in codon 453 (exon 16) of MYBPC3 was identified as the presumable cause of a translation reading frame shift. Taken together 15 living mutation carriers were investigated. Six deceased family members (with five cases of premature sudden cardiac death (SCD) in families MM and NP) were either obligate or suspected mutation carriers. In addition to these mutations a 25-bp deletion in intron 32 of MYBPC3 was identified in family MM (five carriers) and in a fourth family (MiR, one HCM patient, three deletion carriers). In agreement with the loss of the regular splicing branch point in the altered intron 32, a splicing deficiency was observed in an exon trapping experiment using MYBPC3 exon 33 as a test substrate. Varying disease profiles assessed using standard clinical, ECG and echocardiographic procedures in conjunction with mutation analysis led to the following conclusions: (1) In family MM the DeltaE927 deletion in MYH7 was assumed to be associated with complete penetrance. Two cases of reported SCD might have been related to this mutation. (2) The two families, HH and NP, distantly related by a common founder, and both suffering from a 2-bp deletion in exon 16 of MYBPC3 differed in their average phenotypes. In family NP, four cases of cardiac death were documented, whereas no cardiac-related death was reported from family HH. These results support the notion that mutations in HCM genes may directly

  16. Cardiac troponin and tropomyosin: structural and cellular perspectives to unveil the Hypertrophic Cardiomyopathy phenotype

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    Mayra de A. Marques

    2016-09-01

    Full Text Available Inherited myopathies affect both skeletal and cardiac muscle and are commonly associated with genetic dysfunctions, leading to the production of anomalous proteins. In cardiomyopathies, mutations frequently occur in sarcomeric genes, but the cause-effect scenario between genetic alterations and pathological processes remains elusive. Hypertrophic cardiomyopathy (HCM was the first cardiac disease associated with a genetic background. Since the discovery of the first mutation in the β-myosin heavy chain, more than 1,400 new mutations in 11 sarcomeric genes have been reported, awarding HCM the title of the disease of the sarcomere. The most common macroscopic phenotypes are left ventricle and interventricular septal thickening, but because the clinical profile of this disease is quite heterogeneous, these phenotypes are not suitable for an accurate diagnosis. The development of genomic approaches for clinical investigation allows for diagnostic progress and understanding at the molecular level. Meanwhile, the lack of accurate in vivo models to better comprehend the cellular events triggered by this pathology has become a challenge. Notwithstanding, the imbalance of Ca2+ concentrations, altered signaling pathways, induction of apoptotic factors, and heart remodeling leading to abnormal anatomy have already been reported. Of note, a misbalance of signaling biomolecules, such as kinases and tumor suppressors (e.g., Akt and p53, seems to participate in apoptotic and fibrotic events. In HCM, structural and cellular information about defective sarcomeric proteins and their altered interactome is emerging but still represents a bottleneck for developing new concepts in basic research and for future therapeutic interventions. This review focuses on the structural and cellular alterations triggered by HCM-causing mutations in troponin and tropomyosin proteins and how structural biology can aid in the discovery of new platforms for therapeutics. We

  17. Cardiac Troponin and Tropomyosin: Structural and Cellular Perspectives to Unveil the Hypertrophic Cardiomyopathy Phenotype

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    Marques, Mayra de A.; de Oliveira, Guilherme A. P.

    2016-01-01

    Inherited myopathies affect both skeletal and cardiac muscle and are commonly associated with genetic dysfunctions, leading to the production of anomalous proteins. In cardiomyopathies, mutations frequently occur in sarcomeric genes, but the cause-effect scenario between genetic alterations and pathological processes remains elusive. Hypertrophic cardiomyopathy (HCM) was the first cardiac disease associated with a genetic background. Since the discovery of the first mutation in the β-myosin heavy chain, more than 1400 new mutations in 11 sarcomeric genes have been reported, awarding HCM the title of the “disease of the sarcomere.” The most common macroscopic phenotypes are left ventricle and interventricular septal thickening, but because the clinical profile of this disease is quite heterogeneous, these phenotypes are not suitable for an accurate diagnosis. The development of genomic approaches for clinical investigation allows for diagnostic progress and understanding at the molecular level. Meanwhile, the lack of accurate in vivo models to better comprehend the cellular events triggered by this pathology has become a challenge. Notwithstanding, the imbalance of Ca2+ concentrations, altered signaling pathways, induction of apoptotic factors, and heart remodeling leading to abnormal anatomy have already been reported. Of note, a misbalance of signaling biomolecules, such as kinases and tumor suppressors (e.g., Akt and p53), seems to participate in apoptotic and fibrotic events. In HCM, structural and cellular information about defective sarcomeric proteins and their altered interactome is emerging but still represents a bottleneck for developing new concepts in basic research and for future therapeutic interventions. This review focuses on the structural and cellular alterations triggered by HCM-causing mutations in troponin and tropomyosin proteins and how structural biology can aid in the discovery of new platforms for therapeutics. We highlight the

  18. Risk factors for sudden cardiac death in childhood hypertrophic cardiomyopathy: A systematic review and meta-analysis.

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    Norrish, Gabrielle; Cantarutti, Nicoletta; Pissaridou, Eleni; Ridout, Deborah A; Limongelli, Giuseppe; Elliott, Perry M; Kaski, Juan Pablo

    2017-07-01

    Aims To perform a systematic literature review and meta-analysis of clinical risk factors for sudden cardiac death (SCD) in childhood hypertrophic cardiomyopathy. Methods Medline and PubMed databases were searched for original articles published in English from 1963 through to December 2015 that included patients under 18 years of age with a primary or secondary end-point of either SCD or SCD-equivalent events (aborted cardiac arrest or appropriate implantable cardioverter-defibrillator discharge) or cardiovascular death (CVD). Results Twenty-five studies (3394 patients) met the inclusion criteria. We identified four conventional major risk factors that were evaluated in at least four studies and that we found to be statistically associated with an increased risk of death in at least two studies: previous adverse cardiac event (pooled hazard ratio [HR] 5.4, 95% confidence interval [CI] 3.67-7.95, p cardiomyopathy means that the evidence base for individual risk factors is not robust. We have identified four clinical parameters that are likely to be associated with increased risk of SCD, SCD-equivalent events or CVD. Multi-centre prospective studies are needed in order to further determine the relevance of these factors in predicting SCD in childhood hypertrophic cardiomyopathy and to identify novel risk markers. Condensed abstract A systematic review and meta-analysis of clinical risk factors predicting sudden cardiac death in childhood hypertrophic cardiomyopathy was performed, identifying four 'major' factors: previous adverse cardiac event; non-sustained ventricular tachycardia; syncope; and extreme left ventricular hypertrophy. Well-designed multi-centre studies are required in the future in order to confirm these findings.

  19. Midventricular Hypertrophic Cardiomyopathy with Apical Aneurysm: Potential for Underdiagnosis and Value of Multimodality Imaging

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    Archana Sivanandam

    2016-01-01

    Full Text Available We illustrate a case of midventricle obstructive HCM and apical aneurysm diagnosed with appropriate use of multimodality imaging. A 75-year-old African American woman presented with a 3-day history of chest pain and dyspnea with elevated troponins. Her electrocardiogram showed sinus rhythm, left atrial enlargement, left ventricular hypertrophy, prolonged QT, and occasional ectopy. After medical therapy optimization, she underwent coronary angiography for an initial diagnosis of non-ST segment elevation myocardial infarction. Her coronaries were unremarkable for significant disease but her left ventriculogram showed hyperdynamic contractility of the midportion of the ventricle along with a large dyskinetic aneurysmal apical sac. A subsequent transthoracic echocardiogram provided poor visualization of the apical region of the ventricle but contrast enhancement identified an aneurysmal pouch distal to the midventricular obstruction. To further clarify the diagnosis, cardiac magnetic resonance imaging with contrast was performed confirming the diagnosis of midventricular hypertrophic cardiomyopathy with apical aneurysm and fibrosis consistent with apical scar on delayed enhancement. The patient was medically treated and subsequently underwent elective implantable defibrillator placement in the ensuing months for recurrent nonsustained ventricular tachycardia and was initiated on prophylactic oral anticoagulation with warfarin for thromboembolic risk reduction.

  20. High resolution melting: improvements in the genetic diagnosis of hypertrophic cardiomyopathy in a Portuguese cohort

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    Santos Susana

    2012-03-01

    Full Text Available Abstract Background Hypertrophic Cardiomyopathy (HCM is a complex myocardial disorder with a recognized genetic heterogeneity. The elevated number of genes and mutations involved in HCM limits a gene-based diagnosis that should be considered of most importance for basic research and clinical medicine. Methodology In this report, we evaluated High Resolution Melting (HRM robustness, regarding HCM genetic testing, by means of analyzing 28 HCM-associated genes, including the most frequent 4 HCM-associated sarcomere genes, as well as 24 genes with lower reported HCM-phenotype association. We analyzed 80 Portuguese individuals with clinical phenotype of HCM allowing simultaneously a better characterization of this disease in the Portuguese population. Results HRM technology allowed us to identify 60 mutated alleles in 72 HCM patients: 49 missense mutations, 3 nonsense mutations, one 1-bp deletion, one 5-bp deletion, one in frame 3-bp deletion, one insertion/deletion, 3 splice mutations, one 5'UTR mutation in MYH7, MYBPC3, TNNT2, TNNI3, CSRP3, MYH6 and MYL2 genes. Significantly 22 are novel gene mutations. Conclusions HRM was proven to be a technique with high sensitivity and a low false positive ratio allowing a rapid, innovative and low cost genotyping of HCM. In a short return, HRM as a gene scanning technique could be a cost-effective gene-based diagnosis for an accurate HCM genetic diagnosis and hopefully providing new insights into genotype/phenotype correlations.

  1. [Hypertrophic cardiomyopathy: a rare cause of vascular dementia. A case report].

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    Ben Hamouda, Ibtissem; Tougourti, Mohamed Néjib; Hamza, Mohsen

    2002-07-01

    Herein, we report a case of a 51 year old man who experienced three ischemic cerebral infarcts in a time of few months. The patient consulted after the third accident. Neurological presentation included pseudobulbar syndrome with a mild cognitive deficit, aphasia, left hemiparesia, hemiasomatognosia and homonymous lateral hemianopsia. Cerebral tomodensitometry and magnetic resonance imaging evidenced large infarcts images involving right middle cerebral artery territory and bilateral borderline zones in the junction of the territories of the middle and posterior cerebral arteries. Ambulatory 24 hours ECG recording (Holter) revealed two hits of non-sustained ventricular tachycardia. Transoesophageal echocardiography conveyed to the diagnosis of hypertrophic cardiomyopathy and displayed the presence of a left auricular thrombus. Anticoagulant therapy and rehabilitation allowed a substantial recovering of the patient's cognitive functions and wasting of the intracardiac thrombus. The clinical features observed in our patient meet the recommended DSM IV diagnosis criteria of vascular dementia, an exceptional complication of HCM. The clinical findings, neuroimagery investigation results, and the chronological link between cerebral attacks and cognitive function deterioration argue for a demential syndrome of vascular origin resulting from multiple embolic infarcts involving medium sized arteries (multi-infarct dementia). The authors emphasize the rarity of such observation. HCM must be considered as a potential cause of embolic stroke and likewise a multi-infarct dementia.

  2. Hypertrophic cardiomyopathy with midventricular obstruction and apical aneurysm formation in a single family: case report

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    Paraskevaidis Stylianos

    2009-06-01

    Full Text Available Abstract Background Hypertrophic cardiomyopathy (HCM is an extremely heterogeneous disease. An under recognized and very often missed subgroup within this broad spectrum concerns patients with left ventricular (LV apical aneurysms in the absence of coronary artery disease. Case presentation We describe a case of HCM with midventricular obstruction and apical aneurysm formation in 3 patients coming from a single family. This HCM pattern was detected by 2D-echocardiography and confirmed by cardiac magnetic resonance imaging. A cardioverter defibrillator was implanted in one of the patients because of non-sustained ventricular tachycardia detected in 24-h Holter monitoring and an abrupt drop in systolic blood pressure during maximal exercise test. The defibrillator activated 8 months after implantation by suppression of a ventricular tachycardia providing anti-tachycardia pacing. The patient died due to refractory heart failure 2 years after initial evaluation. The rest of the patients are stable after a 2.5-y follow-up period. Conclusion The detection of apical aneurysm by echocardiography in HCM patients may be complicated. Ventricular tachycardia arising from the scarred aneurysm wall may often occur predisposing to sudden death.

  3. Relationship of race to sudden cardiac death in competitive athletes with hypertrophic cardiomyopathy.

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    Maron, Barry J; Carney, Kevin P; Lever, Harry M; Lewis, Jannet F; Barac, Ivan; Casey, Susan A; Sherrid, Mark V

    2003-03-19

    The goal of this study was to determine the impact of race on identification of hypertrophic cardiomyopathy (HCM). Sudden death in young competitive athletes is due to a variety of cardiovascular diseases (CVDs) and, most commonly, HCM. These catastrophes have become an important issue for African Americans, although HCM has been previously regarded as rare in this segment of the U.S. population. We studied the relationship of race to the prevalence of CVDs causing sudden death in our national athlete registry, and compared these findings with a representative multicenter hospital-based cohort of patients with HCM. Of 584 athlete deaths, 286 were documented to be due to CVD at ages 17 +/- 3 years; 156 (55%) were white, and 120 (42%) were African American. Most were male (90%), and 67% participated in basketball and football. Among the 286 cardiovascular deaths, most were due to HCM (n = 102; 36%) or anomalous coronary artery of wrong sinus origin (n = 37; 13%). Of the athletes who died of HCM, 42 (41%) were white, but 56 (55%) were African American. In contrast, of 1,986 clinically identified HCM patients, only 158 (8%) were African American (p identification of HCM in a hospital-based population (i.e., by seven-fold). This discrepancy suggests that many HCM cases go unrecognized in the African American community, underscoring the need for enhanced clinical recognition of HCM to create the opportunity for preventive measures to be employed in high-risk patients with this complex disease.

  4. In vivo natriuretic peptide reporter assay identifies chemical modifiers of hypertrophic cardiomyopathy signalling.

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    Becker, Jason R; Robinson, Tamara Y; Sachidanandan, Chetana; Kelly, Amy E; Coy, Shannon; Peterson, Randall T; MacRae, Calum A

    2012-03-01

    Despite increased understanding of the fundamental biology regulating cardiomyocyte hypertrophy and heart failure, it has been challenging to find novel chemical or genetic modifiers of these pathways. Traditional cell-based methods do not model the complexity of an intact cardiovascular system and mammalian models are not readily adaptable to chemical or genetic screens. Our objective was to create an in vivo model suitable for chemical and genetic screens for hypertrophy and heart failure modifiers. Using the developing zebrafish, we established that the cardiac natriuretic peptide genes (nppa and nppb), known markers of cardiomyocyte hypertrophy and heart failure, were induced in the embryonic heart by pathological cardiac stimuli. This pathological induction was distinct from the developmental regulation of these genes. We created a luciferase-based transgenic reporter line that accurately modelled the pathological induction patterns of the zebrafish nppb gene. Utilizing this reporter line, we were able to show remarkable conservation of pharmacological responses between the larval zebrafish heart and adult mammalian models. By performing a focused screen of chemical agents, we were able to show a distinct response of a genetic model of hypertrophic cardiomyopathy to the histone deacetylase inhibitor, Trichostatin A, and the mitogen-activated protein kinase kinase 1/2 inhibitor, U0126. We believe this in vivo reporter line will offer a unique approach to the identification of novel chemical or genetic regulators of myocardial hypertrophy and heart failure.

  5. Alcohol septal ablation for obstructive hypertrophic cardiomyopathy: outcomes in young, middle-aged, and elderly patients.

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    Leonardi, Robert A; Townsend, Jacob C; Patel, Chetan A; Wolf, Bethany J; Todoran, Thomas M; Powers, Eric R; Steinberg, Daniel H; Fernandes, Valerian L; Nielsen, Christopher D

    2013-11-01

    We compared the efficacy and safety of alcohol septal ablation (ASA) for obstructive hypertrophic cardiomyopathy (HCM) in young, middle-aged, and elderly patients. Intersociety guidelines suggest based on limited evidence that young patients with medically refractory symptoms of obstructive HCM should undergo surgical myectomy while elderly patients may be more appropriate for ASA. Data for 360 patients undergoing 389 ASAs were prospectively collected and retrospectively analyzed according to age. Young (elderly (≥65 years) patients comprised 28, 40, and 32% of the study population, respectively. Young patients had thicker left ventricular septal walls at baseline, and elderly patients had more comorbidity and dyspnea. Resting, mean left ventricular outflow tract gradients (LVOTGs) were similar across the age groups at baseline (62, 66, and 68 mm Hg, respectively; P = NS for all comparisons). LVOTGs and dyspnea were significantly and similarly improved in all age groups immediately after ASA and through 12 months of follow-up (P elderly patients (9.1 and 6.3% vs. 20.8%, respectively; P ≤ 0.016 for elderly vs. others). Mortality rates for young and middle-aged patients were lower than for elderly patients, but the differences were not statistically significant. Patients undergoing ASA had significant and similar improvements in LVOTGs and symptoms regardless of age. Procedural complications were increased in elderly patients, who had numerically but not statistically significantly higher mortality rates. Copyright © 2012 Wiley Periodicals, Inc.

  6. Vector electrocardiographic alterations after percutaneous septal ablation in obstructive hypertrophic cardiomyopathy: possible anatomic causes

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    Pérez Riera Andrés Ricardo

    2002-01-01

    Full Text Available OBJECTIVE: Analyze the dromotropic disturbances (vector-electrocardiographic, and the possible anatomic causes, provoked by selective alcohol injection in the septal branch, for percutaneous treatment, of obstructive hypertrophic cardiomyopathy. METHODS: Ten patients with a mean age of 52.7 years underwent percutaneous septal ablation (PTSA from october 1998; all in functional class III/IV. Twelve-lead electrocardiogram was performed prior to and during PTSA, and later electrocardiogram and vectorcardiogram according to Frank's method. The patients were followed up for 32 months. RESULTS: On electrocardiogram (ECG prior to PTSA all patients had sinus rhythm and left atrial enlargement, 8 left ventricular hypertrophy of systolic pattern. On ECG immediately after PTSA, 8 had complete right bundle-branch block; 1 transient total atrioventricular block; 1 alternating transient bundle-branch block either right or hemiblock. On late ECG 8 had complete right bundle-branch block confirmed by vectorcardiogram, type 1 or Grishman. CONCLUSION: Septal fibrosis following alcohol injection caused a predominance of complete right bundle-branch block, different from surgery of myotomy/myectomy.

  7. Coexistent coronary artery disease or myocardial bridging in patients with hypertrophic cardiomyopathy using coronary CT angiography

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    Lee, Jae Hwan; Chun, Eun Ju; Kim, Yeo Koon; Yoo, Jin Young; Choi, Sang Il; Choi, Dong Ju [Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

    2015-07-15

    To evaluate the prevalence of coexistent coronary artery disease (CAD) or myocardial bridging (MB) in patients with hypertrophic cardiomyopathy (HCM) using coronary CT angiography (CCTA) and assess the role of CCTA. The prevalence of obstructive CAD (> 50% luminal reduction) and MB (partial and full encasement) were assessed in 150 patients with HCM diagnosed by clinical findings, electrocardiography, and echocardiography of 19588 consecutive patients who underwent CCTA for suspected CAD. The overall feasibility of coronary artery visualization was 98.9% with CCTA. In patients with HCM, the prevalence of obstructive CAD and MB (14.7% partial and 28.0% full encasement) were 23.3% and 42.7%, respectively. Age, hypertension, family history of premature CAD, Framingham risk score and severe chest pain were associated with CAD, whereas male gender and septal type were associated with MB (all p < 0.05). In comparison to invasive coronary angiography (n = 37), the diagnostic accuracy of CCTA for the detection of CAD and full encasement MB was 89.2% and 86.5%, respectively. One-quarter of patients with HCM had coexistent obstructive CAD or full encasement MB. CCTA can be a feasible and accurate noninvasive imaging modality for the detection of CAD and MB in patients with HCM.

  8. Long-Term Prognosis after Myectomy in Hypertrophic Obstructive Cardiomyopathy with Severe Left Ventricular Hypertrophy.

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    An, Shuoyan; Fan, Chaomei; Yang, Yinjian; Hang, Fei; Wang, Zhimin; Zhang, Yuhui; Zhang, Jian

    2018-01-05

    Patients with hypertrophic obstructive cardiomyopathy (HOCM) and severe left ventricular hypertrophy (maximal left ventricular wall thickness ≥30 mm) are at high risk of sudden cardiac death (SCD). In this study, we aimed to determine whether HOCM patients with severe hypertrophy had a lower incidence of SCD after myectomy. HOCM patients with severe hypertrophy were consecutively enrolled from Fuwai Hospital in China between 2000 and 2013. Long-term outcomes were retrospectively compared between the 2 groups, namely the myectomy group and medical group. A total of 244 patients (118 in the myectomy group and 126 in the medical group) were involved. The mean follow-up durations for the myectomy and medical groups were 5.07 ± 3.73 and 6.23 ± 4.15 years, respectively. During the follow-up period, the annual cardiovascular mortality rate was 0.84% in the myectomy group and 2.04% in the medical group (p = 0.041). The annual SCD rate was 0.33% in the myectomy group and 1.40% in the medical group (p = 0.040). Multivariate Cox regression analysis showed that myectomy was independently associated with lower rates of cardiovascular death and SCD. In HOCM patients with severe hypertrophy, those that underwent myectomy had a lower risk of cardiovascular death and SCD than those treated with medicines only. © 2018 S. Karger AG, Basel.

  9. Myocardial deformation from tagged MRI in hypertrophic cardiomyopathy using an efficient registration strategy

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    Piella, G.; De Craene, M.; Oubel, E.; Larrabide, I.; Huguet, M.; Bijnens, B. H.; Frangi, A. F.

    2009-02-01

    This paper combines different parallelization strategies for speeding up motion and deformation computation by non-rigid registration of a sequence of images. The registration is performed in a two-level acceleration approach: (1) parallelization of each registration process using MPI and/or threads, and (2) distribution of the sequential registrations over a cluster. On a 24-node double quad-core Intel Xeon (2.66 GHz CPU, 16 GB RAM) cluster, the method is demonstrated to efficiently compute the deformation of a cardiac sequence reducing the computation time from more than 3 hours to a couple of minutes (for low downsampled images). It is shown that the distribution of the sequential registrations over the cluster together with the parallelization of each pairwise registration by multithreading lowers the computation time towards values compatible with clinical requirements (a few minutes per patient). The combination of MPI and multithreading is only advantageous for large input data sizes. Performances are assessed for the specific scenario of aligning cardiac sequences of taggedMagnetic Resonance (tMR) images, with the aim of comparing strain in healthy subjects and hypertrophic cardiomyopathy (HCM) patients. In particular, we compared the distribution of systolic strain in both populations. On average, HCM patients showed lower average values of strain with larger deviation due to the coexistence of regions with impaired deformation and regions with normal deformation.

  10. Phenotypic overlap in hypertrophic cardiomyopathy: apical hypertrophy, midventricular obstruction, and apical aneurysm.

    Science.gov (United States)

    Minami, Yuichiro; Haruki, Shintaro; Hagiwara, Nobuhisa

    2014-12-01

    Within the diverse phenotypic spectrum of hypertrophic cardiomyopathy (HCM), subgroups of patients with apical hypertrophy (APH), midventricular obstruction (MVO), and apical aneurysm (APA) have emerged. While previous studies have suggested the existence of considerable overlap between APH, MVO, and APA, there are still many unanswered questions. Therefore, we attempted to clarify the relationship of the above three phenotypes of HCM with respect to prevalence, overlap, and outcomes. Among the 544 study HCM patients (mean follow-up period: 11.6±7.4 years), 170 with APH (31.3%), 51 with MVO (9.4%), and 24 with APA (4.4%) were examined. There was phenotypic overlap between APH and MVO in 17 patients, APH and APA in 14 patients, and MVO and APA in 14 patients. Furthermore, a combination of APH, MVO, and APA was observed in eight patients. Detailed analysis of the relationship between overlapping phenotypes and the prognosis showed that APA patients without a history of APH had an extremely poor outcome (probability of the combined endpoint of sudden death and potentially lethal arrhythmic events ≥50%). Conversely, APH patients without MVO had a strikingly good outcome (probability of the combined endpoint <5%). Other patients had an intermediate outcome (probability of the combined endpoint 10-40%). Our results suggest that overlap between these three forms of HCM is substantial, and that detailed classification of the overlapping phenotypes is clinically meaningful. Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  11. T1 mapping for detection of left ventricular myocardial fibrosis in hypertrophic cardiomyopathy: A preliminary study

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    Lu, Minjie [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Zhao, Shihua, E-mail: coolkan@163.com [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Yin, Gang; Jiang, Shiliang; Zhao, Tao; Chen, Xiuyu [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Tian, Liangxin [Department of Cardiac Surgery, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Zhang, Yan; Wei, Yunqing; Liu, Qiong [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); He, Zuoxiang [Department of Nuclear Medicine, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Xue, Hui [Siemens Healthcare, 737 N. Michigan Avenue, Suite 1600 Chicago, IL 60611 (United States); An, Jing [Siemens Shenzhen Magnetic Resonance Ltd. Application Dept. Siemens MRI center, Gaoxin C. Ave.,2nd, Hi-Tech Industrial Park, Shenzhen (China); Shah, Saurabh [Siemens Healthcare, 737 N. Michigan Avenue, Suite 1600 Chicago, IL 60611 (United States)

    2013-05-15

    Purpose: To investigate the diagnostic value of T1 mapping imaging of evaluating fibrosis in patients with hypertrophic cardiomyopathy (HCM). Materials and methods: 21 subjects with HCM and 18 healthy volunteers underwent conventional late gadolinium enhancement (LGE) imaging and T1 mapping imaging. The region of myocardium in HCM is divided into remote area of LGE, peri-LGE, LGE (halo-like LGE and typical patchy LGE). These regions combined with normal volunteers’ myocardium were calculated by the reduced percent of T1 value (RPTV). Results: The RPTV in healthy volunteers was no significant comparing with that in the remote area of LGE in HCM subjects (3.98 ± 3.19 vs. 3.34 ± 2.75, P > 0.05). There were significant statistical differences in pairwise among the remote area of LGE, peri-LGE, halo-like LGE and typical patchy LGE in the RPTV (P < 0.0001). ROC curves indicated that the T1 mapping imaging has a greater area under the curve comparing with that of traditional LGE imaging (0.975 ± 0.07 vs. 0.753 ± 0.26, P < 0.0001). Conclusions: HCM has a high prevalence of fibrosis and with varying severity. T1 mapping imaging can be a useful method to evaluate the severity of the fibrosis in HCM.

  12. Clinical significance of {sup 123}I-MIBG myocardial scintigraphy in patients with hypertrophic cardiomyopathy

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    Ido, Akira; Hasebe, Naoyuki; Nakamura, Hideki [Asahikawa Medical Coll., Hokkaido (Japan)] [and others

    1997-09-01

    We studied the abnormality of myocardial sympathetic nervous system in patients with hypertrophic cardiomyopathy using {sup 123}I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in comparison with the parameters of other clinical examinations. In 50 patients with HCM, the heart to mediastinum {sup 123}I-MIBG uptake ratio (H/M) was significantly low and washout rate (WR) of {sup 123}I-MIBG was significantly high respectively compared with normal subjects (n=8). H/M was negatively correlated with serum norepinephrine level, wall thickness or left ventricle, left ventricular mass index, left ventricular end diastolic pressure respectively, and WR was positively correlated with those parameters respectively. On the other hand, LF/HF calculated by spectral analysis in holter electrocardiogram was positively correlated with H/M, and negatively correlated with WR. In HCM, H/M in patients with subjective symptoms was significantly lower than that without subjective symptoms, and WR in patients with paroxysmal atrial fibrillation was significantly higher than that without paroxysmal atrial fibrillation. This study revealed that H/M and WR reflected the severity and the difference of disease type in HCM. In conclusion, {sup 123}I-MIBG contributes to evaluating more details in diagnosis and pathophysiology of HCM. (author)

  13. Computational Modeling of Blood Flow and Valve Dynamics in Hearts with Hypertrophic Cardiomyopathy

    Science.gov (United States)

    Zheng, Xudong; Mittal, Rajat; Abraham, Theodore; Pinheiro, Aurelio

    2010-11-01

    Hypertrophic Cardiomyopathy (HCM) is a cardiovascular disease manifested by the thickening of the ventricular wall and often leads to a partial obstruction to the blood flow out of the left ventricle. HCM is recognized as one of the most common causes of sudden cardiac death in athletes. In a heart with HCM, the hypertrophy usually narrows the blood flow pathway to the aorta and produces a low pressure zone between the mitral valve and the hypertrophy during systole. This low pressure can suck the mitral valve leaflet back and completely block the blood flow into the aorta. In the current study, a sharp interface immersed boundary method flow solver is employed to study the hemodynamics and valve dynamics inside a heart with HCM. The three-dimensional motion and configuration of the left ventricle including mitral valve leaflets and aortic valves are reconstructed based on echo-cardio data sets. The mechanisms of aortic obstruction associated with HCM are investigated. The long term objective of this study is to develop a computational tool to aid in the assessment and surgical management of HCM.

  14. Effects of diltiazem on myocardial perfusion abnormalities during exercise in patients with hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Sugihara, Hiroki; Taniguchi, Yoko; Ito, Kazuki [Kyoto Prefectural Univ. of Medicine (Japan)] [and others

    1998-12-01

    The effect of diltiazem on myocardial ischemia in patients with hypertrophic cardiomyopathy (HCM) was evaluated by exercise myocardial {sup 201}Tl single photon emission computed tomography (SPECT). Exercise myocardial SPECT was performed before and 8 weeks after oral administration of diltiazem (180 mg/day) in 20 patients with HCM who showed transient perfusion defects on exercise myocardial {sup 201}Tl SPECT under control conditions. SPECT images were divided into 17 segments. The {sup 201}Tl perfusion defects were visually scored and evaluated as the defect score. The transient dilation index was calculated as an index of subendocardial ischemia. Improvement of the defect score was demonstrated in 15 patients after the administration of diltiazem. The mean defect score decreased significantly from 9.90{+-}5.17 to 5.50{+-}4.89 (p<0.0001). Although 16 of 20 patients showed an abnormal transient dilation index before diltiazem treatment, 16 showed improvement and 13 of these normalized after diltiazem therapy. The mean transient dilation index decreased from 1.16{+-}0.10 to 1.02{+-}0.09 (p<0.0001). In conclusion, diltiazem prevents or diminishes myocardial ischemia in patients with HCM. (author)

  15. Bilateral brachial plexus blocks in a patient of hypertrophic obstructive cardiomyopathy with hypertensive crisis.

    Science.gov (United States)

    Pai, Rohini V Bhat; Hegde, Harihar V; Santhosh, McB; Roopa, S; Deshpande, Shrinivas S; Rao, P Raghavendra

    2013-01-01

    Hypertrophic obstructive cardiomyopathy (HOCM) is a challenge to anesthesiologists due to the complex pathophysiology involved and various perioperative complications associated with it. We present a 50-year-old man, a known case of HOCM, who successfully underwent emergency haemostasis, and debridement of the traumatically amputated right upper limb and the contused lacerated wound on the left forearm under bilateral brachial plexus blocks. His co-morbidities included hypertension (in hypertensive crisis) and diabetes mellitus. He was full stomach and also had an anticipated difficult airway. The management included invasive pressure monitoring and labetalol infusion for emergent control of blood pressure. The regional anaesthesia technique required careful consideration to the dosage of local anaesthetics and staggered performance of brachial plexus blocks on each of the upper limbs to avoid local anaesthetic toxicity. Even though bilateral brachial plexus blocks are rarely indicated, it seemed to be the most appropriate anaesthetic technique in our patient. With careful consideration of the local anaesthetic toxicity and meticulous technique, bilateral brachial plexus blocks can be successfully performed in those patients where general anaesthesia is deemed to be associated with higher risk.

  16. Clinical outcomes associated with sarcomere mutations in hypertrophic cardiomyopathy: a meta-analysis on 7675 individuals.

    Science.gov (United States)

    Sedaghat-Hamedani, Farbod; Kayvanpour, Elham; Tugrul, Oguz Firat; Lai, Alan; Amr, Ali; Haas, Jan; Proctor, Tanja; Ehlermann, Philipp; Jensen, Katrin; Katus, Hugo A; Meder, Benjamin

    2017-08-24

    Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease, which goes along with increased risk for sudden cardiac death (SCD). Despite the knowledge about the different causal genes, the relationship between individual genotypes and phenotypes is incomplete. We retrieved PubMed/Medline literatures on genotype-phenotype associations in patients with HCM and mutations in MYBPC3, MYH7, TNNT2, and TNNI3. Altogether, 51 studies with 7675 HCM patients were included in our meta-analysis. The average frequency of mutations in MYBPC3 (20%) and MYH7 (14%) was higher than TNNT2 and TNNI3 (2% each). The mean age of HCM onset for MYH7 mutation positive patients was the beginning of the fourth decade, significantly earlier than patients without sarcomeric mutations. A high male proportion was observed in TNNT2 (69%), MYBPC3 (62%) and mutation negative group (64%). Cardiac conduction disease, ventricular arrhythmia and heart transplantation (HTx) rate were higher in HCM patients with MYH7 mutations in comparison to MYBPC3 (p MYH7 is earlier and leads to a more severe phenotype than in patient without such mutations. Furthermore, patients with sarcomeric mutations are more susceptible to SCD. The present study further supports the clinical interpretation of sarcomeric mutations in HCM patients.

  17. The MYH7 p.R787H mutation causes hypertrophic cardiomyopathy in two unrelated families.

    Science.gov (United States)

    Purushotham, G; Madhumohan, K; Anwaruddin, Mohammad; Nagarajaram, Ha; Hariram, Vuppaladadhiam; Narasimhan, Calambur; Bashyam, Murali D

    2010-01-01

    Familial hypertrophic cardiomyopathy (FHC) is a Mendelian disorder usually caused by mutations in any one of more than 12 genes, most of which encode sarcomere proteins. The disease exhibits extensive genetic heterogeneity, and it is important to identify mutations that result in adverse symptoms and/or lethality in affected individuals. An analysis of disease-causing mutations has been initiated in the Indian population to determine prevalent mutations. FHC was detected using echocardiography and by analysis of clinical symptoms and family history. The disease-causing mutation was identified using polymerase chain reaction DNA sequencing. The p.R787H mutation was identified in the MYH7 gene in two FHC families. Sequence and structure analysis suggested impaired binding of the mutant protein to the myosin essential light chain. Although the mutation results in variable clinical symptoms in the affected individuals, probably owing to the effect of modifier genes and/or environmental factors, it does not appear to be a lethal mutation.

  18. Genetic variations of beta-MYH7 in Venezuelan patients with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Rodríguez, Rosalva; Guerrero, David; Rivas, Yoyna; Lacruz, Andrea; Flores, Yris

    2014-03-01

    Hypertrophic cardiomyopathy (HCM) is a cardiac disease, characterized by marked hypertrophy and genetic variability. HCM has been associated with sarcomere protein mutations, being cardiac beta-myosin (coded by the MYH7 gene) and myosin binding protein C (coded by the MYBPC3 gene) the most frequently affected proteins. As in Venezuela only the clinical analysis are performed in HCM patients, we decided to search for genetic variations in the MYH7 gene. Coding regions, including the junction exon-intron of the MYH7 gene, were studied in 58 HCM patients, whose samples were collected at the ASCARDIO Hospital (Barquisimeto, Lara state, Venezuela) and 106 control subjects from the ASCARDIO Hospital and the IVIC (Barquisimeto Lara state and Miranda, Venezuela, respectively). The blood samples were analyzed by genomic DNA isolation, followed by polymerase chain reaction and sequence analysis. The screening of the MYH7 gene revealed eight already reported polymorphic variants, as well as two intronic variations in these HCM patients. Neither any missense mutations nor other pathological mutations in the MYH7 gene were found in the HCM patients.

