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Sample records for cardiac troponin mutations

  1. Cardiac troponin T mutations in Chinese patients with hypertrophic cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    吴恒芳; 杨笛; 万文辉; 卞智萍; 徐晋丹; 马文珠; 张寄南

    2004-01-01

    @@ Hypertrophic cardiomyopathy (HCM) is a myocardial disorder characterized by unexplained ventricular hypertrophy and myofibrillar disarray, with a prevalence of about 0.2% in general population. HCM is associated with gene abnormalities. Nearly 200 mutations have been described in ten genes in patients with HCM.1 Cardiac troponin T (cTnT) is an essential component of the troponin complex and plays a central role in the calcium regulation of contractions in cardiac myocytes

  2. Distinct conformational and functional effects of two adjacent pathogenic mutations in cardiac troponin I at the interface with troponin T

    OpenAIRE

    Akhter, Shirin; Jin, J.-P.

    2015-01-01

    The α-helix in troponin I (TnI) at the interface with troponin T (TnT) is a highly conserved structure. A point mutation in this region, A116G, was found in human cardiac TnI in a case of cardiomyopathy. An adjacent dominantly negative mutation found in turkey cardiac TnI (R111C, equivalent to K117C in human and K118C in mouse) decreased diastolic function and blunted beta-adrenergic response in transgenic mice. To investigate the functional importance of the TnI–TnT interface and pathologica...

  3. Distinct conformational and functional effects of two adjacent pathogenic mutations in cardiac troponin I at the interface with troponin T.

    Science.gov (United States)

    Akhter, Shirin; Jin, J-P

    2015-01-01

    The α-helix in troponin I (TnI) at the interface with troponin T (TnT) is a highly conserved structure. A point mutation in this region, A116G, was found in human cardiac TnI in a case of cardiomyopathy. An adjacent dominantly negative mutation found in turkey cardiac TnI (R111C, equivalent to K117C in human and K118C in mouse) decreased diastolic function and blunted beta-adrenergic response in transgenic mice. To investigate the functional importance of the TnI-TnT interface and pathological impact of the cardiac TnI mutations, we engineered K118C and A117G mutations in mouse cardiac TnI for functional studies. Despite their adjacent locations, A117G substitution results in faster mobility of cardiac TnI in SDS-PAGE whereas K118C decreases gel mobility, indicating significant and distinct changes in overall protein conformation. Consistently, monoclonal antibody epitope analysis demonstrated distinct local and remote conformational alterations in the two mutant proteins. Protein binding assays showed that K118C, but not A117G, decreased the relative binding affinity of cardiac TnI for TnT. K118C mutation decreased binding affinity for troponin C in a Ca(2+)-dependent manner, whereas A117G had a similar but less profound effect. Protein kinase A phosphorylation or truncation to remove the cardiac specific N-terminal extension of cardiac TnI resulted in similar conformational changes in the region interfacing with TnT and minimized the functional impacts of the mutations. The data demonstrate potent conformational and functional impacts of the TnT-interfacing helix in TnI and suggest a role of the N-terminal extension of cardiac TnI in modulating TnI-TnT interface functions.

  4. Hypertrophy, fibrosis, and sudden cardiac death in response to pathological stimuli in mice with mutations in cardiac troponin T

    NARCIS (Netherlands)

    Maass, AH; Ikeda, K; Oberdorf-Maass, S; Maier, SKG; Leinwand, LA

    2004-01-01

    Background-Transgenic mouse models expressing a missense mutation (R92Q) or a splice donor site mutation (trunc) in the cardiac troponin T (cTnT) model familial hypertrophic cardiomyopathy (FHC) in humans. Although males from these strains share the unusual property of having significantly smaller v

  5. Cardiac troponins and high-sensitivity cardiac troponin assays.

    Science.gov (United States)

    Conrad, Michael J; Jarolim, Petr

    2014-03-01

    Measurement of circulating cardiac troponins I and T has become integral to the diagnosis of myocardial infarction. This article discusses the structure and function of the troponin complex and the release of cardiac troponin molecules from the injured cardiomyocyte into the circulation. An overview of current cardiac troponin assays and their classification according to sensitivity is presented. The diagnostic criteria, role, and usefulness of cardiac troponin for myocardial infarction are discussed. In addition, several examples are given of the usefulness of high-sensitivity cardiac troponin assays for short-term and long-term prediction of adverse events.

  6. Molecular Modeling of Cardiac Troponin

    Science.gov (United States)

    Manning, Edward P.

    The cardiac thin filament regulates interactions of actin and myosin, the force-generating elements of muscular contraction. Over the past several decades many details have been discovered regarding the structure and function of the cardiac thin filament and its components, including cardiac troponin (cTn). My hypothesis is that signal propagation occurs between distant ends of the cardiac troponin complex through calcium-dependent alterations in the dynamics of cTn and tropomyosin (Tm). I propose a model of the thin filament that encompasses known structures of cTn, Tm and actin to gain insight into cardiac troponin's allosteric regulation of thin filament dynamics. By performing molecular dynamics simulations of cTn in conjunction with overlapping Tm in two conditions, with and without calcium bound to site II of cardiac troponin C (cTnC), I found a combination of calcium-dependent changes in secondary structure and dynamics throughout the cTn-Tm complex. I then applied this model to investigate familial hypertrophic cardiomyopathy (FHC), a disease of the sarcomere that is one of the most commonly occurring genetic causes of heart disease. Approximately 15% of known FHC-related mutations are found in cardiac troponin T (cTnT), most of which are in or flank the alpha-helical N-tail domain TNT1. TNT1 directly interacts with overlapping Tm coiled coils. Using this model I identified effects of TNT1 mutations that propagate to the cTn core where site II of cTnC, the regulatory site of calcium binding in the thin filament, is located. Specifically, I found that mutations in TNT1 alter the flexibility of TNT1 and that the flexibility of TNT1 is inversely proportional to the cooperativity of calcium activation of the thin filament. Further, I identified a pathway of propagation of structural and dynamic changes linking TNT1 to site II of cTnC. Mutation-induced changes at site II cTnC alter calcium coordination which corresponds to biophysical measurements of calcium

  7. The importance of intrinsically disordered segments of cardiac troponin in modulating function by phosphorylation and disease-causing mutations

    Directory of Open Access Journals (Sweden)

    Maria Papadaki

    2016-11-01

    Full Text Available Troponin plays a central role in regulation of muscle contraction. It is the Ca2+ switch of striated muscles including the heart and in the cardiac muscle is physiologically modulated by PKA-dependent phosphorylation at Ser22 and 23. Many cardiomyopathy-related mutations affect Ca2+ regulation and/or disrupt the relationship between Ca2+ binding and phosphorylation. Unlike the mechanism of heart activation, the modulation of Ca2+-sensitivity by phosphorylation of the cardiac specific N-terminal segment of TnI (1-30 is structurally subtle and has proven hard to investigate. The crystal structure of cardiac troponin describes only the relatively stable core of the molecule and the crucial mobile parts of the molecule are missing including TnI C terminal region, TnI (1-30, TnI (134-149 (‘inhibitory’ peptide and the C-terminal 28 amino acids of TnT that are intrinsically disordered.Recent studies over the years have been performed to answer this matter by building structural models of cardiac troponin in phosphorylated and dephosphorylated states based on peptide NMR studies. Now these have been updated by more recent concepts derived from molecular dynamic simulations treating troponin as a dynamic structure. The emerging model confirms the stable core structure of troponin and the mobile structure of the intrinsically disordered segments. We will discuss how we can describe these segments in terms of dynamic transitions between a small number of states with the probability distributions being altered by phosphorylation and by HCM or DCM-related mutations that can explain how Ca2+-sensitivity is modulated by phosphorylation and the effects of mutations.

  8. Structural and Functional Effects of Cardiomyopathy-Causing Mutations in the Troponin T-Binding Region of Cardiac Tropomyosin.

    Science.gov (United States)

    Matyushenko, Alexander M; Shchepkin, Daniil V; Kopylova, Galina V; Popruga, Katerina E; Artemova, Natalya V; Pivovarova, Anastasia V; Bershitsky, Sergey Y; Levitsky, Dmitrii I

    2017-01-10

    Hypertrophic cardiomyopathy (HCM) is a severe heart disease caused by missense mutations in genes encoding sarcomeric proteins of cardiac muscle. Many of these mutations are identified in the gene encoding the cardiac isoform of tropomyosin (Tpm), an α-helical coiled-coil actin-binding protein that plays a key role in Ca(2+)-regulated contraction of cardiac muscle. We employed various methods to characterize structural and functional features of recombinant human Tpm species carrying HCM mutations that lie either within the troponin T-binding region in the C-terminal part of Tpm (E180G, E180V, and L185R) or near this region (I172T). The results of our structural studies show that all these mutations affect, although differently, the thermal stability of the C-terminal part of the Tpm molecule: mutations E180G and I172T destabilize this part of the molecule, whereas mutation E180V strongly stabilizes it. Moreover, various HCM-causing mutations have different and even opposite effects on the stability of the Tpm-actin complexes. Studies of reconstituted thin filaments in the in vitro motility assay have shown that those HCM-associated mutations that lie within the troponin T-binding region of Tpm similarly increase the Ca(2+) sensitivity of the sliding velocity of the filaments and impair their relaxation properties, causing a marked increase in the sliding velocity in the absence of Ca(2+), while mutation I172T decreases the Ca(2+) sensitivity and has no influence on the sliding velocity under relaxing conditions. Finally, our data demonstrate that various HCM mutations can differently affect the structural and functional properties of Tpm and cause HCM by different molecular mechanisms.

  9. Familial hypertrophic cardiomyopathy related cardiac troponin C L29Q mutation alters length-dependent activation and functional effects of phosphomimetic troponin I*.

    Directory of Open Access Journals (Sweden)

    Alison Y Li

    Full Text Available The Ca(2+ binding properties of the FHC-associated cardiac troponin C (cTnC mutation L29Q were examined in isolated cTnC, troponin complexes, reconstituted thin filament preparations, and skinned cardiomyocytes. While higher Ca(2+ binding affinity was apparent for the L29Q mutant in isolated cTnC, this phenomenon was not observed in the cTn complex. At the level of the thin filament in the presence of phosphomimetic TnI, L29Q cTnC further reduced the Ca(2+ affinity by 27% in the steady-state measurement and increased the Ca(2+ dissociation rate by 20% in the kinetic studies. Molecular dynamics simulations suggest that L29Q destabilizes the conformation of cNTnC in the presence of phosphomimetic cTnI and potentially modulates the Ca(2+ sensitivity due to the changes of the opening/closing equilibrium of cNTnC. In the skinned cardiomyocyte preparation, L29Q cTnC increased Ca(2+ sensitivity in a highly sarcomere length (SL-dependent manner. The well-established reduction of Ca(2+ sensitivity by phosphomimetic cTnI was diminished by 68% in the presence of the mutation and it also depressed the SL-dependent increase in myofilament Ca(2+ sensitivity. This might result from its modified interaction with cTnI which altered the feedback effects of cross-bridges on the L29Q cTnC-cTnI-Tm complex. This study demonstrates that the L29Q mutation alters the contractility and the functional effects of the phosphomimetic cTnI in both thin filament and single skinned cardiomyocytes and importantly that this effect is highly sarcomere length dependent.

  10. Inherited cardiomyopathies caused by troponin mutations

    Institute of Scientific and Technical Information of China (English)

    Qun-Wei Lu; Xiao-Yan Wu; Sachio Morimoto

    2013-01-01

    Genetic investigations of cardiomyopathy in the recent two decades have revealed a large number of mutations in the genes encoding sarcomeric proteins as a cause of inherited hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), or restrictive cardiomyopathy (RCM). Most functional analyses of the effects of mutations on cardiac muscle contraction have revealed significant changes in the Ca2+-regulatory mechanism, in which cardiac troponin (cTn) plays important structural and functional roles as a key regulatory protein. Over a hundred mutations have been identified in all three subunits of cTn, i.e., cardiac troponins T, I, and C. Recent studies on cTn mutations have provided plenty of evidence that HCM- and RCM-linked mutations increase cardiac myofilament Ca2+ sensitivity, while DCM-linked mutations decrease it. This review focuses on the functional consequences of mutations found in cTn in terms of cardiac myofilament Ca2+ sensitivity, ATPase activity, force generation, and cardiac troponin I phosphorylation, to understand potential molecular and cellular pathogenic mechanisms of the three types of inherited cardiomyopathy.

  11. Computational Studies of the Effect of the S23D/S24D Troponin I Mutation on Cardiac Troponin Structural Dynamics

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    Cheng, Yuanhua; Lindert, Steffen; Kekenes-Huskey, Peter; Rao, Vijay S.; Solaro, R. John; Rosevear, Paul R.; Amaro, Rommie; McCulloch, Andrew D.; McCammon, J. Andrew; Regnier, Michael

    2014-01-01

    During β-adrenergic stimulation, cardiac troponin I (cTnI) is phosphorylated by protein kinase A (PKA) at sites S23/S24, located at the N-terminus of cTnI. This phosphorylation has been shown to decrease KCa and pCa50, and weaken the cTnC-cTnI (C-I) interaction. We recently reported that phosphorylation results in an increase in the rate of early, slow phase of relaxation (kREL,slow) and a decrease in its duration (tREL,slow), which speeds up the overall relaxation. However, as the N-terminus of cTnI (residues 1–40) has not been resolved in the whole cardiac troponin (cTn) structure, little is known about the molecular-level behavior within the whole cTn complex upon phosphorylation of the S23/S24 residues of cTnI that results in these changes in function. In this study, we built up the cTn complex structure (including residues cTnC 1–161, cTnI 1–172, and cTnT 236–285) with the N-terminus of cTnI. We performed molecular-dynamics (MD) simulations to elucidate the structural basis of PKA phosphorylation-induced changes in cTn structure and Ca2+ binding. We found that introducing two phosphomimic mutations into sites S23/S24 had no significant effect on the coordinating residues of Ca2+ binding site II. However, the overall fluctuation of cTn was increased and the C-I interaction was altered relative to the wild-type model. The most significant changes involved interactions with the N-terminus of cTnI. Interestingly, the phosphomimic mutations led to the formation of intrasubunit interactions between the N-terminus and the inhibitory peptide of cTnI. This may result in altered interactions with cTnC and could explain the increased rate and decreased duration of slow-phase relaxation seen in myofibrils. PMID:25296321

  12. A Green Tea Catechin Normalizes the Enhanced Ca2+ Sensitivity of Myofilaments Regulated by a Hypertrophic Cardiomyopathy Associated Mutation in Human Cardiac Troponin I (K206I)

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    Warren, Chad M.; Karam, Chehade N.; Wolska, Beata M.; Kobayashi, Tomoyoshi; de Tombe, Pieter P.; Arteaga, Grace M.; Bos, J. Martijn; Ackerman, Michael J.; Solaro, R. John

    2015-01-01

    Background Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease characterized by thickening of ventricular walls and decreased left ventricular chamber volume. The majority of HCM-associated mutations are found in genes encoding sarcomere proteins. Herein, we set out to functionally characterize a novel HCM-associated mutation (K206I-TNNI3), and elucidate the mechanism of dysfunction at the level of myofilament proteins. Methods and Results The male index case was diagnosed with HCM after an out-of-hospital cardiac arrest which was followed by comprehensive clinical evaluation, transthoracic echocardiography, and clinical genetic testing. To determine molecular mechanism(s) of the mutant human cardiac troponin I (K206I), we tested the Ca2+ dependence of thin filament-activated myosin-S1-ATPase activity in a reconstituted, regulated, actomyosin system comparing wildtype human troponin complex, 50% mix of K206I/wildtype, or 100% K206I. We also exchanged native troponin detergent extracted fibers with reconstituted troponin containing either wildtype or a 65% mix of K206I/wildtype, and measured force generation. The Ca2+ sensitivity of the myofilaments containing the K206I variant was significantly increased, and when treated with 20 μM EGCG (green tea) was restored back to wildtype levels in ATPase and force measurements. The K206I mutation impairs the ability of the troponin I to inhibit ATPase activity in the absence of Ca-hcTnC (calcium-bound-human cardiac troponin C). The ability of Ca-hcTnC to neutralize the inhibition of K206I was greater than with wildtype TnI. Conclusions Compromised interactions of K206I with actin and hcTnC may lead to impaired relaxation and HCM. PMID:26553696

  13. Cardiac troponins in dogs and cats

    DEFF Research Database (Denmark)

    Langhorn, Rebecca; Willesen, Jakob

    2016-01-01

    Cardiac troponins are sensitive and specific markers of myocardial injury. The troponin concentration can be thought of as a quantitative measure of the degree of injury sustained by the heart, however, it provides no information on the cause of injury or the mechanism of troponin release. Conven...