  19. Prevalence and clinical correlates of QT prolongation in patients with hypertrophic cardiomyopathy

    Science.gov (United States)

    Johnson, Jonathan N.; Grifoni, Camilla; Bos, J. Martijn; Saber-Ayad, Maha; Ommen, Steve R.; Nistri, Stefano; Cecchi, Franco; Olivotto, Iacopo; Ackerman, Michael J.

    2011-01-01

    Aims Congenital or acquired QT prolongation is a risk factor for life-threatening arrhythmias. In patients with hypertrophic cardiomyopathy (HCM), the QT interval may be intrinsically prolonged. However, the prevalence, cause, and significance of QT prolongation among patients with HCM are unknown. Methods and results After exclusion of patients on QT-prolonging drugs, a blinded, retrospective analysis of electrocardiograms, echocardiograms, and genotype status in 479 unrelated patients with HCM [201 females, age at diagnosis 41 ± 18 years, maximal left ventricular wall thickness (MLVWT) 22 ± 6 mm] from two independent centres was performed. The mean QTc was 440 ± 28 ms. The QTc exceeded 480 ms in 13% of patients. Age, gender, family history of HCM or sudden cardiac arrest, and genotype status had no association with QTc. Patients with a QTc over 480 ms were more symptomatic at diagnosis (P QT prolongation (QTc > 480 ms) was present in 1 out of 8 patients with HCM. The QTc was partly reflective of the degree of cardiac hypertrophy and left ventricular outflow tract obstruction. Because of its pro-arrhythmic potential and its potential relevance to management and risk stratification, routine QTc assessment should be performed in patients with HCM, particularly when concomitant use of QT-prolonging medications is considered. PMID:21345853

  20. Diagnostic performance of computed tomography for detection of concomitant coronary disease in hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Lei; Ma, Xiaohai; Zhang, Chen; Wang, Zhanhong; Fan, Zhanming [Capital Medical University, Department of Radiology, Beijing Anzhen Hospital, Beijing (China); Ge, Hailong [Capital Medical University, Department of Cardiology, Beijing Anzhen Hospital, Beijing (China); Teraoka, Kunihiko [Tokyo Medical University, Department of Cardiology, Tokyo (Japan)

    2014-10-31

    To evaluate the diagnostic performance of computed tomography (CT) in patients with hypertrophic cardiomyopathy (HCM) and suspected coexistent coronary artery diseases (CADs). Sixty patients were enrolled in this study. Cardiac CT examination included CT coronary angiography (CTCA) and delayed enhancement CT. CT performance in evaluation of the coronary artery was assessed and compared with that of catheter-based coronary angiography (CA). The left ventricle (LV) wall thickness, functional indices and myocardial delayed enhancement (MDE) were measured via cardiac magnetic resonance (CMR) and CT images. Compared with catheter-based CA, CTCA produced a 100 % (24/24) sensitivity, a 94.4 % (34/36) specificity, a 92.3 % (24/26) positive predictive value and a 100 % (34/34) negative predictive value. CT-measured LV wall thickness and functional indices were correlated with those measured via CMR (P < 0.01), though the CT-measured values were smaller than the CMR-measured values. Bland-Altman analysis showed the volume of the focal MDE determined via CT was slightly smaller than that determined using CMR (mean difference: 0.3 cm{sup 3}). For patients with HCM and suspected coexistent CAD, this comprehensive cardiac CT protocol can be helpful in ruling out coronary stenosis and can provide information regarding morphology, function and tissue characterization of the LV myocardium. (orig.)

  1. Bilateral brachial plexus blocks in a patient of hypertrophic obstructive cardiomyopathy with hypertensive crisis

    Directory of Open Access Journals (Sweden)

    Rohini V Bhat Pai

    2013-01-01

    Full Text Available Hypertrophic obstructive cardiomyopathy (HOCM is a challenge to anesthesiologists due to the complex pathophysiology involved and various perioperative complications associated with it. We present a 50-year-old man, a known case of HOCM, who successfully underwent emergency haemostasis, and debridement of the traumatically amputated right upper limb and the contused lacerated wound on the left forearm under bilateral brachial plexus blocks. His co-morbidities included hypertension (in hypertensive crisis and diabetes mellitus. He was full stomach and also had an anticipated difficult airway. The management included invasive pressure monitoring and labetalol infusion for emergent control of blood pressure. The regional anaesthesia technique required careful consideration to the dosage of local anaesthetics and staggered performance of brachial plexus blocks on each of the upper limbs to avoid local anaesthetic toxicity. Even though bilateral brachial plexus blocks are rarely indicated, it seemed to be the most appropriate anaesthetic technique in our patient. With careful consideration of the local anaesthetic toxicity and meticulous technique, bilateral brachial plexus blocks can be successfully performed in those patients where general anaesthesia is deemed to be associated with higher risk.

  2. Echocardiography as a Screening Test for Myocardial Scarring in Children with Hypertrophic Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Gregory Compton

    2016-01-01

    Full Text Available Introduction. Hypertrophic cardiomyopathy (HCM is burdened with morbidity and mortality including tachyarrhythmias and sudden cardiac death. These complications are attributed in part to the formation of proarrhythmic scars in the myocardium. The presence of extensive LGE is a risk factor for adverse outcomes in HCM. Late gadolinium enhancement (LGE cardiac magnetic resonance imaging (cMRI is the standard for the noninvasive evaluation of myocardial scars. However, echocardiography represents an attractive screening tool for myocardial scarring. The aim of this study was to compare the suitability of echocardiography to detect myocardial scars to the standard of cMRI-LGE. Methods. The cMRI studies and echocardiograms from 56 consecutive children with HCM were independently evaluated for the presence of cMRI-LGE and echocardiographic evidence of scarring by expert readers. Results. Echocardiography had a high sensitivity (93% and negative predictive value (94% in comparison to LGE. The false positive rate was high, leading to a low specificity (37% and a low positive predictive value (35%. Conclusions. Given the poor specificity and positive predictive value, echocardiography is not a suitable screening test for the presence of myocardial scarring in children with HCM. However, children without echocardiographic evidence of myocardial scarring may not need to undergo cardiac magnetic resonance imaging to “rule in” LGE.

  3. Cardiovascular magnetic resonance imaging in hypertrophic cardiomyopathy: the importance of clinical context.

    Science.gov (United States)

    Quarta, Giovanni; Aquaro, Giovanni Donato; Pedrotti, Patrizia; Pontone, Gianluca; Dellegrottaglie, Santo; Iacovoni, Attilio; Brambilla, Paolo; Pradella, Silvia; Todiere, Giancarlo; Rigo, Fausto; Bucciarelli-Ducci, Chiara; Limongelli, Giuseppe; Roghi, Alberto; Olivotto, Iacopo

    2017-12-22

    In patients with suspected or established hypertrophic cardiomyopathy (HCM), cardiovascular magnetic resonance (CMR) is widely employed for clinical management, given its multimodality approach capable of providing unique information on cardiac morphology, function, and tissue characterization. Guidance regarding all aspects of HCM diagnosis and management is provided by the comprehensive 2014 European Society of Cardiology (ESC) guidelines on HCM. CMR should be performed in centres with recognized expertise in heart muscle diseases, by physicians who are familiar with the whole HCM disease spectrum, differential diagnoses, and pitfalls. Because CMR is usually performed and interpreted by physicians not directly involved in patient care, detailed, bidirectional, and standardized communication becomes essential to obtain best results and avoid misinterpretation. In order to maximize the potential of CMR, it is of paramount importance that reporting physicians are provided with the essential clinical information and that, in turn, referring physicians are given a core set of CMR morphological, functional, and tissue characterization results following the test. This article aims to summarize the current knowledge on the role of CMR in managing HCM and, in addition, to review the importance of the clinical context in which the report is provided, in both adult and paediatric population, highlighting implications for clinical research. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  4. Ineffective and prolonged apical contraction is associated with chest pain and ischaemia in apical hypertrophic cardiomyopathy.

    Science.gov (United States)

    Stephenson, Edward; Monney, Pierre; Pugliese, Francesca; Malcolmson, James; Petersen, Steffen E; Knight, Charles; Mills, Peter; Wragg, Andrew; O'Mahony, Constantinos; Sekhri, Neha; Mohiddin, Saidi A

    2018-01-15

    To investigate the hypothesis that persistence of apical contraction into diastole is linked to reduced myocardial perfusion and chest pain. Apical hypertrophic cardiomyopathy (HCM) is defined by left ventricular (LV) hypertrophy predominantly of the apex. Hyperdynamic contractility resulting in obliteration of the apical cavity is often present. Apical HCM can lead to drug-refractory chest pain. We retrospectively studied 126 subjects; 76 with apical HCM and 50 controls (31 with asymmetrical septal hypertrophy (ASH) and 19 with non-cardiac chest pain and culprit free angiograms and structurally normal hearts). Perfusion cardiac magnetic resonance imaging (CMR) scans were assessed for myocardial perfusion reserve index (MPRi), late gadolinium enhancement (LGE), LV volumes (muscle and cavity) and regional contractile persistence (apex, mid and basal LV). In apical HCM, apical MPRi was lower than in normal and ASH controls (p<0.05). In apical HCM, duration of contractile persistence was associated with lower MPRi (p<0.01) and chest pain (p<0.05). In multivariate regression, contractile persistence was independently associated with chest pain (p<0.01) and reduced MPRi (p<0.001). In apical HCM, regional contractile persistence is associated with impaired myocardial perfusion and chest pain. As apical myocardium makes limited contributions to stroke volume, apical contractility is also largely ineffective. Interventions to reduce apical contraction and/or muscle mass are potential therapies for improving symptoms without reducing cardiac output. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Risk stratification for sudden cardiac death in hypertrophic cardiomyopathy: systematic review of clinical risk markers.

    Science.gov (United States)

    Christiaans, Imke; van Engelen, Klaartje; van Langen, Irene M; Birnie, Erwin; Bonsel, Gouke J; Elliott, Perry M; Wilde, Arthur A M

    2010-03-01

    We performed a systematic literature review of recommended 'major' and 'possible' clinical risk markers for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). We searched the Medline, Embase and Cochrane databases for articles published between 1971 and 2007. We included English language reports on HCM patients containing follow-up data on the endpoint (sudden) cardiac death using survival analysis. Analysis was undertaken using the quality of reporting of meta-analyses (QUORUM) statement checklist. The quality was checked using a quality assessment form from the Cochrane Collaboration. Thirty studies met inclusion criteria and passed quality assessment. The use of the six major risk factors (previous cardiac arrest or sustained ventricular tachycardia, non-sustained ventricular tachycardia, extreme left ventricular hypertrophy, unexplained syncope, abnormal blood pressure response, and family history of sudden death) in risk stratification for SCD as recommended by international guidelines was supported by the literature. In addition, left ventricular outflow tract obstruction seems associated with a higher risk of SCD. Our systematic review provides sound evidence for the use of the six major risk factors for SCD in the risk stratification of HCM patients. Left ventricular outflow tract obstruction could be included in the overall risk profile of patients with a marked left ventricular outflow gradient under basal conditions.

  6. Evaluation of left ventricular function, rotation, twist and untwist in patients with hypertrophic cardiomyopathy.

    Science.gov (United States)

    He, Xue-Wei; Song, Ze-Zhou

    2013-01-01

    Hypertrophic cardiomyopathy (HCM) is a disease with an autosomal-dominant pattern of inheritance associated with a variety of disease courses, age of onset, symptom severity, left ventricular outflow obstruction and risk for sudden cardiac death. Left ventricular systolic function is typically normal in most HCM patients using conventional echocardiographic indexes; however, myocardial systolic and diastolic function are reduced, and the mechanism of myocardial dysfunction remains unclear. Echocardiography is an invaluable tool for the diagnosis and assessment of hemodynamic condition, evaluation of therapy and outcome, and follow-up of patients with HCM. The recent advent of speckle tracking imaging provides a novel index for the noninvasive assessment of left ventricular myocardial dysfunction, and has been confirmed by many studies. A search for original articles focusing on HCM and its associated twist and untwist mechanisms was performed in the MEDLINE and PubMed databases with no date restrictions. All articles identified were English-language, full-text publications. The reference lists of identified articles were also searched for additional articles and reviews.

  7. Speckle tracking echocardiography to assess regional ventricular function in patients with apical hypertrophic cardiomyopathy

    Science.gov (United States)

    Saccheri, María Cristina; Cianciulli, Tomás Francisco; Morita, Luis Alberto; Méndez, Ricardo José; Beck, Martín Alejandro; Guerra, Juan Enrique; Cozzarin, Alberto; Puente, Luciana Jimena; Balletti, Lorena Romina; Lax, Jorge Alberto

    2017-01-01

    AIM To explore regional systolic strain of midwall and endocardial segments using speckle tracking echocardiography in patients with apical hypertrophic cardiomyopathy (HCM). METHODS We prospectively assessed 20 patients (mean age 53 ± 16 years, range: 18-81 years, 10 were male), with apical HCM. We measured global longitudinal peak systolic strain (GLPSS) in the midwall and endocardium of the left ventricle. RESULTS The diastolic thickness of the 4 apical segments was 16.25 ± 2.75 mm. All patients had a normal global systolic function with a fractional shortening of 50% ± 8%. In spite of supernormal left ventricular (LV) systolic function, midwall GLPSS was decreased in all patients, more in the apical (-7.3% ± -8.8%) than in basal segments (-15.5% ± -6.93%), while endocardial GLPPS was significantly greater and reached normal values (apical: -22.8% ± -7.8%, basal: -17.9% ± -7.5%). CONCLUSION This study shows that two-dimensional strain was decreased mainly confined to the mesocardium, while endocardium myocardial deformation was preserved in HCM and allowed to identify subclinical LV dysfunction. This transmural heterogeneity in systolic strain had not been previously described in HCM and could be explained by the distribution of myofibrillar disarray in deep myocardial areas. The clinical application of this novel finding may help further understanding of the pathophysiology of HCM. PMID:28515855

  8. Increased left ventricular torsion in hypertrophic cardiomyopathy mutation carriers with normal wall thickness

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    Marcus Tim J

    2011-01-01

    Full Text Available Abstract Background Increased left ventricular (LV torsion has been observed in patients with manifest familial hypertrophic cardiomyopathy (HCM, and is thought to be caused by subendocardial dysfunction. We hypothesize that increased LV torsion is already present in healthy mutation carriers with normal wall thickness. Methods Seventeen carriers with an LV wall thickness Results LV volumes, mass and circumferential strain were comparable between groups, whereas LV ejection fraction, torsion and TECS-ratio were increased in carriers compared to controls (63 ± 3% vs. 60 ± 3%, p = 0.04, 10.1 ± 2.5° vs. 7.7 ± 1.2°, p = 0.001, and 0.52 ± 0.14°/% vs. 0.42 ± 0.10°/%, p = 0.02, respectively. Conclusions Carriers with normal wall thickness display increased LV torsion and TECS-ratio with respect to controls, which might be due to subendocardial myocardial dysfunction. As similar abnormalities are observed in patients with manifest HCM, the changes in healthy carriers may be target for clinical intervention to delay or prevent the onset of hypertrophy.

  9. Anaesthesia management of a patient with hypertrophic obstructive cardiomyopathy undergoing Morrow′s septal myectomy

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    Naresh Kumar Agarwal

    2007-01-01

    Full Text Available Hypertrophic obstructive cardiomyopathy (HOCM is a rare disorder. There is paucity of literature on anaesthetic management of this disorder. Aim of this case report is to highlight the anaesthetic problems encountered during management of such patients. A thirty-five year old male was admitted with atypical chest pain for last one year. X-ray chest revealed cardiomegaly (CT ratio 0.6. Electrocardiographic findings were left axis deviation with left ventricular hypertrophy. On echocardiography, there was moderate mitral regurgitation (MR, systolic anterior motion (SAM of anterior mitral leaflet and prominent systolic narrowing of left ventricle cavity. Transoesophageal echocardiography (TOE also showed an anomalous muscle bundle stretching into LV causing obstruction. Preload was kept high. Systemic vascular resistance (SVR was maintained, avoiding use of vasodilators and inotropes. Morrow′s septal myectomy was done. Anomalous muscle bundle was excised. On postoperative TOE, there was no MR and no obstruction. Optimal anaesthetic management in such patients involves maintaining adequate preload, systemic vascular resistance and minimal outflow obstruction. Other considerations are to maintain haemodynamic stability, sinus rhythm and afterload. Transoesophageal echocardiography is an extremely useful monitoring device in such patients.

  10. Effect of Left Ventricular Outflow Tract Obstruction on Left Atrial Mechanics in Hypertrophic Cardiomyopathy

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    Lynne K. Williams

    2015-01-01

    Full Text Available Left atrial (LA volumes are known to be increased in hypertrophic cardiomyopathy (HCM and are a predictor of adverse outcome. In addition, LA function is impaired and is presumed to be due to left ventricular (LV diastolic dysfunction as a result of hypertrophy and myocardial fibrosis. In the current study, we assess the incremental effect of outflow tract obstruction (and concomitant mitral regurgitation on LA function as assessed by LA strain. Patients with HCM (50 obstructive, 50 nonobstructive were compared to 50 normal controls. A subset of obstructive patients who had undergone septal myectomy was also studied. Utilising feature-tracking software applied to cardiovascular magnetic resonance images, LA volumes and functional parameters were calculated. LA volumes were significantly elevated and LA ejection fraction and strain were significantly reduced in patients with HCM compared with controls and were significantly more affected in patients with obstruction. LA volumes and function were significantly improved after septal myectomy. LVOT obstruction and mitral regurgitation appear to further impair LA mechanics. Septal myectomy results in a significant reduction in LA volumes, paralleled by an improvement in function.

  11. Myosin-binding Protein C Compound Heterozygous Variant Effect on the Phenotypic Expression of Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Rafael, Julianny Freitas; Cruz, Fernando Eugênio Dos Santos; Carvalho, Antônio Carlos Campos de; Gottlieb, Ilan; Cazelli, José Guilherme; Siciliano, Ana Paula; Dias, Glauber Monteiro

    2017-04-01

    Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disease caused by mutations in genes encoding sarcomere proteins. It is the major cause of sudden cardiac death in young high-level athletes. Studies have demonstrated a poorer prognosis when associated with specific mutations. The association between HCM genotype and phenotype has been the subject of several studies since the discovery of the genetic nature of the disease. This study shows the effect of a MYBPC3 compound variant on the phenotypic HCM expression. A family in which a young man had a clinical diagnosis of HCM underwent clinical and genetic investigations. The coding regions of the MYH7, MYBPC3 and TNNT2 genes were sequenced and analyzed. The proband present a malignant manifestation of the disease, and is the only one to express HCM in his family. The genetic analysis through direct sequencing of the three main genes related to this disease identified a compound heterozygous variant (p.E542Q and p.D610H) in MYBPC3. A family analysis indicated that the p.E542Q and p.D610H alleles have paternal and maternal origin, respectively. No family member carrier of one of the variant alleles manifested clinical signs of HCM. We suggest that the MYBPC3-biallelic heterozygous expression of p.E542Q and p.D610H may cause the severe disease phenotype seen in the proband. Resumo A cardiomiopatia hipertrófica (CMH) é uma doença autossômica dominante causada por mutações em genes que codificam as proteínas dos sarcômeros. É a principal causa de morte súbita cardíaca em atletas jovens de alto nível. Estudos têm demonstrado um pior prognóstico associado a mutações específicas. A associação entre genótipo e fenótipo em CMH tem sido objeto de diversos estudos desde a descoberta da origem genética dessa doença. Este trabalho apresenta o efeito de uma mutação composta em MYBPC3 na expressão fenotípica da CMH. Uma família na qual um jovem tem o diagnóstico clínico de CMH foi

  12. Correlation between myocardial fibrosis and the occurrence of atrial fibrillation in hypertrophic cardiomyopathy: A cardiac magnetic resonance imaging study

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    Pujadas, S., E-mail: sandrapujadas@gmail.co [Cardiac Imaging Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, Av. Pare M Claret 167, 08025 Barcelona (Spain); Vidal-Perez, R. [Cardiac Imaging Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, Av. Pare M Claret 167, 08025 Barcelona (Spain); Hidalgo, A. [Radiology Department, Hospital de la Santa Creu i Sant Pau, Av. Pare M Claret 167, 08025 Barcelona (Spain); Leta, R.; Carreras, F.; Barros, A. [Cardiac Imaging Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, Av. Pare M Claret 167, 08025 Barcelona (Spain); Bayes-Genis, A. [Cardiomyopathy and Cardiac Transplant Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, Av. Pare M Claret 167, 08025 Barcelona (Spain); Subirana, M.T. [Congenital Heart Disease Unit, Hospital de la Santa Creu i Sant Pau, Av. Pare M Claret 167, 08025 Barcelona (Spain); Pons-Llado, Guillem [Cardiac Imaging Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, Av. Pare M Claret 167, 08025 Barcelona (Spain)

    2010-08-15

    Cardiac magnetic resonance imaging (CMR) in hypertrophic cardiomyopathy (HCM) often shows delayed contrast enhancement (DE) representing regions of focal myocardial fibrosis. Atrial fibrillation (AF) is a commonly reported complication of HCM. We determined the relationship between the presence of left ventricular myocardial fibrosis (LVMF) detected by DE-CMR and the occurrence AF in a series of patients with HCM. 67 patients with HCM (47 males; mean age 50.1 {+-} 18.5 years) were studied by CMR measuring mass of LVMF, left ventricular mass, volume and function, and left atrial (LA) area. AF was present in 17 (25%) patients. LVMF was observed in 57% of patients. AF was significantly more frequent in patients who also showed LVMF, compared with the group without LVMF (42.1% vs. 3.4%, respectively; p < 0.0001). LA size was larger in patients showing DE (LA area: 37.4 {+-} 11.1 vs. 25.9 {+-} 6.8 cm{sup 2}; respectively, p = 0.0001). AF in HCM is related with myocardial fibrosis detected by DE-CMR and dilatation of the LA. This fact adds to the proven adverse prognostic value of myocardial fibrosis in HCM, thus, reinforcing the usefulness of this technique in the assessment of these patients.

  13. Exome sequencing identifies a novel MYH7 p.G407C mutation responsible for familial hypertrophic cardiomyopathy.

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    Guo, Qianqian; Xu, Yuejuan; Wang, Xike; Guo, Ying; Xu, Rang; Sun, Kun; Chen, Sun

    2014-10-01

    Hypertrophic cardiomyopathy (HCM), characterized by myocardial hypertrophy, is the most common cause of sudden cardiac arrest in young individuals. More than 270 mutations have been found to be responsible for familial HCM to date; mutations in MYH7, which encodes the β-myosin heavy chain (β-MHC) and MYBPC3, which encodes the myosin binding protein C, are seen most often. This study aimed to screen a pathogenic mutation causing HCM in a large family and assess its possible impact on the function of the specific protein. Exome sequencing was applied in the proband for searching a novel mutation; segments bearing the specific mutation were analyzed by polymerase chain reaction and direct sequencing. A novel p.G407C mutation in the β-MHC gene (MYH7) was identified to be responsible for familial HCM in this family. The mutation may cause damage to the second structure of the protein despite the fact that patients bearing the mutation may have a relatively benign prognosis in this family. The clinical details of the p.G407C mutation are described for the first time in this study. Our report shows a good genotype-phenotype consistency and makes it possible for genetic counseling in this family.

  14. A Rare Case of Hypertrophic Cardiomyopathy with Subendocardial Late Gadolinium Enhancement in an Apical Aneurysm with Thrombus

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    Yusuke Morita

    2014-01-01

    Full Text Available The mechanisms responsible for the development of apical aneurysms in cases of hypertrophic cardiomyopathy (HCM are currently unclear but likely involve multiple factors. Here, we present a case of HCM with marked subendocardial fibrosis involving the apical and proximal portions of the left ventricle. A 71-year-old man with left ventricular hypertrophy presented with signs and symptoms of heart failure. The presence of asymmetrical left ventricular hypertrophy and bilateral, thickened ventricular walls with an apical aneurysm on transthoracic echocardiography suggested a diagnosis of HCM with ventricular dysfunction. No intraventricular pressure gradients with obstruction were identified. Late gadolinium enhancement (LGE with cardiac magnetic resonance imaging and endomyocardial biopsies showed subendocardial fibrosis involving the apical aneurysm and proximal portion. Whereas LGE in a transmural pattern is commonly observed in HCM apical aneurysms, subendocardial LGE, as noted in the present case, is a relatively rare occurrence. Thus, the present case may provide unique insights into the adverse remodeling process and formation of apical aneurysms in cases of HCM.

  15. A rare case of hypertrophic cardiomyopathy with subendocardial late gadolinium enhancement in an apical aneurysm with thrombus.

    Science.gov (United States)

    Morita, Yusuke; Kato, Takao; Okano, Mitsumasa; Su, Kanae; Kimura, Masahiro; Minamino, Eri; Nakane, Eisaku; Izumi, Toshiaki; Miyamoto, Shoichi; Haruna, Tetsuya; Inoko, Moriaki

    2014-01-01

    The mechanisms responsible for the development of apical aneurysms in cases of hypertrophic cardiomyopathy (HCM) are currently unclear but likely involve multiple factors. Here, we present a case of HCM with marked subendocardial fibrosis involving the apical and proximal portions of the left ventricle. A 71-year-old man with left ventricular hypertrophy presented with signs and symptoms of heart failure. The presence of asymmetrical left ventricular hypertrophy and bilateral, thickened ventricular walls with an apical aneurysm on transthoracic echocardiography suggested a diagnosis of HCM with ventricular dysfunction. No intraventricular pressure gradients with obstruction were identified. Late gadolinium enhancement (LGE) with cardiac magnetic resonance imaging and endomyocardial biopsies showed subendocardial fibrosis involving the apical aneurysm and proximal portion. Whereas LGE in a transmural pattern is commonly observed in HCM apical aneurysms, subendocardial LGE, as noted in the present case, is a relatively rare occurrence. Thus, the present case may provide unique insights into the adverse remodeling process and formation of apical aneurysms in cases of HCM.

  16. Complex I deficiency due to selective loss of Ndufs4 in the mouse heart results in severe hypertrophic cardiomyopathy.

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    Edward T Chouchani

    Full Text Available Mitochondrial complex I, the primary entry point for electrons into the mitochondrial respiratory chain, is both critical for aerobic respiration and a major source of reactive oxygen species. In the heart, chronic dysfunction driving cardiomyopathy is frequently associated with decreased complex I activity, from both genetic and environmental causes. To examine the functional relationship between complex I disruption and cardiac dysfunction we used an established mouse model of mild and chronic complex I inhibition through heart-specific Ndufs4 gene ablation. Heart-specific Ndufs4-null mice had a decrease of ∼ 50% in complex I activity within the heart, and developed severe hypertrophic cardiomyopathy as assessed by magnetic resonance imaging. The decrease in complex I activity, and associated cardiac dysfunction, occurred absent an increase in mitochondrial hydrogen peroxide levels in vivo, accumulation of markers of oxidative damage, induction of apoptosis, or tissue fibrosis. Taken together, these results indicate that diminished complex I activity in the heart alone is sufficient to drive hypertrophic cardiomyopathy independently of alterations in levels of mitochondrial hydrogen peroxide or oxidative damage.

  17. Clinical and Echocardiographic Evaluation of Regional Systolic Function Detected by Tissue Doppler Imaging in Hypertrophic Cardiomyopathy

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    A Sadeghpour

    2009-09-01

    Full Text Available Background: Hypertrophic cardiomyopathy (HCM is the most common type of the genetic cardiovasculardiseases. Regarding to tremendous heterogeneity in the phenotypic expression of HCM, which is generally unrelatedto genotype, we aimed to study, clinical and echocardiographic parameters such as Tissue Doppler Imaging(TDI in various subtypes of HCM patients and evaluate the influence of race and gender in Iranian patients.Methods: Patients with HCM underwent a complete clinical and echocardiographic study including TDI toassess regional systolic contraction( in the 12 segments and early diastolic annular velocity (Em from theseptal mitral annulus.Results: The study comprised 41 patients (20 women, mean age = 41 ± 15 years with mean LVEF 55%±4.8%and mean maximal septal thickness 2.07cm. Considering LVOT gradient>30mmHg, hypertrophic obstructivecardiomyopathy (HOCM was found in 18 (45%. Asymmetric septal hypertrophy (ASH existed in 27 patients(67%, systolic anterior motion of anterior mitral leaflet (SAM in 25 persons (64%. Nineteen patients (46.3%were included in NYHA function class (FC II and 6 (14.7% in FC III or higher. We found syncope in 10(24.4%, chest pain in 4 (9.8%, atrial fibrilation in 14.6 % and ventricular arrhythmias in (17.1% of patients.History of ICD was seen in 7 (17.1% and PPM in 9 cases. Mean E’ velocity was 5.44± 1.65 cm/sec and S velocity5.70± 1.49 cm/sec with significant lower S velocity and E’ in syncope patients. Overall, HOCM patients hadgrade II diastolic dysfunction with E/É >15(17.54±7.46. Majority (25 of cases (61% were categorized in typeIII of HCM. RV involvement was observed in 11 patients (28.2%.No significant differences existed betweenprevalence of syncope and dysrhythmia among HCM and HOCM patients.Conclusion: In our study, we found lower detection of latent HOCM, compared to other studies, suggestive ofinadequate use of appropriate provocative maneuvers such as exercise stress echocardiography and amyl

  18. Fibroma cardíaco mimetizando cardiomiopatia hipertrófica Cardiac fibroma mimicking hypertrophic cardiomyopathy

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    Luís Alberto Dallan

    1989-12-01

    Full Text Available É relatado o caso de paciente com queixa de dor precordial, dispnéia e arritmia desde a adolescência, tratada clinicamente por mais de 10 anos. Nesse período, foi submetida a inúmeros exames ângio e ecocardiográficos, com suspeita inicial de endomiocardiofibrose e, posteriormente, de cardiomiopatia hipertrófica de ventrículo esquerdo. Como houve piora progressiva da sintomatologia e ausência de resposta à medicação, foi encaminhada ao nosso Serviço, onde se diagnosticou fibroma de ventrículo esquerdo. Foi submetida, com sucesso, à ressecção cirúrgica do tumor, sendo realizada reconstrução geométrica do ventrículo esquerdo. Apresenta boa evolução, decorridos dois anos, com remissão completa dos sintomas. Destacamos a dificuldade no diagnóstico diferencial desses tumores benignos e de crescimento lento, com as cardiomiopatias hipertróficas do ventrículo esquerdo.A 33 year-old woman was seen, for the first time, ten years ago, for evaluation of a recurrent chest pain, dyspnea and arrhythmia. She was submitted to echocardiographic studies and a cardiac catheterization. The diagnoses was endomyocardial fibrosis at first, and hypertrophic cardiomyopathy after. Despite treatment with propranolol and quinidine, the episodes of dyspnea and tachyarrhythmias became more frequent and severe, and the patient was guided to our Service. Cardiac re-catheterization, echocardiographic and computed tomography studies identified in traumural cardiac fibroma and the patient was referred for surgical treatment. The cardiac fibroma was successfully resected on extracorporeal bypass and with cardioplegic arrest of the heart. Repair of the heart was accomplished with a patch placed to close the left ventricular cavity. The postoperative course was uncomplicated, and she remains assymptomatic two years later. We have emphazied tha this tumor often produces clinically obscure disease, simulating particularly the left ventricle hypertrophic

  19. Exercise in patients with hypertrophic cardiomyopathy: A review of current evidence, national guideline recommendations and a proposal for a new direction to fitness.

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    Hindieh, Waseem; Adler, Arnon; Weissler-Snir, Adaya; Fourey, Dana; Harris, Sarah; Rakowski, Harry

    2017-04-01

    Hypertrophic cardiomyopathy is a common genetic disorder with a prevalence of 1:500 in the general population. Amongst a varied spectrum of clinical presentations, the most feared complication of this cardiac disorder is sudden cardiac death. Although only a minority of patients with hypertrophic cardiomyopathy who suffer sudden cardiac death or resuscitated cardiac arrest do so during exercise, strenuous physical activity is regarded as an important trigger for these tragic outcomes. Furthermore, during exercise, patients with hypertrophic cardiomyopathy may develop augmentation of left ventricular outflow tract obstruction, myocardial ischemia, diastolic dysfunction and/or inappropriate vasodilation in non-exercising vascular beds. This in turn may lead to exertional dyspnea, chest pain or syncope. Accordingly, patients with hypertrophic cardiomyopathy are disqualified from competitive sports and in many cases are recommended to avoid strenuous physical activity of any kind. Nevertheless, avoidance of physical activity comes with a price. The positive effects of regular exercise have been extensively reported to convey a wide range of benefits including reduced cardiovascular events, weight reduction and improved wellbeing. Therefore, finding the right exercise level that will offer some of the benefits of physical activity without increasing the risk of sudden cardiac death is of utmost importance. In this review, we discuss the current evidence for and against exercise in this patient population and review national guideline recommendations. We also propose alternative fitness strategies including a novel fitness program implemented by our hypertrophic cardiomyopathy center which may be of particular usefulness for hypertrophic cardiomyopathy patients. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  20. Outcomes of Alcohol Septal Ablation in Younger Patients With Obstructive Hypertrophic Cardiomyopathy.

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    Liebregts, Max; Faber, Lothar; Jensen, Morten K; Vriesendorp, Pieter A; Januska, Jaroslav; Krejci, Jan; Hansen, Peter R; Seggewiss, Hubert; Horstkotte, Dieter; Adlova, Radka; Bundgaard, Henning; Ten Berg, Jurriën M; Veselka, Josef

    2017-06-12

    The aim of this study was to describe the safety and outcomes of alcohol septal ablation (ASA) in younger patients with obstructive hypertrophic cardiomyopathy. The American College of Cardiology Foundation/American Heart Association guidelines reserve ASA for older patients and patients with serious comorbidities. Data on long-term age-specific outcomes after ASA are scarce. A total of 1,197 patients (mean age 58 ± 14 years) underwent ASA for obstructive hypertrophic cardiomyopathy. Patients were divided into young (≤50 years), middle-age (51 to 64 years), and older (≥65 years) groups. Thirty-day mortality and pacemaker implantation rates were lower in young compared with older patients (0.3% vs. 2% [p = 0.03] and 8% vs. 16% [p Heart Association functional class I or II at last follow-up. During a mean follow-up period of 5.4 ± 4.2 years, 165 patients (14%) died. Annual mortality rates of young, middle-age, and older patients were 1%, 2%, and 5%, respectively (p alcohol had a higher all-cause mortality rate (0.6% vs. 1.4% per year in patients treated with <2.5 ml, p = 0.03). ASA in younger patients with obstructive hypertrophic cardiomyopathy was safe and effective for relief of symptoms at long-term follow-up. The authors propose that the indication for ASA can be broadened to younger patients. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  1. Hypertrophic Cardiomyopathy: New Evidence Since the 2011 American Cardiology of Cardiology Foundation and American Heart Association Guideline.

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    Fraiche, Ariane; Wang, Andrew

    2016-07-01

    Since publication of the 2011 American College of Cardiology Foundation (ACCF) and American Heart Association (AHA) Guideline for the diagnosis and treatment of hypertrophic cardiomyopathy (HCM), more recent studies offer greater insights about this condition. With increased recognition of the role of sarcomere protein mutations and myocardial structural abnormalities in the pathophysiology of this disease, new evidence offers potential improvements for the management of patients with HCM. In this review of studies published since 2011, we highlight several studies that may impact diagnostic considerations, risk stratification, and treatment of symptoms in HCM.

  2. Apical aneurysm and myocardial bridging in a patient with hypertrophic cardiomyopathy: association or consequence of the myocardial bridging?

    Science.gov (United States)

    Foucault, Anthony; Hilpert, Loic; Hédoire, Francois; Saloux, Eric; Gomes, Sophie; Pellissier, Arnaud; Scanu, Patrice; Champ-Rigot, Laure; Milliez, Paul

    2012-01-01

    The identification of high-risk patients with hypertrophic cardiomyopathy (HC) for primary prevention of sudden cardiac death (SCD) remains a challenging issue, since major risk factors sometimes lack specificity. We report the case of a patient with HC and association of apical aneurysm and myocardial bridging who had been initially not implanted because she had only one major risk factor. She subsequently experienced a sustained ventricular tachycardia that finally motivated the implantation. We conclude that it is never an easy decision to implant a preventive implantable cardioverter-defibrillator (ICD). Nevertheless, additional criteria for a better selection of patients who would benefit from an ICD implant are certainly useful.

  3. Peripheral blood derived induced pluripotent stem cells (iPSCs from a female with familial hypertrophic cardiomyopathy

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    Samantha Barratt Ross

    2017-04-01

    Full Text Available Induced pluripotent stem cells (iPSCs were generated from peripheral blood mononuclear cells (PBMCs obtained from a 62-year-old female with familial hypertrophic cardiomyopathy (HCM. PBMCs were reprogrammed to a pluripotent state following transfection with non-integrative episomal vectors carrying reprogramming factors OCT4, SOX2, LIN28, KLF4 and L-MYC. iPSCs were shown to express pluripotency markers, possess trilineage differentiation potential, carry rare variants identified in DNA isolated directly from the patient's whole blood, have a normal karyotype and no longer carry episomal vectors for reprogramming. This line is a useful resource for identifying unknown genetic causes of HCM.

  4. Functional effects of losartan in hypertrophic cardiomyopathy-a randomised clinical trial.

    Science.gov (United States)

    Axelsson, Anna; Iversen, Kasper; Vejlstrup, Niels; Ho, Carolyn Y; Havndrup, Ole; Kofoed, Klaus F; Norsk, Jakob; Jensen, Morten; Bundgaard, Henning

    2016-02-15

    There is a lack of disease-modifying treatments in hypertrophic cardiomyopathy (HCM). The aim of this randomised, placebo-controlled study was to assess if losartan could improve or ameliorate deterioration of cardiac function and exercise capacity. Echocardiography, exercise test and MRI or CT were performed at baseline and after 12 months in 133 patients (52±13 years, 35% female) randomly allocated to losartan (100 mg/day) or placebo. Losartan had no effect on systolic function compared with placebo (mean difference for left ventricular ejection fraction (LVEF) 0% (95% CI -3% to 4%), p=0.84 or global longitudinal strain 0.7% (95% CI -0.2% to 1.6%), p=0.13). Neither Doppler measures of diastolic function, left atrial volume (mean difference 2 mL/m(2) (95% CI -4 to 8 mL/m(2)) p=0.53) nor exercise capacity (mean difference -0.3 metabolic equivalents (METS) (95% CI -1.0 to 0.3 METS), p=0.28) differed between the treatment groups. At follow-up, there was further progression of disease, with the most prominent impairment being an increase in left atrial volume of 6 mL/m(2) (95% CI 3 to 9 mL/m(2), plosartan had no effect on cardiac function or exercise capacity compared with placebo. Losartan fail to improve myocardial performance and failed to alter the progression of the disease. These findings do not support the use of angiotensin II receptor blockers as disease modifiers in adult patients with overt HCM. NCT01447654-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  5. Myocardial Extracellular Volume Is not Associated With Malignant Ventricular Arrhythmias in High-risk Hypertrophic Cardiomyopathy.

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    Mirelis, Jesús G; Sánchez-González, Javier; Zorio, Esther; Ripoll-Vera, Tomas; Salguero-Bodes, Rafael; Filgueiras-Rama, David; González-López, Esther; Gallego-Delgado, María; Fernández-Jiménez, Rodrigo; Soleto, María Jesús; Núñez, Juana; Pizarro, Gonzalo; Sanz, Javier; Fuster, Valentín; García-Pavía, Pablo; Ibáñez, Borja

    2017-03-21

    Myocardial interstitial fibrosis, a hallmark of hypertrophic cardiomyopathy (HCM), has been proposed as an arrhythmic substrate. Fibrosis is associated with increased extracellular volume (ECV), which can be quantified by computed tomography (CT). We aimed to analyze the association between CT-determined ECV and malignant ventricular arrhythmias. A retrospective case-control observational study was conducted in HCM patients with implantable cardioverter-defibrillator, undergoing a CT-protocol with continuous iodine contrast infusion to determine equilibrium ECV. Left ventricular septal and lateral CT-determined ECV was compared between prespecified cases (malignant arrhythmia any time before CT scan) and controls (no prior malignant arrhythmias) and among ECV tertiles. A total of 78 implantable cardioverter-defibrillator HCM patients were included; 24 were women, with a mean age of 52.1 ± 15.6 years. Mean ECV ± standard deviation in the septal left ventricular wall and was 29.8% ± 6.3% in cases (n = 24) vs 31.9% ± 8.5% in controls (n = 54); P = .282. Mean ECV in the lateral wall was 24.5% ± 6.8% in cases vs 28.2% ± 7.4% in controls; P = .043. On comparison of the entire population according to septal ECV tertiles, no significant differences were found in the number of patients receiving appropriate shocks. Conversely, we found a trend (P = .056) for a higher number of patients receiving appropriate shocks in the lateral ECV lowest tertile. Extracellular volume was not increased in implantable cardioverter-defibrillator HCM patients with malignant ventricular arrhythmias vs those without arrhythmias. Our findings do not support the use of ECV (a surrogate of diffuse fibrosis) as a predictor of arrhythmias in high-risk HCM patients. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  6. A cost-effectiveness model of genetic testing for the evaluation of families with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Ingles, Jodie; McGaughran, Julie; Scuffham, Paul A; Atherton, John; Semsarian, Christopher

    2012-04-01

    Traditional management of families with hypertrophic cardiomyopathy (HCM) involves periodic lifetime clinical screening of family members, an approach that does not identify all gene carriers owing to incomplete penetrance and significant clinical heterogeneity. Limitations in availability and cost have meant genetic testing is not part of routine clinical management for many HCM families. To determine the cost-effectiveness of the addition of genetic testing to HCM family management, compared with clinical screening alone. A probabilistic Markov decision model was used to determine cost per quality-adjusted life-year and cost for each life-year gained when genetic testing is included in the management of Australian families with HCM, compared with the conventional approach of periodic clinical screening alone. The incremental cost-effectiveness ratio (ICER) was $A785 (£510 or €587) per quality-adjusted life-year gained, and $A12 720 (£8261 or €9509) per additional life-year gained making genetic testing a very cost-effective strategy. Sensitivity analyses showed that the cost of proband genetic testing was an important variable. As the cost of proband genetic testing decreased, the ICER decreased and was cost saving when the cost fell below $A248 (£161 or €185). In addition, the mutation identification rate was also important in reducing the overall ICER, although even at the upper limits, the ICER still fell well within accepted willingness to pay bounds. The addition of genetic testing to the management of HCM families is cost-effective in comparison with the conventional approach of regular clinical screening. This has important implications for the evaluation of families with HCM, and suggests that all should have access to specialised cardiac genetic clinics that can offer genetic testing.

  7. Very late effects of dual chamber pacing therapy for obstructive hypertrophic cardiomyopathy.

    Science.gov (United States)

    Lucon, Adrien; Palud, Laurent; Pavin, Dominique; Donal, Erwan; Behar, Nathalie; Leclercq, Christophe; Mabo, Philippe; Daubert, Jean-Claude

    2013-01-01

    The very long-term effects of dual chamber pacing as a primary treatment for hypertrophic obstructive cardiomyopathy (HOCM) are poorly known and controversial. To examine the intermediate- and long-term clinical and haemodynamic effects of permanent dual chamber pacing in patients presenting with HOCM. Between 1991 and 2007, 51 patients (mean age 59 ± 14 years) presenting with HOCM and New York Heart Association (NYHA) functional class ≥ II despite optimal medical therapy underwent implantation of DDD pacemakers with or without a defibrillator and were followed for 11.5 years (range 0.4-21.8 years). During follow-up, no patient underwent myectomy or septal alcohol ablation. NYHA functional class and other disease manifestations decreased significantly over 1-2 years of follow-up and remained stable thereafter. The left intraventricular (LV) gradient decreased by a mean of 78% over 1-2 years, reaching 89% at end of follow-up, along with disappearance of systolic anterior motion of the mitral valve. Mean LV ejection fraction decreased from a mean of 64 ± 8% before pacing to 56 ± 9% at end of follow-up (P=0.05), while LV end-diastolic diameter did not change significantly. The 5- and 10-year actuarial survival rates were 90% and 65%, respectively. Among 22 deaths, 10 were due to cardiovascular and 12 to non-cardiovascular causes; two patients underwent cardiac transplantation after 8 and 13 years of DDD pacing, respectively. In this sample of patients with HOCM, DDD pacing alleviated symptoms and improved haemodynamic function over the very long term. The merits of this treatment should be revisited in a controlled trial. Copyright © 2013. Published by Elsevier Masson SAS.

  8. Development of a communication aid for explaining hypertrophic cardiomyopathy genetic test results.

    Science.gov (United States)

    Smagarinsky, Yana; Burns, Charlotte; Spinks, Catherine; Semsarian, Christopher; Ingles, Jodie

    2017-01-01

    Large gene panels are now commonplace for hypertrophic cardiomyopathy (HCM), increasing the yield of uncertain genetic findings. Few resources exist which aim to facilitate communication of HCM genetic test results. We sought to develop, pilot, and refine a communication aid for probands receiving HCM genetic test results. Development was a multi-step process involving expertise of a multidisciplinary team, literature review, and empirical experience. The aid went through an iterative revision process throughout the piloting phase to incorporate feedback. HCM probands attending a specialized multidisciplinary HCM clinic, aged ≥ 18 years and genetic test results available for disclosure between May and August 2016, or recently received their gene results (January-April 2015) were eligible. A purposive sampling strategy was employed, recruiting those attending clinic during the study period or those who could attend without difficulty. We developed and pilot tested a genetic counsellor-led communication aid. Based on clinical expertise, the aid addresses (a) what genetic testing is, (b) implications for the patient, (c) reasoning for variant classification, and (d) implications for the family. Pilot data were sought to assess knowledge, feasibility, and acceptability using a self-report survey 2 weeks post-intervention. Twelve of 13 participants completed the follow-up questionnaire. Participants valued the individualised nature of the aid, recommended use of the aid, and indicated genetic knowledge, and family communication was better facilitated. Iterative modification of images helped to more simply depict important genetic concepts. We have developed a tool that is feasible, acceptable, and helpful to patients receiving genetic results. This is an important first step, and trial of the aid to assess effectiveness compared to usual care will follow.

  9. Evaluation of subcutaneous ICD early performance in hypertrophic cardiomyopathy from the pooled EFFORTLESS and IDE cohorts.

    Science.gov (United States)

    Lambiase, Pier D; Gold, Michael R; Hood, Margaret; Boersma, Lucas; Theuns, Dominic A M J; Burke, Martin C; Weiss, Raul; Russo, Andrea M; Kääb, Stefan; Knight, Bradley P

    2016-05-01

    The subcutaneous implantable cardioverter-defibrillator (S-ICD) is a potential alternative to transvenous systems in hypertrophic cardiomyopathy (HCM) where lead complications are a significant issue. To compare the S-ICD efficacy of defibrillation threshold (DFT) testing, arrhythmia therapy, and complications in HCM versus non-HCM patients. Outcomes of patients with HCM implanted with S-ICD were compared to non-HCM S-ICD recipients using pooled data from a total of 872 subjects enrolled in the EFFORTLESS Registry and US IDE study. The cohort included 99 HCM (75% male) and 773 non-HCM (72% male) patients with a median follow-up of 637 days. The HCM cohort was younger and more likely to receive a primary-prevention S-ICD (88.5% vs 67.5%, P One year postoperative complication-free rates were similar: 92.7% in HCM (with no lead complications) versus 89.5% in non-HCM. There were 3 appropriate shocks for ventricular tachycardia in 3 HCM patients that were all converted by the first shock. Overall final shock conversion efficacy was 100% in HCM versus 98% in non-HCM (P = ns). Inappropriate shocks occurred in 12.5% of HCM patients and 10.3% of non-HCM patients (P = ns), being reduced by 47% using dual-zone programming. These initial data indicate the S-ICD is safe and effective in patients with HCM who are at high risk of ventricular arrhythmias and pass preimplantation electrocardiogram screening. Inappropriate shocks were mainly due to T-wave oversensing, but there were no lead complications requiring reintervention. Copyright © 2016. Published by Elsevier Inc.

  10. CASE OF DIAGNOSIS OF APICAL FORM OF HYPERTROPHIC CARDIOMYOPATHY WITH A PATIENT WITH PROGRESSIVE ANGINA CLINIC

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    N. S. Krylova

    2015-01-01

    Full Text Available Objective of work: to describe the apical form of hypertrophic cardiomyopathy (AFHC developing under the "mask" of the ischemic heart disease not diagnosed for a long period.Materials and methods. Patient B., 73 y.o., female, was brought to the cardiology department with complains of severe pressing pain behind the breastbone caused with no apparent reason and lasting for over 4 hours. The following examination of the patient was performed: electrocardiography (ECG, echocardiography (EchoCG, Holter ECG monitoring, coronary angiography (CAG, ventriculography.Results. The final diagnosis for the patient was set on the basis of the following readings: ECG data (basic rhythm – atrial fibrillation, left ventricle (LV hypertrophy, negative T-waves in leads V1–6, ST segment depression up to 1–2 mm in leads V4–6, EchoCG (hypertrophy of apical segments of the LV with decreasing of its cavity, moderate dilatation of the left atrium, intraventricular obstruction in the apical third of the LV with the maximum pressure gradient of up to 48 mm Hg., CAG (stenotic lesions of coronary arteries were found, ventriculography (LV volume is not increased, no violations of local contractility, narrowing of the LV cavity in the lower third is observed with thinning in the apex, which indicatesexpressed apical hypertrophy of the LV myocard. AFHC, apical form with moderate obstruction in the lower third of the left ventricle. Stress angina syndrome. CAG and ventriculography were main diagnostic methods that allowed setting the final diagnosis.Conclusion. The clinical case sets forth the peculiarities of diagnostics, therapy, and post-therapy management of patients with this form of AFHC.

  11. The association between brain natriuretic peptide and tissue Doppler parameters in children with hypertrophic cardiomyopathy

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    Taliha Öner

    2016-01-01

    Full Text Available In this study, we investigated the association between brain natriuretic peptide (BNP levels and tissue Doppler imaging measurements and also screening for deadly mutations in patients with hypertrophic cardiomyopathy (HCM. We enrolled 20 patients diagnosed with HCM (age:10.7±5 years (1-17, 85% male, weight:42.25±23.10 kg, height:141.80±32.45 cm and 20 age, gender and body weight-matched control subjects. We performed electrocardiography, transthoracic echocardiography, and tissue Doppler echocardiography in each group, as well as genetic tests (for Arg403Gln, Arg453Cys, Arg719Trp and Arg719Gln mutations in MYH7 Exons 13, 14, 19 and BNP in the patients. The patients were divided into two groups according to the presence (Group 1 or absence (Group 2 of left ventricular (LV outflow tract obstruction. QTc dispersion and the LV ejection fraction and left atrial (LA volume index were increased in Group 1. The LA volume index and the mitral and septal E/Ea ratio and septum Z-score were increased while the mitral lateral annulus and septal annulus Ea wave velocities and the mitral and tricuspid E/A ratio were decreased in patients with high levels of BNP compared to those with normal BNP levels. There were no mutations that are associated with increased risk of sudden death found in patients included in this study. In the light of our data, we conclude that such parameters BNP levels above the 98 pg/mL, septal thickness Z-score ˃6, and higher mitral and septal E/Ea ratios can be used for management of patients with HCM according to life-threatening conditions.

  12. Clinical significance of left ventricular apical aneurysms in hypertrophic cardiomyopathy patients: the role of diagnostic electrocardiography.

    Science.gov (United States)

    Ichida, Masaru; Nishimura, Yoshioki; Kario, Kazuomi

    2014-10-01

    Some patients with hypertrophic cardiomyopathy (HCM) develop left ventricular apical aneurysm, leading to serious cardiovascular complications. The aims of this study were to identify the incidence and clinical course of HCM patients with apical aneurysms in Japan, and to evaluate the role of electrocardiography (ECG) as a screening test to detect apical aneurysms in HCM patients. In a retrospective, single center analysis of a population of 247 HCM patients, 21 patients (8.5%) had left ventricular apical aneurysms. Their mean age was 60 ± 14 years (range: 23-77 years) at study entry. Over 4.7 ± 3.3 years of follow-up, 10 patients (47.6%) experienced an adverse clinical event (annual event rate: 10.1%/y), including five implantable cardioverter-defibrillator (ICD) implantations for ventricular tachycardia/ventricular fibrillation (VT/VF), an appropriate discharge of ICD for VT/VF, and four nonfatal thromboembolic strokes. Two patients developed systolic dysfunction (ejection fraction <50%). No sudden cardiac death or progressive heart failure was detected. Fourteen patients showed ST-segment elevation (≥ 1 mm) in V3 through V5 of ECG. In four patients, progression of the ST-segment elevation was recognized. When the ST-segment elevation was used to identify apical aneurysms in HCM patients, the sensitivity was 66.7%, and the specificity was 98.7%. Apical aneurysms in HCM patients in Japan are not rare, and are associated with serious cardiovascular complications. The early diagnosis of apical aneurysms can be achieved by serial ECG. Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  13. Atrial Fibrillation in Hypertrophic Cardiomyopathy: Is the Extent of Septal Hypertrophy Important?

    Science.gov (United States)

    Park, Kyoung-Min; Im, Sung Il; Kim, Eun Kyoung; Lee, Sang-Chol; Park, Seung-Jung; Kim, June Soo; On, Young Keun

    2016-01-01

    Hypertrophic cardiomyopathy (HCM) is a cardiac disease associated with a high incidence of atrial fibrillation (AF). Recent studies have suggested that interventricular septum thickness may influence the risk stratification of patients with AF. We evaluated the effects of septal hypertrophy on morbidity and mortality in patients with HCM. Patients were followed for a median of 6.1 years and were divided into two groups according to the extent of septal hypertrophy. A total of 1,360 HCM patients were enrolled: 482 (33%) apical or apicoseptal, 415 (28%) asymmetric septal, 388 (27%) basal septal, 38 (2.6%) concentric, and 37 (2.5%) diffuse and mixed type. Ninety-two all-cause deaths and 21 cardiac deaths occurred. The total event rates were significantly higher for patients with HCM with more extensive septal hypertrophy (group A) compared to those with HCM ± focal septal hypertrophy (group B), regardless of type (p<0.001). Arrhythmias occurred in 502 patients, with a significantly higher incidence in group A than in group B (p<0.001). Among patients with arrhythmias, the incidence of AF was significantly higher in group A than group B (p<0.001). In univariate Cox analysis, a greater extent of septal hypertrophy (p<0.001), E/E´ ratio (p = 0.011), and mitral regurgitation grade (p = 0.003) were significantly associated with developing AF. In multivariate Cox analyses, a greater extent of septal hypertrophy [odds ratio (OR) 5.44 (2.29-12.92), p<0.001] in patients with HCM was significantly associated with developing AF. In conclusion, a greater extent of septal hypertrophy is an independent predictor of progression to AF in patients with HCM.

  14. Helical distribution of hypertrophy in patients with hypertrophic cardiomyopathy: prevalence and clinical implications.

    Science.gov (United States)

    Viliani, Dafne; Pozo, Eduardo; Aguirre, Norma; Cecconi, Alberto; Olivera, María J; Caballero, Paloma; Jiménez-Borreguero, Luis J; Alfonso, Fernando

    2017-11-01

    Recently a novel pattern of helical distribution of hypertrophy has been described in patients with hypertrophic cardiomyopathy (HCM). Our aim was to determine its prevalence and potential implications in an unselected cohort. One-hundred- and eight consecutive patients diagnosed with HCM by cardiac magnetic resonance (CMR) were included (median clinical follow up of 1718 days). All clinical and complementary test information was prospectively collected. The presence of a helical pattern was assessed by a simple measurement of the maximal left ventricle (LV) wall thickness (LVWT) for each of the 17 classical LV segments and it was classified in one of three types according to its extension. A helical distribution was detected in 58% of patients, and was associated to a higher incidence of left ventricular outflow tract obstruction (LVOT; 35% vs. 10%; p = 0.005) and systolic anterior motion of the mitral valve (SAM; 30% vs. 13%, p = 0.053). No significant difference in the maximal LVWT was observed. However, the presence of a helical pattern showed a significant association with non sustained ventricular tachycardia (NSVT; 22% vs. 7%; p = 0.029) and was associated to a higher risk of sudden cardiac death (SCD) calculated with the European society of cardiology (ESC) calculator (p = 0.006). Notably, patients with a more extense spiral had a higher incidence of heart failure (75% vs. 34%, p = 0.012) and all-cause death (21 vs. 3%, p = 0.049). A helical pattern is frequent in HCM and can be readily assessed on CMR standard cine sequences. In conclusion, a helical pattern carries negative clinical implications and is associated to a higher estimated risk of SCD.

  15. Comparison of different quantification methods of late gadolinium enhancement in patients with hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Spiewak, Mateusz, E-mail: mspiewak@ikard.p [First Department of Coronary Artery Disease, Magnetic Resonance Unit, Institute of Cardiology, ul. Alpejska 42, 04-628 Warsaw (Poland); Malek, Lukasz A., E-mail: lmalek@ikard.p [First Department of Coronary Artery Disease, Magnetic Resonance Unit, Institute of Cardiology, ul. Alpejska 42, 04-628 Warsaw (Poland); Misko, Jolanta, E-mail: jmisko@wp.p [Magnetic Resonance Unit, Institute of Cardiology, ul. Alpejska 42, 04-628 Warsaw (Poland); Chojnowska, Lidia, E-mail: lchojnowska@ikard.p [First Department of Coronary Artery Disease, Institute of Cardiology, ul. Alpejska 42, 04-628 Warsaw (Poland); Milosz, Barbara, E-mail: barbara-milosz@tlen.p [Magnetic Resonance Unit, Institute of Cardiology, ul. Alpejska 42, 04-628 Warsaw (Poland); Klopotowski, Mariusz, E-mail: mklopotowski@hotmail.co [First Department of Coronary Artery Disease, Institute of Cardiology, ul. Alpejska 42, 04-628 Warsaw (Poland); Petryka, Joanna, E-mail: joannapetryka@hotmail.co [First Department of Coronary Artery Disease, Magnetic Resonance Unit, Institute of Cardiology, ul. Alpejska 42, 04-628 Warsaw (Poland); Dabrowski, Maciej, E-mail: macidabro@yahoo.co [First Department of Coronary Artery Disease, Institute of Cardiology, ul. Alpejska 42, 04-628 Warsaw (Poland); Kepka, Cezary, E-mail: ckepka@ikard.p [First Department of Coronary Artery Disease, Magnetic Resonance Unit, Institute of Cardiology, ul. Alpejska 42, 04-628 Warsaw (Poland); Ruzyllo, Witold, E-mail: w.ruzyllo@ikard.p [First Department of Coronary Artery Disease, Institute of Cardiology, ul. Alpejska 42, 04-628 Warsaw (Poland)

    2010-06-15

    Aim: There is no consensus regarding the technique of quantification of late gadolinium enhancement (LGE). The aim of the study was to compare different methods of LGE quantification in patients with hypertrophic cardiomyopathy (HCM). Methods: Cardiac magnetic resonance was performed in 33 patients with HCM. First, LGE was quantified by visual assessment by the team of experienced readers and compared with different thresholding techniques: from 1SD to 6SD above mean signal intensity (SI) of remote myocardium, above 50% of maximal SI of the enhanced area (full-width at half maximum, FWHM) and above peak SI of remote myocardium. Results: LGE was present in 25 (78%) of patients. The median mass of LGE varied greatly depending on the quantification method used and was highest with the utilization of 1SD threshold [75.5 g, interquartile range (IQR): 63.3-112.3 g] and lowest for FWHM method (8.4 g, IQR: 4.3-13.3 g). There was no difference in mass of LGE as assessed with 6SD threshold and FWHM when compared to visual assessment (p = 0.19 and p = 0.1, respectively); all other thresholding techniques provided significant differences in the median LGE size when compared to visual analysis. Results for all thresholds, except FWHM were significantly correlated with visual assessment with the strongest correlation for 6SD (rho = 0.956, p < 0.0001). Conclusions: LGE quantification with the use of a threshold of 6SD above the mean SI of the remote myocardium provided the best agreement with visual assessment in patients with HCM.

  16. Effects of hypertrophy and fibrosis on regional and global functional heterogeneity in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Chang, Sung-A; Lee, Sang-Chol; Choe, Yeon Hyeon; Hahn, Hye-Jin; Jang, Shin Yi; Park, Sung-Ji; Choi, Jin-Oh; Park, Seung Woo; Oh, Jae K

    2012-12-01

    Hypertrophic cardiomyopathy (HCM) is a disease that typically has heterogeneous hypertrophy and dysfunction of the myocardium. Cardiac magnetic resonance imaging (CMR) can be used to accurately assess ventricular wall thickness and regional fibrosis. We investigated the effects of hypertrophy and fibrosis on the heterogeneity of regional and global myocardial function in HCM. Forty patients who were diagnosed with HCM were consecutively enrolled. Echocardiography and CMR with delayed hyper-enhancement imaging (DHE) was performed for each patient. Left ventricular (LV) regional and global longitudinal strain (SL(R) and SL(G)) were obtained by two-dimensional speckle tracking method on echocardiography. With CMR, regional myocardial wall thickness was measured, and the amount of DHE was calculated semi-quantitatively in each segment. Overall, 720 segments were analyzed. SL(R) was significantly decreased in the hypertrophied segments (thickness > 11 mm) and segments with DHE (P < 0.001). SL(R) was correlated with myocardial wall thickness (r = 0.47, P = 0.001) and amount of regional DHE (r = 0.39, P < 0.001). On multivariate analysis, regional LV wall thickness and amount of DHE were the only independent determinants of SL(R). SL(G) was associated with LV diastolic functional parameters in echocardiography, total DHE volume, and LV mass index. Total DHE volume and LV mass index were independent determinants of SL(G) on multivariate analysis. The extent of regional myocardial fibrosis is associated with regional myocardial function independently of morphological changes of the myocardium, and the correlation extended to global LV function. In this context, DHE may be a useful parameter to discover early myocardial dysfunction independently of LV hypertrophy.

  17. Recent Advances in the Molecular Genetics of Familial Hypertrophic Cardiomyopathy in South Asian Descendants

    Science.gov (United States)

    Kraker, Jessica; Viswanathan, Shiv Kumar; Knöll, Ralph; Sadayappan, Sakthivel

    2016-01-01

    The South Asian population, numbered at 1.8 billion, is estimated to comprise around 20% of the global population and 1% of the American population, and has one of the highest rates of cardiovascular disease. While South Asians show increased classical risk factors for developing heart failure, the role of population-specific genetic risk factors has not yet been examined for this group. Hypertrophic cardiomyopathy (HCM) is one of the major cardiac genetic disorders among South Asians, leading to contractile dysfunction, heart failure, and sudden cardiac death. This disease displays autosomal dominant inheritance, and it is associated with a large number of variants in both sarcomeric and non-sarcomeric proteins. The South Asians, a population with large ethnic diversity, potentially carries region-specific polymorphisms. There is high variability in disease penetrance and phenotypic expression of variants associated with HCM. Thus, extensive studies are required to decipher pathogenicity and the physiological mechanisms of these variants, as well as the contribution of modifier genes and environmental factors to disease phenotypes. Conducting genotype-phenotype correlation studies will lead to improved understanding of HCM and, consequently, improved treatment options for this high-risk population. The objective of this review is to report the history of cardiovascular disease and HCM in South Asians, present previously published pathogenic variants, and introduce current efforts to study HCM using induced pluripotent stem cell-derived cardiomyocytes, next-generation sequencing, and gene editing technologies. The authors ultimately hope that this review will stimulate further research, drive novel discoveries, and contribute to the development of personalized medicine with the aim of expanding therapeutic strategies for HCM. PMID:27840609

  18. Distribution of Hypertrophy and Late Gadolinium Enhancement in Children and Adolescents with Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Windram, Jonathan D; Benson, Lee N; Dragelescu, Andreea; Yoo, Shi-Joon; Mertens, Luc; Wong, Derek; Grosse-Wortmann, Lars

    2015-01-01

    While well characterized in adult patients, the pattern of hypertrophy and the extent of myocardial scarring in hypertrophic cardiomyopathy (HCM) are insufficiently known. The aim of this study was to assess the hypertrophy patterns and the prevalence and clinical significance of scars in the hearts of young patients with HCM. A retrospective analysis of the imaging findings of 38 children (aged 12.83 ± 2 years, 30 males) with HCM who underwent cardiac magnetic resonance imaging (CMR) was performed. In addition to left ventricular mass and volumes, the examinations were assessed for the pattern of hypertrophy and presence of late gadolinium enhancement (LGE). A myocardial signal intensity ≥6 standard deviations above the mean of normal myocardium defined positive LGE. Left ventricular mass index averaged 110 ± 34 g/m(2) . Nineteen children (50%) had diffuse septal, 13 (34%) diffuse concentric and 6 (16%) isolated basal hypertrophy. Seven children (18%) had LGE. Patients with LGE had a greater left ventricular mass index than those without (136 ± 34 g/m(2) vs. 104 ± 31 g/m(2) , P = .025). The only two patients who presented with an episode of aborted sudden cardiac death had LGE (P = .03). The most common hypertrophy pattern in children with HCM was diffuse septal hypertrophy. The incidence of LGE observed is lower than that reported in adults. The presence of LGE appears to confer a risk for adverse events. © 2015 Wiley Periodicals, Inc.

  19. Differentiating left ventricular hypertrophy in athletes from that in patients with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Caselli, Stefano; Maron, Martin S; Urbano-Moral, Josè A; Pandian, Natesa G; Maron, Barry J; Pelliccia, Antonio

    2014-11-01

    Identification of hypertrophic cardiomyopathy (HC) in young athletes is challenging when left ventricular (LV) wall thickness is between 13 and 15 mm. The aim of this study was to revise the ability of simple echocardiographic and clinical variables for the differential diagnosis of HC versus athlete's heart. Twenty-eight athletes free of cardiovascular disease were compared with 25 untrained patients with HC, matched for LV wall thickness (13 to 15 mm), age, and gender. Clinical, electrocardiographic, and echocardiographic variables were compared. Athletes had larger LV cavities (60 ± 3 vs 45 ± 5 mm, p 40 mm excluded HC with sensitivity of 92% and specificity of 71% (p <0.001). Athletes showed higher e' velocity by tissue Doppler imaging than patients with HC (12.5 ± 1.9 vs 9.3 ± 2.3 cm/second, p <0.001), with values <11.5 cm/second yielding sensitivity of 81% and specificity of 61% for the diagnosis of HC (p <0.001). Absence of diffuse T-wave inversion on electrocardiography (specificity 92%) and negative family history for HC (specificity 100%) also proved useful for excluding HC. In conclusion, in athletes with LV hypertrophy in the "gray zone" with HC, LV cavity size appears the most reliable criterion to help in diagnosis, with a cut-off value of <54 mm useful for differentiation from athlete's heart. Other criteria, including LV diastolic dysfunction, absence of T-wave inversion on electrocardiography, and negative family history, further aid in the differential diagnosis. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Identification of high risk patients with hypertrophic cardiomyopathy in a northern Greek population

    Directory of Open Access Journals (Sweden)

    Karvounis Charalambos

    2009-07-01

    Full Text Available Abstract Background The percentage of hypertrophic cardiomyopathy (HCM patients who are in high risk for Sudden Death (SD constitutes only a minority of all HCM population but the incidence of SD in this subset is high (at least 5% annually. The identification of this small but important proportion of high risk HCM patients has been the clue in the clinical evaluation of these patients. Methods Our study cohort consisted from 123 patients with HCM who are currently followed up in our Institution. Five clinical risk factors were assessed: a family history of premature SD, unexplained syncope, Non Sustained Ventricular Tachycardia (NSVT on 24-h ECG monitoring, Abnormal Blood Pressure Response (ABPR during upright exercise testing and Maximum left ventricular Wall Thickness (MWT ≥30 mm. The purpose of our study was the identification of high risk HCM patients coming from Northern Greece. Results Fifteen patients (12.2% of the whole cohort had MWT ≥ 30 mm, 30 patients (24.4% had an ABPR to exercise, 17 patients (13.8% had episodes of NSVT in 24-h Holter monitoring, 17 patients (13.8% suffered from syncope, and 8 patients (6.5% had a positive family history of premature SD. Data analysis revealed that 74 patients (60.1% had none risk factor. Twenty four patients (19.5% had 1 risk factor, 17 patients (13.8% had 2 risk factors, 4 patients (3.25% had 3 risk factors, and 4 patients (3.25% had 4 risk factors, while none patient had 5 risk factors. Twenty five patients (20.3% had 2 or more risk factors. Conclusion This study for the first time confirms that, although a 60% of patients with HCM coming from a regional Greek population are in low risk for SD, a substantial proportion (almost 20% carries a high risk for SD justifying prophylactic therapy with amiodaron or ICD implantation.

  1. Recent Advances in the Molecular Genetics of Familial Hypertrophic Cardiomyopathy in South Asian Descendants

    Directory of Open Access Journals (Sweden)

    Jessica Kraker

    2016-10-01

    Full Text Available The South Asian population, numbered at 1.8 billion, is estimated to comprise around 20% of the global population and 1% of the American population, and has one of the highest rates of cardiovascular disease. While South Asians show increased classical risk factors for developing heart failure, the role of population-specific genetic risk factors has not yet been examined for this group. Hypertrophic cardiomyopathy (HCM is one of the major cardiac genetic disorders among South Asians, leading to contractile dysfunction, heart failure, and sudden cardiac death. This disease displays autosomal dominant inheritance, and it is associated with a large number of variants in both sarcomeric and non-sarcomeric proteins. South Asians, a population with large ethnic diversity, potentially carries region-specific polymorphisms. There is high variability in disease penetrance and phenotypic expression of variants associated with HCM. Thus, extensive studies are required to decipher pathogenicity and the physiological mechanisms of these variants, as well as the contribution of modifier genes and environmental factors to disease phenotypes. Conducting genotype-phenotype correlation studies will lead to improved understanding of HCM and, consequently, improved treatment options for this high-risk population. The objective of this review is to report the history of cardiovascular disease and HCM in South Asians, present previously published pathogenic variants, and introduce current efforts to study HCM using induced pluripotent stem cell-derived cardiomyocytes, next-generation sequencing, and gene editing technologies. The authors ultimately hope that this review will stimulate further research, drive novel discoveries, and contribute to the development of personalized medicine with the aim of expanding therapeutic strategies for HCM.