  14. Cardiac troponin elevations among critically ill patients.

    NARCIS (Netherlands)

    Klein Gunnewiek, J.M.T.; Hoeven, J.G. van der

    2004-01-01

    PURPOSE OF THE REVIEW: Elevated levels of cardiac troponins, indicative of the presence of cardiac injury, have been reported in critically ill patients. In this review, the incidence, significance, and clinical relevance of elevated troponin levels among this group of patients will be discussed. RE

  15. Troponin Ⅰ,cardiac diastolic dysfunction and restrictive cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    Xu-pei HUANG; Jian-feng DU

    2004-01-01

    Cardiomyopathies are diseases of heart muscle that are associated with cardiac dysfunction. Molecular genetic studies performed to date have demonstrated that the damage or mutations in several sarcomeric contractile protein genes are associated with the development of the diseases. In this review, cardiac troponin Ⅰ, one of the sarcomeric thin filament protein, will be discussed regarding its role in cardiac function, its deficiency-related diastolic dysfunction, and the mutation of this protein-mediated restrictive cardiomyopathy.

  16. A Systematic Review of Phenotypic Features Associated With Cardiac Troponin I Mutations in Hereditary Cardiomyopathies

    DEFF Research Database (Denmark)

    Mogensen, Jens; Hey, Thomas; Lambrecht, Sascha

    2015-01-01

    , before genetic testing can be used for individual risk assessment and prediction of prognosis, it is important to investigate if there is a relation between the clinical disease expression (phenotype) of the condition and mutations in specific disease genes (genotype). METHODS: We reviewed the literature...

  17. Characteristics of cardiac troponin measurements.

    Science.gov (United States)

    Christenson, Eric; Christenson, Robert H

    2013-12-01

    Cardiac troponin I (cTnI) and T (cTnT) have displaced myoglobin and creatine kinase-MB as the preferred markers of myocardial injury and have become the cornerstones for diagnosis of myocardial infarction (MI). Current guidelines for MI diagnosis give specific recommendations for cTnI and cTnT assays including instructions to reliably measure values in the range of the 99th percentile of a normal reference cohort with good precision, for example, 10% total coefficient of variation. Unfortunately, the nomenclature system that has evolved for cTnI and cTnT is haphazard and unsystematic. It is key to recognize that not all cTnI and cTnT measurement methods are equivalent; hence, knowledge of local measurements is essential for effective evaluation of patients presenting with suspected non-ST elevation MI. For cTnI, the amino acid sequences frequently targeted for effective measurement include residues 41-49 and 83-93 because these regions of the molecule are stable, helping make the assays reproducible. Use of the recommended cutoff at the 99th percentile of a normal cohort is related to improved patient outcomes. Therefore, use of a troponin assay with good measurement characteristics at the 99th percentile, often referred to as 'sensitive assays', is important for patient outcomes. cTnI and cTnT assays with higher sensitivity are becoming available, and their utilization for measurement in asymptomatic populations may be useful for risk assessment and management in the future. However there is currently no evidence that these high-sensitivity assays confer an advantage in the context of MI diagnosis. Currently cTnI assays are not standardized; thus, there can be a substantial difference in values depending on the assay used. An international effort toward standardization is ongoing, but is not anticipated to be completed and implemented for a few years. Our purpose here is to add insight to important characteristics of troponin measurement techniques and how these

  18. Troponin not just a simple cardiac marker: prognostic significance of cardiac troponin

    Institute of Scientific and Technical Information of China (English)

    Benny Mulyanto Setiadi; LEI Han; CHANG Jing

    2009-01-01

    Objective The object of this study was to review the role of cardiac troponin as a prognostic factor in acute coronary syndrome patients of varying circumstances.Data sources The data used in this review were obtained mainly from the studies of cardiac troponin reported in pubmed from 1981 to 2006.Study selection Relevant articles on studies of cardiac troponin were selected.Results Elevated cardiac troponin in patients with ST elevation and non ST elevation myocardial infarction was associated with adverse outcomes, including a higher incidence of congestive heart failure, shock, and death. Patients with elevated cardiac troponin value seemed to benefit more from invasive strategies including a percutaneous coronary intervention and bypass surgery, but elevated cardiac troponin was also correlated with adverse outcomes, including a higher degree of failure, shock, and mortality in patients undergoing percutaneous coronary intervention; a higher degree of perioperative myocardial infarction, low cardiac output syndrome, cardiopulmonary resuscitation, and new-onset ventricular arrhythmia in patients undergoing bypass surgery were also observed. Elevated troponin after a percutaneous coronary intervention seemed to be associated with short-term adverse outcomes rather than long-term adverse outcomes, unless the elevation of the troponin post percutaneous coronary intervention was quite high (about 5 times above normal). On the contrary, elevated cardiac troponin after bypass surgery was more confusing to analyze since it happened in almost all patients. Furthermore, differences in cutoff values and time measurements in some studies add more confusion; thus, further research is warranted.Conclusions The prognostic value of cardiac troponin is demonstrated in almost all acute coronary syndrome patients. In addition to its high sensitivity and specificity, the prognostic value of cardiac troponin is another reason to make it the "golden cardiac marker' of this time.

  19. Expression and assembly of active human cardiac troponin in Escherichia coli.

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    Lassalle, Michael W

    2013-02-01

    Cardiomyopathy-related mutations in human cardiac troponin subunits, including troponin C (hcTnC), troponin I (hcTnI), and troponin T (hcTnT), are well-documented. Recently, it has been recognised that human cardiac troponin (hcTn) is a sophisticated allosteric system. Therefore, the effect of drugs on this protein complex should be studied with assembled hcTn rather than a short fragment of a subunit or the subunit itself. Here, we describe the expression and assembly of active hcTn in Escherichia coli, a novel method that is rapid and simple, and produces large amounts of functional hcTn.

  20. HCM-Linked Δ 160E Cardiac Troponin T Mutation Causes Unique Progressive Structural and Molecular Ventricular Remodeling in Transgenic Mice

    Science.gov (United States)

    Moore, Rachel K.; Grinspan, Lauren Tal; Jimenez, Jesus; Guinto, Pia J.; Ertz-Berger, Briar; Tardiff, Jil C.

    2013-01-01

    Hypertrophic cardiomyopathy (HCM) is a primary disease of cardiac muscle, and one of the most common causes of sudden cardiac death (SCD) in young people. Many mutations in cardiac troponin T (cTnT) lead to a complex form of HCM with varying degrees of ventricular hypertrophy and ~65% of all cTnT mutations occur within or flanking the elongated N-terminal TNT1 domain. Biophysical studies have predicted that distal TNT1 mutations, including Δ160E, cause disease by a novel, yet unknown mechanism as compared to N-terminal mutations. To begin to address the specific effects of this commonly observed cTnT mutation we generated two independent transgenic mouse lines carrying variant doses of the mutant transgene. Hearts from the 30% and 70% cTnT Δ160E lines demonstrated a highly unique, dose-dependent disruption in cellular and sarcomeric architecture and a highly progressive pattern of ventricular remodeling. While adult ventricular myocytes isolated from Δ160E transgenic mice exhibited dosage-independent mechanical impairments, decreased sarcoplasmic reticulum calcium load and SERCA2a calcium uptake activity, the observed decreases in calcium transients were dosage-dependent. The latter findings were concordant with measures of calcium regulatory proteins abundance and phosphorylation state. Finally, studies of whole heart physiology in the isovolumic mode demonstrated dose-dependent differences in the degree of cardiac dysfuction. We conclude that the observed clinical severity of the cTnT Δ160E mutation is caused by a combination of direct sarcomeric disruption coupled to a profound disregulation of Ca2+ homeostasis at the cellular level that results in a unique and highly progressive pattern of ventricular remodeling. PMID:23434821

  1. Cardiac troponins in dogs and cats

    DEFF Research Database (Denmark)

    Langhorn, Rebecca; Willesen, Jakob

    2016-01-01

    . Conventionally, the cardiac troponins have been used for diagnosis of acute myocardial infarction in humans and have become the gold standard biomarkers for this indication. They have become increasingly recognized as an objective measure of cardiomyocyte status in both cardiac and noncardiac disease, supplying...

  2. [Analysis of cardiac troponin C gene TNNC1 c. G175C mutation in a Chinese pedigree with familial hypertrophic cardiomyopathy and the correlation between genotype and phenotype].

    Science.gov (United States)

    Xing, X B; Liu, F S; Wang, F; Song, L; Zhao, W N; Liu, J; Zhang, K C; Zhu, Y Z; Shang, X F; Li, R; Liang, Y

    2016-12-24

    Objective: To investigate the genotype-phenotype correlation in Chinese familial hypertrophic cardiomyopathy (HCM )focusing on the cardiac troponin C gene TNNC1 c. G175C mutation. Methods: All family members of a Chinese pedigree with hypertrophic cardiomyopathy admitted in Third People's Hospital of Qingdao in February 2005 and 200 healthy volunteers were included in this study. The coding exons of 30 hypertrophic cardiomyopathy associated genes were identified by whole exons amplification and high-throughput sequencing in the proband, and the identified mutation were further detected through bi-directional Sanger sequencing in all family members and 200 healthy volunteers. Pedigree analysis included clinical manifestation, physical examination, ECG and echocardiogram. Results: A missense mutation c. G175C was identified in the TNNC1 gene in 2 family members, which resulted in a glutamic acid (E) to glutamine (Q) exchange at amino acid residue 59. A mutation c. A1319G was identified in the MYLK2 gene in 1 family member, which resulted in a lysine (K) to arginine (R) exchange at amino acid residue 440. These mutations were absent in 200 healthy controls. The proband carried the two kinds of mutations and expressed various clinical manifestations of heart failure and had history of ventricular tachycardia, paraxial atrial fibrillation, pacemaker implantation, electrocardiogram showed right bundle branch block and echocardiography examination evidenced thickened interventricular septum (23.3 mm) and apex and reduced wall motion of these segments. The daughter of the proband carried the TNNC1 c. G175C mutation and was also diagnosed with asymptomatic HCM by echocardiography with thickened interventricular septum (19 mm) and apex (15 mm). Conclusion: The novel missense mutation of TNNC1 c. G175C might be the disease-causing gene mutation in this Chinese pedigree with familiar HCM.

  3. Cardiomyopathy-related mutation (A30V) in mouse cardiac troponin T divergently alters the magnitude of stretch activation in α- and β-myosin heavy chain fibers.

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    Mickelson, Alexis V; Gollapudi, Sampath K; Chandra, Murali

    2017-01-01

    The present study investigated the functional consequences of the human hypertrophic cardiomyopathy (HCM) mutation A28V in cardiac troponin T (TnT). The A28V mutation is located within the NH2 terminus of TnT, a region known to be important for full activation of cardiac thin filaments. The functional consequences of the A28V mutation in TnT remain unknown. Given how α- and β-myosin heavy chain (MHC) isoforms differently alter the functional effect of the NH2 terminus of TnT, we hypothesized that the A28V-induced effects would be differently modulated by α- and β-MHC isoforms. Recombinant wild-type mouse TnT (TnTWT) and the mouse equivalent of the human A28V mutation (TnTA30V) were reconstituted into detergent-skinned cardiac muscle fibers extracted from normal (α-MHC) and transgenic (β-MHC) mice. Dynamic and steady-state contractile parameters were measured in reconstituted muscle fibers. Step-like length perturbation experiments demonstrated that TnTA30V decreased the magnitude of the muscle length-mediated recruitment of new force-bearing cross bridges (ER) by 30% in α-MHC fibers. In sharp contrast, TnTA30V increased ER by 55% in β-MHC fibers. Inferences drawn from other dynamic contractile parameters suggest that directional changes in ER in TnTA30V + α-MHC and TnTA30V + β-MHC fibers result from a divergent impact on cross bridge-regulatory unit (troponin-tropomyosin complex) cooperativity. TnTA30V-mediated effects on Ca(2+)-activated maximal tension and instantaneous muscle fiber stiffness (ED) were also divergently affected by α- and β-MHC. Our study demonstrates that TnTA30V + α-MHC and TnTA30V + β-MHC fibers show contrasting contractile phenotypes; however, only the observations from β-MHC fibers are consistent with the clinical data for A28V in humans.

  4. Troponin.

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    Ottinger, Daniele; Nash, Patricia

    2013-01-01

    Troponin T and I can be found within the myocardial filaments. Measuring these cardiac troponin levels in full-term newborns and premature infants has not become a common practice in the neonatal intensive care unit and newborn nurseries. Research studies are discovering that an elevation in troponin T and I levels can be directly correlated with the severity of the infant's illness, and it can be potentially prognostic of morbidity. This literature analysis discusses what can be considered normal cardiac troponin levels along with what elevated levels are and possible conditions associated with those elevations.

  5. Dilated cardiomyopathy mutation (R134W in mouse cardiac troponin T induces greater contractile deficits against α-myosin heavy chain than against β-myosin heavy chain

    Directory of Open Access Journals (Sweden)

    Sampath K Gollapudi

    2016-10-01

    Full Text Available Many studies have demonstrated that depressed myofilament Ca2+ sensitivity is common to dilated cardiomyopathy (DCM in humans. However, it remains unclear whether a single determinant — such as myofilament Ca2+ sensitivity — is sufficient to characterize all cases of DCM because the severity of disease varies widely with a given mutation. Because dynamic features dominate in the heart muscle, alterations in dynamic contractile parameters may offer better insight on the molecular mechanisms that underlie disparate effects of DCM mutations on cardiac phenotypes. Dynamic features are dominated by myofilament cooperativity that stem from different sources. One such source is the strong tropomyosin binding region in troponin T (TnT, which is known to modulate crossbridge (XB recruitment dynamics in a myosin heavy chain (MHC-dependent manner. Therefore, we hypothesized that the effects of DCM-linked mutations in TnT on contractile dynamics would be differently modulated by α- and β-MHC. After reconstitution with the mouse TnT equivalent (TnTR134W of the human DCM mutation (R131W, we measured dynamic contractile parameters in detergent-skinned cardiac muscle fiber bundles from normal (α-MHC and transgenic mice (β-MHC. TnTR134W significantly attenuated the rate constants of tension redevelopment, XB recruitment dynamics, XB distortion dynamics, and the magnitude of length-mediated XB recruitment only in α-MHC fiber bundles. TnTR134W decreased myofilament Ca2+ sensitivity to a greater extent in α-MHC (0.14 pCa units than in β-MHC fiber bundles (0.08 pCa units. Thus, our data demonstrate that TnTR134W induces a more severe DCM-like contractile phenotype against α-MHC than against β-MHC background.

  6. Knock-in Mice Harboring a Ca2+ Desensitizing Mutation in Cardiac Troponin C Develop Early Onset Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Bradley K McConnell

    2015-08-01

    Full Text Available The physiological consequences of aberrant Ca2+ binding and exchange with cardiac myofilaments are not clearly understood. In order to examine the effect of decreasing Ca2+ sensitivity of cTnC on cardiac function, we generated knock-in mice carrying a D73N mutation (not known to be associated with heart disease in human patients in cTnC. The D73N mutation was engineered into the regulatory N-domain of cTnC in order to reduce Ca2+ sensitivity of reconstituted thin filaments by increasing the rate of Ca2+ dissociation. In addition, the D73N mutation drastically blunted the extent of Ca2+ desensitization of reconstituted thin filaments induced by cTnI pseudo-phosphorylation. Compared to wild-type mice, heterozygous knock-in mice carrying the D73N mutation exhibited a substantially decreased Ca2+ sensitivity of force development in skinned ventricular trabeculae. Kaplan-Meier survival analysis revealed that median survival time for knock-in mice was twelve weeks. Echocardiographic analysis revealed that knock-in mice exhibited increased left ventricular dimensions with thinner walls. Echocardiographic analysis also revealed that measures of systolic function, such as ejection fraction and fractional shortening, were dramatically reduced in knock-in mice. In addition, knock-in mice displayed electrophysiological abnormalities, namely prolonged QRS and QT intervals. Furthermore, ventricular myocytes isolated from knock-in mice did not respond to β-adrenergic stimulation. Thus, knock-in mice developed pathological features similar to those observed in human patients with dilated cardiomyopathy (DCM. In conclusion, our results suggest that decreasing Ca2+ sensitivity of the regulatory N-domain of cTnC is sufficient to trigger the development of DCM.

  7. Structure and function of cardiac troponin C (TNNC1): Implications for heart failure, cardiomyopathies, and troponin modulating drugs.