  2. MR assessment of absolute myocardial blood flow and vasodilator flow reserve in patients with hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Kawada, Nanaka; Sakuma, Hajime; Takeda, Kan; Nakagawa, Tsuyoshi; Yamakado, Tetsu; Nakano, Takeshi [Mie Univ., Tsu (Japan). School of Medicine

    1997-04-01

    Absolute coronary blood flow per myocardial mass and coronary flow reserve for the entire left ventricle were evaluated in normals and in patients with hypertrophic cardiomyopathy (HCM) by using fast cine MR imaging and fast velocity encoded cine (VENC) MR imaging. Nine healthy volunteers and 8 patients with HCM were studied with a 1.5 T imager. Breath-hold cine MR images encompassing the whole left ventricle were acquired on short axis imaging planes in order to evaluate myocardial mass. A fast VENC MR images were obtained to measure blood flow volume in the coronary sinus before and after dipyridamole administration (TR/TE=15/5 ms, FOV=28 x 22 cm, slice thickness=5 mm). Coronary flow reserve was calculated as a ratio of hyperemic to baseline coronary flow volumes. In the baseline state, coronary blood flow per myocardial mass was significantly lower in patients with HCM than in normal myocardium (0.56{+-}0.23 vs. 0.78{+-}0.27 ml/min/g, p<0.05). After dipyridamole administration, coronary blood flow per myocardial mass in patients with HCM increased substantially less than that in healthy subjects (0.99{+-}0.38 vs. 2.22{+-}0.55 ml/min/g, p<0.01), resulting in the significantly decreased coronary flow reserve ratio in HCM in comparison with that in normal myocardium (1.86{+-}0.56 vs. 3.11{+-}1.37, p<0.05). In conclusion, breath-hold velocity encoded cine MR imaging is a noninvasive technique which can provide assessments of altered coronary blood flow volume per myocardial mass and vasodilator flow reserve in patients with HCM. (author)

  3. Reproducibility of Gadolinium Enhancement Patterns and Wall Thickness in Hypertrophic Cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Granillo, Gaston A., E-mail: grodriguezgranillo@gmail.com; Deviggiano, Alejandro; Capunay, Carlos; Zan, Macarena C. De; Carrascosa, Patricia [Department of Cardiovascular Imaging - Diagnóstico Maipú, Buenos Aires (Argentina)

    2016-07-15

    Reproducibility data of the extent and patterns of late gadolinium enhancement (LGE) in hypertrophic cardiomyopathy (HCM) is limited. To explore the reproducibility of regional wall thickness (WT), LGE extent, and LGE patterns in patients with HCM assessed with cardiac magnetic resonance (CMR). The extent of LGE was assessed by the number of segments with LGE, and by the total LV mass with LGE (% LGE); and the pattern of LGE-CMR was defined for each segment. A total of 42 patients (672 segments) with HCM constituted the study population. The mean WT measurements showed a mean difference between observers of -0.62 ± 1.0 mm (6.1%), with limits of agreement of 1.36 mm; -2.60 mm and intraclass correlation coefficient (ICC) of 0.95 (95% CI 0.93-0.96). Maximum WT measurements showed a mean difference between observers of -0.19 ± 0.8 mm (0.9%), with limits of agreement of 1.32 mm; -1.70 mm, and an ICC of 0.95 (95% CI 0.91-0.98). The % LGE showed a mean difference between observers of -1.17 ± 1.2 % (21%), with limits of agreement of 1.16%; -3.49%, and an ICC of 0.94 (95% CI 0.88-0.97). The mean difference between observers regarding the number of segments with LGE was -0.40 ± 0.45 segments (11%), with limits of agreement of 0.50 segments; -1.31 segments, and an ICC of 0.97 (95% CI 0.94-0.99). The number of segments with LGE might be more reproducible than the percent of the LV mass with LGE.

  4. Hypertrophic cardiomyopathy clinical phenotype is independent of gene mutation and mutation dosage.

    Science.gov (United States)

    Viswanathan, Shiv Kumar; Sanders, Heather K; McNamara, James W; Jagadeesan, Aravindakshan; Jahangir, Arshad; Tajik, A Jamil; Sadayappan, Sakthivel

    2017-01-01

    Over 1,500 gene mutations are known to cause hypertrophic cardiomyopathy (HCM). Previous studies suggest that cardiac β-myosin heavy chain (MYH7) gene mutations are commonly associated with a more severe phenotype, compared to cardiac myosin binding protein-C (MYBPC3) gene mutations with milder phenotype, incomplete penetrance and later age of onset. Compound mutations can worsen the phenotype. This study aimed to validate these comparative differences in a large cohort of individuals and families with HCM. We performed genome-phenome correlation among 80 symptomatic HCM patients, 35 asymptomatic carriers and 35 non-carriers, using an 18-gene clinical diagnostic HCM panel. A total of 125 mutations were identified in 14 genes. MYBPC3 and MYH7 mutations contributed to 50.0% and 24.4% of the HCM patients, respectively, suggesting that MYBPC3 mutations were the most frequent cause of HCM in our cohort. Double mutations were found in only nine HCM patients (7.8%) who were phenotypically indistinguishable from single-mutation carriers. Comparisons of clinical parameters of MYBPC3 and MYH7 mutants were not statistically significant, but asymptomatic carriers had high left ventricular ejection fraction and diastolic dysfunction when compared to non-carriers. The presence of double mutations increases the risk for symptomatic HCM with no change in severity, as determined in this study subset. The pathologic effects of MYBPC3 and MYH7 were found to be independent of gene mutation location. Furthermore, HCM pathology is independent of protein domain disruption in both MYBPC3 and MYH7. These data provide evidence that MYBPC3 mutations constitute the preeminent cause of HCM and that they are phenotypically indistinguishable from HCM caused by MYH7 mutations.

  5. A low prevalence of MYH7/MYBPC3 mutations among familial hypertrophic cardiomyopathy patients in India.

    Science.gov (United States)

    Bashyam, Murali D; Purushotham, Guroji; Chaudhary, Ajay K; Rao, Katika Madhumohan; Acharya, Vishal; Mohammad, Tabrez A; Nagarajaram, Hampapathalu A; Hariram, Vuppaladadhiam; Narasimhan, Calambur

    2012-01-01

    Familial Hypertrophic Cardiomyopathy (FHC) is an autosomal dominant disorder affecting the cardiac muscle and exhibits varied clinical symptoms because of genetic heterogeneity. Several disease causing genes have been identified and most code for sarcomere proteins. In the current study, we have carried out clinical and molecular analysis of FHC patients from India. FHC was detected using echocardiography and by analysis of clinical symptoms and family history. Disease causing mutations in the β-cardiac myosin heavy chain (MYH7) and Myosin binding protein C3 (MYBPC3) genes were identified using Polymerase Chain Reaction-Deoxyribose Nucleic Acid (PCR-DNA) sequencing. Of the 55 patient samples screened, mutations were detected in only nineteen in the two genes; MYBPC3 mutations were identified in 12 patients while MYH7 mutations were identified in five, two patients exhibited double heterozygosity. All four MYH7 mutations were missense mutations, whereas only 3/9 MYPBC3 mutations were missense mutations. Four novel mutations in MYBPC3 viz. c.456delC, c.2128G>A (p.E710K), c.3641G>A (p.W1214X), and c.3656T>C (p.L1219P) and one in MYH7 viz. c.965C>T (p.S322F) were identified. A majority of missense mutations affected conserved amino acid residues and were predicted to alter the structure of the corresponding mutant proteins. The study has revealed a greater frequency of occurrence of MYBPC3 mutations when compared to MYH7 mutations.

  6. Mutations in MYH7 reduce the force generating capacity of sarcomeres in human familial hypertrophic cardiomyopathy.

    Science.gov (United States)

    Witjas-Paalberends, E Rosalie; Piroddi, Nicoletta; Stam, Kelly; van Dijk, Sabine J; Oliviera, Vasco Sequeira; Ferrara, Claudia; Scellini, Beatrice; Hazebroek, Mark; ten Cate, Folkert J; van Slegtenhorst, Marjon; dos Remedios, Cris; Niessen, Hans W M; Tesi, Chiara; Stienen, Ger J M; Heymans, Stephane; Michels, Michelle; Poggesi, Corrado; van der Velden, Jolanda

    2013-08-01

    Familial hypertrophic cardiomyopathy (HCM), frequently caused by sarcomeric gene mutations, is characterized by cellular dysfunction and asymmetric left-ventricular (LV) hypertrophy. We studied whether cellular dysfunction is due to an intrinsic sarcomere defect or cardiomyocyte remodelling. Cardiac samples from 43 sarcomere mutation-positive patients (HCMmut: mutations in thick (MYBPC3, MYH7) and thin (TPM1, TNNI3, TNNT2) myofilament genes) were compared with 14 sarcomere mutation-negative patients (HCMsmn), eight patients with secondary LV hypertrophy due to aortic stenosis (LVHao) and 13 donors. Force measurements in single membrane-permeabilized cardiomyocytes revealed significantly lower maximal force generating capacity (Fmax) in HCMmut (21 ± 1 kN/m²) and HCMsmn (26 ± 3 kN/m²) compared with donor (36 ± 2 kN/m²). Cardiomyocyte remodelling was more severe in HCMmut compared with HCMsmn based on significantly lower myofibril density (49 ± 2 vs. 63 ± 5%) and significantly higher cardiomyocyte area (915 ± 15 vs. 612 ± 11 μm²). Low Fmax in MYBPC3mut, TNNI3mut, HCMsmn, and LVHao was normalized to donor values after correction for myofibril density. However, Fmax was significantly lower in MYH7mut, TPM1mut, and TNNT2mut even after correction for myofibril density. In accordance, measurements in single myofibrils showed very low Fmax in MYH7mut, TPM1mut, and TNNT2mut compared with donor (respectively, 73 ± 3, 70 ± 7, 83 ± 6, and 113 ± 5 kN/m²). In addition, force was lower in MYH7mut cardiomyocytes compared with MYBPC3mut, HCMsmn, and donor at submaximal [Ca²⁺]. Low cardiomyocyte Fmax in HCM patients is largely explained by hypertrophy and reduced myofibril density. MYH7 mutations reduce force generating capacity of sarcomeres at maximal and submaximal [Ca²⁺]. These hypocontractile sarcomeres may represent the primary abnormality in patients with MYH7 mutations.

  7. Minimally invasive septal myectomy for the treatment of hypertrophic obstructive cardiomyopathy and intrinsic mitral valve disease.

    Science.gov (United States)

    Gilmanov, Daniyar Sh; Bevilacqua, Stefano; Solinas, Marco; Ferrarini, Matteo; Kallushi, Enkel; Santarelli, Philippo; Farneti, Pier Andrea; Glauber, Mattia

    2015-01-01

    Transaortic left ventricular septal myectomy described by Morrow is a classical procedure for the treatment of systolic anterior motion of the mitral apparatus associated with hypertrophic obstructive cardiomyopathy (HOCM). We aimed to review our results of transmitral septal myectomy and mitral valve repair/replacement in patients with intrinsic mitral valve disease associated with HOCM, operated on through a minimally invasive approach. Between 2005 and 2014, 19 patients [7 men (37%); mean (SD) age, 69.4 (14.5) years] were treated with minimally invasive approach for degenerative mitral regurgitation and HOCM. Preoperative peak left ventricular outflow tract (LVOT) gradient was 66 (24) mm Hg. Severe mitral regurgitation was diagnosed in 16 cases (84%). New York Heart Association functional class III to IV heart failure was present in 13 patients (68%). Fifteen patients (79%) underwent mitral valve replacement, and four patients (21%) underwent mitral valve repair. Left ventricular outflow tract obstruction was corrected directly in all patients via the mitral valve with septal myectomy/myotomy, avoiding aortotomy in majority of the patients. No significant prolongation of extracorporeal circulation/aortic cross-clamping times was observed (P = 0.41 and P = 0.67, respectively) when compared with a similar population without HOCM. No iatrogenic ventricular septal defect developed in treated patients. No hospital mortality occurred. Resting LVOT gradient reduced at discharge to 13 (22) mm Hg (P = 0.025). Transmitral left ventricular septal myectomy in patients with degenerative mitral valve disease is quite a simple, feasible, and effective technique and does not require aortotomy in most cases. It can be performed with low early mortality and satisfactory resolution of LVOT obstruction in a minimally invasive setting.

  8. Left atrial volume predicts adverse cardiac and cerebrovascular events in patients with hypertrophic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Tani Tomoko

    2011-11-01

    Full Text Available Abstract Aims To prospectively evaluate the relationship between left atrial volume (LAV and the risk of clinical events in patients with hypertrophic cardiomyopathy (HCM. Methods We enrolled a total of 141 HCM patients with sinus rhythm and normal pump function, and 102 patients (73 men; mean age, 61 ± 13 years who met inclusion criteria were followed for 30.8 ± 10.0 months. The patients were divided into two groups with or without major adverse cardiac and cerebrovascular events (MACCE, a composite of stroke, sudden death, and congestive heart failure. Detailed clinical and echocardiographic data were obtained. Results MACCE occurred in 24 patients (18 strokes, 4 congestive heart failure and 2 sudden deaths. Maximum LAV, minimum LAV, and LAV index (LAVI corrected for body surface area (BSA were significantly greater in patients with MACCE than those without MACCE (maximum LAV: 64.3 ± 25.0 vs. 51.9 ± 16.0 ml, p = 0.005; minimum LAV: 33.9 ± 15.1 vs. 26.2 ± 10.9 ml, p = 0.008; LAVI: 40.1 ± 15.4 vs. 31.5 ± 8.7 ml/mm2, p = 0.0009, while there were no differences in the other echocardiographic parameters. LAV/BSA of ≥ 40.4 ml/m2 to identify patients with cardiovascular complications with a sensitivity of 73% and a specificity of 88%. Conclusion LAVI may be an effective marker for detecting the risk of MACCE in patients with HCM and normal pump function.

  9. Evaluating the utility of circulating biomarkers of collagen synthesis in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Ellims, Andris H; Taylor, Andrew J; Mariani, Justin A; Ling, Liang-Han; Iles, Leah M; Maeder, Micha T; Kaye, David M

    2014-03-01

    In hypertrophic cardiomyopathy (HCM), accumulation of myocardial collagen may play a central role in the pathogenesis of diastolic dysfunction and arrhythmia. Previous studies have suggested that peripheral levels of byproducts of collagen synthesis are reflective of myocardial extracellular matrix metabolism, although this has not been validated in detail. Given the potential clinical utility of such biomarkers, we sought to validate the assumed relationship between peripheral markers and myocardial fibrosis in HCM. Fifty patients with HCM and 25 healthy controls underwent peripheral venous sampling to determine plasma concentrations of key collagen precursors (procollagen I and III N-terminal propeptides [PINP, PIIINP]). Contrast-enhanced cardiac magnetic resonance imaging was performed to quantify regional (by late-gadolinium enhancement) and diffuse (by T1 mapping) myocardial fibrosis. Nineteen subjects also underwent simultaneous arterial and coronary sinus blood sampling (to derive transcardiac concentration gradients of PINP, PIIINP, and C-terminal telopeptide of type I collagen) and right heart catheterization. Despite cardiac magnetic resonance evidence of regional (late-gadolinium enhancement quantity, 6.4±8.0%) and diffuse (T1 time, 478±79 ms) myocardial fibrosis in patients with HCM, peripheral levels of collagen precursors were similar compared with control subjects (PINP, 45.9±22.9 versus 53.4±25.9 μg/L; P=0.21; PIIINP, 4.8±1.7 versus 4.4±1.1 μg/L; P=0.26). No significant net positive transcardiac concentration gradient was detected for either biomarker of collagen synthesis. The cardiac contribution to peripheral levels of byproducts of collagen synthesis in patients with HCM is insignificant. Furthermore, peripheral levels of these biomarkers do not accurately reflect myocardial collagen content in these patients.

  10. Orthostatic blood pressure test for risk stratification in patients with hypertrophic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Julia Münch

    Full Text Available Hypertrophic cardiomyopathy (HCM is the most common cause of sudden cardiac death (SCD in young adults, mainly ascribed to ventricular tachycardia (VT. Assuming that VT is the major cause of (pre- syncope in HCM patients, its occurrence is essential for SCD risk stratification and primarily preventive ICD-implantation. However, evidence of VT during syncope is often missing. As the differentiation of potential lethal causes for syncope such as VT from more harmless reasons is crucial, HCM patients were screened for orthostatic dysregulation by using a simple orthostatic blood pressure test.Over 15 months (IQR [9;20] 100 HCM patients (55.8±16.2 yrs, 61% male were evaluated for (pre-syncope and VT (24h-ECGs, device-memories within the last five years. Eighty patients underwent an orthostatic blood pressure test. Logistic regression models were used for statistical analysis.In older patients (>40 yrs a positive orthostatic test result increased the chance of (pre- syncope by a factor of 63 (95%-CI [8.8; 447.9], p<0.001; 93% sensitivity, 95%-CI [76; 99]; 74% specificity, 95%-CI [58; 86]. No correlation with VT was shown. A prolonged QTc interval also increased the chance of (pre- syncope by a factor of 6.6 (95%-CI [2.0; 21.7]; p=0.002.The orthostatic blood pressure test is highly valuable for evaluation of syncope and presyncope especially in older HCM patients, suggesting that orthostatic syncope might be more relevant than previously assumed. Considering the high complication rates due to ICD therapies, this test may provide useful information for the evaluation of syncope in individual risk stratification and may help to prevent unnecessary device implantations, especially in older HCM patients.

  11. Formin homology 2 domain containing 3 variants associated with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Wooten, Eric C; Hebl, Virginia B; Wolf, Matthew J; Greytak, Sarah R; Orr, Nicole M; Draper, Isabelle; Calvino, Jenna E; Kapur, Navin K; Maron, Martin S; Kullo, Iftikhar J; Ommen, Steve R; Bos, J Martijn; Ackerman, Michael J; Huggins, Gordon S

    2013-02-01

    Incomplete penetrance and variable expression of hypertrophic cardiomyopathy (HCM) is well appreciated. Common genetic polymorphisms variants that may affect HCM penetrance and expression have been predicted but are not well established. We performed a case-control genomewide association study to identify common HCM-associated genetic polymorphisms and then asked whether such common variants were more represented in HCM or could explain the heterogeneity of HCM phenotypes. We identified an intronic FHOD3 variant (rs516514) associated with HCM (odds ratio, 2.45; 95% confidence interval, 1.76-3.41; P=1.25×10(-7)) and validated this finding in an independent cohort. Next, we tested FHOD3-V1151I (rs2303510), a nonsynonymous variant in partial linkage disequilibrium with rs516514, and we detected an even stronger association with HCM (P=1.76×10(-9)). Although HCM patients were more likely to carry these, FHOD3 allele subjects homozygous for FHOD3-1151I had similar HCM phenotypes as carriers of the V1151 allele. FHOD3 expression is increased in the setting of HCM, and both alleles of FHOD3-V1151I were detected in HCM myectomy tissue. Previously, FHOD3 was found to be required for formation of the sarcomere, and here we demonstrate that its fly homolog fhos is required for normal adult heart systolic contraction. Here we demonstrate the association of a common nonsynonymous FHOD3 genetic variant with HCM. This discovery further strengthens the potential role of gene mutations and polymorphisms that alter the amino acid sequence of sarcomere proteins and HCM.

  12. Formin Homology 2 Domain Containing 3 (FHOD3) Variants Associated with Hypertrophic Cardiomyopathy

    Science.gov (United States)

    Wooten, Eric C.; Hebl, Virginia Bartleson; Wolf, Matthew J.; Greytak, Sarah R.; Orr, Nicole; Draper, Isabelle; Calvino, Jenna E.; Kapur, Navin K.; Maron, Martin S.; Kullo, Iftikhar J.; Ommen, Steve R.; Bos, J. Martijn; Ackerman, Michael J.; Huggins, Gordon S.

    2013-01-01

    Background Incomplete penetrance and variable expression of Hypertrophic Cardiomyopathy (HCM) is well appreciated. Common genetic polymorphisms variants that may affect HCM penetrance and expression have been predicted but are not well established. Methods and Results We performed a case-control genome wide association (GWA) study to identify common HCM-associated genetic polymorphisms and then asked whether such common variants were more represented in HCM or could explain the heterogeneity of HCM phenotypes. We identified an intronic FHOD3 variant (rs516514) associated with HCM (OR = 2.45 (95% CI 1.76–3.41), p=1.25 × 10−7) and validated this finding in an independent cohort. Next, we tested FHOD3-V1151I (rs2303510), a non-synonymous variant in partial linkage disequilibrium (LD) with rs516514, and we detected an even stronger association with HCM (p=1.76 × 10−9). While HCM patients were more likely to carry these FHOD3 alleles subjects homozygous for FHOD3-1151I had similar HCM phenotypes as carriers of the V1151 allele. FHOD3 expression is increased in the setting of HCM and both alleles of FHOD3-V1151I were detected in HCM myectomy tissue. Previously FHOD3 was found to be required for formation of the sarcomere and here we demonstrate that its fly homolog fhos is required for normal adult heart systolic contraction. Conclusions Here we demonstrate the association of a common non-synonymous FHOD3 genetic variant with HCM. This discovery further strengthens the potential role of gene mutations and polymorphisms that alter the amino acid sequence of sarcomere proteins and HCM. PMID:23255317

  13. Prognostic Implications of Defibrillation Threshold Testing in Patients With Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Francia, Pietro; Adduci, Carmen; Semprini, Lorenzo; Palano, Francesca; Santini, Daria; Musumeci, Beatrice; Santolamazza, Caterina; Volpe, Massimo; Autore, Camillo

    2017-01-01

    In hypertrophic cardiomyopathy (HCM) patients the need for defibrillation threshold (DFT) testing at the time of ICD implantation is debated. Moreover, its prognostic implications have never been explored. In a cohort of HCM patients we sought to (a) investigate factors prompting DFT testing, (b) evaluate ICD efficacy by testing DFT, (c) compare DFT in patients with and without massive LVH, and (d) assess whether DFT testing predicts shock efficacy for spontaneous VT/VF. We retrospectively analyzed a cohort of HCM patients implanted with an ICD. DFT was tested at the discretion of the implanting physician with a 10 J safety margin. During follow-up, ICD interventions were evaluated. The study population included 66 patients. DFT was determined in 25 (38%) patients. Age (HR: 0.95; 95%CI: 0.92-0.98; P = 0.004) and massive LVH (HR: 6.0; 95%CI: 2.03-18.8; P = 0.001) affected the decision to test DFT. DFT was at least 10 J less than maximal ICD output in 25/25. Safety margin was similar among patients with and without massive LVH (15 ± 3 J vs. 14 ± 2 J; P = 0.42). During follow-up (median 53 months) 15 shocks were delivered for 12 VT/VF in 7 patients. One VF ended spontaneously after a failed shock. Of 4 unsuccessful shocks, 2 occurred in 1 patient with DFT testing and 2 were delivered in 2 patients without. All unsuccessful shocks were ≤35 J. Young age and massive LVH prompt DFT testing. Contemporary ICDs are safe and effective in HCM patients independently from the magnitude of LVH. DFT testing does not predict shock efficacy for spontaneous VT/VF. © 2016 Wiley Periodicals, Inc.

  14. Myocardial perfusion abnormality and effects of Ca channel blockers on myocardial ischemia in patients with hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Taniguchi, Yoko [Kyoto Prefectural Univ. of Medicine (Japan)

    1997-03-01

    The purpose of this study was to investigate the frequency of myocardial ischemia and characteristic regions of myocardial hypoperfusion during stress in patients with hypertrophic cardiomyopathy. Furthermore, the effects of Ca channel blocker (verapamil, diltiazem) on myocardial ischemia were studied. One hundred patients with hypertrophic cardiomyopathy underwent exercise {sup 201}Tl SPECT. Sixty-eight patients had one or more {sup 201}Tl abnormalities. Of the 68 patients with {sup 201}Tl abnormalities, 56 had reversible {sup 201}Tl abnormalities and 12 had fixed defect. {sup 201}Tl abnormalities were frequently distributed in the anterior and posterior areas of junction between the ventricular septum and the free wall and the apex. Of the 56 patients with reversible {sup 201}Tl abnormalities, 40 patients underwent one more exercise {sup 201}Tl SPECT after 8 weeks of oral administration of verapamil or diltiazem. The {sup 201}Tl defect was visually scored as the defect score. Transient dilation index was calculated as an index of subendocardial ischemia. The mean defect score decreased significantly from 9.80{+-}4.35 to 5.50{+-}4.63 after verapamil and from 9.90{+-}5.17 to 5.50{+-}4.89 after diltiazem. Mean transient dilation index decreased from 1.20{+-}0.12 to 1.08{+-}0.09 after treatment with verapamil and from 1.16{+-}0.10 to 1.02{+-}0.09 after treatment with diltiazem. (K.H.)

  15. [Mutations in sarcomeric genes MYH7, MYBPC3, TNNT2, TNNI3, and TPM1 in patients with hypertrophic cardiomyopathy].

    Science.gov (United States)

    García-Castro, Mónica; Coto, Eliecer; Reguero, Julián R; Berrazueta, José R; Alvarez, Victoria; Alonso, Belén; Sainz, Rocío; Martín, María; Morís, Cesar

    2009-01-01

    Mutation of a sarcomeric gene is the most frequent cause of hypertrophic cardiomyopathy. For each such gene, however, previous studies have reported a range of different mutation frequencies, and clinical manifestations have been highly heterogeneous, both of which limit the use of genetic information in clinical practice. Our aim was to determine the frequency of mutations in the sarcomeric genes MYH7, MYBPC3, TNNT2, TNNI3, and TPM1 in a cohort of Spanish patients with hypertrophic cardiomyopathy. We used sequencing to analyze the coding regions of these five genes in 120 patients (29% with a family history) and investigated how the patient phenotype varied with the gene mutated. In total, 32 patients were found to have mutations: 10 in MYH7 (8%), 20 in MYBPC3 (16%), 2 in TNNT2, 1 in TPM1 and none in TNNI3. Overall, 61% of mutations had not been described before. Two patients had two mutations (i.e., double mutants). There was no difference in the mean age at diagnosis or the extent of the hypertrophy between those with MYH7 mutations and those with MYBPC3 mutations. Some 26% of patients had a mutation in one of the five sarcomeric genes investigated. More than half of the mutations had not been described before. The MYBPC3 gene was the most frequently mutated, followed by MYH7. No phenotypic differences were observed between carriers of the various mutations, which makes it difficult to use genetic information to stratify risk in these patients.

  16. Doppler echocardiography underestimates the prevalence and magnitude of mid-cavity obstruction in patients with symptomatic hypertrophic cardiomyopathy.

    Science.gov (United States)

    Malcolmson, James W; Hamshere, Stephen M; Joshi, Abhishek; O'Mahony, Constantinos; Dhinoja, Mehul; Petersen, Steffen E; Sekhri, Neha; Mohiddin, Saidi A

    2017-08-02

    To evaluate utility of Doppler echocardiography in the assessment of left ventricular (LV) mid-cavity obstructive (LVMCO) hypertrophic cardiomyopathy (HCM). LVMCO is a relatively under-diagnosed complication of HCM and may occur alone or in combination with LV outflow tract obstruction (LVOTO). Identifying and quantifying LVMCO and differentiating it from LVOTO has important implications for patient management. We aimed to assess diagnostic performance of Doppler echocardiography in the assessment of suspected LV obstruction. Forty symptomatic HCM patients with suspected obstruction underwent cardiac catheterization, and comparison of location and magnitude of Doppler derived gradients with synchronous invasive measurements (reference standard), at rest and isoprenaline stress (IS). Doppler's diagnostic accuracy for any obstruction (≥30 mmHg) in this cohort was 75% with false positive and false negative rates of 2.5 and 22.5%, respectively. During subanalysis, Doppler's diagnostic accuracy for isolated LVOTO in this selected cohort is 83% with false positive and false negative rates of 4 and 12.5%, respectively. For LVMCO, the accuracy is only 50%, with false positive and false negative rates of 10 and 40%, respectively. Doppler gradients for isolated LVOTO were similar to invasive: 85 ± 51 and 87 ± 35 mmHg, respectively (P = 0.77). Doppler gradients in LVMCO were consistently lower than invasive: 45 ± 38 and 81 ± 31 mmHg, respectively (P = 0.0002). Mid-systolic flow cessation and/or contamination of spectral signals were identified as causes of Doppler-derived inaccuracies. Doppler echocardiography under-diagnoses and underestimates severity of LVMCO in symptomatic HCM patients. Recognition of abrupt mid-systolic flow cessation and invasive measurements may improve detection of LVMCO in HCM. © 2017 Wiley Periodicals, Inc.

  17. Assessment of nonischemic fibrosis in hypertrophic cardiomyopathy: comparison of gadopentetate dimeglumine and gadobenate dimeglumine for enhanced cardiovascular magnetic resonance imaging.

    Science.gov (United States)

    Rudolph, Andre; von Knobelsdorff-Brenkenhoff, Florian; Wassmuth, Ralf; Prothmann, Marcel; Utz, Wolfgang; Schulz-Menger, Jeanette

    2014-05-01

    To compare whether the higher relaxivity contrast agent gadobenate is superior for the identification of nonischemic late gadolinium enhancement (LGE) in hypertrophic cardiomyopathy (HCM) compared to standard relaxivity agents such as gadopentetate. Fifteen patients with HCM and positive LGE based on routine cardiac magnetic resonance (CMR) with 0.2 mmol/kg gadopentetate were enrolled. Each patient thereafter underwent a second enhanced CMR exam with 0.2 mmol/kg gadobenate using the same CMR protocol. LGE was assessed in a short axis stack acquired after contrast administration using an inversion recovery gradient echo sequence. Two independent blinded readers quantified LGE by manual planimetry. The signal intensities of injured myocardium, remote myocardium, left ventricular cavity, and air were measured in identical locations using anatomical landmarks and dedicated software. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. No adverse events related to contrast administration occurred. Gadobenate dimeglumine showed a higher SNR of injured myocardium (45.4 ± 24.0 vs. 31.1 ± 16.6, P = 0.002) and a higher CNR between remote and injured myocardium (37.6 ± 25.0 vs. 26.5 ± 17.6, P = 0.006) compared to gadopentetate dimeglumine. The amount of LGE (based on the same postprocessing criteria and definitions) was higher with gadobenate dimeglumine (12.7 ± 8.5 g vs. 9.4 ± 5.6 g, P = 0.005). There was no difference in intra- and interobserver variability between gadopentetate dimeglumine and gadobenate dimeglumine. CMR with the high relaxivity contrast agent gadobenate dimeglumine reveals significantly more tissue with LGE in patients with HCM. Copyright © 2013 Wiley Periodicals, Inc.

  18. Malignant effects of multiple rare variants in sarcomere genes on the prognosis of patients with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Wang, Jizheng; Wang, Yilu; Zou, Yubao; Sun, Kai; Wang, Zhimin; Ding, Hu; Yuan, Jinqing; Wei, Wei; Hou, Qing; Wang, Hu; Liu, Xuan; Zhang, Hongju; Ji, Yun; Zhou, Xianliang; Sharma, Ravi K; Wang, Daowen; Ahmad, Ferhaan; Hui, Rutai; Song, Lei

    2014-09-01

    Although genetic testing has been recommended in patients with hypertrophic cardiomyopathy (HCM) in current clinical practice, its utility in prognostic prediction remains to be ascertained. We assessed the dosage effect of rare variants in sarcomere genes on the long-term outcomes of HCM. A total of 529 unrelated HCM patients were prospectively recruited and followed for 4.7 ± 3.2 years. Eight sarcomere genes were screened with targeted resequencing and identified variants were validated through Sanger sequencing. After polymorphisms and likely neutral rare variants were excluded, the patients were segregated into three groups based on the dosage of rare variants: no rare variant, a single rare variant, and multiple rare variants. Multiple rare variants were identified in 7.2% (38/529) of the study patients. Patients with multiple rare variants were younger at diagnosis, and had greater maximum LV wall thicknesses and larger left atria. The risk for cardiovascular death in patients with multiple rare variants was higher than in those without rare variants (P =10⁻⁵) or in those with a single rare variant (P = 2 × 10⁻⁵). Multivariable analysis revealed that multiple rare variants were a risk factor for cardiovascular death [hazard ratio (HR) 3.74, 95% confidence interval (CI) 1.84-7.58, P = 0.0003], as well as sudden cardiac death (HR 3.57, 95% CI 1.23-10.35, P = 0.019) and heart failure-related death (HR 4.62, 95% CI 1.67-12.76, P = 0.003). The presence of multiple rare variants in sarcomere genes is a risk factor for malignant outcomes in HCM, and may be appropriate to consider as a criterion in the risk stratification of HCM patients. © 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.

  19. Reverse redistribution of Tc-99m-tetrofosmin in exercise myocardial SPECT in patients with hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Sugihara, Hiroki; Taniguchi, Yoko; Kinoshita, Noriyuki [Kyoto Prefectural Univ. of Medicine (Japan)] [and others

    1998-10-01

    We examined the usefulness of Tc-99m-tetrofosmin in detecting exercise induced perfusion abnormalities in patients with hypertrophic cardiomyopathy (HCM) and to clarify time-related changes in myocardial distribution of Tc-99m-tetrofosmin after a single injection. We studied 44 consecutive patients with HCM by means of exercise/rest Tc-99m-tetrofosmin single photon emission computed tomography (SPECT). After injecting 370 MBq of Tc-99m-tetrofosmin at the peak exercise, the early SPECT imaging was performed at 30 min (EX-30) and the delayed imaging at 180 min (EX-180). Immediately after the delayed imaging, 740 MBq of Tc-99m-tetrofosmin was injected in the resting state, and the rest SPECT imaging was performed 30 min later. Exercise-induced regional perfusion defects and/or apparent reversible left ventricular cavity dilation were identified in 26 (68.2%) of the 44 patients. When EX-30 images and EX-180 images were compared, reverse redistribution was confirmed in 36 patients (81.8%). Reverse redistribution was detected most frequently in the septal portion of the anterior wall, followed by the septal portion of the posterior wall and the septum. Exercise/rest Tc-99m-tetrofosmin myocardial imaging was a useful method for assessing myocardial perfusion abnormalities in patients with HCM. Reverse redistribution was detected very frequently on early and delayed images of exercise. We assumed that reverse redistribution may reflect a retention disorder of Tc-99m-tetrofosmin caused by some metabolic dysfunction of myocytes. (author)

  20. CD36 abnormality and impaired myocardial long-chain fatty acid uptake in patients with hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Okamoto, Fumio; Tanaka, Takao; Sohmiya, Koichi; Kawamura, Keishiro [Osaka Medical Coll., Takatsuki (Japan)

    1998-07-01

    In this study, in order to discover the relationship between hypertrophic cardiomyopathy (HCM) and the CD36 molecular abnormality, the expression level of platelet CD36 and CD36 cDNA in 55 HCM patients was analyzed. Twelve patients showed negligible (<5%) CD36 expression on their platelets. Among them, one was found to be homozygous for the C-478{yields}T substitution and 6 were heterozygous for the C-478{yields}T substitution. In 9 patients, CD36 was expressed by less than 50% of the platelets. One of them was found to be heterozygous for the C-478{yields}T substitution. Two other patients were also found to be heterozygous for this point mutation, although their platelets expressed CD36. Thus, 23 out of 55 (41.8%) HCM patients had negligible (<5%) or reduced (<50%) levels of CD36 expression on platelets, or had a point mutation of CD36 cDNA. These 55 HCM patients were also evaluated with myocardial scintigraphy both for long-chain fatty acid (LCFA) uptake and perfusion, which showed a moderate to severe discrepancy between myocardial LCFA accumulation and myocardial perfusion in 95.5% of the patients (21/23). On the other hand, 70% of the patients with normal (>90%) CD36 expression (14/20) did not show any severe discrepancies between myocardial LCFA accumulation and myocardial perfusion. These data could suggest that abnormal myocardial LCFA metabolism seen in HCM patients may be related to abnormality of the CD36 molecule, and that abnormalities of this molecule may be linked to the cause of some types of HCM. (K.H.)

  1. Myocardial blood flow and metabolism in patients with hypertrophic cardiomyopathy. A study with carbon-11 acetate and positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Ishiwata, Sugao; Maruno, Hirotaka; Nishiyama, Shinichiro; Seki, Akira [Toranomon Hospital, Tokyo (Japan); Senda, Michio; Toyama, Hinako

    1997-03-01

    The underlying pathophysiology of hypertrophic cardiomyopathy (HCM) is still unclear. Positron emission tomography is a suitable and promising technique for the detection of possible metabolic consequences of the disease. To assess regional myocardial blood flow and metabolism, 19 asymptomatic or only mildly symptomatic patients with HCM and 10 normal control subjects were studied using carbon-11 acetate and fluorine-18-labelled deoxyglucose (FDG) as tracers of myocardial blood flow (Ao), oxygen consumption (k), and exogenous glucose utilization. In the patients, regional Ao in the hypertrophied septum and apex (H) was similar to that in the nonhypertrophied free wall (N) (91.3{+-}3.9% vs 92.9{+-}3.1%; p=NS). However, the k values were significantly lower in H than in N (0.044{+-}0.012 vs 0.060{+-}0.016/min, p<0.0001). The k value in N and normal control subjects (0.062{+-}0.013) was similar. Postprandial FDG uptake was lower in H than in N (70{+-}16 vs 91{+-}7%; p<0.0001) in 16 patients and slightly higher in 3 patients. Fasting FDG study showed increased FDG uptake in H in 3 out of 13 patients, suggesting a disorder of the myocardial microvascular circulation. A relative decrease in hypertrophied septal and apical oxidative metabolism and glucose utilization without any corresponding perfusion defect could reflect abnormal regional aerobic metabolism in the disproportionately thickened myocardium in patients with HCM. This suggests that a primary myocardial metabolic defect might be present in patients with HCM. (author)

  2. Hypertrophic Cardiomyopathy in Children, Adolescents, and Young Adults Associated With Low Cardiovascular Mortality With Contemporary Management Strategies.

    Science.gov (United States)

    Maron, Barry J; Rowin, Ethan J; Casey, Susan A; Lesser, John R; Garberich, Ross F; McGriff, Deepa M; Maron, Martin S

    2016-01-05

    Youthful age has been considered the time of greatest risk for patients with hypertrophic cardiomyopathy (HCM), largely because of the possibility of sudden death. The last 2 decades have witnessed more reliable identification of at-risk patients and utilization of implantable cardioverter-defibrillators for prevention of sudden death, and other contemporary treatment options. Whether such management advances have significantly altered the considerable mortality rate for young HCM patients remains unresolved. We studied long-term outcome in 474 consecutive HCM patients between 7 and 29 years of age presenting at 2 referral institutions. Over 7.1±5.1 years of follow-up (6.0 [3.0, 10.0]), 452 patients (95%) survived, with 95% experiencing no or mild symptoms. HCM-related death occurred in 18 patients (3%; 0.54%/y): arrhythmic sudden death (n=12), progressive heart failure and heart transplant complications (n=5), or postoperatively (n=1). In contrast, aborted life-threatening events occurred in 63 other high-risk patients (13%) with implantable cardioverter-defibrillator interventions for ventricular tachyarrhythmias (n=31), resuscitated out-of-hospital cardiac arrest (n=20), or heart transplant for advanced heart failure (n=12), 1.8%/y, 3-fold higher than HCM mortality. Five- and 10-year survival (considering only HCM deaths) was high (97% and 94%, respectively), virtually identical to that reported in middle-aged adult HCM patients (98% and 94%, P=0.23). In a large hospital-based cohort of young HCM patients, representing an age group considered at greatest risk, low mortality rates can be achieved with the application of contemporary cardiovascular treatment strategies, largely because of reliable identification of high-risk patients who benefited from implantable cardioverter-defibrillators for sudden death prevention, thereby creating the opportunity for extended longevity and good quality of life. © 2015 American Heart Association, Inc.

  3. ENerGetIcs in hypertrophic cardiomyopathy: traNslation between MRI, PET and cardiac myofilament function (ENGINE study).

    Science.gov (United States)

    Güçlü, A; Germans, T; Witjas-Paalberends, E R; Stienen, G J M; Brouwer, W P; Harms, H J; Marcus, J T; Vonk, A B A; Stooker, W; Yilmaz, A; Klein, P; Ten Berg, J M; Kluin, J; Asselbergs, F W; Lammertsma, A A; Knaapen, P; van Rossum, A C; van der Velden, J

    2013-12-01

    Hypertrophic cardiomyopathy (HCM) is an autosomal dominant heart disease mostly due to mutations in genes encoding sarcomeric proteins. HCM is characterised by asymmetric hypertrophy of the left ventricle (LV) in the absence of another cardiac or systemic disease. At present it lacks specific treatment to prevent or reverse cardiac dysfunction and hypertrophy in mutation carriers and HCM patients. Previous studies have indicated that sarcomere mutations increase energetic costs of cardiac contraction and cause myocardial dysfunction and hypertrophy. By using a translational approach, we aim to determine to what extent disturbances of myocardial energy metabolism underlie disease progression in HCM. Hypertrophic obstructive cardiomyopathy (HOCM) patients and aortic valve stenosis (AVS) patients will undergo a positron emission tomography (PET) with acetate and cardiovascular magnetic resonance imaging (CMR) with tissue tagging before and 4 months after myectomy surgery or aortic valve replacement + septal biopsy. Myectomy tissue or septal biopsy will be used to determine efficiency of sarcomere contraction in-vitro, and results will be compared with in-vivo cardiac performance. Healthy subjects and non-hypertrophic HCM mutation carriers will serve as a control group. Our study will reveal whether perturbations in cardiac energetics deteriorate during disease progression in HCM and whether these changes are attributed to cardiac remodelling or the presence of a sarcomere mutation per se. In-vitro studies in hypertrophied cardiac muscle from HOCM and AVS patients will establish whether sarcomere mutations increase ATP consumption of sarcomeres in human myocardium. Our follow-up imaging study in HOCM and AVS patients will reveal whether impaired cardiac energetics are restored by cardiac surgery.

  4. Genotype-phenotype correlation between the cardiac myosin binding protein C mutation A31P and hypertrophic cardiomyopathy in a cohort of Maine Coon cats

    DEFF Research Database (Denmark)

    Granström, S; Godiksen, M T N; Christiansen, M

    2015-01-01

    OBJECTIVES: A missense mutation (A31P) in the cardiac myosin binding protein C gene has been associated with hypertrophic cardiomyopathy (HCM) in Maine Coon cats. The aim of this study was to investigate the effect of A31P on development of HCM, myocardial diastolic dysfunction detected by color...

  5. Faster cross-bridge detachment and increased tension cost in human hypertrophic cardiomyopathy with the R403Q MYH7 mutation

    NARCIS (Netherlands)

    E.R. Witjas-Paalberends (E. Rosalie); C. Ferrara (Claudia); B. Scellini (Beatrice); N. Piroddi (Nicoletta); J. Montag (Judith); C. Tesi (Chiara); G.J.M. Stienen (Ger); M. Michels (Michelle); C.Y. Ho (Carolyn); T. Kraft (Theresia); C. Poggesi (Corrado); J. van der Velden (Jolanda)

    2014-01-01

    textabstractThe first mutation associated with hypertrophic cardiomyopathy (HCM) is the R403Q mutation in the gene encoding β-myosin heavy chain (β-MyHC). R403Q locates in the globular head of myosin (S1), responsible for interaction with actin, and thus motor function of myosin. Increased

  6. Pregnancy in women with hypertrophic cardiomyopathy : data from the European Society of Cardiology initiated Registry of Pregnancy and Cardiac disease (ROPAC)

    NARCIS (Netherlands)

    Goland, S.; van Hagen, I. M.; Elbaz-Greener, G.; Elkayam, U.; Shotan, A.; Merz, W. M.; Enar, S. C.; Gaisin, I. R.; Pieper, P. G.; Johnson, M. R.; Hall, R.; Blatt, A.; Roos-Hesselink, J. W.

    2017-01-01

    Aims We report the maternal and foetal outcomes at birth and after 6 months in a cohort of pregnant women with hypertrophic cardiomyopathy (HCM). Although most women with HCM tolerate pregnancy well, there is an increased risk of obstetric and cardiovascular complications. Methods and results All

  7. Hypertrophic cardiomyopathy: Cardiac structural and microvascular abnormalities as evaluated with multi-parametric MRI

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yu-Dong, E-mail: njmu_zyd@163.com [Department of Radiology, the First Affiliated Hospital with Nanjing Medical University (China); Li, Meijiao, E-mail: newgljyk@163.com [Department of Radiology, Peking University First Hospital (China); Qi, Liang, E-mail: qiliang1120@126.com [Department of Radiology, the First Affiliated Hospital with Nanjing Medical University (China); Wu, Chen-Jiang, E-mail: njmu_wcj@163.com [Department of Radiology, the First Affiliated Hospital with Nanjing Medical University (China); Wang, Xiaoying, E-mail: cjr.wangxiaoying@vip.163.com [Department of Radiology, Peking University First Hospital (China)

    2015-08-15

    Highlights: • LGE-present HCM had lower K{sup trans}, higher V{sub e} and MTT against LGE-absent HCM and normal group. • LGE-absent had significantly higher V{sub e} and MTT against normal group. • K{sup trans} was not changed between LGE-absent and normal group Microcirculatory dysfunction in HCM closely correlated to structural abnormality. - Abstract: Purpose: To determine the relationship between myocardial structural and microvascular abnormality in hypertrophic cardiomyopathy (HCM) by multi-parametric cardiac MRI. Materials and methods: Twenty-four HCM and eighteen controls were retrospectively included. Left ventricle mass (LVM), LV end-systolic and end-diastolic volume (LVESV, LVEDV), LV ejection fraction (LVEF), and 16-segment wall thickness at ES and ED (SESWT, SEDWT) were assessed with a 2D cine-MRI. Myocardial perfusion (reflected by K{sup trans}), interstitial volume (V{sub e}) and mean transmit time (MTT) were evaluated with a model-dependent dynamic contrast-enhanced MRI. Myocardial fibrosis was assessed with late gadolinium enhancement (LGE) imaging. Results: K{sup trans} was significantly decreased in LGE-present (0.74 ± 0.15 mL/g/min) against LGE-absent (0.55 ± 0.14 mL/g/min, p = 0.030) and normal group (0.81 ± 0.32 mL/g/min, p < 0.001), but was unchanged in LGE-absent against normal group (p > 0.05). V{sub e} and MTT were significantly increased in LGE-present (V{sub e}: 26.7 ± 15.7%; MTT: 28.6 ± 21.3 s) against LGE-absent (37.6 ± 18.3%; 49.8 ± 30.5 s) and normal group (19.7 ± 6.9%; 15.1 ± 3.9 s; all p < 0.001), and were significantly increased in LGE-absent against normal group (p < 0.001). LGE significantly correlated to K{sup trans}, V{sub e}, MTT, and SESWT (ρ = 0.232, −0.247, −0.443, and −0.207, respectively). K{sup trans} negatively correlated to SEDWT and SESWT (ρ = −0.224 and −0.231). V{sub e} and MTT positively correlated to SEDWT (V{sub e}: ρ = 0.223; MTT: ρ = 0.239) and SESWT (V{sub e}: ρ = 0.248; MTT:

  8. Transaortic Chordal Cutting: Mitral Valve Repair for Obstructive Hypertrophic Cardiomyopathy With Mild Septal Hypertrophy.

    Science.gov (United States)

    Ferrazzi, Paolo; Spirito, Paolo; Iacovoni, Attilio; Calabrese, Alice; Migliorati, Katrin; Simon, Caterina; Pentiricci, Samuele; Poggio, Daniele; Grillo, Massimiliano; Amigoni, Pietro; Iascone, Maria; Mortara, Andrea; Maron, Barry J; Senni, Michele; Bruzzi, Paolo

    2015-10-13

    In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM) and mild septal hypertrophy, mitral valve (MV) abnormalities may play an important role in MV displacement into the left ventricular (LV) outflow tract. Therefore, isolated myectomy may not relieve outflow obstruction and symptoms, and MV replacement is often the surgical alternative. This study sought to assess the clinical and hemodynamic results of cutting thickened secondary MV chordae combined with a shallow septal muscular resection in severely symptomatic patients with obstructive HCM and mild septal hypertrophy. Clinical features were compared before surgery and at most recent clinical evaluation in 39 consecutive patients with obstructive HCM. Over a 23 ± 2 months follow-up, New York Heart Association functional class decreased from 2.9 ± 0.5 pre-operatively to 1.1 ± 1.1 post-operatively (p < 0.001), with no patient in class III at most recent evaluation. The resting outflow gradient decreased from 82 ± 43 mm Hg to 9 ± 5 mm Hg (p < 0.001) and septal thickness decreased from 17 ± 1 mm to 14 ± 2 mm (p < 0.001). No patient had MV prolapse or flail and 1 had residual moderate-to-severe MV regurgitation at most recent evaluation. MV geometry before and after surgery was compared with that of 25 consecutive patients with similar clinical profile and septal thickness that underwent isolated myectomy. After adjustment for differences in pre-operative values between the groups, the post-operative anterior MV leaflet-annulus ratio was 17% greater and tenting area 24% smaller in patients with chordal cutting, indicating that MV apparatus had moved to a more normal posterior position within the LV cavity, preventing MV systolic displacement into the outflow tract and outflow obstruction. This procedure relieves heart failure symptoms, abolishes LV outflow gradient, and avoids MV replacement in patients with obstructive HCM and mild septal thickness. Copyright © 2015 American

  9. Additional value of screening for minor genes and copy number variants in hypertrophic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Irene Mademont-Soler

    Full Text Available Hypertrophic cardiomyopathy (HCM is the most prevalent inherited heart disease. Next-generation sequencing (NGS is the preferred genetic test, but the diagnostic value of screening for minor and candidate genes, and the role of copy number variants (CNVs deserves further evaluation.Three hundred and eighty-seven consecutive unrelated patients with HCM were screened for genetic variants in the 5 most frequent genes (MYBPC3, MYH7, TNNT2, TNNI3 and TPM1 using Sanger sequencing (N = 84 or NGS (N = 303. In the NGS cohort we analyzed 20 additional minor or candidate genes, and applied a proprietary bioinformatics algorithm for detecting CNVs. Additionally, the rate and classification of TTN variants in HCM were compared with 427 patients without structural heart disease.The percentage of patients with pathogenic/likely pathogenic (P/LP variants in the main genes was 33.3%, without significant differences between the Sanger sequencing and NGS cohorts. The screening for 20 additional genes revealed LP variants in ACTC1, MYL2, MYL3, TNNC1, GLA and PRKAG2 in 12 patients. This approach resulted in more inconclusive tests (36.0% vs. 9.6%, p<0.001, mostly due to variants of unknown significance (VUS in TTN. The detection rate of rare variants in TTN was not significantly different to that found in the group of patients without structural heart disease. In the NGS cohort, 4 patients (1.3% had pathogenic CNVs: 2 deletions in MYBPC3 and 2 deletions involving the complete coding region of PLN.A small percentage of HCM cases without point mutations in the 5 main genes are explained by P/LP variants in minor or candidate genes and CNVs. Screening for variants in TTN in HCM patients drastically increases the number of inconclusive tests, and shows a rate of VUS that is similar to patients without structural heart disease, suggesting that this gene should not be analyzed for clinical purposes in HCM.

  10. Additional value of screening for minor genes and copy number variants in hypertrophic cardiomyopathy

    Science.gov (United States)

    Yotti, Raquel; Espinosa, Maria Angeles; Pérez-Serra, Alexandra; Fernandez-Avila, Ana Isabel; Coll, Monica; Méndez, Irene; Iglesias, Anna; del Olmo, Bernat; Riuró, Helena; Cuenca, Sofía; Allegue, Catarina; Campuzano, Oscar; Picó, Ferran; Ferrer-Costa, Carles; Álvarez, Patricia; Castillo, Sergio; Garcia-Pavia, Pablo; Gonzalez-Lopez, Esther; Padron-Barthe, Laura; Díaz de Bustamante, Aranzazu; Darnaude, María Teresa; González-Hevia, José Ignacio; Brugada, Josep; Fernandez-Aviles, Francisco; Brugada, Ramon

    2017-01-01

    Introduction Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited heart disease. Next-generation sequencing (NGS) is the preferred genetic test, but the diagnostic value of screening for minor and candidate genes, and the role of copy number variants (CNVs) deserves further evaluation. Methods Three hundred and eighty-seven consecutive unrelated patients with HCM were screened for genetic variants in the 5 most frequent genes (MYBPC3, MYH7, TNNT2, TNNI3 and TPM1) using Sanger sequencing (N = 84) or NGS (N = 303). In the NGS cohort we analyzed 20 additional minor or candidate genes, and applied a proprietary bioinformatics algorithm for detecting CNVs. Additionally, the rate and classification of TTN variants in HCM were compared with 427 patients without structural heart disease. Results The percentage of patients with pathogenic/likely pathogenic (P/LP) variants in the main genes was 33.3%, without significant differences between the Sanger sequencing and NGS cohorts. The screening for 20 additional genes revealed LP variants in ACTC1, MYL2, MYL3, TNNC1, GLA and PRKAG2 in 12 patients. This approach resulted in more inconclusive tests (36.0% vs. 9.6%, p<0.001), mostly due to variants of unknown significance (VUS) in TTN. The detection rate of rare variants in TTN was not significantly different to that found in the group of patients without structural heart disease. In the NGS cohort, 4 patients (1.3%) had pathogenic CNVs: 2 deletions in MYBPC3 and 2 deletions involving the complete coding region of PLN. Conclusions A small percentage of HCM cases without point mutations in the 5 main genes are explained by P/LP variants in minor or candidate genes and CNVs. Screening for variants in TTN in HCM patients drastically increases the number of inconclusive tests, and shows a rate of VUS that is similar to patients without structural heart disease, suggesting that this gene should not be analyzed for clinical purposes in HCM. PMID:28771489

  11. Atrial fibrillation and thromboembolism in patients with hypertrophic cardiomyopathy: systematic review.

    Science.gov (United States)

    Guttmann, Oliver P; Rahman, M Shafiqur; O'Mahony, Constantinos; Anastasakis, Aris; Elliott, Perry M

    2014-03-01

    HCM is commonly associated with AF. Current guidelines for AF management omit detailed advice for HCM because of a lack of clinical prediction tools that estimate the risk of developing AF and an absence of adequately powered treatment studies. To critically review current literature on atrial fibrillation (AF) and thromboembolism in hypertrophic cardiomyopathy (HCM) and meta-analyse prevalence and incidence. PubMed and Web of Science. Studies investigating AF and stroke in HCM as primary or secondary endpoint. Two investigators independently reviewed and extracted data from the identified articles. A random effect meta-regression model and I(2) statistics were used for analysis. A population of 7381 patients (33 studies) revealed overall AF prevalence of 22.45% (95% CI 20.13% to 24.77%), I(2)=78.9% (p<0.001). Overall prevalence of thromboembolism in HCM patients with AF was 27.09% (95% CI 20.94% to 33.25%), I(2)=61.4% ( p<0.01). Overall AF incidence was 3.08% per 100 patients per year (95% CI 2.63% to 3.54%, I(2)=86.5%, p<0.001) and incidence of thromboembolism in HCM patients with AF was 3.75% per 100 patients per year (95% CI 2.88% to 4.61%), I(2)=37.9% (p=0.1). Left atrial (LA) dimension and age were common predictors for AF and thromboembolism. Meta-analysis revealed an LA diameter of 38.03 mm (95% CI 34.62% to 41.44%) in sinus rhythm and 45.37 mm (95% CI 41.64% to 49.04%) in AF. There were no randomised controlled trials of therapy; anticoagulation was associated with lower stroke incidence but data on other interventions were limited and contradictory. AF is common in HCM and associated with high thromboembolic risk. LA dimension and age are independently associated with AF but the literature is insufficient to create robust clinical tools to predict AF or thromboembolism. Most data suggest that AF patients should be anticoagulated.

  12. Cardiac magnetic field map topology quantified by Kullback-Leibler entropy identifies patients with hypertrophic cardiomyopathy

    Science.gov (United States)

    Schirdewan, A.; Gapelyuk, A.; Fischer, R.; Koch, L.; Schütt, H.; Zacharzowsky, U.; Dietz, R.; Thierfelder, L.; Wessel, N.

    2007-03-01

    Hypertrophic cardiomyopathy (HCM) is a common primary inherited cardiac muscle disorder, defined clinically by the presence of unexplained left ventricular hypertrophy. The detection of affected patients remains challenging. Genetic testing is limited because only in 50%-60% of all HCM diagnoses an underlying mutation can be found. Furthermore, the disease has a varied clinical course and outcome, with many patients having little or no discernible cardiovascular symptoms, whereas others develop profound exercise limitation and recurrent arrhythmias or sudden cardiac death. Therefore prospective screening of HCM family members is strongly recommended. According to the current guidelines this includes serial echocardiographic and electrocardiographic examinations. In this study we investigated the capability of cardiac magnetic field mapping (CMFM) to detect patients suffering from HCM. We introduce for the first time a combined diagnostic approach based on map topology quantification using Kullback-Leibler (KL) entropy and regional magnetic field strength parameters. The cardiac magnetic field was recorded over the anterior chest wall using a multichannel-LT-SQUID system. CMFM was calculated based on a regular 36 point grid. We analyzed CMFM in patients with confirmed diagnosis of HCM (HCM, n =33, 43.8±13 years, 13 women, 20 men), a control group of healthy subjects (NORMAL, n =57, 39.6±8.9 years; 22 women and 35 men), and patients with confirmed cardiac hypertrophy due to arterial hypertension (HYP, n =42, 49.7±7.9 years, 15 women and 27 men). A subgroup analysis was performed between HCM patients suffering from the obstructive (HOCM, n =19) and nonobstructive (HNCM, n =14) form of the disease. KL entropy based map topology quantification alone identified HCM patients with a sensitivity of 78.8% and specificity of 86.9% (overall classification rate 84.8%). The combination of the KL parameters with a regional field strength parameter improved the overall

  13. Reproducibility of in-vivo diffusion tensor cardiovascular magnetic resonance in hypertrophic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    McGill Laura-Ann

    2012-12-01

    Full Text Available Abstract Background Myocardial disarray is an important histological feature of hypertrophic cardiomyopathy (HCM which has been studied post-mortem, but its in-vivo prevalence and extent is unknown. Cardiac Diffusion Tensor Imaging (cDTI provides information on mean intravoxel myocyte orientation and potentially myocardial disarray. Recent technical advances have improved in-vivo cDTI, and the aim of this study was to assess the interstudy reproducibility of quantitative in-vivo cDTI in patients with HCM. Methods and results A stimulated-echo single-shot-EPI sequence with zonal excitation and parallel imaging was implemented. Ten patients with HCM were each scanned on 2 different days. For each scan 3 short axis mid-ventricular slices were acquired with cDTI at end systole. Fractional anisotropy (FA, mean diffusivity (MD, and helix angle (HA maps were created using a cDTI post-processing platform developed in-house. The mean ± SD global FA was 0.613 ± 0.044, MD was 0.750 ± 0.154 × 10-3 mm2/s and HA was epicardium −34.3 ± 7.6°, mesocardium 3.5 ± 6.9° and endocardium 38.9 ± 8.1°. Comparison of initial and repeat studies showed global interstudy reproducibility for FA (SD = ± 0.045, Coefficient of Variation (CoV = 7.2%, MD (SD = ± 0.135 × 10-3 mm2/s, CoV = 18.6% and HA (epicardium SD = ± 4.8°; mesocardium SD = ± 3.4°; endocardium SD = ± 2.9°. Reproducibility of FA was superior to MD (p = 0.003. Global MD was significantly higher in the septum than the reference lateral wall (0.784 ± 0.188 vs 0.750 ± 0.154 x10-3 mm2/s, p  Conclusions To the best of our knowledge, this is the first study to assess the interstudy reproducibility of DTI in the human HCM heart in-vivo and the largest cDTI study in HCM to date. Our results show good reproducibility of FA, MD and HA which indicates that current technology yields robust in-vivo measurements that have potential clinical value. The

  14. Impact of chronic use of cibenzoline on left ventricular pressure gradient and left ventricular remodeling in patients with hypertrophic obstructive cardiomyopathy.

    Science.gov (United States)

    Hamada, Mareomi; Ikeda, Shuntaro; Ohshima, Kiyotaka; Nakamura, Masayuki; Kubota, Norio; Ogimoto, Akiyoshi; Shigematsu, Yuji

    2016-03-01

    Cibenzoline, a class Ia antiarrhythmic drug, is useful for reducing the left ventricular pressure gradient (LVPG) in patients with hypertrophic obstructive cardiomyopathy (HOCM). However, chronic effects of cibenzoline on LVPG and left ventricular (LV) remodeling are unknown. Forty-one patients with HOCM participated in this study. Echocardiographic, electrocardiographic, and brain natriuretic peptide (BNP) data collected before and after cibenzoline treatment were compared. From the relation between LVPG and plasma concentration of cibenzoline, an efficacious plasma concentration of cibenzoline was estimated. The mean follow-up period was 74.2±47.1 months. The LVPG decreased from 104.8±62.6mmHg to 27.6±30.5mmHg (pcomplications. Copyright © 2015. Published by Elsevier Ltd.

  15. Alcohol-related cardiomyopathy in the Seychelles.

    Science.gov (United States)

    Pinn, G; Bovet, P

    1991-10-21

    To determine the frequency and features of alcohol-related cardiomyopathy in the Seychelles. The study was multifaceted investigation involving: a randomised cross-sectional survey of drinking habits in the general population; a cross-sectional survey of blood alcohol levels in patients admitted to hospital; a prospective case series of all consecutive patients hospitalised with alcohol-related cardiomyopathy; a retrospective review of medical records; and an analysis of volatile oils and trace metals in alcoholic drinks. Data on drinking habits were obtained from a randomised sample of 1309 adults from the total population of the Seychelles (66,000). All clinical data were obtained from patients in the Victoria Hospital, which is the single reference hospital of the country. Hospitalised patients with alcohol-related cardiomyopathy were treated initially with vitamin B1 and/or diuretics. The survey of alcohol habits revealed that 75% of the male population were regular alcohol consumers, with 19% of men consuming more than 100 g of alcohol per day. The estimated annual consumption of alcohol per capita was 26.4 L for men and 3.5 L for women. The survey of blood alcohol levels showed that 28% of male and 13% of female patients had raised alcohol levels at hospital admission. Throughout 1989, 96 patients were diagnosed as having alcohol-related cardiomyopathy and 12 of these had beriberi. The majority of young patients responded with marked diuresis within four hours of a single administration of thiamine. Overall, one-third of all male medical admissions were due to alcohol-related disease. The pathological effects of alcohol consumption were detected in 47% of autopsies and in 20% there was evidence of alcohol-related cardiomyopathy. These findings confirm the high frequency of alcohol-related disease in general and cardiomyopathy in particular.

  16. Efficacy and safety of alcohol septal ablation in patients over 65 years old with obstructive hypertrophic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Cheddadi L

    2017-03-01

    Full Text Available Laila Cheddadi,1 Olivier Lairez,1–4 Thibault Lhermusier,1,5 Francisco Campelo-Parada,1 Michel Galinier,1,3,4 Didier Carrié,1,3,5 Nicolas Boudou1 1Department of Cardiology, University Hospital of Rangueil, 2Department of Nuclear Medicine, 3Cardiac Imaging Center, Toulouse University Hospital, 4Medical School of Rangueil, 5Medical School of Purpan, University Paul Sabatier, Toulouse, France Background: The performance of alcohol septal ablation (ASA in elderly symptomatic patients with drug-refractory obstructive hypertrophic cardiomyopathy is still to be confirmed. The objective of this study was to compare the efficacy and safety of ASA in patients under and over 65 years old.Methods and results: Fifty-one consecutive patients with obstructive hypertrophic cardiomyopathy who underwent ASA were retrospectively included and reviewed for in-hospital major acute cardiac events and follow-up. Twenty-eight patients were over 65 years old. Left ventricular outflow tract obstruction at rest, use of diuretic and average dose of diuretic were higher in patients over 65 years old. There was no difference in hospital stay between patients under and over 65 years old. Among patients over 65 years old, 2 (7% died before being discharged. Major acute cardiac events were more frequent in patients over 65 years old in comparison with younger patients (43% versus 9%, respectively, P=0.007. The average follow-up duration was 16±15 months. There was no difference between patients under and over 65 years old regarding the efficacy of the procedure with a decrease of the New York Heart Association class of 1.3±0.6 and 1.4±0.7 (P=0.510 and the maximum left ventricular outflow tract gradient of 86±57 and 81±36 mmHg (P=0.733, respectively.Conclusion: Elderly patients have the same benefits as younger patients after ASA but have more complications including mortality events. Keywords: alcohol septal ablation, hypertrophic cardiomyopathy, elderly

  17. [Clinical and gene mutation analysis of three children with late-onset glycogen storage disease type Ⅱ with hypertrophic cardiomyopathy].

    Science.gov (United States)

    Luo, J H; Qiu, W J; Fang, D; Ye, J; Han, L S; Zhang, H W; Yu, Y G; Liang, L L; Gu, X F

    2017-06-02

    Objective: To investigate the clinical and laboratory features of three children with late-onset type Ⅱ glycogen storage disease(GSD) who presented with hypertrophic cardiomyopathy and to analyze the effect of five mutations identified on the acid-α-glucosidase (GAA) activity and stability. Method: Three cases of children with muscle weakness were included in this study.GAA activity was analyzed in Dried Blood Spot of the patients.DNA was extracted from peripheral blood in all the patients and their parents and subjected to polymerase chain reaction and directly sequencing of GAA gene.Five mutant pcDNA3.1-myc-his-GAA expression plasmids(p.G478R, p.P361L, p.P266S, p.Q323X, p.R672Q) were constructed and transient instantaneously transfected into 293T cells to analyze the enzyme activity and stability of GAA. Result: All the three children had the onset of disease at 3 years or 1.5 years of age.They presented with developmental delay, muscle weakness and hypertrophic cardiomyopathy.GAA activity of 3 patients was 2.65, 3.55 and 1.51 pmol(punch·h)(8.00-98.02)respectively. Genetic analysis found 5 mutations (p.G478R, p. P361L, p. P266S, p. Q323X, p. R672Q), and all of these 3 cases had clinical manifestations and were diagnosed as late-onset type Ⅱ glycogen storage disease.Five mutant pcDNA3.1-myc-his-GAA expression plasmids were transfected into 293T cells.Five mutant enzyme activities were found to be only 9.9%-22.5% of the wild-type enzyme activity and the protein expression of the five mutants was 32.0%-63.9% compared with the wild type. Conclusion: This study reports 3 children with late-onset GSD Ⅱ accompanied by hypertrophic cardiomyopathy and compensatory stage of cardiac function in addition to limb muscle weakness.Five pathogenic mutations were identified, and these 5 mutations result in decreased GAA activity and GAA expression by in vitro functional analysis.

  18. β-Myosin heavy chain variant Val606Met causes very mild hypertrophic cardiomyopathy in mice, but exacerbates HCM phenotypes in mice carrying other HCM mutations.

    Science.gov (United States)

    Blankenburg, Robert; Hackert, Katarzyna; Wurster, Sebastian; Deenen, René; Seidman, J G; Seidman, Christine E; Lohse, Martin J; Schmitt, Joachim P

    2014-07-07

    Approximately 40% of hypertrophic cardiomyopathy (HCM) is caused by heterozygous missense mutations in β-cardiac myosin heavy chain (β-MHC). Associating disease phenotype with mutation is confounded by extensive background genetic and lifestyle/environmental differences between subjects even from the same family. To characterize disease caused by β-cardiac myosin heavy chain Val606Met substitution (VM) that has been identified in several HCM families with wide variation of clinical outcomes, in mice. Unlike 2 mouse lines bearing the malignant myosin mutations Arg453Cys (RC/+) or Arg719Trp (RW/+), VM/+ mice with an identical inbred genetic background lacked hallmarks of HCM such as left ventricular hypertrophy, disarray of myofibers, and interstitial fibrosis. Even homozygous VM/VM mice were indistinguishable from wild-type animals, whereas RC/RC- and RW/RW-mutant mice died within 9 days after birth. However, hypertrophic effects of the VM mutation were observed both in mice treated with cyclosporine, a known stimulator of the HCM response, and compound VM/RC heterozygous mice, which developed a severe HCM phenotype. In contrast to all heterozygous mutants, both systolic and diastolic function of VM/RC hearts was severely impaired already before the onset of cardiac remodeling. The VM mutation per se causes mild HCM-related phenotypes; however, in combination with other HCM activators it exacerbates the HCM phenotype. Double-mutant mice are suitable for assessing the severity of benign mutations. © 2014 American Heart Association, Inc.

  19. COXPD9 an Evolving Multisystem Disease; Congenital Lactic Acidosis, Sensorineural Hearing Loss, Hypertrophic Cardiomyopathy, Cirrhosis and Interstitial Nephritis.

    Science.gov (United States)

    Bursle, C; Narendra, A; Chuk, R; Cardinal, J; Justo, R; Lewis, B; Coman, D

    2017-01-01

    We present the second report of combined oxidative phosphorylation deficiency-9. The infant presented in the neonatal period with poor feeding, lactic acidosis and sensorineural hearing loss. He subsequently developed a lethal hypertrophic cardiomyopathy during infancy. Cirrhosis and interstitial nephritis were identified at autopsy. Exome sequencing has detected compound heterozygous mutations in the MRPL3 gene which encodes a large mitochondrial ribosome subunit protein. We identified a known heterozygous variant NM_007208 c.950>G (Pro317Arg) in the MRPL3 gene and a novel heterozygous mutation NM_007208 c.49delC p.(Arg17Aspfs*57). Mutations in MRPL3 have previously been shown to alter ribosome assembly and cause abnormal function of multiple respiratory chain complexes. Our case adds to the evolving knowledge of disorders of mitochondrial translation.

  20. The familial hypertrophic cardiomyopathy-associated myosin mutation R403Q accelerates tension generation and relaxation of human cardiac myofibrils.

    Science.gov (United States)

    Belus, Alexandra; Piroddi, Nicoletta; Scellini, Beatrice; Tesi, Chiara; D'Amati, Giulia; Girolami, Francesca; Yacoub, Magdi; Cecchi, Franco; Olivotto, Iacopo; Poggesi, Corrado

    2008-08-01

    The R403Q mutation in beta-myosin heavy chain was the first mutation to be identified as responsible for familial hypertrophic cardiomyopathy (FHC). In spite of extensive work on the functional sequelae of this mutation, the mechanism by which the mutant protein causes the disease has not been definitely identified. Here we directly compare contraction and relaxation mechanics of single myofibrils from left ventricular samples of one patient carrying the R403Q mutation to those from a healthy control heart. Tension generation and relaxation following sudden increase and decrease in [Ca(2+)] were much faster in the R403Q myofibrils with relaxation rates being the most affected parameters. The results show that the R403Q mutation leads to an apparent gain of protein function but a greater energetic cost of tension generation. Increased energy cost of tension generation may be central to the FHC disease process, help explain some unresolved clinical observations, and carry significant therapeutic implications.