    Science.gov (United States)

    Li, Monica X; Hwang, Peter M

    2015-10-25

    In striated muscle, the protein troponin complex turns contraction on and off in a calcium-dependent manner. The calcium-sensing component of the complex is troponin C, which is expressed from the TNNC1 gene in both cardiac muscle and slow-twitch skeletal muscle (identical transcript in both tissues) and the TNNC2 gene in fast-twitch skeletal muscle. Cardiac troponin C (cTnC) is made up of two globular EF-hand domains connected by a flexible linker. The structural C-domain (cCTnC) contains two high affinity calcium-binding sites that are always occupied by Ca(2+) or Mg(2+) under physiologic conditions, stabilizing an open conformation that remains anchored to the rest of the troponin complex. In contrast, the regulatory N-domain (cNTnC) contains a single low affinity site that is largely unoccupied at resting calcium concentrations. During muscle activation, calcium binding to cNTnC favors an open conformation that binds to the switch region of troponin I, removing adjacent inhibitory regions of troponin I from actin and allowing muscle contraction to proceed. Regulation of the calcium binding affinity of cNTnC is physiologically important, because it directly impacts the calcium sensitivity of muscle contraction. Calcium sensitivity can be modified by drugs that stabilize the open form of cNTnC, post-translational modifications like phosphorylation of troponin I, or downstream thin filament protein interactions that impact the availability of the troponin I switch region. Recently, mutations in cTnC have been associated with hypertrophic or dilated cardiomyopathy. A detailed understanding of how calcium sensitivity is regulated through the troponin complex is necessary for explaining how mutations perturb its function to promote cardiomyopathy and how post-translational modifications in the thin filament affect heart function and heart failure. Troponin modulating drugs are being developed for the treatment of cardiomyopathies and heart failure.

  8. Cardiac troponin assays in the management of heart failure.

    Science.gov (United States)

    Torre, Matthew; Jarolim, Petr

    2015-02-20

    Cardiac troponins I and T are established biomarkers of cardiac injury. Testing for either of these two cardiac troponins has long been an essential component of the diagnosis of acute myocardial infarction. In addition, cardiac troponin concentrations after acute myocardial infarction predict future adverse events including development of ischemic heart failure and chronic elevations of cardiac troponin correlate with heart failure severity. These predictions and correlations are particularly obvious when cardiac troponin concentrations are measured using the new high sensitivity cardiac troponin assays. Thus, a growing body of literature suggests that cardiac troponin testing may have important clinical implications for heart failure patients with reduced or preserved ejection fraction. In this review, we explore the prognostic utility of measuring cardiac troponin concentrations in patients with acute or chronic heart failure and in populations at risk of developing heart failure and the relationship between cardiac troponin levels and disease severity. We also summarize the ongoing debates and research on whether serial monitoring of cardiac troponin levels may become a useful tool for guiding therapeutic interventions in patients with heart failure.

  9. Molecular basis of calcium-sensitizing and desensitizing mutations of the human cardiac troponin C regulatory domain: a multi-scale simulation study.

    Directory of Open Access Journals (Sweden)

    Peter Michael Kekenes-Huskey

    Full Text Available Troponin C (TnC is implicated in the initiation of myocyte contraction via binding of cytosolic Ca²⁺ and subsequent recognition of the Troponin I switch peptide. Mutations of the cardiac TnC N-terminal regulatory domain have been shown to alter both calcium binding and myofilament force generation. We have performed molecular dynamics simulations of engineered TnC variants that increase or decrease Ca²⁺ sensitivity, in order to understand the structural basis of their impact on TnC function. We will use the distinction for mutants that are associated with increased Ca²⁺ affinity and for those mutants with reduced affinity. Our studies demonstrate that for GOF mutants V44Q and L48Q, the structure of the physiologically-active site II Ca²⁺ binding site in the Ca²⁺-free (apo state closely resembled the Ca²⁺-bound (holo state. In contrast, site II is very labile for LOF mutants E40A and V79Q in the apo form and bears little resemblance with the holo conformation. We hypothesize that these phenomena contribute to the increased association rate, k(on, for the GOF mutants relative to LOF. Furthermore, we observe significant positive and negative positional correlations between helices in the GOF holo mutants that are not found in the LOF mutants. We anticipate these correlations may contribute either directly to Ca²⁺ affinity or indirectly through TnI association. Our observations based on the structure and dynamics of mutant TnC provide rationale for binding trends observed in GOF and LOF mutants and will guide the development of inotropic drugs that target TnC.

  10. High-sensitive cardiac troponin T

    Institute of Scientific and Technical Information of China (English)

    Ru-Yi Xu; Xiao-Fa Zhu; Ye Yang; Ping Ye

    2013-01-01

    Cardiac troponin is the preferred biomarker for the diagnosis of acute myocardial infarction (AMI). The recent development of a high-sensitive cardiac troponin T (hs-cTnT) assay permits detection of very low levels of cTnT. Using the hs-cTnT assay improves the overall diagnostic accuracy in patients with suspected AMI, while a negative result also has a high negative predictive value. The gain in sensitivity may be particularly important in patients with a short duration from symptom onset to admission. Measurement of cardiac troponin T with the hs-cTnT assay may provide strong prognostic information in patients with acute coronary syndromes, stable coronary artery disease, heart failure and even in the general population; however, increased sensitivity comes at a cost of decreased specificity. Serial testing, as well as clinical context and co-existing diseases, are likely to become increasingly important for the interpretation of hs-cTnT assay results.

  11. The R21C Mutation in Cardiac Troponin I Imposes Differences in Contractile Force Generation between the Left and Right Ventricles of Knock-In Mice

    Directory of Open Access Journals (Sweden)

    Jingsheng Liang

    2015-01-01

    Full Text Available We investigated the effect of the hypertrophic cardiomyopathy-linked R21C (arginine to cysteine mutation in human cardiac troponin I (cTnI on the contractile properties and myofilament protein phosphorylation in papillary muscle preparations from left (LV and right (RV ventricles of homozygous R21C+/+ knock-in mice. The maximal steady-state force was significantly reduced in skinned papillary muscle strips from the LV compared to RV, with the latter displaying the level of force observed in LV or RV from wild-type (WT mice. There were no differences in the Ca2+ sensitivity between the RV and LV of R21C+/+ mice; however, the Ca2+ sensitivity of force was higher in RV-R21C+/+ compared with RV-WT and lower in LV- R21C+/+ compared with LV-WT. We also observed partial loss of Ca2+ regulation at low [Ca2+]. In addition, R21C+/+-KI hearts showed no Ser23/24-cTnI phosphorylation compared to LV or RV of WT mice. However, phosphorylation of the myosin regulatory light chain (RLC was significantly higher in the RV versus LV of R21C+/+ mice and versus LV and RV of WT mice. The difference in RLC phosphorylation between the ventricles of R21C+/+ mice likely contributes to observed differences in contractile force and the lower tension monitored in the LV of HCM mice.

  12. An in silico analysis of troponin I mutations in hypertrophic cardiomyopathy of Indian origin.

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    Gayatri Ramachandran

    Full Text Available Hypertrophic Cardiomyopathy (HCM is an autosomal dominant disorder of the myocardium which is hypertrophied resulting in arrhythmias and heart failure leading to sudden cardiac death (SCD. Several sarcomeric proteins and modifier genes have been implicated in this disease. Troponin I, being a part of the Troponin complex (troponin I, troponin C, troponin T, is an important gene for sarcomeric function. Four mutations (1 novel were identified in Indian HCM cases, namely, Pro82Ser, Arg98Gln, Arg141Gln and Arg162Gln in Troponin I protein, which are in functionally significant domains. In order to analyse the effect of the mutations on protein stability and protein-protein interactions within the Troponin complex, an in silico study was carried out. The freely available X-ray crystal structure (PDB ID: 1JIE was used as the template to model the protein followed by loop generation and development of troponin complex for both the troponin I wild type and four mutants (NCBI ID: PRJNA194382. The structural study was carried out to determine the effect of mutation on the structural stability and protein-protein interactions between three subunits in the complex. These mutations, especially the arginine to glutamine substitutions were found to result in local perturbations within the troponin complex by creating/removing inter/intra molecular hydrogen bonds with troponin T and troponin C. This has led to a decrease in the protein stability and loss of important interactions between the three subunits. It could have a significant impact on the disease progression when coupled with allelic heterogeneity which was observed in the cases carrying these mutations. However, this can be further confirmed by functional studies on protein levels in the identified cases.

  13. Predictors of cardiac troponin release after a marathon.

    NARCIS (Netherlands)

    Eijsvogels, T.M.H.; Hoogerwerf, M.D.; Maessen, M.F.; Seeger, J.P.; George, K.P.; Hopman, M.T.E.; Thijssen, D.H.J.

    2015-01-01

    OBJECTIVES: Exercise leads to an increase in cardiac troponin I in healthy, asymptomatic athletes after a marathon. Previous studies revealed single factors to relate to post-race cardiac troponin I levels. Integrating these factors into our study, we aimed to identify independent predictors for the

  14. Disease causing mutations of troponin alter regulated actin state distributions.

    Science.gov (United States)

    Chalovich, Joseph M

    2012-12-01

    Striated muscle contraction is regulated primarily through the action of tropomyosin and troponin that are bound to actin. Activation requires Ca(2+) binding to troponin and/or binding of high affinity myosin complexes to actin. Mutations within components of the regulatory complex may lead to familial cardiomyopathies and myopathies. In several cases examined, either physiological or pathological changes in troponin alter the distribution among states of actin-tropomyosin-troponin that differ in their abilities to stimulate myosin ATPase activity. These observations open possibilities for managing disorders of the troponin complex. Furthermore, analyses of mutant forms of troponin give insights into the regulation of striated muscle contraction.

  15. Cardiac troponin: an emerging cardiac biomarker in animal health

    Directory of Open Access Journals (Sweden)

    Vishal V. Undhad

    Full Text Available Analysis of cardiac troponin I (cTn I and T (cTnT are considered the “gold standard” for the non-invasive diagnosis of myocardial injury in human and animals. It has replaced traditionally used cardiac biomarkers such as myoglobin, lactate dehydrogenase (LDH, creatine kinase (CK and CK-MB due to its high sensitivity and specificity for the detection of myocardial injury. Cardiac troponins are proteins that control the calcium-mediated interaction between actin and myosin, allowing contraction at the sarcomere level. Concentration of the cTn can be correlated microscopic lesion and loss of immunolabeling in myocardium damage. Troponin concentration remains elevated in blood for 1-2wks so that wide window is available for diagnosis of myocardial damage. The cTn test has >95% specificity and sensitivity and test is less time consuming (10 to 15 minutes and less costly (INR 200 to INR 500. [Vet. World 2012; 5(8.000: 508-511

  16. Drug-Induced Rhabdomyolysis with Elevated Cardiac Troponin T

    DEFF Research Database (Denmark)

    Egholm, Gro; Pareek, Manan

    2015-01-01

    The essential role of cardiac troponin in the diagnosis of acute myocardial infarction has led to the development of high-sensitivity assays, which are able to detect very small amounts of myocardial necrosis. The high-sensitivity cardiac troponin T assay, however, is not entirely specific...... for myocardial injury. This case report describes a 48-year-old woman, who, two years after cardiac transplantation, presented with rhabdomyolysis. During the course of the disease, her troponin T level was elevated on repeated occasions, but other definitive evidence of myocardial injury was not found...

  17. Recurrent and founder mutations in the Netherlands : mutation p.K217del in troponin T2, causing dilated cardiomyopathy

    NARCIS (Netherlands)

    Otten, E.; Deprez, R. H. Lekanne Dit; Weiss, M. M.; van Slegtenhorst, M.; Joosten, M.; van der Smagt, J. J.; Kerstjens-Frederikse, W. S.; Roofthooft, M. T. R.; Balk, A. H. M. M.; van den Berg, M. P.; van Tintelen, J. P.; Ruiter, J.S.; de Jonge, N.

    2010-01-01

    Background. About 30% of dilated cardiomyopathy (DCM) cases are familial. Mutations are mostly found in the genes encoding lanain A/C, beta-myosin heavy chain and the sarcomeric protein cardiac troponin-T (TNNT2). Mutations in TNNT2 are reported in approximately 3% of DCM patients. The overall pheno

  18. Mutations in troponin T associated with Hypertrophic Cardiomyopathy increase Ca(2+)-sensitivity and suppress the modulation of Ca(2+)-sensitivity by troponin I phosphorylation.

    Science.gov (United States)

    Messer, Andrew E; Bayliss, Christopher R; El-Mezgueldi, Mohammed; Redwood, Charles S; Ward, Douglas G; Leung, Man-Ching; Papadaki, Maria; Dos Remedios, Cristobal; Marston, Steven B

    2016-07-01

    We investigated the effect of 7 Hypertrophic Cardiomyopathy (HCM)-causing mutations in troponin T (TnT) on troponin function in thin filaments reconstituted with actin and human cardiac tropomyosin. We used the quantitative in vitro motility assay to study Ca(2+)-regulation of unloaded movement and its modulation by troponin I phosphorylation. Troponin from a patient with the K280N TnT mutation showed no difference in Ca(2+)-sensitivity when compared with donor heart troponin and the Ca(2+)-sensitivity was also independent of the troponin I phosphorylation level (uncoupled). The recombinant K280N TnT mutation increased Ca(2+)-sensitivity 1.7-fold and was also uncoupled. The R92Q TnT mutation in troponin from transgenic mouse increased Ca(2+)-sensitivity and was also completely uncoupled. Five TnT mutations (Δ14, Δ28 + 7, ΔE160, S179F and K273E) studied in recombinant troponin increased Ca(2+)-sensitivity and were all fully uncoupled. Thus, for HCM-causing mutations in TnT, Ca(2+)-sensitisation together with uncoupling in vitro is the usual response and both factors may contribute to the HCM phenotype. We also found that Epigallocatechin-3-gallate (EGCG) can restore coupling to all uncoupled HCM-causing TnT mutations. In fact the combination of Ca(2+)-desensitisation and re-coupling due to EGCG completely reverses both the abnormalities found in troponin with a TnT HCM mutation suggesting it may have therapeutic potential.

  19. Effect of prolonged walking on cardiac troponin levels.

    NARCIS (Netherlands)

    Eijsvogels, T.M.H.; George, K.; Shave, R.; Gaze, D.; Levine, B.D.; Hopman, M.T.E.; Thijssen, D.H.J.

    2010-01-01

    Increased cardiac troponin I (cTnI), a marker for cardiac damage, has been reported after strenuous exercise in young subjects. However, little is known about changes in cTnI after moderate-intensity exercise in a heterogenous population or which factors may contribute to this change in cTnI levels.

  20. Distance measurements in cardiac troponin C.

    Science.gov (United States)

    Wang, C L; Leavis, P C

    1990-01-01

    Intramolecular distance measurements were made in cardiac troponin C (cTnC) by fluorescence energy transfer using Eu3+ or Tb3+ as energy donors and Nd3+ or an organic chromophore as acceptors. The laser-induced luminescence of bound Eu3+ is quenched in Eu1Nd1cTnC with a lifetime of 0.328 ms, compared with 0.43 ms for Eu2cTnC. The enhanced decay corresponds to an energy transfer efficiency of 0.25, or a distance of 1.1 nm between the two high affinity sites. We have also labeled cTnC with 4-dimethylaminophenylazophenyl-4'-maleimide (DAB-Mal) at the two cysteine residues (Cys-35 and Cys-84). Energy transfer measurements were carried out between Tb3+ bound to the high affinity sites and the labels attached to the domain containing the low affinity site. Upon uv irradiation at pH 6.7, Tb1cTnCDAB emits tyrosine-sensitized Tb3+ luminescence that decays bioexponentially with lifetimes of 1.29 and 0.76 ms. The shorter lifetime is ascribed to energy transfer from Tb3+ to the DAB labels, yielding an average distance of 3.4 nm between the donor and the acceptors. At pH 5.0, however, the luminescence decays exclusively with a single lifetime of 1.31 ms, suggesting that under these conditions all Tb3+ ions are more than 5.2 nm away from the label. Thus cTnC, like skeletal TnC, undergoes a pH-dependent conformational transition which converts an elongated structure at lower pH's to a rather compact conformation in a more physiological medium.