  1. [Screening and analysis of the mutations on beta-myosin heavy chain gene in 3 Chinese families with hypertrophic cardiomyopathy].

    Science.gov (United States)

    Feng, Xiu-li; Fan, Xin-ping; Yang, Zhong-wei; Yang, Fu-hui

    2011-02-01

    To detect gene mutations on beta-myosin heavy chain gene MYH7 in 3 Chinese families with hypertrophic cardiomyopathy (HCM), and to analyze the correlation between genotype and phenotype. A denaturing high-performance liquid chromatography (DHPLC) and sequencing mutation screening of the exons (exon3-23) coding for MYH7 gene were performed in 3 Chinese families with HCM. In this study, we identified several mutations in MYH7. A mutation of Thr441Met previously reported in a patient with Laing distal myopathy was first identified in one Chinese pedigree. This study illustrated the high frequency of mutation in MYH7 gene in Chinese HCM families. Different mutations and carriers of the MYH7 gene present phenotypic heterogeneity. Mutation screening and analysis in HCM family could therefore facilitate the early HCM diagnosis and would be helpful for the prediction, prevention and early treatment of HCM linked with MYH7 gene mutation.

  2. Perioperative management of an elderly patient of hypertrophic obstructive cardiomyopathy for knee arthroplasty and the role of peripheral nerve blocks

    Directory of Open Access Journals (Sweden)

    Sunny Rupal

    2013-01-01

    Full Text Available This case report exemplifies how the anaesthetic technique of general anesthesia with continuous bilateral femoral nerve block for bilateral knee arthroplasty was well chosen for the management of perioperative complications in an elderly patient with hypertrophic obstructive cardiomyopathy (HOCM. A 69-year-old female patient of HOCM was scheduled for bilateral total knee replacement. Echocardiography revealed severe left ventricular outflow tract obstruction with peak systolic gradient of 56 mmHg. The surgery was conducted under general anaesthesia with invasive monitoring and bilateral continuous femoral nerve blocks for postoperative analgesia. Postoperatively, she developed pulmonary oedema due to the liberal administration of fluids. This complication was successfully managed without interrupting the management of pain. Management of patients with HOCM for noncardiac surgery requires knowledge of variable presentation of two forms of disease. Also, this case report highlights the practical advantage of continuous femoral nerve block (CFNBs over epidural anaesthesia.

  3. Prediction of Fetal Hypertrophic Cardiomyopathy in Diabetic Pregnancies Compared with Postnatal Outcome

    Science.gov (United States)

    Elmekkawi, Sherif F.; Mansour, Ghada M.; Elsafty, Mohammed S.E.; Hassanin, Alaa S.; Laban, Mohamed; Elsayed, Heba M.

    2015-01-01

    OBJECTIVE The aim of this study was to estimate the accuracy of prenatal assessment of interventricular septum (IVS) thickness, right myocardial wall thickness (RMWT), and left myocardial wall thickness (LMWT) by two-dimensional (2D) ultrasound for the prediction of perinatal mortality and postnatal diagnosis of hypertrophic cardiomyopathy (HCM) among diabetic pregnant women. SUBJECTS AND METHODS A total of 120 diabetic pregnant women at 35 weeks or more were enrolled in this study from January 1, 2012, to June 30, 2014, at Ain Shams Maternity Hospital, Cairo, Egypt. The 2D ultrasound was done once for all the participants at the time of recruitment; IVS thickness, RMWT, and LMWT were measured. The glycosylated hemoglobin (HbA1c) levels of the participants were recorded. Neonatal assessment including postnatal echocardiography was done after 48 hours. Postnatal results were compared with the prenatal predictive results. RESULTS Higher thickness values for IVS, RMW, and LMW were obtained in the uncontrolled diabetic cases (HbA1c > 6.5%) than in the controlled diabetic cases (HbA1c < 6.5%; P < 0.01). Of the included 120 neonates, 10 (8.3%) were stillborn, 99 (82.5%) had a five-minute Apgar score ≥7, and 4 (3.3%) had a five-minute Apgar score ≤3. The four neonates with severe neonatal distress died after admission to neonatal intensive care unit within one week after delivery. Out of 110 live-born neonates, 4 (3.6%) neonates had a low ejection fraction (EF) (<50%) due to HCM; of them 2 (1.8%) died within one week after delivery, while 2 (1.8%) survived. Another two (1.8%) neonates died from severe respiratory distress syndrome. A cutoff value of ≥4.5 mm for prenatal IVS thickness was predictive of neonatal distress due to HCM with a sensitivity of 82%, specificity of 68%, and diagnostic accuracy of 72%. A cutoff value of <1.18 for the ratio of IVS thickness to LMWT had a sensitivity of 82%, specificity of 72%, and diagnostic accuracy of 74% for the prediction of

  4. Prediction of Fetal Hypertrophic Cardiomyopathy in Diabetic Pregnancies Compared with Postnatal Outcome

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    Sherif F. Elmekkawi

    2015-01-01

    Full Text Available Objective The aim of this study was to estimate the accuracy of prenatal assessment of interventricular septum (IVS thickness, right myocardial wall thickness (RMWT, and left myocardial wall thickness (LMWT by two-dimensional (2D ultrasound for the prediction of perinatal mortality and postnatal diagnosis of hypertrophic cardiomyopathy (HCM among diabetic pregnant women. Subjects and Methods A total of 120 diabetic pregnant women at 35 weeks or more were enrolled in this study from January 1, 2012, to June 30, 2014, at Ain Shams Maternity Hospital, Cairo, Egypt. The 2D ultrasound was done once for all the participants at the time of recruitment; IVS thickness, RMWT, and LMWT were measured. The glycosylated hemoglobin (HbA1c levels of the participants were recorded. Neonatal assessment including postnatal echocardiography was done after 48 hours. Postnatal results were compared with the prenatal predictive results. Results Higher thickness values for IVS, RMW, and LMW were obtained in the uncontrolled diabetic cases (HbA1c > 6.5% than in the controlled diabetic cases (HbA1c < 6.5%; P < 0.01. Of the included 120 neonates, 10 (8.3% were stillborn, 99 (82.5% had a five-minute Apgar score ≥7, and 4(3.3% had a five-minute Apgar score ≤3. The four neonates with severe neonatal distress died after admission to neonatal intensive care unit within one week after delivery. Out of 110 live-born neonates, 4 (3.6% neonates had a low ejection fraction (EF (<50% due to HCM; of them 2 (1.8% died within one week after delivery, while 2 (1.8% survived. Another two (1.8% neonates died from severe respiratory distress syndrome. A cutoff value of ≥4.5 mm for prenatal IVS thickness was predictive of neonatal distress due to HCM with a sensitivity of 82%, specificity of 68%, and diagnostic accuracy of 72%. A cutoff value of <1.18 for the ratio of IVS thickness to LMWT had a sensitivity of 82%, specificity of 72%, and diagnostic accuracy of 74% for the prediction

  5. Screening mutations in myosin binding protein C3 gene in a cohort of patients with Hypertrophic Cardiomyopathy

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    Maneiro Emilia

    2010-04-01

    Full Text Available Abstract Background MyBPC3 mutations are amongst the most frequent causes of hypertrophic cardiomyopathy, however, its prevalence varies between populations. They have been associated with mild and late onset disease expression. Our objectives were to establish the prevalence of MyBPC3 mutations and determine their associated clinical characteristics in our patients. Methods Screening by Single Strand Conformation Polymorphisms (SSCP and sequencing of the fragments with abnormal motility of the MyBPC3 gene in 130 unrelated consecutive HCM index cases. Genotype-Phenotype correlation studies were done in positive families. Results 16 mutations were found in 20 index cases (15%: 5 novel [D75N, V471E, Q327fs, IVS6+5G>A (homozygous, and IVS11-9G>A] and 11 previously described [A216T, R495W, R502Q (2 families, E542Q (3 families, T957S, R1022P (2 families, E1179K, K504del, K600fs, P955fs and IVS29+5G>A]. Maximum wall thickness and age at time of diagnosis were similar to patients with MYH7 mutations [25(7 vs. 27(8, p = 0.16], [46(16 vs. 44(19, p = 0.9]. Conclusions Mutations in MyBPC3 are present in 15% of our hypertrophic cardiomyopathy families. Severe hypertrophy and early expression are compatible with the presence of MyBPC3 mutations. The genetic diagnosis not only allows avoiding clinical follow up of non carriers but it opens new possibilities that includes: to take preventive clinical decisions in mutation carriers than have not developed the disease yet, the establishment of genotype-phenotype relationship, and to establish a genetic diagnosis routine in patients with familial HCM.

  6. T1 Mapping in Discrimination of Hypertrophic Phenotypes: Hypertensive Heart Disease and Hypertrophic Cardiomyopathy: Findings From the International T1 Multicenter Cardiovascular Magnetic Resonance Study.

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    Hinojar, Rocio; Varma, Niharika; Child, Nick; Goodman, Benjamin; Jabbour, Andrew; Yu, Chung-Yao; Gebker, Rolf; Doltra, Adelina; Kelle, Sebastian; Khan, Sitara; Rogers, Toby; Arroyo Ucar, Eduardo; Cummins, Ciara; Carr-White, Gerald; Nagel, Eike; Puntmann, Valentina O

    2015-12-01

    The differential diagnosis of left ventricular (LV) hypertrophy remains challenging in clinical practice, in particular, between hypertrophic cardiomyopathy (HCM) and increased LV wall thickness because of systemic hypertension. Diffuse myocardial disease is a characteristic feature in HCM, and an early manifestation of sarcomere-gene mutations in subexpressed family members (G+P- subjects). This study aimed to investigate whether detecting diffuse myocardial disease by T1 mapping can discriminate between HCM versus hypertensive heart disease as well as to detect genetically driven interstitial changes in the G+P- subjects. Patients with diagnoses of HCM or hypertension (HCM, n=95; hypertension, n=69) and G+P- subjects (n=23) underwent a clinical cardiovascular magnetic resonance protocol (3 tesla) for cardiac volumes, function, and scar imaging. T1 mapping was performed before and >20 minutes after administration of 0.2 mmol/kg of gadobutrol. Native T1 and extracellular volume fraction were significantly higher in HCM compared with patients with hypertension (P15 mm (P2 SD above the mean of the normal range. Native T1 was an independent discriminator between HCM and hypertension, over and above extracellular volume fraction, LV wall thickness and indexed LV mass. Native T1 was also useful in separating G+P- subjects from controls. Native T1 may be applied to discriminate between HCM and hypertensive heart disease and detect early changes in G+P- subjects. © 2015 American Heart Association, Inc.

  7. Tissue Doppler Imaging Combined with Advanced 12-Lead ECG Analysis Might Improve Early Diagnosis of Hypertrophic Cardiomyopathy in Childhood

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    Femlund, E.; Schlegel, T.; Liuba, P.

    2011-01-01

    Optimization of early diagnosis of childhood hypertrophic cardiomyopathy (HCM) is essential in lowering the risk of HCM complications. Standard echocardiography (ECHO) has shown to be less sensitive in this regard. In this study, we sought to assess whether spatial QRS-T angle deviation, which has shown to predict HCM in adults with high sensitivity, and myocardial Tissue Doppler Imaging (TDI) could be additional tools in early diagnosis of HCM in childhood. Methods: Children and adolescents with familial HCM (n=10, median age 16, range 5-27 years), and without obvious hypertrophy but with heredity for HCM (n=12, median age 16, range 4-25 years, HCM or sudden death with autopsy-verified HCM in greater than or equal to 1 first-degree relative, HCM-risk) were additionally investigated with TDI and advanced 12-lead ECG analysis using Cardiax(Registered trademark) (IMED Co Ltd, Budapest, Hungary and Houston). Spatial QRS-T angle (SA) was derived from Kors regression-related transformation. Healthy age-matched controls (n=21) were also studied. All participants underwent thorough clinical examination. Results: Spatial QRS-T angle (Figure/ Panel A) and septal E/Ea ratio (Figure/Panel B) were most increased in HCM group as compared to the HCM-risk and control groups (p less than 0.05). Of note, these 2 variables showed a trend toward higher levels in HCM-risk group than in control group (p=0.05 for E/Ea and 0.06 for QRS/T by ANOVA). In a logistic regression model, increased SA and septal E/Ea ratio appeared to significantly predict both the disease (Chi-square in HCM group: 9 and 5, respectively, p less than 0.05 for both) and the risk for HCM (Chi-square in HCM-risk group: 5 and 4 respectively, p less than 0.05 for both), with further increased predictability level when these 2 variables were combined (Chi-square 10 in HCM group, and 7 in HCM-risk group, p less than 0.01 for both). Conclusions: In this small material, Tissue Doppler Imaging and spatial mean QRS-T angle

  8. Subendocardial motion in hypertrophic cardiomyopathy: assessment from long- and short-axis views by pulsed tissue Doppler imaging

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    Tabata, T.; Oki, T.; Yamada, H.; Abe, M.; Onose, Y.; Thomas, J. D.

    2000-01-01

    BACKGROUND: Tissue Doppler imaging (TDI) is a recently developed technique that allows the instantaneous measurement of intrinsic regional myocardial motion velocity. Pulsed TDI is capable of separately assessing left ventricular (LV) regional motion velocity caused by circumferential and longitudinal fiber contraction. This particular feature of function is still controversial in patients with hypertrophic cardiomyopathy (HC). METHODS: To better characterize intrinsic circumferential and longitudinal LV systolic myocardial function in HC, we used pulsed TDI to measure short- and long-axis LV motion velocities, respectively. The subendocardial motion velocity patterns at the middle of the LV posterior wall (PW) and ventricular septum (IVS) in LV parasternal and apical long-axis views were recorded by pulsed TDI in 19 patients with nonobstructive HC and in 21 normal controls (NC). RESULTS: Peak short- and long-axis systolic subendocardial velocities in both the LV PW and IVS were significantly smaller in the HC group than in the NC group, and the time to peak velocity was significantly delayed. Furthermore, peak PW systolic velocity was significantly greater along the long axis than along the short axis in the NC group (8.8 +/- 1.5 cm/s vs 8.2 +/- 1.4 cm/s, P <.05), whereas the opposite was observed in the HC group (6.1 +/- 1.2 cm/s vs 7.5 +/- 1.0 cm/s, P <.0001). No significant differences were found in either group between the long- and short-axis IVS velocities (HC: 5.9 +/- 1.4 cm/s vs 5.5 +/- 1.3 cm/s; NC: 7.8 +/- 1.3 cm/s vs 7.9 +/- 1.6 cm/s). CONCLUSIONS: By using the capability of pulsed TDI for the evaluation of intrinsic myocardial velocity instantaneously in a specific region and direction, we found impairment of LV myocardial systolic function in patients with HC not only in the hypertrophied IVS but also in the nonhypertrophied LV PW. We also found a greater decrease in LV PW velocities along the long axis than the short axis, suggesting greater

  9. Coexistence of Digenic Mutations in Both Thin (TPM1) and Thick (MYH7) Filaments of Sarcomeric Genes Leads to Severe Hypertrophic Cardiomyopathy in a South Indian FHCM.

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    Selvi Rani, Deepa; Nallari, Pratibha; Dhandapany, Perundurai S; Rani, Jhansi; Meraj, Khunza; Ganesan, Mala; Narasimhan, Calambur; Thangaraj, Kumarasamy

    2015-05-01

    Mutations in sarcomeric genes are the leading cause for cardiomyopathies. However, not many genetic studies have been carried out on Indian cardiomyopathy patients. We performed sequence analyses of a thin filament sarcomeric gene, α-tropomyosin (TPM1), in 101 hypertrophic cardiomyopathy (HCM) patients and 147 dilated cardiomyopathy (DCM) patients against 207 ethnically matched healthy controls, revealing 13 single nucleotide polymorphisms (SNPs). Of these, one mutant, S215L, was identified in two unrelated HCM cases-patient #1, aged 44, and patient #2, aged 65-and was cosegregating with disease in these families as an autosomal dominant trait. In contrast, S215L was completely absent in 147 DCM and 207 controls. Patient #1 showed a more severe disease phenotype, with poor prognosis and a family history of sudden cardiac death, than patient #2. Therefore, these two patients and the family members positive for S215L were further screened for variations in MYH7, MYBPC3, TNNT2, TNNI3, MYL2, MYL3, and ACTC. Interestingly, two novel thick filaments, D896N (homozygous) and I524K (heterozygous) mutations, in the MYH7 gene were identified exclusively in patient #1 and his family members. Thus, we strongly suggest that the coexistence of these digenic mutations is rare, but leads to severe hypertrophy in a South Indian familial hypertrophic cardiomyopathy (FHCM).

  10. Magnetic resonance imaging of hypertrophic cardiomyopathy. Evaluation of diastolic function; MRT-Bildgebung bei hypertropher Kardiomyopathie (HCM). Evaluation der diastolischen Funktion

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    Schwarz, F.; 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); Schwab, F. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer Klinische Radiologie, Muenchen (Germany); Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Josef Lissner Laboratory for Biomedical Imaging, Institut fuer Klinische Radiologie, Muenchen (Germany); Beckmann, B.M.; Schuessler, F.; Kaeaeb, S. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Medizinische Klinik und Poliklinik I, Muenchen (Germany); Zinsser, D.; Goelz, T. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer Klinische Radiologie, Muenchen (Germany)

    2013-01-15

    Hypertrophic cardiomyopathy (HCM) has a prevalence of approximately 0.2% and is clinically asymptomatic in many patients or presents with unspecific symptoms. This explains the importance of imaging for the diagnosis of HCM as well as for the assessment of the clinical course. The definitive finding in HCM is myocardial hypertrophy with thickening of the ventricular wall {>=} 15 mm. While echocardiography is an excellent screening tool magnetic resonance imaging (MRI) allows a comprehensive analysis of the heart in HCM. This includes a detailed analysis of the distribution and extent of myocardial hypertrophy, a thorough evaluation of systolic and diastolic cardiac function, the assessment of the presence and extent of dynamic outflow tract obstruction as well as the description of the systolic anterior motion (SAM) phenomenon of the mitral valve with secondary mitral insufficiency. When contrast material is administered, additional information about myocardial perfusion as well as the presence and extent of myocardial fibrosis can be obtained. This study compared systolic functional parameters as well as end systolic and end diastolic wall thickness of patients with and without diastolic dysfunction. (orig.) [German] Die hypertrophe Kardiomyopathie (HCM) hat eine Praevalenz von ca. 0,2% und verlaeuft in vielen Faellen zeitlebens klinisch asymptomatisch. Falls es zur Ausbildung von Symptomen kommt, sind diese oft unspezifisch. Dies erklaert den Stellenwert der Bildgebung bei der Erstdiagnose und Verlaufsbeurteilung der HCM. Leitbefund ist eine myokardiale Hypertrophie mit Wanddicken von {>=} 15 mm. Waehrend die Echokardiographie ein hervorragendes Screeningverfahren ist, erlaubt die MRT eine umfassende Feindiagnostik bei der HCM, zu der gezaehlt werden: eine genaue Darstellung des Verteilungsmusters und des Schweregrads der Hypertrophie, eine detaillierte Analyse der linksventrikulaeren systolischen und diastolischen Funktion, eine Beurteilung und Quantifizierung

  11. Left Ventricular Outflow Tract Obstruction in Hypertrophic Cardiomyopathy Patients Without Severe Septal Hypertrophy: Implications of Mitral Valve and Papillary Muscle Abnormalities Assessed Using Cardiac Magnetic Resonance and Echocardiography.

    Science.gov (United States)

    Patel, Parag; Dhillon, Ashwat; Popovic, Zoran B; Smedira, Nicholas G; Rizzo, Jessica; Thamilarasan, Maran; Agler, Deborah; Lytle, Bruce W; Lever, Harry M; Desai, Milind Y

    2015-07-01

    In patients with hypertrophic cardiomyopathy and left ventricular outflow tract (LVOT) obstruction, but without basal septal hypertrophy, we sought to identify mitral valve (MV) and papillary muscle (PM) abnormalities that predisposed to LVOT obstruction, using echo and cardiac magnetic resonance. We studied 121 patients with hypertrophic cardiomyopathy hypertrophic cardiomyopathy (age, 49±17 years; 60% men; 57% on β-blockers) with a basal septal thickness of ≤1.8 cm who underwent echocardiography (rest+stress) and cine cardiac magnetic resonance. Echo measurements included maximal LVOT gradient (rest/provocable), MV leaflet length (parasternal long, 4 and 3-chamber views), and abnormal chordal attachment to mid/base of anterior MV. Cine cardiac magnetic resonance measurements included basal septal thickness, number/area of PM heads, and bifid PM mobility (in systole and diastole). Mean basal septal thickness, LVOT gradient, and LV ejection fraction were 1.5±0.3 cm, 72±54 mm Hg, and 61±6%, respectively. The number of anterolateral and posteromedial PM heads was 2.7±0.7 and 2.6±0.7, respectively. Anterolateral and posteromedial PM areas were 19.9±7 cm(2) and 17.1±6 cm(2), respectively. PM mobility was 11±6°. On multivariable analysis, predictors of maximal LVOT gradient were basal septal thickness, bifid PM mobility, anterior mitral leaflet length, and abnormal chordal attachment to base of anterior mitral leaflet. Forty-five patients underwent surgery to relieve LVOT obstruction, of which 52% needed an additional nonmyectomy (MV repair/replacement or PM reorientation) approach. In hypertrophic cardiomyopathy patients without significant LV hypertrophy, in addition to basal septal thickness, anterior MV length, abnormal chordal attachment, and bifid PM mobility are associated with LVOT obstruction. In such patients, additional procedures on MV and PM (±myectomy) could be considered. © 2015 American Heart Association, Inc.

  12. Successful anaesthetic management of a case of hypertrophic obstructive cardiomyopathy posted for elective caesarean section using epidural anaesthesia with 0.75% Ropivacaine

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    Anjali R Bhure

    2011-01-01

    Full Text Available Hypertrophic obstructive cardiomyopathy (HOCM is a complex cardiovascular disorder with autosomal dominant inheritance and an incidence of 0.1-0.5% in pregnant females. Anaesthetic management of a pregnant female with HOCM posted for elective caesarean section is a challenge, as even minor hemodynamic insults may lead to life-threatening complications. We report successful management of one such patient using epidural anaesthesia with 0.75% Ropivacaine.

  13. Desmin-related cardiomyopathy: an unfolding story

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    McLendon, Patrick M.

    2011-01-01

    The intermediate filament protein desmin is an integral component of the cardiomyocyte and serves to maintain the overall structure and cytoskeletal organization within striated muscle cells. Desmin-related myopathy can be caused by mutations in desmin or associated proteins, which leads to intracellular accumulation of misfolded protein and production of soluble pre-amyloid oligomers, which leads to weakened skeletal and cardiac muscle. In this review, we examine the cellular phenotypes in relevant animal models of desmin-related cardiomyopathy. These models display characteristic sarcoplasmic protein aggregates. Aberrant protein aggregation leads to mitochondrial dysfunction, abnormal metabolism, and altered cardiomyocyte structure. These deficits to cardiomyocyte function may stem from impaired cellular proteolytic mechanisms. The data obtained from these models allow a more complete picture of the pathology in desmin-related cardiomyopathy to be described. Moreover, these studies highlight the importance of desmin in maintaining cardiomyocyte structure and illustrate how disrupting this network can be deleterious to the heart. We emphasize the similarities observed between desmin-related cardiomyopathy and other protein conformational disorders and speculate that therapies to treat this disease may be broadly applicable to diverse protein aggregation-based disorders. PMID:21784990

  14. Prognostic value of non-sustained ventricular tachycardia and the potential role of amiodarone treatment in hypertrophic cardiomyopathy: assessment in an unselected non-referral based patient population

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    Cecchi, F; Olivotto, I; Montereggi, A; Squillatini, G; Dolara, A; Maron, B

    1998-01-01

    Background—Amiodarone has been reported to reduce the likelihood of sudden death in patients with hypertrophic cardiomyopathy (HCM). However, data regarding the clinical course in HCM have traditionally come from selected referral populations biased toward assessment of high risk patients.
Aims—To evaluate antiarrhythmic treatment for sudden death in an HCM population not subject to tertiary referral bias, closely resembling the true disease state present in the community.
Methods—Cardiovascular mortality was assessed in relation to the occurrence of non-sustained ventricular tachycardia (NSVT) on 24 or 48 hour ambulatory Holter recording, a finding previously regarded as a marker for sudden death, particularly when the arrhythmia was frequent, repetitive or prolonged. 167 consecutive patients were analysed by multiple Holter ECG recordings (mean (SD) 157 (129) hours) and followed for a mean of 10 (5) years. Only patients with multiple repetitive NSVT were treated with amiodarone, and in relatively low doses (220 (44) mg/day).
Results—Nine HCM related deaths occurred: 8 were the consequence of congestive heart failure, but only 1 was sudden and unexpected. Three groups of patients were segregated based on their NSVT profile: group 1 (n = 39), multiple (⩾ 2 runs) and repetitive bursts (on ⩾ 2 Holters) of NSVT, or prolonged runs of ventricular tachycardia, included 4 deaths due to heart failure; group 2 (n = 38), isolated infrequent bursts of NSVT, included 1 sudden death; group 3 (n = 90), without NSVT, included 4 heart failure deaths. Kaplan-Meier survival analysis showed no significant differences in survival between the three groups throughout follow up.
Conclusions—In an unselected patient population with HCM, isolated, non-repetitive bursts of NSVT were not associated with adverse prognosis and so this arrhythmia does not appear to justify chronic antiarrhythmic treatment. Amiodarone, administered in relatively low

  15. Human Engineered Cardiac Tissues Created Using Induced Pluripotent Stem Cells Reveal Functional Characteristics of BRAF-Mediated Hypertrophic Cardiomyopathy.

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    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

  16. Association of angiotensin-converting enzyme activity and polymorphism with echocardiographic measures in familial and nonfamilial hypertrophic cardiomyopathy

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    P.C. Buck

    2009-08-01

    Full Text Available Angiotensin-converting enzyme (ACE activity and polymorphism contribute significantly to the prognosis of patients with cardiomyopathy. The aim of this study was to determine the activity and type of ACE polymorphism in patients with familial and nonfamilial hypertrophic cardiomyopathy (HCM and to correlate these with echocardiographic measurements (echo-Doppler. We studied 136 patients (76 males with HCM (69 familial and 67 nonfamilial cases. Mean age was 41 ± 17 years. DNA was extracted from blood samples for the polymerase chain reaction and the determination of plasma ACE levels. Left ventricular mass, interventricular septum, and wall thickness were measured. Mean left ventricular mass index, interventricular septum and wall thickness in familial and nonfamilial forms were 154 ± 63 and 174 ± 57 g/m² (P = 0.008, 19 ± 5 and 21 ± 5 mm (P = 0.02, and 10 ± 2 and 12 ± 3 mm (P = 0.0001, respectively. ACE genotype frequencies were DD = 35%, ID = 52%, and II = 13%. A positive association was observed between serum ACE activity and left ventricular mass index (P = 0.04. Logistic regression showed that ACE activity was twice as high in patients with familial HCM and left ventricular mass index ≥190 g/m² compared with the nonfamilial form (P = 0.02. No other correlation was observed between ACE polymorphisms and the degree of myocardial hypertrophy. In conclusion, ACE activity, but not ACE polymorphisms, was associated with the degree of myocardial hypertrophy in the patients with HCM.

  17. Disease stage classification in hypertrophic cardiomyopathy by dual analysis of iodine-123-labeled metaiodobenzylguanidine and thallium-201 myocardial scintigraphies

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    Hiasa, Go [Ehime Univ., Matsuyama (Japan). School of Medicine

    2001-08-01

    Many patients with hypertrophic cardiomyopathy (HCM) gradually changes from typical myocardial hypertrophy to dilated cardiomyopathy-like features. However, it is difficult to estimate the disease stage in HCM. To determine the disease stage, dual analysis of iodine-123-labeled metaiodobenzylguanidine ({sup 123}I-MIBG) and thallium-201 ({sup 201}Tl) myocardial scintigraphies were performed in 108 HCM patients. According to the scintigraphic distribution patterns, patients were divided into three groups. Group A (n=15): normal distributions of both {sup 123}I-MIBG and {sup 201}Tl, group B (n=71): normal {sup 201}Tl and low {sup 123}I-MIBG patterns, group C (n=22): low distributions of both scintigraphies. The decrease in {sup 201}Tl uptake was observed in only group C. Concerning {sup 123}I-MIBG, heart-to-mediastinum ratio (H/M) and washout rate (WOR) had good correlations with left ventricular systolic functions. H/M was decreased and WOR was increased in order of C, B and A groups. Left ventricular diastolic function reflected by isovolumic relaxation time was longer in group B than in group A. Attenuated left ventricular hypertrophy, enlarged left ventricular volumes, impaired left ventricular functions and serious clinical symptoms were observed in only group C. Myocardial sympathetic abnormalities in group B may be mainly due to myocardial hypertrophy, and those in group C may be due to myocardial injury. Dual analysis of {sup 123}I-MIBG and {sup 201}Tl scintigraphies may be useful to classify disease stages of HCM. (author)

  18. 3.0 T magnetic resonance myocardial perfusion imaging for semi-quantitative evaluation of coronary microvascular dysfunction in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Yin, Liang; Xu, Hai-Yan; Zheng, Sui-Sheng; Zhu, Ying; Xiao, Jiang-Xi; Zhou, Wei; Yu, Si-Si; Gong, Liang-Geng

    2017-12-01

    This study aimed to assess coronary microvascular dysfunction (CMD) differences in hypertrophic cardiomyopathy (HCM) patients using cardiac magnetic resonance (CMR) first-pass perfusion and late gadolinium enhancement imaging. Forty-seven patients with HCM and twenty-one healthy volunteers underwent CMR at rest. Imaging protocols included short axis cine, first-pass myocardial perfusion, and late gadolinium enhancement (LGE). Left ventricular end-diastolic wall thickness (EDTH), LGE, time to peak (T peak ), maximal up-slope (Slope max ), and peak signal intensity (SI peak ) were assessed for each myocardial segment. The HCM myocardial segments were grouped by the degree of LGE and hypertrophy. T peak , SI peak , Slope max and EDTH in multiple groups were assessed and compared by ANOVA test/Kruskal-Wallis test. The Spearman correlation test was used to determine the relationships between EDTH, LGE and perfusion parameters (T peak , Slope max and SI peak ). Compared to control group segments, T peak increased while Slope max and SI peak decreased in non-LGE/non-hypertrophic segments and LGE/hypertrophic segments in the HCM group, while T peak increased more significantly in LGE/hypertrophic segments (all p hypertrophic segments of HCM patients, and it may be helpful in the early diagnosis of coronary microvascular dysfunction in HCM. This abnormal perfusion is associated with the severity of myocardial fibrosis and the degree of hypertrophy.

  19. Síndrome Leopard e miocardiopatia hipertrófica: uma associação relacionada à morte súbita Síndrome leopard y miocardiopatía hipertrófica: una asociación relacionada a la muerte súbita Leopard syndrome and hypertrophic cardiomyopathy: an association related to sudden death

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    Murillo de Oliveira Antunes

    2009-06-01

    Full Text Available Relatamos a rara associação entre síndrome Leopard e miocardiopatia hipertrófica em mulher de 27 anos, pouco sintomática, que veio para estratificação e prevenção de risco de morte súbita. Portadora de uma síndrome rara, que se manifesta com pequenas máculas disseminadas pelo corpo, além de alterações oculares, genitais, cardíacas e de crescimento. A associação de miocardiopatia hipertrófica com fatores de risco de morte súbita determinou a indicação do implante de cardiodesfibrilador (CDI para prevenção primária.Relatamos la rara asociación entre síndrome Leopard y miocardiopatía hipertrófica en una mujer de 27 años, poco sintomática, que vino para estratificación y prevención de riesgo de muerte súbita. Portadora de un síndrome raro, que se manifiesta con pequeñas manchas diseminadas por el cuerpo, además de alteraciones oculares, genitales, cardíacas y de crecimiento. La asociación de miocardiopatía hipertrófica con factores de riesgo de muerte súbita determinó la indicación del implante de cardiodesfibrilador (CDI para prevención primaria.We describe an uncommon association between Leopard syndrome and hypertrophic cardiomyopathy in a 27-year-old woman, who was little symptomatic and came for sudden death risk stratification and prevention. She has a rare syndrome, whose symptoms are maculae over the body and abnormalities in eyes, genital organs, heart and in growth. Association of hypertrophic cardiomyopathy with sudden death risk factors determined the implantation of cardioverter-defibrillator (ICD for primary prevention.

  20. The flexibility of two tropomyosin mutants, D175N and E180G, that cause hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiaochuan; Suphamungmee, Worawit [Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118 (United States); Janco, Miro; Geeves, Michael A. [School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ (United Kingdom); Marston, Steven B. [National Heart and Lung Institute, Imperial College London, London W12 0NN (United Kingdom); Fischer, Stefan, E-mail: stefan.fischer@iwr.uni-heidelberg.de [Computational Biochemistry Group, University of Heidelberg, Heidelberg D-69120 (Germany); Lehman, William, E-mail: wlehman@bu.edu [Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118 (United States)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer Well-known tropomyosin mutants, D175N and E180G are linked to cardiomyopathies. Black-Right-Pointing-Pointer The structural mechanics of D175N and E180G tropomyosins have been investigated. Black-Right-Pointing-Pointer D175N and E180G mutations increase both local and global tropomyosin flexibility. Black-Right-Pointing-Pointer In muscle, this increased flexibility will enhance myosin interactions on actin. Black-Right-Pointing-Pointer Extra myosin interaction can alter cardiac Ca{sup 2+}-switching, leading to dysfunction. -- Abstract: Point mutations targeting muscle thin filament proteins are the cause of a number of cardiomyopathies. In many cases, biological effects of the mutations are well-documented, whereas their structural and mechanical impact on filament assembly and regulatory function is lacking. In order to elucidate molecular defects leading to cardiac dysfunction, we have examined the structural mechanics of two tropomyosin mutants, E180G and D175N, which are associated with hypertrophic cardiomyopathy (HCM). Tropomyosin is an {alpha}-helical coiled-coil dimer which polymerizes end-to-end to create an elongated superhelix that wraps around F-actin filaments of muscle and non-muscle cells, thus modulating the binding of other actin-binding proteins. Here, we study how flexibility changes in the E180G and D175N mutants might affect tropomyosin binding and regulatory motion on F-actin. Electron microscopy and Molecular Dynamics simulations show that E180G and D175N mutations cause an increase in bending flexibility of tropomyosin both locally and globally. This excess flexibility is likely to increase accessibility of the myosin-binding sites on F-actin, thus destabilizing the low-Ca{sup 2+} relaxed-state of cardiac muscle. The resulting imbalance in the on-off switching mechanism of the mutants will shift the regulatory equilibrium towards Ca{sup 2+}-activation of cardiac muscle, as is observed in affected

  1. Effect of cellular and extracellular pathology assessed by T1 mapping on regional contractile function in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Swoboda, Peter P; McDiarmid, Adam K; Erhayiem, Bara; Law, Graham R; Garg, Pankaj; Broadbent, David A; Ripley, David P; Musa, Tarique A; Dobson, Laura E; Foley, James R; Fent, Graham J; Page, Stephen P; Greenwood, John P; Plein, Sven

    2017-02-20

    Regional contractile dysfunction is a frequent finding in hypertrophic cardiomyopathy (HCM). We aimed to investigate the contribution of different tissue characteristics in HCM to regional contractile dysfunction. We prospectively recruited 50 patients with HCM who underwent cardiovascular magnetic resonance (CMR) studies at 3.0 T including cine imaging, T1 mapping and late gadolinium enhancement (LGE) imaging. For each segment of the American Heart Association model segment thickness, native T1, extracellular volume (ECV), presence of LGE and regional strain (by feature tracking and tissue tagging) were assessed. The relationship of segmental function, hypertrophy and tissue characteristics were determined using a mixed effects model, with random intercept for each patient. Individually segment thickness, native T1, ECV and the presence of LGE all had significant associations with regional strain. The first multivariable model (segment thickness, LGE and ECV) demonstrated that all strain parameters were associated with segment thickness (P T1) all strain parameters were associated with both segment thickness (P T1 (P T1 but not markers of extracellular fibrosis (ECV or LGE). These findings suggest that impairment of contractility in HCM is mediated by mechanisms other than extracellular expansion that include cellular changes in structure and function. The cellular mechanisms leading to increased native T1 and its prognostic significance remain to be established.