  1. Cardiac troponin I levels in canine pyometra

    Directory of Open Access Journals (Sweden)

    Hagman Ragnvi

    2007-02-01

    Full Text Available Abstract Background Myocardial injury may contribute to unexpected deaths due to pyometra. To detect myocardial damage, measurement of cardiac troponin I (cTnI is currently the most sensitive and specific method. The aims of the present study were to evaluate presence of myocardial damage in canine pyometra by analysis of cTnI, to explore whether myocardial injury was associated with systemic inflammatory response syndrome (SIRS and to evaluate whether other clinical or laboratory parameters were associated with cTnI increase. Methods Preoperative plasma levels of cTnI were investigated in 58 female dogs with pyometra and 9 controls. The value of physical examination findings, haematological, serum biochemical and pro-inflammatory (CRP and TNF-α parameters as possible predictors of increased cTnI levels was also evaluated. Results Seven dogs with pyometra (12% and one control dog (11% had increased levels of cTnI. In the pyometra group, the levels ranged between 0.3–0.9 μg l-1 and in the control dog the level was 0.3 μg l-1. The cTnI levels did not differ significantly between the two groups. No cardiac abnormalities were evident on preoperative physical examinations. Four of the pyometra patients died within two weeks of surgery, of which two were examined post mortem. In one of these cases (later diagnosed with myocarditis and disseminated bacterial infection the cTnI levels increased from 0.9 μg l-1 preoperatively to 180 μg l-1 the following day when also heart arrhythmia was also detected. The other patient had cTnI levels of 0.7 μg l-1 with no detectable heart pathology post mortem. CTnI increase was not associated with presence of SIRS. There was a trend for the association of cTnI increase with increased mortality. No preoperative physical examination findings and few but unspecific laboratory parameters were associated with increased cTnI levels. Conclusion Increased cTnI levels were observed in 12% of the dogs with pyometra. The

  2. Cardiac troponin I levels in canine pyometra.

    Science.gov (United States)

    Hagman, Ragnvi; Lagerstedt, Anne-Sofie; Fransson, Boel A; Bergström, Annika; Häggström, Jens

    2007-02-28

    Myocardial injury may contribute to unexpected deaths due to pyometra. To detect myocardial damage, measurement of cardiac troponin I (cTnI) is currently the most sensitive and specific method. The aims of the present study were to evaluate presence of myocardial damage in canine pyometra by analysis of cTnI, to explore whether myocardial injury was associated with systemic inflammatory response syndrome (SIRS) and to evaluate whether other clinical or laboratory parameters were associated with cTnI increase. Preoperative plasma levels of cTnI were investigated in 58 female dogs with pyometra and 9 controls. The value of physical examination findings, haematological, serum biochemical and pro-inflammatory (CRP and TNF-alpha) parameters as possible predictors of increased cTnI levels was also evaluated. Seven dogs with pyometra (12%) and one control dog (11%) had increased levels of cTnI. In the pyometra group, the levels ranged between 0.3-0.9 microg l-1 and in the control dog the level was 0.3 microg l-1. The cTnI levels did not differ significantly between the two groups. No cardiac abnormalities were evident on preoperative physical examinations. Four of the pyometra patients died within two weeks of surgery, of which two were examined post mortem. In one of these cases (later diagnosed with myocarditis and disseminated bacterial infection) the cTnI levels increased from 0.9 microg l-1 preoperatively to 180 microg l-1 the following day when also heart arrhythmia was also detected. The other patient had cTnI levels of 0.7 microg l-1 with no detectable heart pathology post mortem. CTnI increase was not associated with presence of SIRS. There was a trend for the association of cTnI increase with increased mortality. No preoperative physical examination findings and few but unspecific laboratory parameters were associated with increased cTnI levels. Increased cTnI levels were observed in 12% of the dogs with pyometra. The proportions of dogs with cTnI increase did

  3. Cardiac troponin I levels in canine pyometra

    Science.gov (United States)

    Hagman, Ragnvi; Lagerstedt, Anne-Sofie; Fransson, Boel A; Bergström, Annika; Häggström, Jens

    2007-01-01

    Background Myocardial injury may contribute to unexpected deaths due to pyometra. To detect myocardial damage, measurement of cardiac troponin I (cTnI) is currently the most sensitive and specific method. The aims of the present study were to evaluate presence of myocardial damage in canine pyometra by analysis of cTnI, to explore whether myocardial injury was associated with systemic inflammatory response syndrome (SIRS) and to evaluate whether other clinical or laboratory parameters were associated with cTnI increase. Methods Preoperative plasma levels of cTnI were investigated in 58 female dogs with pyometra and 9 controls. The value of physical examination findings, haematological, serum biochemical and pro-inflammatory (CRP and TNF-α) parameters as possible predictors of increased cTnI levels was also evaluated. Results Seven dogs with pyometra (12%) and one control dog (11%) had increased levels of cTnI. In the pyometra group, the levels ranged between 0.3–0.9 μg l-1 and in the control dog the level was 0.3 μg l-1. The cTnI levels did not differ significantly between the two groups. No cardiac abnormalities were evident on preoperative physical examinations. Four of the pyometra patients died within two weeks of surgery, of which two were examined post mortem. In one of these cases (later diagnosed with myocarditis and disseminated bacterial infection) the cTnI levels increased from 0.9 μg l-1 preoperatively to 180 μg l-1 the following day when also heart arrhythmia was also detected. The other patient had cTnI levels of 0.7 μg l-1 with no detectable heart pathology post mortem. CTnI increase was not associated with presence of SIRS. There was a trend for the association of cTnI increase with increased mortality. No preoperative physical examination findings and few but unspecific laboratory parameters were associated with increased cTnI levels. Conclusion Increased cTnI levels were observed in 12% of the dogs with pyometra. The proportions of dogs

  4. Dephosphorylation specificities of protein phosphatase for cardiac troponin I, troponin T, and sites within troponin T

    Directory of Open Access Journals (Sweden)

    2006-03-01

    Full Text Available Protein dephosphorylation by protein phosphatase 1 (PP1, acting in concert with protein kinase C (PKC and protein kinase A (PKA, is a pivotal regulatory mechanism of protein phosphorylation. Isolated rat cardiac myofibrils phosphorylated by PKC/PKA and dephosphorylated by PP1 were used in determining dephosphorylation specificities, Ca2+-stimulated Mg2+ATPase activities, and Ca2+ sensitivities. In reconstituted troponin (Tn complex, PP1 displayed distinct substrate specificity in dephosphorylation of TnT preferentially to TnI, in vitro. In situ phosphorylation of cardiomyocytes with calyculin A, a protein phosphatase inhibitor, resulted in an increase in the phosphorylation stiochiometry of TnT (0.3 to 0.5 (67%, TnI (2.6 to 3.6 (38%, and MLC2 (0.4 to 1.7 (325%. These results further confirmed that though MLC2 is the preferred target substrate for protein phosphatase in the thick filament, the Tn complex (TnI and TnT from thin filament and C-protein in the thick filament are also protein phosphatase substrates. Our in vitro dephosphorylation experiments revealed that while PP1 differentially dephosphorylated within TnT at multiple sites, TnI was uniformly dephosphorylated. Phosphopeptide maps from the in vitro experiments show that TnT phosphopeptides at spots 4A and 4B are much more resistant to PP1 dephosphorylation than other TnT phosphopeptides. Mg2+ATPase assays of myofibrils phosphorylated by PKC/PKA and dephosphorylated by PP1 delineated that while PKC and PKA phosphorylation decreased the Ca2+-stimulated Mg2+ATPase activities, dephosphorylation antagonistically restored it. PKC and PKA phosphorylation decreased Ca2+ sensitivity to 3.6 µM and 5.0 µM respectively. However, dephosphorylation restored the Mg2+ATPase activity of PKC (99% and PKA (95%, along with the Ca2+ sensitivities (3.3 µM and 3.0 µM, respectively.

  5. Cardiac Troponin I, Creatine Phosphokinase and Myoglobine Levels in Preeclampsia

    Directory of Open Access Journals (Sweden)

    Ahmet Kale

    2005-01-01

    Full Text Available To evaluate minor myocardial injury in preeclamptic pregnancies by serum markers of cardiac troponin-I, creatine phosphokinase and myoglobine. Group I consisted of 45 preeclamptic pregnancies, Group 2 consisted of uncomplicated pregnancies. The groups were compared for maternal age, parity, mean troponin–I, creatine phosphokinase and myoglobine values. Student-t test were used in statistical analyses. Significance was accepted as p<0.05. Cardiac troponin-I levels were statistically significantly higher in preeclamptic pregnancies (0,97 ± 0,11ng/ml than control groups (0,12 ± 0.09 ng/ml (p<0.001. No statistically significant difference was found with mean levels of creatine phosphokinase and myoglobin levels between two groups. Higher values of troponin-I’in preeclamptic patients is thought to be a result of myocardial injury and associated with pregnancy-induced hypertension.

  6. Effects of calcium binding and the hypertrophic cardiomyopathy A8V mutation on the dynamic equilibrium between closed and open conformations of the regulatory N-domain of isolated cardiac troponin C.

    Science.gov (United States)

    Cordina, Nicole M; Liew, Chu K; Gell, David A; Fajer, Piotr G; Mackay, Joel P; Brown, Louise J

    2013-03-19

    Troponin C (TnC) is the calcium-binding subunit of the troponin complex responsible for initiating striated muscle contraction in response to calcium influx. In the skeletal TnC isoform, calcium binding induces a structural change in the regulatory N-domain of TnC that involves a transition from a closed to open structural state and accompanying exposure of a large hydrophobic patch for troponin I (TnI) to subsequently bind. However, little is understood about how calcium primes the N-domain of the cardiac isoform (cTnC) for interaction with the TnI subunit as the open conformation of the regulatory domain of cTnC has been observed only in the presence of bound TnI. Here we use paramagnetic relaxation enhancement (PRE) to characterize the closed to open transition of isolated cTnC in solution, a process that cannot be observed by traditional nuclear magnetic resonance methods. Our PRE data from four spin-labeled monocysteine constructs of isolated cTnC reveal that calcium binding triggers movement of the N-domain helices toward an open state. Fitting of the PRE data to a closed to open transition model reveals the presence of a small population of cTnC molecules in the absence of calcium that possess an open conformation, the level of which increases substantially upon Ca(2+) binding. These data support a model in which calcium binding creates a dynamic equilibrium between the closed and open structural states to prime cTnC for interaction with its target peptide. We also used PRE data to assess the structural effects of a familial hypertrophic cardiomyopathy point mutation located within the N-domain of cTnC (A8V). The PRE data show that the Ca(2+) switch mechanism is perturbed by the A8V mutation, resulting in a more open N-domain conformation in both the apo and holo states.

  7. Cardiac troponins in the elderly: interpretation of elevated levels

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Elderly patients with myocardial infarction commonly present with symptoms other than chest pain. The clinician evaluation of the elderly may rely on laboratory methods more so than in younger patients. Fortunately, advances in laboratory science have brought newer biomarkers of cardiac injury to the clinical arena including cardiac troponins I and T(cTnI,cTnT). These regulatory components of the contractile apparatus are sensitive indicators of myocardial injury. Their central role in the current definition of acute myocardial infarction highlights their utility in the diagnosis of acute myocardial ischemic syndromes. The troponins are also released in some clinical situations where thrombotic complications of coronary artery disease and resultant acute myocardial infarction have not occurred. Examples of these conditions include conditions like myocarditis, pulmonary embolism, sepsis, and acute stroke. Elevated troponins in these conditions are thought to emanate from injured myocardial cells and in most circumstances have been associated with adverse outcomes. Interpretation of elevated troponin in the elderly requires consideration of other possible conditions.

  8. Troponin test

    Science.gov (United States)

    TroponinI; TnI; TroponinT; TnT; Cardiac-specific troponin I; Cardiac-specific troponin T; cTnl; cTnT ... your heart not getting enough blood flow.) The troponin test may also be done to help detect ...

  9. Evaluation of a high-sensitivity assay for measurement of canine and feline serum cardiac troponin I

    DEFF Research Database (Denmark)

    Langhorn, Rebecca; Willesen, Jakob; Tarnow, Inge;

    2013-01-01

    Cardiac troponins are established as the gold standard biomarkers for acute cardiac injury. As even small elevations of cardiac troponins have prognostic relevance in people, it is important to investigate the performance of sensitive assays for use in veterinary medicine....

  10. Molecular and Functional Characterization of Novel Hypertrophic Cardiomyopathy Susceptibility Mutations in TNNC1- Encoded Troponin C

    Science.gov (United States)

    Landstrom, Andrew P.; Parvatiyar, Michelle S.; Pinto, Jose R.; Marquardt, Michelle L.; Bos, J. Martijn; Tester, David J.; Ommen, Steve R.; Potter, James D.; Ackerman, Michael J.

    2008-01-01

    Hypertrophic Cardiomyopathy (HCM) is a common primary cardiac disorder defined by a hypertrophied left ventricle, is one of the main causes of sudden death in young athletes and has been associated with mutations in most sarcomeric proteins (tropomyosin, Troponin T and I, and actin, etc.). Many of these mutations appear to affect the functional properties of cardiac troponin C (cTnC), i.e., by increasing the Ca2+-sensitivity of contraction, a hallmark of HCM, and surprisingly, prior to this report, cTnC had not been classified as a HCM susceptibility gene. In this study, we show that mutations occurring in the human cTnC (HcTnC) gene (TNNC1) have the same prevalence (~0.4%) as well established HCM-susceptibility genes that encode other sarcomeric proteins. Comprehensive open reading frame/splice site mutation analysis of TNNC1 performed on 1025 unrelated HCM patients over the last 10 years revealed novel missense mutations in TNNC1: A8V, C84Y, E134D, and D145E. Functional studies with these recombinant HcTnC HCM mutations showed increased Ca2+ sensitivity of force development (A8V, C84Y and D145E) and force recovery (A8V and D145E). These results are consistent with the HCM functional phenotypes seen with other sarcomeric HCM mutations (E134D showed no changes in these parameters). This is the largest cohort analysis of TNNC1 in HCM that details the discovery of at least three novel HCM-associated mutations and more strongly links TNNC1 to HCM along with functional evidence that supports a central role for its involvement in the disease. These types of studies may help to further define TNNC1 as an HCM-susceptibility gene that has already been established for the other members of the Troponin complex. PMID:18572189

  11. Application of Cardiac Troponin in Cardiovascular Diseases Other Than Acute Coronary Syndrome.

    Science.gov (United States)

    Eggers, Kai M; Lindahl, Bertil

    2017-01-01

    Increased cardiac troponin concentrations in acute coronary syndrome (ACS) identify patients with ongoing cardiomyocyte necrosis who are at increased risk. However, with the use of more precise assays, cardiac troponin increases are commonly noted in other cardiovascular conditions as well. This has generated interest in the use of cardiac troponin for prognostic assessment and clinical management of these patients. In this review, we have summarized the data from studies investigating the implications of cardiac troponin concentrations in various acute and chronic conditions beyond ACS, i.e., heart failure, myocarditis, Takotsubo cardiomyopathy, aortic dissection, supraventricular arrhythmias, valve disease, pulmonary arterial hypertension, stroke, and in the perioperative setting. Cardiac troponin concentrations are often detectable and frankly increased in non-ACS conditions, in particular when measured with high-sensitivity (hs) assays. With the exception of myocarditis and Takotsubo cardiomyopathy, cardiac troponin concentrations carry strong prognostic information, mainly with respect to mortality, or incipient and/or worsening heart failure. Studies investigating the prognostic benefit associated with cardiac troponin-guided treatments however, are almost lacking and the potential role of cardiac troponin in the management of non-ACS conditions is not defined. Increased cardiac troponin indicates increased risk for adverse outcome in patients with various cardiovascular conditions beyond ACS. Routine measurement of cardiac troponin concentrations can however, not be generally recommended unless there is a suspicion of ACS. Nonetheless, any finding of an increased cardiac troponin concentration in a patient without ACS should at least prompt the search for possible underlying conditions and these should be managed meticulously according to current guidelines to improve outcome. © 2016 American Association for Clinical Chemistry.

  12. The effect of exercise training on the course of cardiac troponin T and I levels: three independent training studies

    NARCIS (Netherlands)

    Linden, van der N.; Klinkenberg, L.J.J.; Leenders, M.; Tieland, C.A.B.; Verdijk, L.; Groot, de C.P.G.M.; Loon, van L.J.C.

    2015-01-01

    With the introduction of high-sensitive assays, cardiac troponins became potential biomarkers for risk stratification and prognostic medicine. Observational studies have reported an inverse association between physical activity and basal cardiac troponin levels. However, causality has never been dem

  13. High-sensitivity Cardiac Troponin Elevation after Electroconvulsive Therapy: A Prospective, Observational Cohort Study.