  2. Evaluation of a motion artifacts removal approach on breath-hold cine-magnetic resonance images of hypertrophic cardiomyopathy subjects

    Science.gov (United States)

    Betancur, Julián.; Simon, Antoine; Schnell, Frédéric; Donal, Erwan; Hernández, Alfredo; Garreau, Mireille

    2013-11-01

    The acquisition of ECG-gated cine magnetic resonance images of the heart is routinely performed in apnea in order to suppress the motion artifacts caused by breathing. However, many factors including the 2D nature of the acquisition and the use of di erent beats to acquire the multiple-view cine images, cause this kind of artifacts to appear. This paper presents the qualitative evaluation of a method aiming to remove motion artifacts in multipleview cine images acquired on patients with hypertrophic cardiomyopathy diagnosis. The approach uses iconic registration to reduce for in-plane artifacts in long-axis-view image stacks and in-plane and out-of-plane motion artifacts in sort-axis-view image stack. Four similarity measures were evaluated: the normalized correlation, the normalized mutual information, the sum of absolute voxel di erences and the Slomka metric proposed by Slomka et al. The qualitative evaluation assessed the misalignment of di erent anatomical structures of the left ventricle as follows: the misalignment of the interventricular septum and the lateral wall for short-axis-view acquisitions and the misalignment between the short-axis-view image and long-axis-view images. Results showed the correction using the normalized correlation as the most appropriated with an 80% of success.

  3. [Ascending Aorta Replacement and Extended Myectomy for Acute Aortic Dissection and Coexistent Hypertrophic Obstructive Cardiomyopathy;Report of a Case].

    Science.gov (United States)

    Suzuki, Tomoyuki; Hata, Masaki; Yamaya, Kazuhiro; Saitou, Takeshi; Haba, Fumiya; Matsuno, Masahiro

    2017-12-01

    Emergent ascending aortic replacement and extended myectomy were performed in a woman with acute aortic dissection who was aged 63 years. Preoperative transthoracic echocardiography performed in the intensive care unit showed only slight left ventricular outflow tract (LVOT) obstruction, but intraoperative transesophageal echocardiography after induction of anesthesia revealed pericardial effusion, systolic anterior motion(SAM), and associated mitral regurgitation(MR). Perioperative SAM and MR are sometimes facilitated under various hemodynamic conditions, but in this case, the left ventricular wall was thick and LVOT appeared to be obstructive by a hypertrophied septum. Structural hypertrophic obstructive cardiomyopathy (HOCM) was diagnosed, and septal myectomy and aortic replacement were performed. After ascending aortic replacement and simultaneous extended myectomy with resection of abnormal band, weaning from cardiopulmonary bypass was smooth without SAM and MR. The patient was discharged from hospital 24 days postoperatively with no major complications. Extended myectomy should be considered if structural HOCM is diagnosed, even when aortic replacement for the dissected aorta is the primary procedure.

  4. The R403Q myosin mutation implicated in familial hypertrophic cardiomyopathy causes disorder at the actomyosin interface.

    Directory of Open Access Journals (Sweden)

    Niels Volkmann

    2007-11-01

    Full Text Available Mutations in virtually all of the proteins comprising the cardiac muscle sarcomere have been implicated in causing Familial Hypertrophic Cardiomyopathy (FHC. Mutations in the beta-myosin heavy chain (MHC remain among the most common causes of FHC, with the widely studied R403Q mutation resulting in an especially severe clinical prognosis. In vitro functional studies of cardiac myosin containing the R403Q mutation have revealed significant changes in enzymatic and mechanical properties compared to wild-type myosin. It has been proposed that these molecular changes must trigger events that ultimately lead to the clinical phenotype.Here we examine the structural consequences of the R403Q mutation in a recombinant smooth muscle myosin subfragment (S1, whose kinetic features have much in common with slow beta-MHC. We obtained three-dimensional reconstructions of wild-type and R403Q smooth muscle S1 bound to actin filaments in the presence (ADP and absence (apo of nucleotide by electron cryomicroscopy and image analysis. We observed that the mutant S1 was attached to actin at highly variable angles compared to wild-type reconstructions, suggesting a severe disruption of the actin-myosin interaction at the interface.These results provide structural evidence that disarray at the molecular level may be linked to the histopathological myocyte disarray characteristic of the diseased state.

  5. Vascular Endothelial Growth Factor Is Associated with the Morphologic and Functional Parameters in Patients with Hypertrophic Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Radek Pudil

    2015-01-01

    Full Text Available Background. Hypertrophic cardiomyopathy (HCM is mostly autosomal dominant disease of the myocardium, which is characterized by myocardial hypertrophy. Vascular endothelial growth factor (VEGF is involved in myocyte function, growth, and survival. The aim of study was to analyze the clinical significance of VEGF in structural and functional changes in patient with HCM. Methods. In a group of 21 patients with nonobstructive HCM, we assessed serum VEGF and analyzed its association with morphological and functional parameters. Compared to healthy controls, serum VEGF was increased: 199 (IQR: 120.4–260.8 ng/L versus 20 (IQR: 14.8–37.7 ng/L, P<0.001. VEGF levels were associated with left atrium diameter (r=0.51, P=0.01, left ventricle ejection fraction (r=-0.56, P=0.01, fractional shortening (r=-0.54, P=0.02, left ventricular mass (r=0.61, P=0.03, LV mass index (r=0.46, P=0.04, vena cava inferior diameter (r=0.65, P=0.01, and peak gradient of tricuspid regurgitation (r=0.46, P=0.03. Conclusions. Increased VEGF level is associated with structural and functional parameters in patients with HCM and serves as a potential tool for diagnostic process of these patients.

  6. Investigation of Mutations in Exons 12-15 MYH7 Gene in Hypertrophic Cardiomyopathie Patients Using PCR-SSCP Technique

    Directory of Open Access Journals (Sweden)

    Soraya Heydari

    2013-10-01

    Full Text Available Background: Hypertrophic cardiomyopathy (HCM is the most common kind of Mendelian inherited heart disease, affects 0.2% of the global population. HCM is also the most common cause of sudden cardiac death in individuals younger than 35 years old. To date more than 900 individual mutations has been identified in over 20 genes, such as MYH7, MYBPC3, and TNNT2. Interestingly, most of these genes encode sarcomeric proteins. In the present study, we investigated the possible presence of mutation in exons 12-15 MYH7 gene, which has already been reported to accommodate some mutations, in 30 patients with HCM in Chaharmahal va Bakhtiyari province. Materials and Methods: DNA was extracted using standard phenol-chloroform method and then was used for amplification and gel electroploresis by PCR-SSCP procedure. Finally, the suspected cases were selected for the direct sequencing and the results were analyzed using chromas software.Results: There is no mutation in these exons, but two polymorphisms including: 5811 C>T and 5845 G> were found in the exon 12 of 1 and 5 separate patients, respectively.Conclusion: In this study with respect to none amino acid codon changes arisen from these polymorphisms, we concluded that mutations in these exons of MYH7 gene have a very low contribution in patients in this province and this is necessary to study other exons for better assessment.

  7. Cardiac troponin T mutations result in allele-specific phenotypes in a mouse model for hypertrophic cardiomyopathy

    Science.gov (United States)

    Tardiff, Jil C.; Hewett, Timothy E.; Palmer, Bradley M.; Olsson, Charlotte; Factor, Stephen M.; Moore, Russell L.; Robbins, Jeffrey; Leinwand, Leslie A.

    1999-01-01

    Multiple mutations in cardiac troponin T (cTnT) can cause familial hypertrophic cardiomyopathy (FHC). Patients with cTnT mutations generally exhibit mild or no ventricular hypertrophy, yet demonstrate a high frequency of early sudden death. To understand the functional basis of these phenotypes, we created transgenic mouse lines expressing 30%, 67%, and 92% of their total cTnT as a missense (R92Q) allele analogous to one found in FHC. Similar to a mouse FHC model expressing a truncated cTnT protein, the left ventricles of all R92Q lines are smaller than those of wild-type. In striking contrast to truncation mice, however, the R92Q hearts demonstrate significant induction of atrial natriuretic factor and β-myosin heavy chain transcripts, interstitial fibrosis, and mitochondrial pathology. Isolated cardiac myocytes from R92Q mice have increased basal sarcomeric activation, impaired relaxation, and shorter sarcomere lengths. Isolated working heart data are consistent, showing hypercontractility and diastolic dysfunction, both of which are common findings in patients with FHC. These mice represent the first disease model to exhibit hypercontractility, as well as a unique model system for exploring the cellular pathogenesis of FHC. The distinct phenotypes of mice with different TnT alleles suggest that the clinical heterogeneity of FHC is at least partially due to allele-specific mechanisms. J. Clin. Invest. 104:469-481 (1999). PMID:10449439

  8. Myocardial glucose metabolism is different between hypertrophic cardiomyopathy and hypertensive heart disease associated with asymmetrical septal hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Shiba, Nobuyuki; Kagaya, Yutaka; Ishide, Nobumasa; Takeyama, Daiya; Yamane, Yuriko; Chida, Masanobu; Otani, Hiroki; Shirato, Kunio [Tohoku Univ., Sendai (Japan). School of Medicine; Ido, Tatsuo

    1997-06-01

    Myocardial glucose metabolism has been shown to be heterogeneous in patients with hypertrophic cardiomyopathy (HCM). We tested the hypothesis that myocardial glucose metabolism differs between patients with HCM and those with hypertensive heart disease (HHD) associated with asymmetrical septal hypertrophy. We studied 12 patients with HCM, 7 HHD patients associated with asymmetrical septal hypertrophy using {sup 18}F 2-deoxyglucose (FDG) and positron emission tomography. We calculated % FDG fractional uptake in the interventricular septum and posterolateral wall. Heterogeneity of FDG uptake was evaluated by % interregional coefficient of variation of FDG fractional uptake in each wall segment. In both the interventricular septum and posterolateral wall, % FDG fractional uptake was not significantly different between the two groups. The % interregional coefficient of variation for both interventricular septum (10.6{+-}1.6 vs. 4.1{+-}0.5, p<0.01) and posterolateral wall (5.9{+-}0.7 vs. 3.8{+-}0.5, p< 0.05) was significantly larger in patients with HCM than in HHD patients associated with asymmetrical septal hypertrophy. Echocardiography demonstrated that the degree of asymmetrical septal hypertrophy was similar between the two groups. These results suggest that myocardial glucose metabolism may be more heterogeneous in patients with HCM compared to HHD patients associated with asymmetrical septal hypertrophy, although the left ventricular shape is similar. The difference in the heterogeneity might have resulted from differences in the pathogeneses of the two diseases. (author)

  9. Kinetics of a single cross-bridge in familial hypertrophic cardiomyopathy heart muscle measured by reverse Kretschmann fluorescence

    Science.gov (United States)

    Mettikolla, Prasad; Calander, Nils; Luchowski, Rafal; Gryczynski, Ignacy; Gryczynski, Zygmunt; Borejdo, Julian

    2010-01-01

    Familial hypertrophic cardiomyopathy (FHC) is a serious heart disease that often leads to a sudden cardiac death of young athletes. It is believed that the alteration of the kinetics of interaction between actin and myosin causes FHC by making the heart to pump blood inefficiently. We set out to check this hypothesis ex vivo. During contraction of heart muscle, a myosin cross-bridge imparts periodic force impulses to actin. The impulses are analyzed by fluorescence correlation spectroscopy (FCS) of fluorescently labeled actin. To minimize observation volume and background fluorescence, we carry out FCS measurements in surface plasmon coupled emission mode in a reverse Kretschmann configuration. Fluorescence is a result of near-field coupling of fluorophores excited in the vicinity of the metal-coated surface of a coverslip with the surface plasmons propagating in the metal. Surface plasmons decouple on opposite sides of the metal film and emit in a directional manner as far-field p-polarized radiation. We show that the rate of changes of orientation is significantly faster in contracting cardiac myofibrils of transgenic mice than wild type. These results are consistent with the fact that mutated heart muscle myosin translates actin faster in in vitro motility assays.

  10. Abnormal Calcium Handling Properties Underlie Familial Hypertrophic Cardiomyopathy Pathology in Patient-Specific Induced Pluripotent Stem Cells

    Science.gov (United States)

    Lan, Feng; Lee, Andrew S.; Liang, Ping; Sanchez-Freire, Veronica; Nguyen, Patricia K.; Wang, Li; Han, Leng; Yen, Michelle; Wang, Yongming; Sun, Ning; Abilez, Oscar J.; Hu, Shijun; Ebert, Antje D.; Navarrete, Enrique G.; Simmons, Chelsey S.; Wheeler, Matthew; Pruitt, Beth; Lewis, Richard; Yamaguchi, Yoshinori; Ashley, Euan A.; Bers, Donald M.; Robbins, Robert C.; Longaker, Michael T.; Wu, Joseph C.

    2013-01-01

    Summary Familial hypertrophic cardiomyopathy (HCM) is a prevalent hereditary cardiac disorder linked to arrhythmia and sudden cardiac death. While the causes of HCM have been identified as genetic mutations in the cardiac sarcomere, the pathways by which sarcomeric mutations engender myocyte hypertrophy and electrophysiological abnormalities are not understood. To elucidate the mechanisms underlying HCM development, we generated patient-specific induced pluripotent stem cell cardiomyocytes (iPSC-CMs) from a ten-member family cohort carrying a hereditary HCM missense mutation (Arg663His) in the MYH7 gene. Diseased iPSC-CMs recapitulated numerous aspects of the HCM phenotype including cellular enlargement and contractile arrhythmia at the single-cell level. Calcium (Ca2+) imaging indicated dysregulation of Ca2+ cycling and elevation in intracellular Ca2+ ([Ca2+]i) are central mechanisms for disease pathogenesis. Pharmacological restoration of Ca2+ homeostasis prevented development of hypertrophy and electrophysiological irregularities. We anticipate that these findings will help elucidate the mechanisms underlying HCM development and identify novel therapies for the disease. PMID:23290139

  11. Mutation of the MYH7 gene in a child with hypertrophic cardiomyopathy and Wolff-Parkinson-White syndrome.

    Science.gov (United States)

    Bobkowski, Waldemar; Sobieszczańska, Małgorzata; Turska-Kmieć, Anna; Nowak, Agnieszka; Jagielski, Józef; Gonerska, Marzena; Lebioda, Arleta; Siwińska, Aldona

    2007-01-01

    Familial hypertrophic cardiomyopathy (HCM) displays autosomal dominant inheritance with incomplete penetration of defective genes. Data concerning the familial occurrence of ventricular preexcitation, i.e. Wolff-Parkinson-White (WPW) syndrome, also indicate autosomal dominant inheritance. In the literature, only a gene mutation on chromosome 7q3 has been described in familial HCM coexisting with WPW syndrome to date. The present paper describes the case of a 7-year-old boy with HCM and coexisting WPW syndrome. On his chromosome 14, molecular diagnostics revealed a C 9123 mutation (arginine changed into cysteine in position 453) in exon 14 in a copy of the gene for beta-myosin heavy chain (MYH7). It is the first known case of mutation of the MYH7 gene in a child with both HCM and WPW. Since no linkage between MYH7 mutation and HCM with WPW syndrome has been reported to date, we cannot conclude whether the observed mutation is a common cause for both diseases, or this patient presents an incidental co-occurrence of HCM (caused by MYH7 mutation) and WPW syndrome.

  12. [The genotype-phenotype correlation of the MYH7 gene c.1273G > a mutation in familial hypertrophic cardiomyopathy].

    Science.gov (United States)

    Wang, Hu; Zou, Yu-Bao; Song, Lei; Wang, Ji-Zheng; Sun, Kai; Song, Xiao-Dong; Gao, Shuo; Zhang, Chan-Na; Hui, Ru-Tai

    2009-05-01

    To investigate the genotype-phenotype correlation in Chinese familial hypertrophic cardiomyopathy (HCM), peripheral blood samples were collected from 7 members of a Chinese HCM family, and 120 normal subjects were recruited as control. The full encoding exons and flanking sequences of the cardiac troponin T (TNNT2) gene, beta-myosin heavy chain (MYH7) gene and myosin binding protein C (MYBPC3) gene were amplified and the products were sequenced directly to detect the mutations. A missense mutation, c.1273G>A, was identified in exon 14 of the MYH7 gene in 4 members of the Chinese HCM family, which resulted a glycine (Gly) to arginine (Arg) exchange at amino acid residue 425. The 425th glycine amino acid residue is highly conservative across the different species. The clinical phenotypes among the family members who carried this mutation presented significant individual differences. The c.1273G>A mutation of the MYH7 gene might be the causal mutation of the familial HCM. The heterogeneity of phenotypes suggested that multiple factors may be involved in the pathogenesis of HCM.

  13. Somatic MYH7, MYBPC3, TPM1, TNNT2 and TNNI3 mutations in sporadic hypertrophic cardiomyopathy.

    Science.gov (United States)

    Núñez, Lucía; Gimeno-Blanes, Juan Ramón; Rodríguez-García, María Isabel; Monserrat, Lorenzo; Zorio, Esther; Coats, Caroline; McGregor, Christopher G; Hernandez del Rincón, Juan Pedro; Castro-Beiras, Alfonso; Hermida-Prieto, Manuel

    2013-01-01

    Hypertrophic cardiomyopathy (HCM) is a clinically heterogeneous genetic heart disease characterized by left ventricular hypertrophy in the absence of another disease that could explain the wall thickening. Elucidation of the genetic basis of HCM lead to the identification of several genes encoding sarcomeric proteins, such as MYH7, MYBPC3, TPM1, TNNT2, and TNNI3. Sarcomeric genes are mutated in approximately 40% of HCM patients and a possible explanation for the incomplete yield of mutation-positive HCM may be somatic mutations. We studied 104 unrelated patients with non-familial HCM. Patients underwent clinical evaluation and mutation screening of 5 genes implicated in HCM (MYH7, MYBPC3, TPM1, TNNT2, and TNNI3) in genomic DNA isolated from resected cardiac tissue; 41 of 104 were found to carry a mutation, but as several patients carried the same mutations, the total amount of different mutations was 37; 20 of these mutations have been previously described, and pathogenicity has been assessed. To determine the effect of the 17 new mutations an in silico assay was performed and it predicted that 4 variants were damaging mutations. All identified variants were also seen in the DNA isolated from the corresponding blood, which demonstrated the absence of somatic mutations. Somatic mutations in MYH7, MYBPC3, TPM1, TNNT2, and TNNI3 do not represent an important etiologic pathway in HCM.

  14. Short-limb dwarfism and hypertrophic cardiomyopathy in a patient with paternal isodisomy 14: 45,XYidic(14)(p11)

    Energy Technology Data Exchange (ETDEWEB)

    Walter, C.A.; Moore, C.M.; Kaye, C.I. [Univ. of Texas Health Science Center, San Antonio, TX (United States)] [and others

    1996-11-11

    Uniparental disomy (UPD) has been shown to result in specific disorders either due to imprinting and/or homozygosity of mutant alleles. Here we present the findings in a child with paternal UPD14. Ultrasound evaluation was performed at 30 weeks of gestation because of abnormally large uterine size. Pertinent ultrasound findings included polyhydramnios, short limbs, abnormal position of hands, small thorax, and nonvisualization of the fetal stomach. Postnatally the infant was found to have a low birth weight, short birth length, contractures, short limbs, and a small thorax with upslanting ribs. Assisted ventilation and gastrostomy were required. At age 6 months, the infant required hospitalization for hypertrophic cardiomyopathy which responded to Atenolol{reg_sign}. Initial cytogenetic studies demonstrated an apparently balanced de novo Robertsonian translocation involving chromosomes 14 and a karyotype designation of 45,XY,t(14q14q). No indication of mosaicism for trisomy 14 was observed in metaphase spreads prepared from peripheral blood lymphocytes or skin-derived fibroblasts. C-band and fluorescence in situ hybridization results demonstrated that the chromosome was dicentric. DNA analyses showed paternal uniparental isodisomy for chromosome 14. Based on the cytogenetic and DNA results a final karyotype designation of 45,XY,idic(14)(p11) was assigned to this infant with paternal isodisomy of chromosome 14. 41 refs., 5 figs., 2 tabs.

  15. Cardiac MRI assessed left ventricular hypertrophy in differentiating hypertensive heart disease from hypertrophic cardiomyopathy attributable to a sarcomeric gene mutation

    Energy Technology Data Exchange (ETDEWEB)

    Sipola, Petri [Kuopio University Hospital, Department of Clinical Radiology, Kuopio (Finland); University of Eastern Finland, Institute of Clinical Medicine, Faculty of Health Sciences, Kuopio (Finland); Magga, Jarkko; Peuhkurinen, Keijo [Kuopio University Hospital, Department of Medicine, Kuopio (Finland); Husso, Minna [Kuopio University Hospital, Department of Clinical Radiology, Kuopio (Finland); Jaeaeskelaeinen, Pertti; Kuusisto, Johanna [Kuopio University Hospital, Department of Medicine, Kuopio (Finland); Kuopio University Hospital, Heart Center, P.O. Box 1777, Kuopio (Finland)

    2011-07-15

    To evaluate the value of cardiac magnetic resonance imaging (CMRI)-assessed left ventricular hypertrophy (LVH) in differentiating between hypertensive heart disease and hypertrophic cardiomyopathy (HCM). 95 unselected subjects with mild-to-moderate hypertension, 24 patients with HCM attributable to the D175N mutation of the {alpha}-tropomyosin gene and 17 control subjects were studied by cine CMRI. Left ventricular (LV) quantitative and qualitative characteristics were evaluated. LV maximal end-diastolic wall thickness, wall thickness-to-LV volume ratio, end-diastolic septum thickness and septum-to-lateral wall thickness ratio were useful measures for differentiating between LVH due to hypertension and HCM. The most accurate measure for identifying patients with HCM was the LV maximal wall thickness {>=}17 mm, with a sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of 90%, 93%, 86%, 95% and 91%, respectively. LV maximal wall thickness in the anterior wall, or regional bulging in left ventricular wall was found only in patients with HCM. LV mass index was not discriminant between patients with HCM and those with LVH due to hypertension. LV maximal thickness measured by CMRI is the best anatomical parameter in differentiating between LVH due to mild-to-moderate hypertension and HCM attributable to a sarcomeric mutation. CMRI assessment of location and quality of LVH is also of value in differential diagnosis. (orig.)

  16. A mutation in the {beta}-myosin rod associated with hypertrophic cardiomyopathy has an unexpected molecular phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Armel, Thomas Z. [Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309 (United States); Leinwand, Leslie A., E-mail: leslie.leinwand@colorado.edu [Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309 (United States)

    2010-01-01

    Hypertrophic cardiomyopathy (HCM) is a common, autosomal dominant disorder primarily characterized by left ventricular hypertrophy and is the leading cause of sudden cardiac death in youth. HCM is caused by mutations in several sarcomeric proteins, with mutations in MYH7, encoding {beta}-MyHC, being the most common. While many mutations in the globular head region of the protein have been reported and studied, analysis of HCM-causing mutations in the {beta}-MyHC rod domain has not yet been reported. To address this question, we performed an array of biochemical and biophysical assays to determine how the HCM-causing E1356K mutation affects the structure, stability, and function of the {beta}-MyHC rod. Surprisingly, the E1356K mutation appears to thermodynamically destabilize the protein, rather than alter the charge profile know to be essential for muscle filament assembly. This thermodynamic instability appears to be responsible for the decreased ability of the protein to form filaments and may be responsible for the HCM phenotype seen in patients.

  17. Identification of an Arg403Gln beta myosin heavy chain gene mutation in a Portuguese family with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Gonçalves, L M; Vieira, M; Faro, C; Ventura, M; Pires, E; Providência, L A

    2000-04-01

    The etiology of Familial Hypertrophic Cardiomyopathy (HCM) is attributed to the mutation of genes that encode sarcomeric proteins in the heart. Until now no gene mutations had been identified in Portuguese families with HCM. The main objective of this study is to describe a Portuguese family with HCM carrying an Arg403Gln mutation in the beta myosin heavy chain gene. With the help of several Molecular Biology tools, 40 families with HCM were studied. In all these families, one member was identified as carrying an Arg403Gln mutation in the beta myosin heavy chain gene. All family members were submitted to a physical exam, EKG and echocardiography. Those carrying a gene mutation were also submitted to Holter monitoring and to magnetic ressonance imaging. Molecular biology techniques are extremely important for the diagnosis of HCM, particularly in healthy carriers. The use of molecular diagnostic tools in HCM is very useful because it allows us to identify the healthy carriers and establish earlier clinical and prevention programs for these individuals.

  18. Multiple gene mutations, not the type of mutation, are the modifier of left ventricle hypertrophy in patients with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Zou, Yubao; Wang, Jizheng; Liu, Xuan; Wang, Yilu; Chen, Yi; Sun, Kai; Gao, Shuo; Zhang, Channa; Wang, Zhimin; Zhang, Yin; Feng, Xinxing; Song, Ying; Wu, Yajie; Zhang, Hongju; Jia, Lei; Wang, Hu; Wang, Dong; Yan, Chaowu; Lu, Minjie; Zhou, Xianliang; Song, Lei; Hui, Rutai

    2013-06-01

    Genotype-phenotype correlation of hypertrophic cardiomyopathy (HCM) has been challenging because of the genetic and clinical heterogeneity. To determine the mutation profile of Chinese patients with HCM and to correlate genotypes with phenotypes, we performed a systematic mutation screening of the eight most commonly mutated genes encoding sarcomere proteins in 200 unrelated Chinese adult patients using direct DNA sequencing. A total of 98 mutations were identified in 102 mutation carriers. The frequency of mutations in MYH7, MYBPC3, TNNT2 and TNNI3 was 26.0, 18.0, 4.0 and 3.5 % respectively. Among the 200 genotyped HCM patients, 83 harbored a single mutation, and 19 (9.5 %) harbored multiple mutations. The number of mutations was positively correlated with the maximum wall thickness. We found that neither particular gene nor specific mutation was correlated to clinical phenotype. In summary, the frequency of multiple mutations was greater in Chinese HCM patients than in the Caucasian population. Multiple mutations in sarcomere protein may be a risk factor for left ventricular wall thickness.

  19. Effect of verapamil on myocardial ischemia in patients with hypertrophic cardiomyopathy; Evaluation by exercise [sup 201]Tl SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Taniguchi, Yoko; Sugihara, Hiroki; Ootsuki, Katsuichi (Kyoto Prefectural Univ. of Medicine (Japan)) (and others)

    1993-01-01

    Effect of verapamil on myocardial ischemia in patients with hypertrophic cardiomyopathy (HCM) was evaluated by exercise stress myocardial [sup 201]Tl SPECT (EX-Tl). EX-Tl was performed before and after 8.8 weeks of oral verapamil (240 mg/day) in 12 patients with HCM who showed transient [sup 201]Tl perfusion defects under control conditions. [sup 201]Tl perfusion defect was visually scored and judged for 4 grades as normal (0), mild defect (1), moderate defect (2), and severe defect (3). Transient dilation index (TDI) was calculated as an index of subendocardial ischemia. Improvements of defect score were demonstrated in 10 patients after administration of verapamil. Two patients showed no change of defect score. Mean defect score decreased significantly from 5.50 to 3.03 (p<0.001). Although 11 of 12 patients showed abnormal TDI under control conditions, 10 of these revealed improvements of TDI and 7 of the 10 disclosed normal TDI after verapamil. Mean TDI decreased from 1.263 to 1.090 significantly (p<0.01). In conclusion, verapamil may improve myocardial ischemia in patients with HCM. (author).

  20. A Pregnancy with Severe Hypertrophic Obstructive Cardiomyopathy after Surgery for an Implantable Cardioverter Defibrillator: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Takashi Mitsui

    2016-01-01

    Full Text Available Hypertrophic obstructive cardiomyopathy (HOCM is cardiac hypertrophy of ventricular myocardium with left ventricular outflow tract obstruction. We report a pregnancy with HOCM after defibrillator implantation surgery. The patient was a 33-year-old nulligravida and was categorized as New York Heart Association class II. Her brain natriuretic peptide (BNP level was 724.6 pg/dL at preconception. She received careful pregnancy management. However, because frequent uterine contractions were observed at 25 weeks and 6 days of pregnancy, she was hospitalized, and magnesium sulfate was started as a tocolytic agent. At 27 weeks and 5 days of pregnancy, she had respiratory discomfort and orthopnea with a sudden decrease in peripheral oxygen saturation. Cardiac ultrasonography showed a worsened condition of HOCM and her BNP level was 1418.0 pg/mL. We performed an emergent cesarean section and she delivered a boy weighing 999 g. The Apgar score was 8 and 9 points at 1 and 5 minutes, respectively. The mother’s heart failure quickly improved after birth and she was discharged at 10 days postoperatively. Fluctuations in circulatory dynamics during pregnancy may sometimes exacerbate heart disease. Therefore, the risks should be fully explained and careful assessment of cardiac function should be performed during pregnancy in patients with severe HOCM.

  1. Cardiomyopathy

    Science.gov (United States)

    Cardiomyopathy is the name for diseases of the heart muscle. These diseases enlarge your heart muscle or ... tissue. Some people live long, healthy lives with cardiomyopathy. Some people don't even realize they have ...

  2. Prognostic value of cardiovascular magnetic resonance imaging for life-threatening arrhythmia detected by implantable cardioverter-defibrillator in Japanese patients with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Hen, Yasuki; Tsugu-Yagawa, Mayuko; Iguchi, Nobuo; Utanohara, Yuko; Takada, Kaori; Machida, Haruhiko; Takara, Ayako; Teraoka, Kunihiko; Inoue, Kanki; Takamisawa, Itaru; Takayama, Morimasa; Yoshikawa, Tsutomu

    2018-01-01

    Implantable cardioverter-defibrillator (ICD) is effective to prevent sudden death in HCM patients. We reviewed ICD records to analyze the relation between life-threatening arrhythmia and late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) in Japanese hypertrophic cardiomyopathy (HCM) patients. In 102 consecutive patients (median age 63 years, 63 males) implanted with an ICD after CMR with gadolinium enhancement (median follow-up 2.8 years), the outcome of life-threatening arrhythmic events (appropriate ICD interventions for ventricular tachycardia or ventricular fibrillation) was examined. Appropriate interventions rate were 10.3% per year for secondary prevention and 7.4% per year for primary prevention. The annualized ICD-related complication rate was 3.7%. 43/91 patients (47%) implanted ICD for primary prevention had maximum wall thickness ≥20 mm plus LGE in ≥4 of 17 left ventricular segments (cut-off value obtained from ROC curve); the appropriate ICD intervention rate was significantly higher in this group than in other patients group (annualized event rate, 11.1 vs. 4.6%; log-rank P = 0.038). A combination of myocardial hypertrophy and LGE is a useful outcome predictive factor for life-threatening ventricular arrhythmia in Japanese HCM patients.

  3. Unexpectedly Low Mutation Rates in Beta-Myosin Heavy Chain and Cardiac Myosin Binding Protein Genes in Italian Patients With Hypertrophic Cardiomyopathy

    Science.gov (United States)

    Roncarati, Roberta; Latronico, Michael VG; Musumeci, Beatrice; Aurino, Stefania; Torella, Annalaura; Bang, Marie-Louise; Jotti, Gloria Saccani; Puca, Annibale A; Volpe, Massimo; Nigro, Vincenzo; Autore, Camillo; Condorelli, Gianluigi

    2011-01-01

    Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease. Fourteen sarcomeric and sarcomere-related genes have been implicated in HCM etiology, those encoding β-myosin heavy chain (MYH7) and cardiac myosin binding protein C (MYBPC3) reported as the most frequently mutated: in fact, these account for around 50% of all cases related to sarcomeric gene mutations, which are collectively responsible for approximately 70% of all HCM cases. Here, we used denaturing high-performance liquid chromatography followed by bidirectional sequencing to screen the coding regions of MYH7 and MYBPC3 in a cohort (n = 125) of Italian patients presenting with HCM. We found 6 MHY7 mutations in 9/125 patients and 18 MYBPC3 mutations in 19/125 patients. Of the three novel MYH7 mutations found, two were missense, and one was a silent mutation; of the eight novel MYBPC3 mutations, one was a substitution, three were stop codons, and four were missense mutations. Thus, our cohort of Italian HCM patients did not harbor the high frequency of mutations usually found in MYH7 and MYBPC3. This finding, coupled to the clinical diversity of our cohort, emphasizes the complexity of HCM and the need for more inclusive investigative approaches in order to fully understand the pathogenesis of this disease. J. Cell. Physiol. 226: 2894–2900, 2011. © 2011 Wiley-Liss, Inc. PMID:21302287

  4. Cardiomyopathy During Pregnancy.

    Science.gov (United States)

    Troiano, Nan H

    2015-01-01

    Cardiomyopathy is an acquired cardiac disorder that, although rare, accounts for a rising proportion of reported pregnancy-related deaths in the United States. During pregnancy, cardiomyopathy may be divided into 2 groups. The first group is peripartum cardiomyopathy; the second group is stratified according to 3 classically defined pathophysiologic presentations: hypertrophic, dilated, or restrictive. Within this second group, the cardiomyopathy can be either idiopathic or due to a specific identified cause. This disorder poses significant risks of morbidity and/or mortality to the pregnant woman and fetus/neonate. This article describes types of cardiomyopathy during pregnancy, perinatal risks, and general management principles with a focus on intrapartum care. Hemodynamic and oxygen transport data are presented to illustrate interpretation of patient assessment findings and the effects of interventions for abnormal maternal and fetal findings.

  5. Enhanced washout of {sup 99m}Tc-tetrofosmin in hypertrophic cardiomyopathy: quantitative comparisons with regional {sup 123}I-BMIPP uptake and wall thickness determined by MRI

    Energy Technology Data Exchange (ETDEWEB)

    Thet-Thet-Lwin, Tohoru; Takeda, Jin; Wu, Yuko; Fumikura, Keiji; Iida, Satoru; Kawano, Iwao; Yamaguchi, Yuji; Itai [Institute of Clinical Medicine, University of Tsukuba, Tennodai 1-1-1, 305-8575, Tsukuba-shi, Ibaraki-ken (Japan)

    2003-07-01

    The diagnostic value of technetium-99m tetrofosmin (TF) washout in hypertrophic cardiomyopathy (HCM) was examined by investigating its relation to the metabolic abnormality depicted by iodine-123 {beta}-methyl-p-iodophenylpentadecanoic acid (BMIPP) uptake and the left ventricular (LV) myocardial wall thickness as measured by magnetic resonance imaging (MRI). TF washout was evaluated in 31 patients with HCM and 23 normal control subjects using 30-min (early) and 3-h (delayed) TF single-photon emission tomography images. The LV myocardial wall was divided into 19 segments and the percentage TF washout, regional BMIPP uptake and LV wall thickness were measured in each segment. Mean TF washout in the patients with HCM was significantly faster than that in normal control subjects (23.7{+-}5.7 vs 13.4{+-}4.1, P<0.0001). In the patients with HCM, TF washout showed an excellent correlation with MRI wall thickness (r=0.82, P<0.0001) and a good inverse correlation with regional BMIPP uptake (r=-0.72, P<0.0001). In addition, a good linear correlation was observed between TF uptake and MRI wall thickness in the 19 regional segments. In conclusion, the degree of TF washout corresponds well with the severity of myocardial wall thickness and the degree of metabolic abnormality in patients with HCM. These results suggest that enhanced TF washout might provide additional clinical information regarding metabolic alterations in HCM. (orig.)

  6. [Analysis of genotype and phenotype correlation of MYH7-V878A mutation among ethnic Han Chinese pedigrees affected with hypertrophic cardiomyopathy].

    Science.gov (United States)

    Wang, Bo; Guo, Ruiqi; Zuo, Lei; Shao, Hong; Liu, Ying; Wang, Yu; Ju, Yan; Sun, Chao; Wang, Lifeng; Zhang, Yanmin; Liu, Liwen

    2017-08-10

    To analyze the phenotype-genotype correlation of MYH7-V878A mutation. Exonic amplification and high-throughput sequencing of 96-cardiovascular disease-related genes were carried out on probands from 210 pedigrees affected with hypertrophic cardiomyopathy (HCM). For the probands, their family members, and 300 healthy volunteers, the identified MYH7-V878A mutation was verified by Sanger sequencing. Information of the HCM patients and their family members, including clinical data, physical examination, echocardiography (UCG), electrocardiography (ECG), and conserved sequence of the mutation among various species were analyzed. A MYH7-V878A mutation was detected in five HCM pedigrees containing 31 family members. Fourteen members have carried the mutation, among whom 11 were diagnosed with HCM, while 3 did not meet the diagnostic criteria. Some of the fourteen members also carried other mutations. Family members not carrying the mutation had normal UCG and ECG. No MYH7-V878A mutation was found among the 300 healthy volunteers. Analysis of sequence conservation showed that the amino acid is located in highly conserved regions among various species. MYH7-V878A is a hot spot among ethnic Han Chinese with a high penetrance. Functional analysis of the conserved sequences suggested that the mutation may cause significant alteration of the function. MYH7-V878A has a significant value for the early diagnosis of HCM.

  7. Delayed-enhancement MRI of apical hypertrophic cardiomyopathy: assessment of the intramural distribution and comparison with clinical symptoms, ventricular arrhythmias, and cine MRI

    Energy Technology Data Exchange (ETDEWEB)

    Amano, Yasuo; Fukushima, Yoshimitsu; Kumita, Shinichiro (Dept. of Radiology, Nippon Medical School, Tokyo (Japan)), email: yas-amano@nifty.com; Takayama, Morimasa (Dept. of Cardiology, Sakakibara Heart Inst., Tokyo (Japan)); Kitamura, Mitsunobu (Coronary Care Unit, Chiba-Hokuso Hospital of Nippon Medical School, Chiba (Japan))

    2011-07-15

    Background: Hypertrophic cardiomyopathy (HCM) is reported to show patchy midwall myocardial hyper enhancement on delayed-enhancement magnetic resonance imaging (DE-MRI). The intramural distribution of myocardial hyper enhancement and its correlation with clinical symptoms, ventricular arrhythmias, and cardiac function have not been described for symptomatic apical HCM. Purpose: To evaluate the features and significance of myocardial hyper enhancement on DE-MRI in symptomatic apical HCM. Material and Methods: Thirteen patients with symptomatic apical HCM and their 65 apical segments were investigated. Myocardial hyper enhancement and regional and global functional parameters were determined with MRI. We investigated the intramural distribution and frequencies of this myocardial hyper enhancement and compared them with the patients' clinical symptoms, the presence of ventricular arrhythmias, and cine MRI. Results: Eight (61.5%) patients with symptomatic apical HCM displayed apical myocardial hyper enhancement, and 22 (33.8%) of the 65 apical segments examined showed myocardial hyper enhancement. Of the myocardial hyper enhancement observed, 81.8% showed a subendocardial pattern.The Hyperenhanced apical myocardium had a lower percentage of systolic myocardial thickening, and was associated with serious symptoms (e.g. syncope) and ventricular arrhythmias. Conclusion: Patients with symptomatic apical HCM showed myocardial hyper enhancement involving the subendocardial layer, which might be related to regional systolic dysfunction, serious clinical symptoms, and ventricular arrhythmias

  8. [Gender effect on cardiomyopathy].

    Science.gov (United States)

    Biagini, Elena; Berardini, Alessandra; Graziosi, Maddalena; Rosmini, Stefania; Pazzi, Chiara; Rapezzi, Claudio

    2012-06-01

    The role of a gender effect (that means differences in clinical manifestations, access to therapies and response to treatments according to gender) in cardiomyopathies remains a matter of debate. Although recent studies have evaluated the differences in the clinical features and prognosis between the two sexes, many issues remain to be elucidated. At present, the only sex-specific condition that affects females is peripartum cardiomyopathy. Recent evidence suggests a pathogenetic role of a prolactin derivative, and ongoing clinical trials are investigating the possibility of targeted therapies using prolactin secretion inhibitors, such as bromocriptine and carbegoline. Although women were considered so far only carriers of X-linked diseases (Anderson-Fabry disease, Danon disease, Hunter syndrome and dystrophinopathies), clinical experience showed a wide spectrum of clinical manifestations in females due to random X chromosome inactivation. Conversely, in mitochondrial diseases (with matrilineal inheritance), cardiomyopathies may occur in the context of clinical multisystemic involvement without significant gender-related differences. Autosomal inherited cardiomyopathies also show different phenotypes and prognostic impact according to gender. The hypothesis of a premenopausal protective role of female hormones towards myocardial involvement has been raised by recent data on transtiretin-related amyloidosis and hypertrophic cardiomyopathy. Preexisting cardiomyopathies may affect pregnancy, labor and delivery in women, since all these conditions are associated with important hemodynamic changes. Women with low-risk hypertrophic cardiomyopathy (asymptomatic and without left ventricular outflow tract gradient) usually can tolerate pregnancy. Conversely, women who are symptomatic before pregnancy or have severe hypertrophy with important outflow tract gradient are at higher risk and should be referred to a tertiary center to be evaluated on a case by case basis

  9. [Cardiomyopathy and ion channel diseases registry: the Szeged CardioGen Registry].

    Science.gov (United States)

    Blazsó, Péter; Kákonyi, Kornél; Forster, Tamás; Sepp, Róbert

    2017-01-01

    The Szeged cardiomyopathy and ion channel diseases registry aims to establish a representative disease-specific registry based on the recruitment of patients with different cardiomyopathies and ion channel diseases followed at the Cardiology Center, University of Szeged. The registry collects patient data on the main forms of primary cardiomyopathies (hypertrophic, dilated, restrictive, arrhythmogenic right ventricular, left ventricular non-compact, tako-tsubo cardiomyopathy) and ion channel diseases (long QT syndrome, short QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia). Patients with hypertrophic cardiomyopathy (388 patients) make up the largest group of patients in the registry. Patients with dilated cardiomyopathy (310 patients) and patients with the long QT syndrome (111 patients) form two other sizable groups. Analyzed data of the group of patients with hypertrophic cardiomyopathy indicate similar figures with regard to disease related mortality and morbidity and clinical parameters. Orv. Hetil., 2017, 158(3), 101-105.

  10. Role of quantitative myocardial positron emission tomography for risk stratification in patients with hypertrophic cardiomyopathy: a 2016 reappraisal

    Energy Technology Data Exchange (ETDEWEB)

    Castagnoli, Helga; Passeri, Alessandro; Berti, Valentina; Sciagra, Roberto [University of Florence, Department of Experimental and Clinical Biomedical Sciences - Nuclear Medicine Unit, Firenze (Italy); Ferrantini, Cecilia; Coppini, Raffaele; Baldini, Katia; Cecchi, Franco; Olivotto, Iacopo [Careggi University Hospital, Referral Center for Myocardial Diseases and Genetic Diagnostics Unit, Florence (Italy)

    2016-12-15

    Myocardial blood flow <1.1 mL/min/g following dipyridamole (Dip-MBF) assessed by positron emission tomography (PET) was identified in 2003 as an important outcome predictor in hypertrophic cardiomyopathy (HCM), based on scans performed in the 90s. However, such extreme Dip-MBF impairment is rarely observed in contemporary cohorts. We, therefore, reassessed the Dip-MBF threshold defining high-risk HCM patients. Dip-MBF was measured using {sup 13}N-ammonia in 100 HCM consecutive patients, prospectively enrolled and followed for 4.0 ± 2.2 years. Outcome was assessed based on tertiles of Dip-MBF. The study end-point was a combination of cardiovascular death, progression to severe functional limitation, cardioembolic stroke, life-threatening ventricular arrhythmias. Global Dip-MBF was 1.95 ± 0.85, ranging from 0.7 to 5.9 mL/min/g. Dip-MBF tertile cut-off values were: 0.73 to 1.53 mL/min/g (lowest), 1.54 to 2.13 mL/min/g (middle), and 2.14 to 5.89 mL/min/g (highest). During follow-up, lowest tertile Dip-MBF was associated with sevenfold independent risk of unfavorable outcome compared to the other two tertiles. Dip-MBF 1.35 mL/min/g was identified as the best threshold for outcome prediction. Regional perfusion analysis showed that all cardiac deaths (n = 4) occurred in patients in the lowest tertile of lateral wall Dip-MBF (≤1.72 mL/min/g); septal Dip-MBF was not predictive. Dip-MBF confirms its role as potent predictor of outcome in HCM. However, the threshold for prediction in a contemporary cohort is higher than that reported in earlier studies. Dip-MBF impairment in the lateral wall, possibly reflecting diffuse disease extending to non-hypertrophic regions, is a sensitive predictor of mortality in HCM. (orig.)

  11. Myocardial scarring on cardiovascular magnetic resonance in asymptomatic or minimally symptomatic patients with “pure” apical hypertrophic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Kim Kyung-Hee

    2012-07-01

    Full Text Available Abstract Background Late gadolinium enhancement (LGE cardiovascular magnetic resonance (CMR enables state-of-the-art in vivo evaluations of myocardial fibrosis. Although LGE patterns have been well described in asymmetrical septal hypertrophy, conflicting results have been reported regarding the characteristics of LGE in apical hypertrophic cardiomyopathy (ApHCM. This study was undertaken to determine 1 the frequency and distribution of LGE and 2 its prognostic implication in ApHCM. Methods Forty patients with asymptomatic or minimally symptomatic pure ApHCM (age, 60.2 ± 10.4 years, 31 men were prospectively enrolled. LGE images were acquired using the inversion recovery segmented spoiled-gradient echo and phase-sensitive inversion recovery sequence, and analyzed using a 17-segment model. Summing the planimetered LGE areas in all short axis slices yielded the total volume of late enhancement, which was subsequently presented as a proportion of total LV myocardium (% LGE. Results Mean maximal apical wall thickness was 17.9±2.3mm, and mean left ventricular (LV ejection fraction was 67.7 ± 8.0%. All but one patient presented with electrocardiographic negative T wave inversion in anterolateral leads, with a mean maximum negative T wave of 7.2 ± 4.7mm. Nine patients (22.5% had giant negative T waves, defined as the amplitude of ≥10mm, in electrocardiogram. LGE was detected in 130 segments of 30 patients (75.0%, occupying 4.9 ± 5.5% of LV myocardium. LGE was mainly detected at the junction between left and right ventricles in 12 (30% and at the apex in 28 (70%, although LGE-positive areas were widely distributed, and not limited to the apex. Focal LGE at the non-hypertrophic LV segments was found in some ApHCM patients, even without LGE of hypertrophied apical segments. Over the 2-year follow-up, there was no one achieving the study end-point, defined as all-cause death, sudden cardiac death and hospitalization for heart failure

  12. {sup 31}P magnetic resonance spectroscopy to measure in vivo cardiac energetics in normal myocardium and hypertrophic cardiomyopathy: Experiences at 3 T

    Energy Technology Data Exchange (ETDEWEB)

    Shivu, Ganesh Nallur [Department of Cardiovascular Medicine, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT (United Kingdom)], E-mail: drgani23@gmail.com; Abozguia, Khalid; Phan, Thanh Trung; Ahmed, Ibrar [Department of Cardiovascular Medicine, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT (United Kingdom); Henning, Anke [Institute for Biomedical Engineering, University and ETH Zurich, Gloriastrasse 35, CH-8092, Zurich CH ETZ F97 (Switzerland); Frenneaux, Michael [Department of Cardiovascular Medicine, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT (United Kingdom)

    2010-02-15

    Background: {sup 31}P magnetic resonance spectroscopy (MRS) allows measurement of in vivo high-energy phosphate kinetics in the myocardium. While traditionally {sup 31}P cardiac spectroscopy is performed at 1.5 T, cardiac MRS at higher field strength can theoretically increase signal to noise ratio (SNR) and spectral resolution therefore improving sensitivity and specificity of the cardiac spectra. The reproducibility and feasibility of performing cardiac spectroscopy at 3 T is presented here in this study in healthy volunteers and patients with hypertrophic cardiomyopathy. Methods: Cardiac spectroscopy was performed using a Phillips 3T Achieva scanner in 37 healthy volunteers and 26 patients with hypertrophic cardiomyopathy (HCM) to test the feasibility of the protocol. To test the reproducibility a single volunteer was scanned eight times on separate occasions. A single voxel {sup 31}P MRS was performed using Image Selected In vivo Spectroscopy (ISIS) volume localization. Results: The mean phosphocreatine/adenosine triphosphate (PCr/ATP) ratio of the eight measurements performed on one individual was 2.11 {+-} 0.25. Bland Altman plots showed a variance of 12% in the measurement of PCr/ATP ratios. The PCr/ATP ratio was significantly reduced in HCM patients compared to controls, 1.42 {+-} 0.51 and 2.11 {+-} 0.57, respectively, P < 0.0001. (All results are expressed as mean {+-} standard deviation). Conclusions: Here we demonstrate that cardiac {sup 31}P MRS at 3 T is a reliable method of measuring in vivo high-energy phosphate kinetics in the myocardium for clinical studies and diagnostics. Based on our data an impairment of cardiac energetic state in patients with hypertrophic cardiomyopathy is indisputable.

  13. Measurement of left ventricular chamber and myocardial volume in hypertrophic cardiomyopathy patients by ECG-gated myocardial perfusion SPECT. Application of a newly developed edge-detection algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, Yoshihiro; Katafuchi, Tetsuro; Hirase, Yoshinori; Sagoh, Masayoshi; Oka, Hisashi [National Cardiovascular Center, Suita, Osaka (Japan); Mori, Hideaki [Siemens-Asahi Medical Technologies, Ltd., Tokyo (Japan); Murase, Kenya [Osaka Univ., Suita (Japan). Medical School

    2002-12-01

    Quantitative gated SPECT (QGS) software has been reported to demonstrate inaccurate edge detection in the left ventricular chamber in hypertrophic cardiomyopathy patients. In this study we developed a method to calculate left ventricular volume (LVV) and left myocardial volume (LMV) from gated SPECT data using a newly developed edge-detection algorithm, and we compared it with the QGS method of calculating LVV and LMV in a phantom study. Our method gave more accurate measurements LVV and LMV whereas the QGS method underestimated LMV. Compared with QGS LVV and LMV, our method yielded better results in the phantom study. (author)

  14. Quantification of myocardial delayed enhancement and wall thickness in hypertrophic cardiomyopathy: Multidetector computed tomography versus magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Lei [Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Rd Beijing (China); Ma, Xiaohai, E-mail: maxi8238@gmail.com [Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Rd Beijing (China); Feuchtner, Gudrun Maria [Department of Radiology II, Innsbruck Medical University, Innsbruck (Austria); Zhang, Chen; Fan, Zhanming [Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Rd Beijing (China)

    2014-10-15

    Objectives: To evaluate the accuracy of multidetector computed tomography (MDCT) in assessing myocardial delayed enhancement and left ventricle wall thickness in hypertrophic cardiomyopathy (HCM) compared with cardiac magnetic resonance (CMR) as the reference standard. Materials and methods: Eighty consecutive patients (59 male; 53.2 ± 13.0 years) were examined with MDCT, followed by CMR 1 day later. Cardiac CT angiography and a delayed CT were performed. CMR was performed according to a standardized protocol. Left ventricle wall thickness and positions of myocardial delayed enhancement were identified in both CMR and CT images according to the American Heart Association left ventricle 17-segment model. Myocardial delayed enhancement was characterized as “dense” (areas with clear defined borders) or “diffuse” and then quantified using both techniques. Results: Left ventricle wall thickness determined by MDCT was significantly correlated with CMR (R = 0.88, P < 0.01). Compared with CMR, MDCT accurately diagnosed 74 of 78 (94.9%) patients and 1243 of 1326 (93.7%) segments. For dense myocardial delayed enhancement, MDCT significantly correlated with CMR (R = 0.88, P < 0.01) and slightly underestimated myocardial delayed enhancement (mean, −3.85%; lower and upper limits of agreement, −13.40% and 5.70%, respectively). Conclusions: MDCT provides reliable quantification of myocardial delayed enhancement and evaluation of left ventricle wall thickness and has a good correlation with CMR in patients with HCM when a comprehensive cardiac CT protocol is used and can be applied for intervention planning.

  15. Differentiation of light-chain cardiac amyloidosis from hypertrophic cardiomyopathy using myocardial mechanical parameters by velocity vector imaging echocardiography.

    Science.gov (United States)

    Zhang, Lu; Zhou, Xiao; Wang, Jing; Mu, Yang; Liu, Bohan; Lv, Wenqing; Wang, Ye; Liu, Hongwei; Liu, Hongbin; Zhi, Guang

    2017-04-01

    We aimed to evaluate the diagnostic efficacy of layered velocity vector imaging (VVI)-derived left ventricular (LV) mechanical parameters in the differential diagnosis of primary light-chain cardiac amyloidosis (AL-CA) and hypertrophic cardiomyopathy (HCM). We recruited 35 subjects with histologically-diagnosed AL-CA, 35 subjects with HCM, and 30 age-matched healthy controls. We used conventional echocardiography and electrocardiogram to evaluate general heart function and electrophysiology properties. Furthermore, we applied two-dimensional VVI echocardiography to assess the layered mechanical parameters during systole, including endocardial and epicardial longitudinal strain (ENDO and EPI LSsys), circumferential strain (CSsys), radial strain (RSsys), rotation (ROT) and twist (TWI), in different LV walls and levels. Two groups of patients had similarly elevated LV wall thickness and mild diastolic dysfunction, but normal ejection fraction. ENDO LSsys of three circular LV levels and six LV walls was markedly decreased in AL-CA patients, with the most prominent reduction in the basal level. The reduction of ENDO and EPI LSsys in HCM subjects was less profound, and was restricted to certain LV wall and levels. AL-CA patients had significantly reduced RSsys in the LV basal level compared with control or HCM patients. Two groups of patients exhibited similar reduction in layered regional CSsys, ROT and TWI. ROC analysis revealed that the sensitivity and specificity of basal ENDO LSsys for predicting AL-CA was 86 and 89%. Assessment of layered LSsys of LV walls and levels by VVI appeared to provide a more sensitive and specific diagnostic index for the differential diagnosis of AL-CA from HCM than conventional echocardiography. Future studies are warranted to evaluate its diagnostic efficacy for AL-CA diagnosis in the large population.

  16. Effects of benazepril in the treatment of feline hypertrophic cardiomyopathy Results of a prospective, open-label, multicenter clinical trial.

    Science.gov (United States)

    Amberger, C N; Glardon, O; Glaus, T; Hörauf, A; King, J N; Schmidli, H; Schröter, L; Lombard, C W

    1999-05-01

    To evaluate the efficacy of benazepril on clinical signs and echocardiographic parameters in cats with primary hypertrophic cardiomyopathy (HCM). ACE-inhibitors have positive effects in man with HCM, and contribute to a reduction of myocardial hypertrophy. Addition of an ACE-inhibitor to the standard treatment of HCM in cats may have beneficial effects. A total of 32 cats which were either asymptomatic or in stabilised congestive heart failure (ISACHC* class Ib, II or IIIa) were included in a one-year, prospective, open-label, clinical trial in 5 centres in Switzerland. 28 of these cats were allocated to one of two treatment groups: 1) standard therapy (ST) alone (n=9), consisting of a long-acting formulation of diltiazem (6-9 mg/kg sid) and optional acetylsalicylic acid (50 mg twice weekly, or 2) the same ST plus benazepril (0.33 - 0.75 mg/kg sid, n=19). Cats treated with benazepril showed a statistically significant decrease (mean +/- SEM, 0.11 +/- 0.03 mm/month, p = 0.002) in the left ventricular wall thickness (LVWD) from baseline, while no change (increase of 0.02 +/- 0.04 mm/month, p=0.66) was observed in cats on ST alone. Differences in LVWD between the two groups reached statistical significance (p=0.02). Benazepril treated cats showed more improvement in clinical signs (20-53%) than cats receiving ST alone (0-20%) but differences between the groups were not statistically significant (p>0.1). No change in septal thickness (IVSD) or left atrial to aortic root ratio (LA/Ao) was observed in either group. Benazepril had some beneficial effects on clinical signs and cardiac remodelling in cats with HCM and was well tolerated. These results, however, need to be confirmed in additional controlled studies. * ISACHC classification is described in the previous paper (Bench-study).

  17. Incidence and predictors of late complete heart block after alcohol septal ablation treatment of hypertrophic obstructive cardiomyopathy.

    Science.gov (United States)

    Schuller, Joseph L; Zipse, Matthew M; Krantz, Mori J; Blaker, Brian; Salcedo, Ernesto; Groves, Bertron M; Messenger, John C; Beaty, Brenda; Sauer, William H

    2015-02-01

    This study was designed to identify the incidence of late complete heart block (CHB) first identified at least 48 hours post alcohol septal ablation (ASA). Septal reduction with ASA is a therapeutic option for patients with symptomatic hypertrophic obstructive cardiomyopathy (HCM). CHB, resulting from the septal infarct, is a known complication with a reported incidence of 9-22%. The incidence of CHB more than 48 hours post-procedure is unknown. Consecutive patients who underwent ASA were analyzed and clinical characteristics associated with late CHB were assessed. Late CHB was defined as first identification of CHB more than 48 hours after ASA. From 2002-2013, 145 subjects underwent 168 ASA procedures and were followed for a mean of 3.2 +/- 2.3 years. The incidence of late CHB was 8.9% (15/168 ASA procedures). Heart block occurred from 48 hours to 3-years post-procedure. In a multivariable model, patients with any CHB were more likely to have had multiple ASA procedures (OR 4.14; 95% CI: 1.24, 13.9; P < 0.05) and high resting and provoked left ventricular outflow tract (LVOT) gradient assessed by catheterization (OR per 10 mmHg gradient 1.14; 95% CI: 1.0, 1.20; P < 0.05). After multivariable adjustment, only a high provokable LVOT gradient remained an independent predictor of late CHB (OR per 10 mmHg gradient 1.14 [95% CI 1.02-1.29]). Late CHB is a common complication of ASA for treatment of symptomatic HCM. Post-discharge electrocardiographic surveillance for atrioventricular conduction disease should be considered after ASA, especially for those with a high provokable LVOT gradient. © 2015, Wiley Periodicals, Inc.

  18. Abnormal papillary muscle morphology is independently associated with increased left ventricular outflow tract obstruction in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Kwon, D H; Setser, R M; Thamilarasan, M; Popovic, Z V; Smedira, N G; Schoenhagen, P; Garcia, M J; Lever, H M; Desai, M Y

    2008-10-01

    Abnormal papillary muscles (PM) are often found in hypertrophic cardiomyopathy (HCM). To assess the relationship between morphological alterations of PM in patients with HCM and left ventricular outflow tract (LVOT) obstruction, using magnetic resonance imaging (MRI) and echocardiography. Fifty-six patients with HCM (mean age 42 years (interquartile range 27, 51), 70% male) and 30 controls (mean age (42 (30, 53) years, 80% male) underwent MRI on a 1.5 T scanner (Siemens, Erlangen, Germany). Standard cine images were obtained in short-axis (base to apex), along with two-, three- and four-chamber views. The presence of bifid PM (none, one or both) and anteroapical displacement of anterolateral PM was recorded by MRI and correlated with resting LVOT gradients obtained by echocardiography. Double bifid PM (70% vs 17%) and anteroapical displacement of anterolateral PM (77% vs 17%) were more prevalent in patients with HCM than in controls (panteroapically displaced PM and double bifid PM had higher resting LVOT gradients than controls (45 (6, 81) vs 12 (0, 12) mm Hg (por=30 mm Hg) peak resting gradient was 7.1 (95% CI 1.4 to 36.7) for anteroapically displaced anterolateral PM and 10.4 (95% CI 1.2 to 91.2) for double bifid PM (both p = 0.005), independent of septal thickness, use of beta-blockers and/or calcium blockers and resting heart rate. Patients with HCM with abnormal PM have a higher degree of resting LVOT gradient, which is independent of septal thickness.

  19. T1 measurements identify extracellular volume expansion in hypertrophic cardiomyopathy sarcomere mutation carriers with and without left ventricular hypertrophy.

    Science.gov (United States)

    Ho, Carolyn Y; Abbasi, Siddique A; Neilan, Tomas G; Shah, Ravi V; Chen, Yucheng; Heydari, Bobak; Cirino, Allison L; Lakdawala, Neal K; Orav, E John; González, Arantxa; López, Begoña; Díez, Javier; Jerosch-Herold, Michael; Kwong, Raymond Y

    2013-05-01

    Myocardial fibrosis is a hallmark of hypertrophic cardiomyopathy (HCM) and a potential substrate for arrhythmias and heart failure. Sarcomere mutations seem to induce profibrotic changes before left ventricular hypertrophy (LVH) develops. To further evaluate these processes, we used cardiac magnetic resonance with T1 measurements on a genotyped HCM population to quantify myocardial extracellular volume (ECV). Sarcomere mutation carriers with LVH (G+/LVH+, n=37) and without LVH (G+/LVH-, n=29), patients with HCM without mutations (sarcomere-negative HCM, n=11), and healthy controls (n=11) underwent contrast cardiac magnetic resonance, measuring T1 times pre- and postgadolinium infusion. Concurrent echocardiography and serum biomarkers of collagen synthesis, hemodynamic stress, and myocardial injury were also available in a subset. Compared with controls, ECV was increased in patients with overt HCM, as well as G+/LVH- mutation carriers (ECV=0.36±0.01, 0.33±0.01, 0.27±0.01 in G+/LVH+, G+/LVH-, controls, respectively; P≤0.001 for all comparisons). ECV correlated with N-terminal probrain natriuretic peptide levels (r=0.58; P60% of overt patients with HCM but absent from G+/LVH- subjects. Both ECV and late gadolinium enhancement were more extensive in sarcomeric HCM than sarcomere-negative HCM. Myocardial ECV is increased in HCM sarcomere mutation carriers even in the absence of LVH. These data provide additional support that fibrotic remodeling is triggered early in disease pathogenesis. Quantifying ECV may help characterize the development of myocardial fibrosis in HCM and ultimately assist in developing novel disease-modifying therapy, targeting interstitial fibrosis.

  20. Effects of amiodarone on erect and supine exercise haemodynamics and exercise capacity in patients with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Frenneaux, M P; Counihan, P J; Porter, A; Lipkin, D P; McKenna, W J

    1992-05-01

    Hypertrophic cardiomyopathy (HCM) is a primary heart muscle disease associated with a high incidence of sudden death. Amiodarone is of benefit in those patients with a high risk profile for sudden death. Amiodarone has also been reported to improve symptoms dramatically in some patients with HCM but to cause functional deterioration in others. In the acute phase of oral amiodarone therapy there are few discernable changes in cardiovascular haemodynamics and the mechanisms of any beneficial effects on symptoms remain unclear. To determine the effect of amiodarone on exercise responses we measured haemodynamic indices in 10 patients during maximal supine- and symptom-limited erect treadmill exercise before and 6 weeks after amiodarone therapy. Following amiodarone therapy there was a significant reduction in resting and peak heart rate during erect exercise (76 +/- 13 vs 97 +/- 19 b.min-1; P = 0.001 and 114 +/- 26 vs 146 +/- 21 b.min-1; P = 0.001 respectively). Despite increases in peak pulmonary and systemic artery pressures with amiodarone therapy there was no difference in the peak left ventricular filling pressure or maximum cardiac output achieved. Similarly, during supine exercise the resting and peak heart rates were less following the 6 weeks amiodarone therapy. Comparison of supine and erect exercise haemodynamic indices demonstrated higher peak LV filling and higher peak systolic and pulmonary artery pressures during supine than during erect exercise (29 +/- 10 vs 25 +/- 12; P less than 0.04; 151 +/- 42 vs 126 +/- 48; P = 0.01 and 66 +/- 27 vs 62 +/- 21; P = 0.08 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

  1. One third of Danish hypertrophic cardiomyopathy patients with MYH7 mutations have mutations [corrected] in MYH7 rod region.

    Science.gov (United States)

    Hougs, Lotte; Havndrup, Ole; Bundgaard, Henning; Køber, Lars; Vuust, Jens; Larsen, Lars Allan; Christiansen, Michael; Andersen, Paal Skytt

    2005-02-01

    Familial hypertrophic cardiomyopathy (FHC) is, in most cases, a disease of the sarcomere, caused by a mutation in one of 10 known sarcomere disease genes. More than 266 mutations have been identified since 1989. The FHC disease gene first characterized MYH7, encodes the cardiac beta-myosin heavy chain, and contains more than 115 of these mutations. However, in most studies, only the region encoding the globular head and the hinge region of the mature cardiac beta-myosin heavy chain have been investigated. Furthermore, most studies carries out screening for mutations in the most prevalent disease genes, and discontinues screening when an apparent disease-associated mutation has been identified. The aim of the present study was to screen for mutations in the rod region of the MYH7 gene in all probands of the cohort, regardless of the known genetic status of the proband. Three disease-causing mutations were identified in the rod region in four probands using capillary electrophoresis single-strand conformation polymorphism as a screening method. All mutations were novel: N1327K, R1712W, and E1753K. Two of the probands had already been shown to carry other FHC-associated mutations. In conclusion, we show that in the Danish cohort we find one third of all MYH7 mutations in the rod-encoding region and we find that two of the patients carrying these mutations also carry mutations in other FHC disease genes stressing the need for a complete screening of all known disease genes in FHC-patients.

  2. Resequencing the whole MYH7 gene (including the intronic, promoter, and 3' UTR sequences) in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Coto, Eliecer; Reguero, Julián R; Palacín, María; Gómez, Juan; Alonso, Belén; Iglesias, Sara; Martín, María; Tavira, Beatriz; Díaz-Molina, Beatriz; Morales, Carlos; Morís, César; Rodríguez-Lambert, José L; Corao, Ana I; Díaz, Marta; Alvarez, Victoria

    2012-09-01

    MYH7 mutations are found in ~20% of hypertrophic cardiomyopathy (HCM) patients. Currently, mutational analysis is based on the sequencing of the coding exons and a few exon-flanking intronic nucleotides, resulting in omission of single-exon deletions and mutations in internal intronic, promoter, and 3' UTR regions. We amplified and sequenced large MYH7 fragments in 60 HCM patients without previously identified sarcomere mutations. Lack of aberrant PCR fragments excluded single-exon deletions in the patients. Instead, we identified several new rare intronic variants. An intron 26 single nucleotide insertion (-5 insC) was predicted to affect pre-mRNA splicing, but allele frequencies did not differ between patients and controls (n = 150). We found several rare promoter variants in the patients compared to controls, some of which were in binding sites for transcription factors and could thus affect gene expression. Only one rare 3' UTR variant (c.*29T>C) found in the patients was absent among the controls. This nucleotide change would not affect the binding of known microRNAs. Therefore, MYH7 mutations outside the coding exon sequences would be rarely found among HCM patients. However, changes in the promoter region could be linked to the risk of developing HCM. Further research to define the functional effect of these variants on gene expression is necessary to confirm the role of the MYH7 promoter in cardiac hypertrophy. Copyright © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  3. A novel approach in the use of radiofrequency catheter ablation of septal hypertrophy in hypertrophic obstructive cardiomyopathy.

    Science.gov (United States)

    Shelke, Abhijeet B; Menon, Rajeev; Kapadiya, Anuj; Yalagudri, Sachin; Saggu, Daljeet; Nair, Sandeep; Narasimhan, C

    Alcohol septal ablation (ASA) is a therapeutic alternative to surgical myectomy in patients with hypertrophic obstructive cardiomyopathy (HOCM). However, the anatomical variability of the septal branch, risk of complete heart block, and late onset ventricular arrhythmias are limitations to its therapeutic usage. There is recent interest in the use of radiofrequency catheter ablation (RFCA) as a therapeutic option in HOCM. We aimed to assess the safety and efficacy of RFCA in the treatment of symptomatic HOCM. Seven patients with symptomatic HOCM (mean age 43.7±15.6 years, five males), and significant left ventricular outflow tract (LVOT) gradient despite optimal drug therapy, underwent ablation of the hypertrophied interventricular septum. These patients had unfavorable anatomy for ASA. Ablation was performed under 3D electro-anatomical system guidance using an open irrigated tip catheter. The region of maximal LV septal bulge as seen on intracardiac echocardiography was targeted. Patients were followed up at 1, 6, and 12 months post-procedure. The mean baseline LVOT gradient by Doppler echocardiography was 81±14.8mm of Hg which reduced to 48.5±22.6 (p=0.0004), 49.8±19.3 (p=0.0004), and 42.8±26.1mm of Hg (p=0.05) at 1, 6, and 12 months respectively. Symptoms improved at least by one NYHA class in all but one patient. One patient developed transient pulmonary edema post-RFA. There were no other complications. RFCA of the hypertrophied septum causes sustained reduction in the LVOT gradient and symptomatic improvement among patients with HOCM. Electroanatomical mapping helps to perform the procedure safely. Copyright © 2016 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  4. A Small Molecule Inhibitor of Sarcomere Contractility Acutely Relieves Left Ventricular Outflow Tract Obstruction in Feline Hypertrophic Cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Joshua A Stern

    Full Text Available Hypertrophic cardiomyopathy (HCM is an inherited disease of the heart muscle characterized by otherwise unexplained thickening of the left ventricle. Left ventricular outflow tract (LVOT obstruction is present in approximately two-thirds of patients and substantially increases the risk of disease complications. Invasive treatment with septal myectomy or alcohol septal ablation can improve symptoms and functional status, but currently available drugs for reducing obstruction have pleiotropic effects and variable therapeutic responses. New medical treatments with more targeted pharmacology are needed, but the lack of preclinical animal models for HCM with LVOT obstruction has limited their development. HCM is a common cause of heart failure in cats, and a subset exhibit systolic anterior motion of the mitral valve leading to LVOT obstruction. MYK-461 is a recently-described, mechanistically novel small molecule that acts at the sarcomere to specifically inhibit contractility that has been proposed as a treatment for HCM. Here, we use MYK-461 to test whether direct reduction in contractility is sufficient to relieve LVOT obstruction in feline HCM. We evaluated mixed-breed cats in a research colony derived from a Maine Coon/mixed-breed founder with naturally-occurring HCM. By echocardiography, we identified five cats that developed systolic anterior motion of the mitral valve and LVOT obstruction both at rest and under anesthesia when prov