    Science.gov (United States)

    Duma, Andreas; Pal, Swatilika; Johnston, Joshua; Helwani, Mohammad A; Bhat, Adithya; Gill, Bali; Rosenkvist, Jessica; Cartmill, Christopher; Brown, Frank; Miller, J Philip; Scott, Mitchell G; Sanchez-Conde, Francisco; Jarvis, Michael; Farber, Nuri B; Zorumski, Charles F; Conway, Charles; Nagele, Peter

    2017-04-01

    While electroconvulsive therapy is widely regarded as a lifesaving and safe procedure, evidence regarding its effects on myocardial cell injury is sparse. The objective of this investigation was to determine the incidence and magnitude of new cardiac troponin elevation after electroconvulsive therapy using a novel high-sensitivity cardiac troponin I assay. This was a prospective cohort study in adult patients undergoing electroconvulsive therapy in a single academic center (up to three electroconvulsive therapy treatments per patient). The primary outcome was new high-sensitivity cardiac troponin I elevation after electroconvulsive therapy, defined as an increase of high-sensitivity cardiac troponin I greater than 100% after electroconvulsive therapy compared to baseline with at least one value above the limit of quantification (10 ng/l). Twelve-lead electrocardiogram and high-sensitivity cardiac troponin I values were obtained before and 15 to 30 min after electroconvulsive therapy; in a subset of patients, an additional 2-h high-sensitivity cardiac troponin I value was obtained. The final study population was 100 patients and a total of 245 electroconvulsive therapy treatment sessions. Eight patients (8 of 100; 8%) experienced new high-sensitivity cardiac troponin I elevation after electroconvulsive therapy with a cumulative incidence of 3.7% (9 of 245 treatments; one patient had two high-sensitivity cardiac troponin I elevations), two of whom had a non-ST-elevation myocardial infarction (incidence 2 of 245; 0.8%). Median high-sensitivity cardiac troponin I concentrations did not increase significantly after electroconvulsive therapy. Tachycardia and/or elevated systolic blood pressure developed after approximately two thirds of electroconvulsive therapy treatments. Electroconvulsive therapy appears safe from a cardiac standpoint in a large majority of patients. A small subset of patients with preexisting cardiovascular risk factors, however, may develop new

  14. Analytical and assay issues for use of cardiac troponin testing for risk stratification in primary care.

    Science.gov (United States)

    Wu, Alan H B; Christenson, Robert H

    2013-08-01

    Cardiac troponin is the standard marker for diagnosis of acute myocardial infarction and risk stratification of patients who present to an emergency department with signs and symptoms of acute cardiac ischemia. Over the past few years, the analytical sensitivity of assays for cardiac troponin has improved significantly to the point where a detectable amount of troponin can be measured in essentially all healthy subjects. Recent studies have shown that use of a highly sensitive troponin assays may provide value to traditional markers of primary disease risk for patients, i.e., for those who have no history of heart disease. There are barriers to the adoption of cardiac troponin for screening high risk cohorts such as the elderly, diabetics and perhaps even the asymptomatic population. Strategies used for the assignment of cutoff concentrations in acute care, i.e., the 99 th percentile, may not be appropriate for primary care as changes over baseline levels may provide more accurate information of risk than cross-sectional results. A review of biological variation has shown that cardiac troponin as a biomarker has low index of individuality, indicating that reference values are of little utility. Whether or not cardiac troponin can be released in reversible injury is a debate that could have significance for detecting minor myocardial injury. A major hurdle for use of troponin in primary care is the lack of assay standardization and nomenclature for the different generations of troponin assays. Standardization requires knowledge of what is released after cardiac injury and what the various cardiac troponin assays are measuring. Currently it is not clear if the cardiac troponin release after ischemic injury is identical to that in circulation of healthy individuals. This may affect the design of future assays and standardization approaches. There is potential that a marker of myocardial injury such as troponin can add to the value of existing indicators and biomarkers

  15. Molecular and immunohistochemical analyses of cardiac troponin T during cardiac development in the Mexican axolotl, Ambystoma mexicanum.

    Science.gov (United States)

    Zhang, C; Pietras, K M; Sferrazza, G F; Jia, P; Athauda, G; Rueda-de-Leon, E; Rveda-de-Leon, E; Maier, J A; Dube, D K; Lemanski, S L; Lemanski, L F

    2007-01-01

    The Mexican axolotl, Ambystoma mexicanum, is an excellent animal model for studying heart development because it carries a naturally occurring recessive genetic mutation, designated gene c, for cardiac nonfunction. The double recessive mutants (c/c) fail to form organized myofibrils in the cardiac myoblasts resulting in hearts that fail to beat. Tropomyosin expression patterns have been studied in detail and show dramatically decreased expression in the hearts of homozygous mutant embryos. Because of the direct interaction between tropomyosin and troponin T (TnT), and the crucial functions of TnT in the regulation of striated muscle contraction, we have expanded our studies on this animal model to characterize the expression of the TnT gene in cardiac muscle throughout normal axolotl development as well as in mutant axolotls. In addition, we have succeeded in cloning the full-length cardiac troponin T (cTnT) cDNA from axolotl hearts. Confocal microscopy has shown a substantial, but reduced, expression of TnT protein in the mutant hearts when compared to normal during embryonic development.

  16. Dilated Cardiomyopathy Mutation (R134W) in Mouse Cardiac Troponin T Induces Greater Contractile Deficits against α-Myosin Heavy Chain than against β-Myosin Heavy Chain

    OpenAIRE

    Gollapudi, Sampath K.; Murali Chandra

    2016-01-01

    Many studies have demonstrated that depressed myofilament Ca2+ sensitivity is common to dilated cardiomyopathy (DCM) in humans. However, it remains unclear whether a single determinant — such as myofilament Ca2+ sensitivity — is sufficient to characterize all cases of DCM because the severity of disease varies widely with a given mutation. Because dynamic features dominate in the heart muscle, alterations in dynamic contractile parameters may offer better insight on the molecular mechanisms...

  17. Serum cardiac troponin T after repeated endurance exercise events.

    Science.gov (United States)

    Bonetti, A; Tirelli, F; Albertini, R; Monica, C; Monica, M; Tredici, G

    1996-05-01

    Recently Dr. Rowe made a hypothesis according to which small areas of myocardial necrosis can be caused by microvascular spasm, related to high catecholamine concentrations and other mechanisms, following extraordinary unremitting endurance exercises or due to the cumulative effect of several endurance events. It was this last suggestion which prompted us to investigate 25 top cyclists, taking part in the 77th Giro d'Italia. Blood samples were obtained the day before the start of the competition and once a week thereafter until the end. We measured myoglobin, lactic dehydrogenase, total creatine kinase, creatine kinase isoenzyme MB and serum cardiac troponin T (Tn-T), a highly sensitive and specific method for the detection of myocardial injury. While at measuring time points which followed we found a significant increase in the serum indicators of muscle damage, compared with their values at the beginning of the race, creatine kinase isoenzyme MB did not rise significantly and cardiac Tn-T was found in the serum of only 5 athletes, repeatedly in some cases, but always below the cut off values considered as indicating myocardial ischemia. On the basis of the behaviour of creatine kinase isoenzyme MB and, above all, of cardiac Tn-T, we can conclude that heavy endurance exercises, repeated daily for 22 days, as was the case in our study, do not seem able to produce, in top athletes, permanent heart damage by means of acute myocardial injury.

  18. Kinetics of Highly Sensitive Troponin T after Cardiac Surgery

    Directory of Open Access Journals (Sweden)

    Amr S. Omar

    2015-01-01

    Full Text Available Perioperative myocardial infarction (PMI confers a considerable risk in cardiac surgery settings; finding the ideal biomarker seems to be an ideal goal. Our aim was to assess the diagnostic accuracy of highly sensitive troponin T (hsTnT in cardiac surgery settings and to define a diagnostic level for PMI diagnosis. This was a single-center prospective observational study analyzing data from all patients who underwent cardiac surgeries. The primary outcome was the diagnosis of PMI through a specific level. The secondary outcome measures were the lengths of mechanical ventilation (LOV, stay in the intensive care unit (LOSICU, and hospitalization. Based on the third universal definition of PMI, patients were divided into two groups: no PMI (Group I and PMI (Group II. Data from 413 patients were analyzed. Nine patients fulfilled the diagnostic criteria of PMI, while 41 patients were identified with a 5-fold increase in their CK-MB (≥120 U/L. Using ROC analysis, a hsTnT level of 3,466 ng/L or above showed 90% sensitivity and 90% specificity for the diagnosis of PMI. Secondary outcome measures in patients with PMI were significantly prolonged. In conclusion, the hsTnT levels detected here paralleled those of CK-MB and a cut-off level of 3466 ng/L could be diagnostic of PMI.

  19. High-sensitive cardiac troponin T measurements in prediction of non-cardiac complications after major abdominal surgery

    NARCIS (Netherlands)

    Noordzij, P. G.; van Geffen, O.; Dijkstra, I. M.; Boerma, D.; Meinders, A. J.; Rettig, T. C D; Eefting, F. D.; van Loon, D.; van de Garde, E. M W; van Dongen, E. P A

    2015-01-01

    BACKGROUND: Postoperative non-cardiac complication rates are as high as 11-28% after high-risk abdominal procedures. Emerging evidence indicates that postoperative cardiac troponin T elevations are associated with adverse outcome in non-cardiac surgery. The aim of this study was to determine the rel

  20. High-sensitive cardiac troponin T measurements in prediction of non-cardiac complications after major abdominal surgery.

    Science.gov (United States)

    Noordzij, P G; van Geffen, O; Dijkstra, I M; Boerma, D; Meinders, A J; Rettig, T C D; Eefting, F D; van Loon, D; van de Garde, E M W; van Dongen, E P A

    2015-06-01

    Postoperative non-cardiac complication rates are as high as 11-28% after high-risk abdominal procedures. Emerging evidence indicates that postoperative cardiac troponin T elevations are associated with adverse outcome in non-cardiac surgery. The aim of this study was to determine the relationship between postoperative high-sensitive cardiac troponin T elevations and non-cardiac complications in patients after major abdominal surgery. This prospective observational single-centre cohort study included patients at risk for coronary artery disease undergoing elective major abdominal surgery. Cardiac troponin was measured before surgery and at day 1, 3, and 7. Multivariable logistic regression analysis was performed to examine the adjusted association for different cut-off concentrations of postoperative myocardial injury and non-cardiac outcome. In 203 patients, 690 high-sensitive cardiac troponin T measurements were performed. Fifty-three patients (26%) had a non-cardiac complication within 30 days after surgery. Hospital mortality was 4% (8/203). An increase in cardiac troponin T concentration ≥100% compared with baseline was a superior independent predictor of non-cardiac postoperative clinical complications (adjusted odds ratio 4.3, 95% confidence interval 1.8-10.1, Pcardiac troponin T increase ≥100% is a strong predictor of non-cardiac 30 day complications, increased hospital stay and hospital mortality in patients undergoing major abdominal surgery. NCT02150486. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Serum cardiac troponin T in unstable angina pectoris patients.

    Science.gov (United States)

    Leowattana, W; Mahanonda, N; Bhuripanyo, K; Pokum, S; Kiartivich, S

    2000-11-01

    Cardiac troponin T (cTnT) is a regulatory contractile protein not normally found in blood. Its detection in the circulation has been shown to be a sensitive and specific marker for myocardial cell damage. In this study, we used a second-generation enzyme immunoassay for cTnT to determine whether its presence in the serum of patients with unstable angina was a prognostic indicator. Thirty patients with unstable angina pectoris (UAP) and 30 patients with Q-wave acute myocardial infarction (AMI) were screened for serum CK-MB activity and cTnT at 6, 12, 24 and 48 hours after the onset of chest pain, All of the mean concentrations of CK-MB activity determined in UAP patients were less than the upper limit of normal (25 U/L). Meanwhile, the mean concentration of cTnT at 6, 12, 24 and 48 hours after onset of chest pain were higher than the cutoff values (0.1 microg/L), We found that one third of UAP patients had serum cTnT at the time of admission more than 0.1 microg/L and that these groups of patients were associated with a high risk for cardiac events. Our results suggested that patients with elevated serum cTnT could be considered as high-risk patients for developing myocardial infarction, Patients with normal cTnT levels and a low or intermediate clinical risk could be stabilized and further stratified noninvasively.

  2. The clinical utility of lipid profile and positive troponin in predicting future cardiac events

    Directory of Open Access Journals (Sweden)

    Arun Kumar

    2012-02-01

    Full Text Available Objective: To study the usefulness of traditional lipid profile levels in screening subjects who had developed chest pain due to cardiac event as indicated by a positive troponin I (TnI test. Methods: In this retrospective study data of the 740 patients presented to the emergency department with symptoms of cardiac ischemia that underwent both troponin and lipid profiles tests were compared with the lipid profiles of 411 normal healthy subjects (controls. The troponin was detected qualitatively when a specimen contains TnI above the 99th percentile (TnI >0.5 ng/ mL. The total cholesterol (TC, high density lipoproteins (HDL, very low density lipoproteins (VLDL, and triacyl glycerol (TG levels were also analyzed and low density lipoprotein level (LDL was calculated using Friedewald ’s formula. Results: Patients with chest pain and positive troponin test (with confirmed cardiac event were found to have significantly elevated levels of TC, TG, LDL and significantly reduced HDL levels when compared to the patients who experienced only chest pain (negative troponin and healthy controls. Conclusions: Traditional lipid profile levels still can be used in screening populations to identify the subjects with high risk of developing cardiac event which is identified by highly sensitive and specific positive troponin test.

  3. Improved troponin T ELISA specific for cardiac troponin T isoform: assay development and analytical and clinical validation.

    Science.gov (United States)

    Müller-Bardorff, M; Hallermayer, K; Schröder, A; Ebert, C; Borgya, A; Gerhardt, W; Remppis, A; Zehelein, J; Katus, H A

    1997-03-01

    The first generation of troponin T ELISA (TnT 1) can yield false-positive results in patients with severe skeletal muscle injury. Therefore, a cardiac-specific second-generation troponin T ELISA (TnT 2) was developed, in which the cross-reactive antibody 1B10 has been replaced by a high-affinity cardiac-specific antibody M11.7. No cross-reactivity of TnT 2 was observed with purified skeletal muscle troponin T (1000 micrograms/L) or in test samples from 43 marathon runners and 24 patients with rhabdomyolysis and highly increased creatine kinase. TnT 2 was increased > 0.2 microgram/L in 5 of 40 patients with renal failure and in 4 of 20 muscular dystrophy patients. The detection limit is 0.012 microgram/L. Day-to-day imprecision (CV) within the range 0.19-14.89 micrograms/L was error of estimate (Sey) of 1.18, 0.01 micrograms/L, and 0.81 microgram/L, respectively.

  4. Cardiac troponin I (CTnI level among children with epileptic seizures

    Directory of Open Access Journals (Sweden)

    Ahmed Anwer Attia Khattab

    2014-09-01

    Conclusion: Cardiac troponin I is a perfect tool for early detection of cases with myocardial dysfunction in epileptic patients – cardiac troponin I is significantly increased in children with epilepsy especially the complicated epilepsy. Cardiac injury in epileptic children is more common in patients with early onset epilepsy, positive prenatal problem, idiopathic epilepsy, abnormal imaging and EEG – elevated TnI levels may be of value in assessing the severity and eventual outcome and mortality risk of the disease in children with epilepsy.

  5. Molecular dynamics simulations of the cardiac troponin complex performed with FRET distances as restraints.

    Directory of Open Access Journals (Sweden)

    Jayant James Jayasundar

    Full Text Available Cardiac troponin (cTn is the Ca(2+-sensitive molecular switch that controls cardiac muscle activation and relaxation. However, the molecular detail of the switching mechanism and how the Ca(2+ signal received at cardiac troponin C (cTnC is communicated to cardiac troponin I (cTnI are still elusive. To unravel the structural details of troponin switching, we performed ensemble Förster resonance energy transfer (FRET measurements and molecular dynamic (MD simulations of the cardiac troponin core domain complex. The distance distributions of forty five inter-residue pairs were obtained under Ca(2+-free and saturating Ca(2+ conditions from time-resolved FRET measurements. These distances were incorporated as restraints during the MD simulations of the cardiac troponin core domain. Compared to the Ca(2+-saturated structure, the absence of regulatory Ca(2+ perturbed the cTnC N-domain hydrophobic pocket which assumed a closed conformation. This event partially unfolded the cTnI regulatory region/switch. The absence of Ca(2+, induced flexibility to the D/E linker and the cTnI inhibitory region, and rotated the cTnC N-domain with respect to rest of the troponin core domain. In the presence of saturating Ca(2+ the above said phenomenon were absent. We postulate that the secondary structure perturbations experienced by the cTnI regulatory region held within the cTnC N-domain hydrophobic pocket, coupled with the rotation of the cTnC N-domain would control the cTnI mobile domain interaction with actin. Concomitantly the rotation of the cTnC N-domain and perturbation of the D/E linker rigidity would control the cTnI inhibitory region interaction with actin to effect muscle relaxation.

  6. Serum cardiac troponin I in acute stroke is related to serum cortisol and TNF-alpha

    DEFF Research Database (Denmark)

    Christensen, Hanne Krarup; Johannesen, Helle Hjorth; Christensen, Anders Fogh

    2004-01-01

    Serum cardiac troponin I (cTnI) is a specific marker of myocardial injury related to in-patient fatality and cardiac injury in acute stroke. We investigated whether cTnI in acute stroke is related to serum cortisol, acute inflammatory response, and insular damage. We also investigated whether c...

  7. Gene Regulation, Alternative Splicing, and Posttranslational Modification of Troponin Subunits in Cardiac Development and Adaptation: A Focused Review

    Directory of Open Access Journals (Sweden)

    Juan-Juan eSheng

    2014-04-01

    Full Text Available Troponin plays a central role in regulating the contraction and relaxation of vertebrate striated muscles. This review focuses on the isoform gene regulation, alternative RNA splicing, and posttranslational modifications of troponin subunits in cardiac development and adaptation. Transcriptional and posttranscriptional regulations such as phosphorylation and proteolysis modifications, and structure-function relationships of troponin subunit proteins are summarized. The physiological and pathophysiological significances are discussed for impacts on cardiac muscle contractility, heart function, and adaptations in health and diseases.

  8. Gene regulation, alternative splicing, and posttranslational modification of troponin subunits in cardiac development and adaptation: a focused review.

    Science.gov (United States)

    Sheng, Juan-Juan; Jin, Jian-Ping

    2014-01-01

    Troponin plays a central role in regulating the contraction and relaxation of vertebrate striated muscles. This review focuses on the isoform gene regulation, alternative RNA splicing, and posttranslational modifications of troponin subunits in cardiac development and adaptation. Transcriptional and posttranscriptional regulations such as phosphorylation and proteolysis modifications, and structure-function relationships of troponin subunit proteins are summarized. The physiological and pathophysiological significances are discussed for impacts on cardiac muscle contractility, heart function, and adaptations in health and diseases.

  9. Serial measurements of high-sensitivity cardiac troponin T after exercise stress test in stable coronary artery disease

    DEFF Research Database (Denmark)

    Axelsson, Anna; Ruwald, Martin Huth; Dalsgaard, Morten;

    2013-01-01

    The aim was to assess serial measurements of high-sensitivity cardiac troponin T (hs-cTNT) post-exercise in patients with stable coronary artery disease (CAD).......The aim was to assess serial measurements of high-sensitivity cardiac troponin T (hs-cTNT) post-exercise in patients with stable coronary artery disease (CAD)....

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

    Directory of Open Access Journals (Sweden)

    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

  11. Clinical and Prognostic Profiles of Cardiomyopathies Caused by Mutations in the Troponin T Gene.

    Science.gov (United States)

    Ripoll-Vera, Tomás; Gámez, José María; Govea, Nancy; Gómez, Yolanda; Núñez, Juana; Socías, Lorenzo; Escandell, Ángela; Rosell, Jorge

    2016-02-01

    Mutations in the troponin T gene (TTNT2) have been associated in small studies with the development of hypertrophic cardiomyopathy characterized by a high risk of sudden death and mild hypertrophy. We describe the clinical course of patients carrying mutations in this gene. We analyzed the clinical characteristics and prognosis of patients with mutations in the TNNT2 gene who were seen in an inherited cardiac disease unit. Of 180 families with genetically studied cardiomyopathies, 21 families (11.7%) were identified as having mutations in TNNT2: 10 families had Arg92Gln, 5 had Arg286His, 3 had Arg278Cys, 1 had Arg92Trp, 1 had Arg94His, and 1 had Ile221Thr. Thirty-three additional genetic carriers were identified through family assessment. The study included 54 genetic carriers: 56% were male, and the mean average age was 41 ± 17 years. There were 33 cases of hypertrophic cardiomyopathy, 9 of dilated cardiomyopathy, and 1 of noncompaction cardiomyopathy, and maximal myocardial thickness was 18.5 ± 6mm. Ventricular dysfunction was present in 30% of individuals and a history of sudden death in 62%. During follow-up, 4 patients died and 14 (33%) received a defibrillator (8 probands, 6 relatives). Mean survival was 54 years. Carriers of Arg92Gln had early disease development, high penetrance, a high risk of sudden death, a high rate of defibrillator implantation, and a high frequency of mixed phenotype. Mutations in the TNNT2 gene were more common in this series than in previous studies. The clinical and prognostic profiles depended on the mutation present. Carriers of the Arg92Gln mutation developed hypertrophic or dilated cardiomyopathy and had a significantly worse prognosis than those with other mutations in TNNT2 or other sarcomeric genes. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  12. Elevation of Cardiac Troponin I in Diagnosis and Progress of Viral Myocarditis

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To investigate whether measurement of serum cardiac troponin I (cTnI) could aid in the diagnosis and the evaluation of progress of viral myocarditis(VMC). Methods The cTnI of serum samples from 282 patients with clinical diagnosis of VMC were determined with ELISA using 2B1.9 and 2F6.6 monoclonal antibodies. The effect of the serum from 25 patients who had sustained high level of cTnI on the capacity and affinity of cardiac muscarinic receptor was evaluated with[3H-QNB] and frozen sliced human cardium. EVs RNA , mutation of mitochondrium DNA(mtDNA) in lymphocyte and cardiac biopsy specimen were assayed by the method of PCR. CVB IgM and neutralizing antibody titer were measured in part of patients. Results The level of serum cTnI in 157 of 282 patients was higher than the upper normal limit (>7.1 μg/L), the positive rate being 55.7%. The rate of cTnI level returning to the normal range was 52.3% and 90.8%, in 3 months and 6 months respectively. The serum from the patients with sustained cTnI elevation inhibited the capacity and affinity of human cardiac M receptor, which resulted in downregulation and desensitization of the receptor; these reactions were similar to those of the serum from patient with dilated cardiomyopathy(DCM). The mutation frequency of mtDNA in lymphocyte and cardiac biopsy specimen in VMC cases were 15.8 and 2.5 times higher than that in normal subjects. The duration of CVB IgM present in serum was much longer and the rates of symptom improvement and arrhythmia disappearance were significantly lower in the patients with higher serum cTnI than in those with normal level cTnI. Conclusion Elevation of serum cTnI seemed to be a good marker for the presence of myocardial injury in VMC patients. Sustained high level of serum cTnI in VMC patients might suggest the development of autoimmune antibodies, cardiac receptor injury and the higher frequency of mtDNA mutation that possibly contributed to DCM process.

  13. Cardiac troponin testing in idiopathic inflammatory myopathies and systemic sclerosis-spectrum disorders: biomarkers to distinguish between primary cardiac involvement and low-grade skeletal muscle disease activity.

    Science.gov (United States)

    Hughes, Michael; Lilleker, James B; Herrick, Ariane L; Chinoy, Hector

    2015-05-01

    Primary cardiac involvement, an under-recognised manifestation of the idiopathic inflammatory myopathies (IIM) and systemic sclerosis (SSc)-spectrum disorders, is associated with significant mortality. Within these two conditions, traditional skeletal muscle enzyme testing may not effectively distinguish between skeletal and cardiac muscle involvement, especially in patients with subclinical cardiac disease. Accurate biomarkers are thus required to screen for cardiac disease, to better inform both therapeutic decision-making and treatment response. The widespread uptake of cardiac troponin testing has revolutionised the management of acute coronary syndromes. While cardiac troponin I (cTnI) appears specific to the myocardium, cardiac troponin T (cTnT) is also expressed by skeletal muscle, including regenerating skeletal muscle tissue. There is increasing interest about the role of cardiac troponins as a putative biomarker of primary cardiac involvement in IIM and SSc-spectrum disorders. Herewith we discuss subclinical cardiac disease in IIM and SSc-spectrum disorders, the respective roles of cTnI and cTnT testing, and the re-expression of cTnT within regenerating skeletal muscle tissue. There remains wide variation in access to cardiac troponin testing nationally and internationally. We propose two pragmatic clinical pathways using cardiac troponins, preferably measuring concomitant cTnT followed by confirmatory (cardiac) cTnI to screen patients for subclinical cardiac disease and/or low-grade skeletal muscle disease activity, and also an agenda for future research.

  14. Cardiac troponins I and T: molecular markers for early diagnosis, prognosis, and accurate triaging of patients with acute myocardial infarction.

    Science.gov (United States)

    Tiwari, Ram P; Jain, Anubhav; Khan, Zakir; Kohli, Veena; Bharmal, R N; Kartikeyan, S; Bisen, Prakash S

    2012-12-01

    Acute myocardial infarction (AMI) is the leading cause of death worldwide, with early diagnosis still being difficult. Promising new cardiac biomarkers such as troponins and creatine kinase (CK) isoforms are being studied and integrated into clinical practice for early diagnosis of AMI. The cardiac-specific troponins I and T (cTnI and cTnT) have good sensitivity and specificity as indicators of myocardial necrosis and are superior to CK and its MB isoenzyme (CK-MB) in this regard. Besides being potential biologic markers, cardiac troponins also provide significant prognostic information. The introduction of novel high-sensitivity troponin assays has enabled more sensitive and timely diagnosis or exclusion of acute coronary syndromes. This review summarizes the available information on the potential of troponins and other cardiac markers in early diagnosis and prognosis of AMI, and provides perspectives on future diagnostic approaches to AMI.

  15. Discordance with 3 Cardiac Troponin I and T Assays: Implications for the 99th Percentile Cutoff.

    Science.gov (United States)

    Ungerer, Jacobus Petrus Johannes; Tate, Jillian Russyll; Pretorius, Carel Jacobus

    2016-08-01

    We compared the 99th percentile reference intervals with 3 modern cardiac troponin assays in a single cohort and tested the hypothesis that the same individuals will be identified as above the cutoff and that differences will be explained by analytical imprecision. Blood was collected from 2005 apparently healthy blood donors. Cardiac troponin was measured with Abbott Architect STAT high sensitive troponin I, Beckman Coulter Access AccuTnI+3, and Roche Elecsys troponin T highly sensitive assays. The 99th percentile cutoff limits were as follows: Abbott cardiac troponin I (cTnI) 28.9 ng/L; Beckman Coulter cTnI 31.3 ng/L; and Roche cardiac troponin T (cTnT) 15.9 ng/L. Correlation among the assays was poor: Abbott cTnI vs Beckman Coulter cTnI, R(2) = 0.18; Abbott cTnI vs Roche cTnT, R(2) = 0.04; and Beckman Coulter cTnI vs Roche cTnT R(2) = 0.01. Of the results above the cutoff 50% to 70% were unique to individual assays, with only 4 out of 20 individuals above the cutoff for all 3 assays. The observed differences among assays were larger than predicted from analytical imprecision. The 99th percentile cutoff values were in agreement with those reported elsewhere. The poor correlation and concordance amongst the assays were notable. The differences found could not be explained by analytical imprecision and indicate the presence of inaccuracy (bias) that is unique to sample and assay combinations. Based on these findings we recommend less emphasis on the cutoff value and greater emphasis on δ values in the diagnosis of myocardial infarction. © 2016 American Association for Clinical Chemistry.

  16. Decision limits and the reporting of cardiac troponin: Meeting the needs of both the cardiologist and the ED physician.

    Science.gov (United States)

    Hickman, Peter E; Lindahl, Bertil; Cullen, Louise; Koerbin, Gus; Tate, Jill; Potter, Julia M

    2015-02-01

    Cardiac troponin is the preferred biomarker for defining the acute coronary syndrome and acute myocardial infarction. Currently, the only decision limit formally endorsed with regard to the cardiac troponins is the 99th percentile. This is a "rule-in" criterion, intended to ensure that only persons with the acute coronary syndrome are reviewed. The 99th percentile is an arbitrary cut point and there are many problems associated with its application, including defining a truly healthy population, the difficulty of standardisation of cardiac troponin assays, especially but not only cardiac troponin I, and the effects of age and sex on this parameter. The Emergency Department (ED) screens many more persons for possible acute coronary syndromes than actually have the condition and their needs are best met by a "rule-out" test that enables them to clear their busy departments of the many persons who do not actually have the condition. The needs of the ED are not optimally met using the 99th percentile. The index of individuality for the cardiac troponins is small and significant changes consistent with an acute coronary syndrome can occur without the 99th percentile being exceeded. It appears that the ED may be better served by use of delta troponin changes rather than the 99th percentile, but there are problems with this approach, particularly in persons who present late when troponin release has plateaued. In addition, there are many non-acute coronary syndrome causes for cardiac troponin release. The needs of the cardiologist and the ED physician are so different that it may be inappropriate for both groups to use the same diagnostic criteria for cardiac troponin, and it is of great importance that cardiac troponin measurement be used as only one part of the assessment of the person presenting with possible acute coronary syndrome.

  17. Impact of statin use on exercise-induced cardiac troponin elevations.

    NARCIS (Netherlands)

    Eijsvogels, T.M.H.; Januzzi, J.L., Jr.; Taylor, B.A.; Isaacs, S.K.; D'Hemecourt, P.; Zaleski, A.; Dyer, S.; Troyanos, C.; Weiner, R.B.; Thompson, P.D.; Baggish, A.L.

    2014-01-01

    Marathon running commonly causes a transient elevation of creatine kinase and cardiac troponin I (cTnI). The use of statins before marathon running exacerbates the release of creatine kinase from skeletal muscle, but the effect of statin use on exercise-induced cTnI release is unknown. We therefore

  18. Relation of cardiac troponin I and microvascular obstruction following ST-elevation myocardial infarction

    DEFF Research Database (Denmark)

    Hallén, Jonas; Jensen, Jesper K; Buser, Peter

    2011-01-01

    Presence of microvascular obstruction (MVO) following primary percutaneous coronary intervention (pPCI) for ST-elevation myocardial infarction (STEMI) confers higher risk of left-ventricular remodelling and dysfunction. Measurement of cardiac troponin I (cTnI) after STEMI reflects the extent...

  19. Cardiac troponin I release and cytokine response during experimental human endotoxaemia

    NARCIS (Netherlands)

    van Bockel, EAP; Tulleken, JE; Kobold, ACM; Ligtenberg, JJM; van der Werf, TS; Spanjersberg, R; Zijlstra, JG

    2003-01-01

    Objective. To study the relationship between cytokine levels and cardiac troponin I (cTnI). Design. Prospective experimental study. Setting. Intensive care unit of a university hospital. Participants. Six healthy male volunteers. Interventions. Endotoxin, 4 ng/kg, was given as a 1-min intravenous in

  20. Characterization of troponin responses in isoproterenol-induced cardiac injury in the Hanover Wistar rat.

    Science.gov (United States)

    York, Malcolm; Scudamore, Cheryl; Brady, Sally; Chen, Christabelle; Wilson, Sharon; Curtis, Mark; Evans, Gareth; Griffiths, William; Whayman, Matthew; Williams, Thomas; Turton, John

    2007-06-01

    The investigations aimed to evaluate the usefulness of cardiac troponins as biomarkers of acute myocardial injury in the rat. Serum from female Hanover Wistar rats treated with a single intraperitoneal (IP) injection of isoproterenol (ISO) was assayed for cardiac troponin I (cTnI) (ACS: 180SE, Bayer), cTnI (Immulite 2000, Diagnostic Products Corporation) and cardiac troponin T (cTnT) (Elecsys 2010, Roche). In a time-course study (50.0 mg/kg ISO), serum cTnI (ACS:180SE) and cTnT increased above control levels at 1 hour postdosing, peaking at 2 hours (cTnI, 4.30 microg/L; cTnT, 1.79 microg/L), and declined to baseline by 48 hours, with histologic cardiac lesions first seen at 4 hours postdosing. The Immulite 2000 assay gave minimal cTnI signals, indicating poor immunoreactivity towards rat cTnI. In a dose-response study (0.25 to 20.0 mg/kg ISO), there was a trend for increasing cTnI (ACS:180SE) values with increasing ISO dose levels at 2 hours postdosing. By 24 hours, cTnI levels returned to baseline although chronic cardiac myodegeneration was present. We conclude that serum cTnI and cTnT levels are sensitive and specific biomarkers for detecting ISO induced myocardial injury in the rat. Serum troponin values reflect the development of histopathologic lesions; however peak troponin levels precede maximal lesion severity.

  1. Serial high sensitivity cardiac troponin T measurement in acute heart failure : insights from the RELAX-AHF study

    NARCIS (Netherlands)

    Felker, G. Michael; Mentz, Robert J.; Teerlink, John R.; Voors, Adriaan A.; Pang, Peter S.; Ponikowski, Piotr; Greenberg, Barry H.; Filippatos, Gerasimos; Davison, Beth A.; Cotter, Gad; Prescott, Margaret F.; Hua, Tsushung A.; Lopez-Pintado, Sara; Severin, Thomas; Metra, Marco

    2015-01-01

    AimsTroponin elevation is common in acute heart failure (AHF) and may be useful for prognostication; however, available data are mixed and many previous studies used older, less sensitive assays. We examined the association between serial measurements of high-sensitivity cardiac troponin T (hs-cTnT)

  2. DIAGNOSTIC EFFICACY OF CARDIAC TROPONIN-T IN ACUTE MYOCARDIAL INFARCTION PATIENTS ADMITTED IN INTENSIVE CARDIAC CARE UNIT

    Directory of Open Access Journals (Sweden)

    Tapan

    2016-03-01

    Full Text Available INTRODUCTION Myocardial infarction is a common and severe manifestation of ischaemic heart disease (IHD. Acute myocardial infarction (AMI is the result of death of heart muscle cells following either from a prolonged or severe ischaemia. The World Health Organisation emphasises IHD as our "Modern Epidemic" and AMI as common cause of sudden death. AIM The present study has been undertaken with the aim to assess the role of cardiac Troponin-T in early diagnosis of AMI and to evaluate its positive roles over CK-MB and LDH enzyme assays. The study also aims to find out the role of cardiac Troponin-T test, where ECG changes are nondiagnostic and inconclusive for AMI. MATERIAL & METHOD One hundred cases of provisionally diagnosed AMI, who were admitted during June 2012 to July 2015 in ICC Unit of TMC & Dr. BRAM Teaching Hospital, formed the subjects for the study. Those patients reported 2 to 10 hours after onset of chest pain were included in this study. Patients reported beyond 10 hours after onset of chest pain of AMI cases and patients having chest pain of non-AMI causes are excluded from the study. The provisional diagnosis of AMI was done on the basis of the history, chest pain, clinical findings and ECG changes. Trop-T test (Troponin-T sensitive rapid test by Muller Bardoff, et al, 1991 as well as CK-MB (creatine kinase-MB isoenzymeassays were performed immediately for each and every patient. Trop-T test was repeated in some selective cases where the early changes were insignificant and the results were compared with those of CK-MB, at different period of the disease onset. RESULTS The rapid cardiac Troponin-T test (CTn-T has 100% specificity for AMI whereas CK-MB and LDH have specificities of 80% and 60% respectively. The CTn-T has diagnostic efficiency of 92% for AMI but ECG has only 69% sensitivity and 80% specificity. The overall diagnostic efficacy of cardiac Troponin-T is higher than that of CK-MB, LDH and ECG (94% versus 92%, 91 % and 72

  3. Outliers as a cause of false cardiac troponin results: investigating the robustness of 4 contemporary assays.

    Science.gov (United States)

    Pretorius, Carel J; Dimeski, Goce; O'Rourke, Peter K; Marquart, Louise; Tyack, Shirley A; Wilgen, Urs; Ungerer, Jacobus P J

    2011-05-01

    It is important that cardiac troponin be measured accurately with a robust method to limit false results with potentially adverse clinical outcomes. In this study, we characterized the robustness of 4 analytical platforms by measuring the outlier rate between duplicate results. We measured cardiac troponin concurrently in duplicate with 4 analyzers on 2391 samples. The outliers were detected from the difference between duplicate results and by calculating a z value: z = (result 1 - result 2) ÷ √(SD1(est)² + SD2(est)²), with z > 3.48 identifying outliers with a probability of 0.0005. The outlier rates were as follows: Abbott Architect i2000SR STAT Troponin-I, 0.10% (0.01%-0.19%); Beckman Coulter Access2 Enhanced AccuTnI, 0.44% (0.25%-0.63%); Roche Cobas e601 TroponinT hs, 0.06% (0.00%-0.13%); and Siemens ADVIA Centaur XP TnI-Ultra, 0.10% (0.01%-0.19%). The occurrence of outliers was higher than statistically expected on all platforms except the Cobas e601 (χ² = 2.7; P = 0.10). A conservative approach with a constant 10% CV and z > 5.0 identified outliers with clear clinical impact and resulted in outlier rates of 0.11% (0.02%-0.20%) with the Architect i2000SR STAT Troponin-I, 0.36% (0.19%-0.53%) with the Access2 Enhanced AccuTnI, 0.02% (0.00%-0.06%) with the Cobas e601 TroponinT hs, and 0.06% (0.00%-0.13%) with the ADVIA Centaur XP TnI-Ultra. Outliers occurred on all analytical platforms, at different rates. Clinicians should be made aware by their laboratory colleagues of the existence of outliers and the rate at which they occur.

  4. Prognostic significance of elevated troponin in non-cardiac hospitalized patients: a systematic review and meta-analysis.

    Science.gov (United States)

    Ahmed, Amna N; Blonde, Ken; Hackam, Daniel; Iansavichene, Alla; Mrkobrada, Marko

    2014-12-01

    Cardiac biomarker troponin can be elevated in patients without a primary cardiac diagnosis and may have prognostic value. We conducted a systematic review to estimate the prevalence and prognostic significance of elevated troponin levels in patients admitted to hospital without a primary cardiac diagnosis. Literature search was done using MEDLINE (1946 to November 2012), EMBASE (1974 to Week 45, 2012), and Cochrane Central Register of Controlled Trials (November 2012). Two independent investigators reviewed full-text studies for final inclusion. We included studies of patients admitted without a primary cardiac diagnosis. Eligible studies compared adverse outcomes in patients with normal versus elevated troponin levels. Twenty-seven studies were included in the meta-analysis. Elevated troponin was associated with increased in-hospital and 30-day mortality (25 studies, 7255 patients, OR 3.88, 95% CI 2.90-5.19, P troponin was also associated with increased risk of long-term mortality at 6 months (9 studies, 5368 patients, OR 4.21, 95% CI 1.84-9.64, P Troponin is an independent predictor of short-term mortality with a pooled adjusted OR of 2.36, 95% CI 1.47-3.76, P troponin in non-cardiac patients is independently associated with increased mortality.

  5. Assessment of inflammatory factors and cardiac troponin T in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Falaknazi Kianoosh

    2009-01-01

    Full Text Available Hemodialysis (HD patients suffer from chronic inflammations which make them at increased risk of cardiovascular diseases. The purpose of this study was to see if there is a significant association between inflammatory factors such as ferritin and C-reactive protein (CRP as well as troponin T in patients on HD. We assessed these serum factors as well as other known cardiac risk factors in 53 patients on HD. The serum ferritin and CRP levels were measured by chemiluminescence′s immune assay while troponin T levels were measured by electrochemist luminescence immune assay. We found that serum concentrations of CRP and ferritin were not significantly higher in patients on HD with known cardiac risk factors (compared with the control group (p< 0.05. However, the serum troponin T levels in HD patients with cardiovascular risk factors were significantly higher than the control group. Our study suggests that elevated serum troponin T levels can play an important role as a predictor of cardiovascular disease in HD patients. Also, inflammatory factors such as CRP and ferritin may be influenced by chronic inflammation or nutritional status of these patients.

  6. Cardiac troponin I and creatine kinase-MB release after different cardiac surgeries.

    Science.gov (United States)

    Mastro, Florinda; Guida, Pietro; Scrascia, Giuseppe; Rotunno, Crescenzia; Amorese, Lillà; Carrozzo, Alessandro; Capone, Giuseppe; Paparella, Domenico

    2015-06-01

    To conduct a comparative study of cardiac troponin I (cTnI) and MB isoenzyme of serum creatine kinase (CK-MB) after different cardiac surgeries. Consecutive cardiac operations under cardiopulmonary bypass (200 adults, 144 men, 68 ± 11 years): 67 coronary artery bypass graft (CABG), 27 aortic valve surgery, 21 mitral valve surgery, 11 thoracic aorta surgery, and 74 combined surgery. Postoperative cTnI and CK-MB were measured on admission to the ICU and at fixed time until the fifth postoperative day. Peak values of cTnI (median 5.8 ng/ml; interquartile range 3.6-11.9) and CK-MB (29.0 ng/ml; 15.6-60.4) were reached mainly within 18 h after the end of surgery (85% of cTnI and 95% of CK-MB highest determinations) without differences among groups. Cardiopulmonary bypass and cross-clamp time significantly correlated with markers' peak values. At multivariate analysis, mitral valve surgery showed greater cTnI, CK-MB, and their cumulative area under the curve than other isolated procedures. Thoracic aorta surgery showed lower cumulative area under the curve for both markers than CABG and combined surgery. Mitral valve surgery had significant later reduction of both markers in comparison with other procedures. No patient in mitral valve surgery group reached cTnI values in the normal laboratory range within 5 postoperative days. Release pattern of cTnI and CK-MB after heart surgery depends on the type of procedure. Mitral valve surgery was characterized by highest and longest elevation of postoperative markers' concentration. Determinants of differences in myocardial injury biomarkers and their prognostic value after valve surgery should be accurately assessed.

  7. Clinical value of high-sensitivity cardiac troponin assays after acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    Yi-rui CAO

    2016-11-01

    Full Text Available In view of a variety of cardiovascular events complicated by acute ischemic stroke, the importance of monitoring myocardial ischemic symptoms and signs, electrocardiogram, echocardiogram and myocardial injury markers has been gradually recognized by clinicians. Cardiac troponin (cTn by conventional assay has been a unique marker of myocardial injury for its extremely high specificity. However, with the utilization of high-sensitivity cardiac troponin (hs-cTn, cTn is no longer exclusive of a disease, but was given more significance in the diagnosis and application value. Therefore, we described the clinical significance of alterations of serum hs-cTn concentration after ischemic stroke. DOI: 10.3969/j.issn.1672-6731.2016.11.015

  8. Effect of dexamethasone on postoperative cardiac troponin T production in pediatric cardiac surgery.

    Science.gov (United States)

    Malagon, Ignacio; Hogenbirk, Karin; van Pelt, Johanes; Hazekamp, Mark G; Bovill, James G

    2005-10-01

    Pediatric cardiac surgery is associated with a temporary rise in cardiac troponin T (cTnT) during the postoperative period. We examined whether dexamethasone given before cardiopulmonary bypass has myocardial protective effects as assessed by the postoperative production of cTnT. Prospective randomized interventional study in the pediatric intensive care unit in a university hospital. Patients were randomly allocated to act as controls or receive a single dose of dexamethasone (1 mg/kg) during induction of anesthesia. cTnT was measured four times postoperatively: immediately after admission to the pediatric intensive care unit (PICU) and 8, 15, and 24 h thereafter. The two groups had similar mean cTnT concentrations on PICU admission: those receiving dexamethasone 1.85 ng/ml (1.55-2.15) and those not receiving it 2 ng/ml (95% confidence interval 1.56-2.51). Concentrations of cTnT 8 h after admission to the PICU differed significantly after 8 h: 1.99 ng/ml (1.53-2.45) in those receiving dexamethasone and 3.08 ng/ml (2.46-3.69) in those not receiving it. After subgroup statistical analysis differences between the two groups remained significant only at 8 h, not those after 15 or 24 h. The use of dexamethasone (1 mg/kg) before cardiopulmonary bypass is associated with a brief but significant reduction in postoperative cTnT production. The clinical significance of this effect is unclear.

  9. NH2-terminal truncations of cardiac troponin I and cardiac troponin T produce distinct effects on contractility and calcium homeostasis in adult cardiomyocytes

    Science.gov (United States)

    Wei, Hongguang

    2014-01-01

    Cardiac troponin I (TnI) has an NH2-terminal extension that is an adult heart-specific regulatory structure. Restrictive proteolytic truncation of the NH2-terminal extension of cardiac TnI occurs in normal hearts and is upregulated in cardiac adaptation to hemodynamic stress or β-adrenergic deficiency. NH2-terminal truncated cardiac TnI (cTnI-ND) alters the conformation of the core structure of cardiac TnI similarly to that produced by PKA phosphorylation of Ser23/24 in the NH2-terminal extension. At organ level, cTnI-ND enhances ventricular diastolic function. The NH2-terminal region of cardiac troponin T (TnT) is another regulatory structure that can be selectively cleaved via restrictive proteolysis. Structural variations in the NH2-terminal region of TnT also alter the molecular conformation and function. Transgenic mouse hearts expressing NH2-terminal truncated cardiac TnT (cTnT-ND) showed slower contractile velocity to prolong ventricular rapid-ejection time, resulting in higher stroke volume. Our present study compared the effects of cTnI-ND and cTnT-ND in cardiomyocytes isolated from transgenic mice on cellular morphology, contractility, and calcium kinetics. Resting cTnI-ND, but not cTnT-ND, cardiomyocytes had shorter length than wild-type cells with no change in sarcomere length. cTnI-ND, but not cTnT-ND, cardiomyocytes produced higher contractile amplitude and faster shortening and relengthening velocities in the absence of external load than wild-type controls. Although the baseline and peak levels of cytosolic Ca2+ were not changed, Ca2+ resequestration was faster in both cTnI-ND and cTnT-ND cardiomyocytes than in wild-type control. The distinct effects of cTnI-ND and cTnT-ND demonstrate their roles in selectively modulating diastolic or systolic functions of the heart. PMID:25518962

  10. Graphene-gated biochip for the detection of cardiac marker Troponin I

    Energy Technology Data Exchange (ETDEWEB)

    Tuteja, Satish K. [CSIR-Institute of Microbial Technology, Sector 39-A, Chandigarh 160036 (India); CSIR-Institute of Microbial Technology, Sector 39-A, Chandigarh 160036 (India); Priyanka,; Bhalla, Vijayender [CSIR-Institute of Microbial Technology, Sector 39-A, Chandigarh 160036 (India); Deep, Akash; Paul, A.K. [AcSIR-Central Scientific Instruments Organization, Sector 30-C, Chandigarh 160030 (India); Suri, C. Raman, E-mail: raman@imtech.res.in [CSIR-Institute of Microbial Technology, Sector 39-A, Chandigarh 160036 (India)

    2014-01-27

    Graphical abstract: -- Highlights: •One step lithium ion intercalation mediated exfoliation process for preparing monolithic graphene sheets. •A micro-device in the drain-source configuration using gold electrodes on a silicon chip. •The label free detection of cardiac biomarker, Troponin I. •Detection limit <0.1 pg mL{sup −1} for Troponin I. -- Abstract: We report lithium ion intercalation mediated efficient exfoliation of graphite to form monolithic graphene sheets which have subsequently been investigated for the development of highly sensitive label-free electrochemical detection platform for cardiac biomarker, Troponin I (cTnI). The spectroscopic and morphological analysis demonstrated the formation of defect free graphene sheets which were successfully employed to fabricate an inter-digited microdevice in a drain-source configuration on a silicon biochip. The graphene gated biochip functionalized with anti-cTnI antibodies used in label free detection of cTnI which exhibited an excellent sensitivity in the picogram range (∼1 pg mL{sup −1}) for cTnI without the use of any enzymatic amplification that promises its potential applicability for bio-molecular detection in clinical diagnosis.

  11. Resting concentrations of cardiac troponin I in fit horses and effect of racing.

    Science.gov (United States)

    Nostell, Katarina; Häggström, Jens

    2008-12-01

    To determine normal resting values for cardiac troponin I (cTnI) in healthy Standardbred, Thoroughbred and Warmblood horses and investigate if racing has an influence on cTnI concentrations. Measuring cTnI concentrations in plasma is the gold standard for detecting myocardial injury in humans. Cardiac troponin I is highly conserved between species and has gained interest as a marker for cardiac injury in horses. Increased levels of cTnI have been reported in association with endurance and short-term strenuous exercise on a treadmill in horses. However, the effect of true racing conditions has not yet been reported. Blood samples for analysis of cTnI concentrations in plasma were collected from 67 Standardbred racehorses, 34 Thoroughbred racehorses and 35 Warmblood dressage horses at rest. Blood samples were also collected prior to and after racing in 22 Standardbred racehorses and 6 Thoroughbred racehorses. All horses except one had resting plasma cTnI concentrations horses 1-2h after the race (1/17 Standardbreds and 2/6 Thoroughbreds) as well as 10-14 h after the race (4/21 Standardbreds and 1/6 Thoroughbreds). Resting cTnI concentrations in horses are low but mildly elevated cTnI concentrations may be detected in some horses 1-14 h after racing. These findings could be of importance when evaluating horses with suspected cardiac disease that recently have performed hard exercise.

  12. Clinical Use of Ultrasensitive Cardiac Troponin I Assay in Intermediate- and High-Risk Surgery Patients

    Directory of Open Access Journals (Sweden)

    Flávia Kessler Borges

    2013-01-01

    Full Text Available Background. Cardiac troponin levels have been reported to add value in the detection of cardiovascular complications in noncardiac surgery. A sensitive cardiac troponin I (cTnI assay could provide more accurate prognostic information. Methods. This study prospectively enrolled 142 patients with at least one Revised Cardiac Risk Index risk factor who underwent noncardiac surgery. cTnI levels were measured postoperatively. Short-term cardiac outcome predictors were evaluated. Results. cTnI elevation was observed in 47 patients, among whom 14 were diagnosed as having myocardial infarction (MI. After 30 days, 16 patients had major adverse cardiac events (MACE. Excluding patients with a final diagnosis of MI, predictors of cTnI elevation included dialysis, history of heart failure, transoperative major bleeding, and elevated levels of pre- and postoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP. Maximal cTnI values showed the highest sensitivity (94%, specificity (75%, and overall accuracy (AUC 0.89; 95% CI 0.80–0.98 for postoperative MACE. Postoperative cTnI peak level (OR 9.4; 95% CI 2.3–39.2 and a preoperative NT-proBNP level ≥917 pg/mL (OR 3.47; 95% CI 1.05–11.6 were independent risk factors for MACE. Conclusions. cTnI was shown to be an independent prognostic factor for cardiac outcomes and should be considered as a component of perioperative risk assessment.

  13. Ultrasensitive cardiac troponin I antibody based nanohybrid sensor for rapid detection of human heart attack.

    Science.gov (United States)

    Bhatnagar, Deepika; Kaur, Inderpreet; Kumar, Ashok

    2017-02-01

    An ultrasensitive cardiac troponin I antibody conjugated with graphene quantum dots (GQD) and polyamidoamine (PAMAM) nanohybrid modified gold electrode based sensor was developed for the rapid detection of heart attack (myocardial infarction) in human. Screen printed gold (Au) electrode was decorated with 4-aminothiophenol for amine functionalization of the Au surface. These amino groups were further coupled with carboxyl functionalities of GQD with EDC-NHS reaction. In order to enhance the sensitivity of the sensor, PAMAM dendrimer was successively embedded on GQD through carbodiimide coupling to provide ultra-high surface area for antibody immobilization. The activated cardiac troponin I (cTnI) monoclonal antibody was immobilized on PAMAM to form nanoprobe for sensing specific heart attack marker cTnI. Various concentrations of cardiac marker, cTnI were electrochemically measured using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) in human blood serum. The modifications on sensor surface were characterized by FTIR and AFM techniques. The sensor is highly specific to cTnI and showed negligible response to non-specific antigens. The sensitivity of the sensor was 109.23μAcm(-2)μg(-1) and lower limit of detection of cTnI was found 20fgmL(-1).

  14. Interdomain orientation of cardiac troponin C characterized by paramagnetic relaxation enhancement NMR reveals a compact state.

    Science.gov (United States)

    Cordina, Nicole M; Liew, Chu Kong; Gell, David A; Fajer, Piotr G; Mackay, Joel P; Brown, Louise J

    2012-09-01

    Cardiac troponin C (cTnC) is the calcium binding subunit of the troponin complex that triggers the thin filament response to calcium influx into the sarcomere. cTnC consists of two globular EF-hand domains (termed the N- and C-domains) connected by a flexible linker. While the conformation of each domain of cTnC has been thoroughly characterized through NMR studies involving either the isolated N-domain (N-cTnC) or C-domain (C-cTnC), little attention has been paid to the range of interdomain orientations possible in full-length cTnC that arises as a consequence of the flexibility of the domain linker. Flexibility in the domain linker of cTnC is essential for effective regulatory function of troponin. We have therefore utilized paramagnetic relaxation enhancement (PRE) NMR to assess the interdomain orientation of cTnC. Ensemble fitting of our interdomain PRE measurements reveals that isolated cTnC has considerable interdomain flexibility and preferentially adopts a bent conformation in solution, with a defined range of relative domain orientations.

  15. TNNI3K is a novel mediator of myofilament function and phosphorylates cardiac troponin I

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hui; Wang, Lin; Song, Li; Zhang, Yan-Wan; Ye, Jue; Xu, Rui-Xia; Shi, Na; Meng, Xian-Min [Core Laboratory, Fu Wai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China)

    2013-02-01

    The phosphorylation of cardiac troponin I (cTnI) plays an important role in the contractile dysfunction associated with heart failure. Human cardiac troponin I-interacting kinase (TNNI3K) is a novel cardiac-specific functional kinase that can bind to cTnI in a yeast two-hybrid screen. The purpose of this study was to investigate whether TNNI3K can phosphorylate cTnI at specific sites and to examine whether the phosphorylation of cTnI caused by TNNI3K can regulate cardiac myofilament contractile function. Co-immunoprecipitation was performed to confirm that TNNI3K could interact with cTnI. Kinase assays further indicated that TNNI3K did not phosphorylate cTnI at Ser23/24 and Ser44, but directly phosphorylated Ser43 and Thr143 in vitro. The results obtained for adult rat cardiomyocytes also indicated that enhanced phosphorylation of cTnI at Ser43 and Thr143 correlated with rTNNI3K (rat TNNI3K) overexpression, and phosphorylation was reduced when rTNNI3K was knocked down. To determine the contractile function modulated by TNNI3K-mediated phosphorylation of cTnI, cardiomyocyte contraction was studied in adult rat ventricular myocytes. The contraction of cardiomyocytes increased with rTNNI3K overexpression and decreased with rTNNI3K knockdown. We conclude that TNNI3K may be a novel mediator of cTnI phosphorylation and contribute to the regulation of cardiac myofilament contraction function.

  16. Label-Free Detection of Cardiac Troponin-I Using Carbon Nanofiber Based Nanoelectrode Arrays

    Science.gov (United States)

    Periyakaruppan, Adaikkappan; Koehne, Jessica Erin; Gandhiraman, Ram P.; Meyyappan, M.

    2013-01-01

    A sensor platform based on vertically aligned carbon nanofibers (CNFs) has been developed. Their inherent nanometer scale, high conductivity, wide potential window, good biocompatibility and well-defined surface chemistry make them ideal candidates as biosensor electrodes. A carbon nanofiber (CNF) multiplexed array has been fabricated with 9 sensing pads, each containing 40,000 carbon nanofibers as nanoelectrodes. Here, we report the use of vertically aligned CNF nanoelectrodes for the detection of cardiac Troponin-I for the early diagnosis of myocardial infarction. Antibody, antitroponin, probe immobilization and subsequent binding to human cardiac troponin-I were characterized using electrochemical impedance spectroscopy and cyclic voltammetry techniques. Each step of the modification process resulted in changes in electrical capacitance or resistance to charge transfer due to the changes at the electrode surface upon antibody immobilization and binding to the specific antigen. This sensor demonstrates high sensitivity, down to 0.2 ng/mL, and good selectivity making this platform a good candidate for early stage diagnosis of myocardial infarction.

  17. Baseline cardiac troponin t levels are elevated in subjects with untreated diabetes mellitus

    DEFF Research Database (Denmark)

    Pareek, M; Nielsen, M L; Leósdóttir, M

    2015-01-01

    and cardiac troponin T in middle-aged or older apparently healthy subjects. Design and method: We examined cross-sectional associations between highsensitivity cardiac troponin T (hsTnT) and FPG categorized as normal fasting glucose (NFG: FPG/=7.0mmol/L), in 535 men and 226 women aged 56-79 years without...... (NFG: 7.55 ng/L +/- standard deviation 3.99 ng/L; IFG: 8.09 ng/L +/- 6.81 ng/L; DM: 10.28 ng/L +/- 7.55 ng/L; p subjects with DM compared to NFG (p subjects with NFG and IFG (p = 0......) defined by the Sokolow-Lyon index and/or Cornell voltage-duration product,FPGcategory remained significantly associated with hsTnT (B = 0.87 [95% CI, 0.35-1.39]; p = 0.001), independently of age (B = 0.29 [95% CI, 0.22-0.36]; p

  18. High-sensitivity cardiac troponin assays: answers to frequently asked questions.

    Science.gov (United States)

    Chenevier-Gobeaux, Camille; Bonnefoy-Cudraz, Éric; Charpentier, Sandrine; Dehoux, Monique; Lefevre, Guillaume; Meune, Christophe; Ray, Patrick

    2015-02-01

    Cardiac troponin (cTn) assays have quickly gained in analytical sensitivity to become what are termed 'high-sensitivity cardiac troponin' (hs-cTn) assays, bringing a flurry of dense yet incomplete literature data. The net result is that cTn assays are not yet standardized and there are still no consensus-built data on how to use and interpret cTn assay results. To address these issues, the authors take cues and clues from multiple disciplines to bring responses to frequently asked questions. In brief, the effective use of hs-cTn hinges on knowing: specific assay characteristics, particularly precision at the 99th percentile of a reference population; factors of variation at the 99th percentile value; and the high-individuality of hs-cTn assays, for which the notion of individual kinetics is more informative than straight reference to 'normal' values. The significance of patterns of change between two assay measurements has not yet been documented for every hs-cTn assay. Clinicians need to work hand-in-hand with medical biologists to better understand how to use hs-cTn assays in routine practice.

  19. Risk Stratification with Serum Cardiac Troponin I in Acute Myocardial Infarction on Admission

    Institute of Scientific and Technical Information of China (English)

    张铸; 苏恩本; 张寄南; 杨志健; 曹克将; 马文珠

    2001-01-01

    Objective To assess the prognostic significance of serum cardiac troponin I (cTnI) concentration in patients with acute myocardial infarction on admission. Methods Serum samples of 108 patients with established AMI were collected on admission for measuring cTnI and were grouped according to the intervals between the onset of chest pain and admission. Results In each of these groups, the serum cTnI concentrations in patients died after admission were significantly higher than those who survived (all P<0.05). Conclusions A higher serum cTnI concentration on admission in patients with AMI was associated with an increased risk of subsequent cardiac death during hospitalization.

  20. Production and Characterisation of Anti-Cardiac Troponin-I Monoclonal Antibodies

    Directory of Open Access Journals (Sweden)

    Kh. H. Haider

    1994-01-01

    Full Text Available Cardiac troponin-I (cTn-I was isolated from bovine left ventricular tissue and used as immunogen. Sixteen murine hybridoma lines were produced with two of them. I D 12 and 5F4, showing a high specificity for cTn-I; both of these monoclonal antibodies (McAbs were isotyped as IgG I with kappa - light chains. The specificity of the McAbs for cTn-1 was confirmed by ELISA, western blotting and by the ability of the antibodies to block actomyosin ATPase inhibition by cTn-I. The McAbs may be useful for human ill vivo imaging of myocardial infarcts and other pathological conditions related to cardiac myocyte damage.

  1. Troponin activator augments muscle force in nemaline myopathy patients with nebulin mutations.

    Science.gov (United States)

    de Winter, Josine Marieke; Buck, Danielle; Hidalgo, Carlos; Jasper, Jeffrey R; Malik, Fady I; Clarke, Nigel F; Stienen, Ger J M; Lawlor, Michael W; Beggs, Alan H; Ottenheijm, Coen A C; Granzier, Henk

    2013-06-01

    Nemaline myopathy-the most common non-dystrophic congenital myopathy-is caused by mutations in thin filament genes, of which the nebulin gene is the most frequently affected one. The nebulin gene codes for the giant sarcomeric protein nebulin, which plays a crucial role in skeletal muscle contractile performance. Muscle weakness is a hallmark feature of nemaline myopathy patients with nebulin mutations, and is caused by changes in contractile protein function, including a lower calcium-sensitivity of force generation. To date no therapy exists to treat muscle weakness in nemaline myopathy. Here, we studied the ability of the novel fast skeletal muscle troponin activator, CK-2066260, to augment force generation at submaximal calcium levels in muscle cells from nemaline myopathy patients with nebulin mutations. Contractile protein function was determined in permeabilised muscle cells isolated from frozen patient biopsies. The effect of 5 μM CK-2066260 on force production was assessed. Nebulin protein concentrations were severely reduced in muscle cells from these patients compared to controls, while myofibrillar ultrastructure was largely preserved. Both maximal active tension and the calcium-sensitivity of force generation were lower in patients compared to controls. Importantly, CK-2066260 greatly increased the calcium-sensitivity of force generation-without affecting the cooperativity of activation-in patients to levels that exceed those observed in untreated control muscle. Fast skeletal troponin activation is a therapeutic mechanism to augment contractile protein function in nemaline myopathy patients with nebulin mutations and with other neuromuscular diseases.

  2. Effect of Exercise and Vitamin E on Cardiac Troponin Alterations in Myocardium and Serum of Rats after Stressful Intense Exercise

    Directory of Open Access Journals (Sweden)

    N.S. AL-Sowyan

    2010-01-01

    Full Text Available Increased concentrations of biomarkers reflecting myocardial stress such as cardiac troponin have been observed following strenuous exercise. The aim of this study was to determine whether the stress of forced exercise would result in injury to the myocardium. The effects of stress induced by short bout strenuous exercise and long term exercise on serum, cardiac and skeletal muscle troponin, also blood glucose and insulin were measured. Moreover, to determine whether vitamin E supplementation could modulate these effects or not. Five groups of rats were investigated, control, strenuous exercised rats, exercised and supplemented rats with vitamin E, long term exercise and long term exercised rats supplemented with vitamin E. Strenuous exercised rats and supplemented rats with vitamin E. produced significant increase in serum, cardiac and skeletal muscle troponin concentration. Long term exercise and long term exercised rats supplemented with vitamin E induced insignificant elevation of serum and muscle troponin concentration with significant increase in cardiac troponin level. In rats subjected to both strenuous and long term exercise and after supplementation of both group with vitamin E, there was a significant decrease in blood glucose and insulin level. These results suggest that stressful exercise induces alteration in myocardial troponin and that training before exercise and vitamin E attenuates the exercise induced heart damage. Accordingly, we can advise individuals who are subjected to strenuous exercise to supplement their diet with vitamin E to protect their heart from myocardial damage and sudden death which may be recorded in some athletes. Furthermore, these results demonstrate another support for the importance of exercise in diabetes mellitus.

  3. Cardiac troponin T and CK-MB mass release after visually successful percutaneous transluminal coronary angioplasty in stable angina pectoris

    DEFF Research Database (Denmark)

    Ravkilde, J; Nissen, H; Mickley, H

    1994-01-01

    The incidence of cardiac troponin T (Tn-T) and creatine kinase (CK) isoenzyme MB mass release was studied in 23 patients with stable angina pectoris undergoing visually successful percutaneous transluminal coronary angioplasty (PTCA). Serial blood samples were drawn for measurement of serum Tn...

  4. Acute-phase proteins, oxidative stress biomarkers, proinflammatory cytokines, and cardiac troponin in Arabian mares affected with pyometra.

    Science.gov (United States)

    El-Bahr, S M; El-Deeb, W M

    2016-09-01

    New biomarkers are essential for diagnosis of pyometra in mares. In this context, 12 subfertile Arabian mares suffered from pyometra were admitted to the Veterinary Teaching Hospital. The basis for diagnosis of pyometra was positive findings of clinical examination and rectal palpation. Blood samples were collected from diseased animals and from five Arabian healthy mares, which were considered as control group. Acute-phase proteins (APP), oxidative stress biomarkers, proinflammatory cytokines, and cardiac troponin I were estimated in the harvested sera of both groups. Clinical examination revealed purulent yellowish fluid discharged from vagina of affected animals and rectal palpation of the reproductive tract revealed uterine distention. The biochemical analysis of the serum revealed significant increase in cardiac troponin I, creatin kinase, alkaline phosphatase, malondialdehyde, tumor necrosis factor α, interleukins 6, prostaglandin F2α, haptoglobin, and serum amyloid A and significant decrease in reduced glutathione, superoxide dismutase (SOD), total antioxidant capacity, and nitric oxide (NO) of mares affected with pyometra compare to control. Cardiac troponin I was positively correlated with aspartate aminotransferase, creatin kinase, malondialdehyde, alkaline phosphatase, tumor necrosis factor α, interleukins 6, prostaglandin F2α, haptoglobin and serum amyloid A and negatively correlated with glutathione, superoxide dismutase, total antioxidant capacity and nitric oxide in serum of mares affected with pyometra. Moreover, there was high positive correlation between proinflammatory cytokines and APP in serum of mares affected with pyometra. The present study suggests cardiac troponin I together with APP, proinflammatory cytokines, and oxidative stress parameters as biomarkers for pyometra in Arabian mares.

  5. Relationship between serum cardiac troponin T level and cardiopulmonary function in stable chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Hattori K

    2015-02-01

    Full Text Available Kumiko Hattori, Takeo Ishii, Takashi Motegi, Yuji Kusunoki, Akihiko Gemma, Kozui Kida Department of Pulmonary Medicine and Oncology; Respiratory Care Clinic, Nippon Medical School, Tokyo, Japan Background: High-sensitivity cardiac troponin T (hs-cTnT in serum is a useful marker of acute myocardial injury, yet information is limited in patients with chronic obstructive pulmonary disease. We aimed to explore the association between hs-cTnT levels and cardiac and pulmonary dysfunction in patients with stable chronic obstructive pulmonary disease and at-risk individuals. Methods: We examined community-dwelling adults with/without chronic obstructive pulmonary disease, with a life-long smoking history, current symptoms of dyspnea during exertion, prolonged coughing, and/or sputum. Serum hs-cTnT concentrations were measured, and subjects underwent pulmonary function tests, high-resolution computed tomography of the chest, an echocardiogram, and a 6-minute walking test. Results: Eighty-six stable patients were identified (mean age 65.5 years; predicted forced expiratory volume in 1 second [FEV1% predicted] 75.0%. Their overall mean hs-cTnT level was 0.008 ng/mL. Logarithmically transformed hs-cTnT levels significantly and positively correlated with age, smoking index, serum high-sensitivity C-reactive protein levels, right ventricle systolic pressure, low attenuation area percentage, and brain natriuretic peptide levels (range r=0.231–0.534, P=0.000 to P=0.042. Further, logarithmically transformed hs-cTnT values significantly and negatively correlated with forced vital capacity, FEV1% predicted, diffusion capacity, arterial oxygen tension, and 6-minute walking distance (range r= -0.482 to -0.377, P=0.000 to P=0.002. Multivariate analyses showed that hs-cTnT values varied independently according to the following three parameters: high-sensitivity C-reactive protein levels (B=0.157, ß=0.450, t=3.571, P=0.001, age (B=0.008, ß=0.352, t=2.789, P=0

  6. Design and rationale of the high-sensitivity Troponin T Rules Out Acute Cardiac Insufficiency Trial.

    Science.gov (United States)

    Hunter, Benton R; Collins, Sean P; Fermann, Gregory J; Levy, Phillip D; Shen, Changyu; Ayaz, Syed Imran; Cole, Mette L; Miller, Karen F; Soliman, Adam A; Pang, Peter S

    2017-01-01

    Acute heart failure (AHF) is a common presentation in the Emergency Department (ED), and most patients are admitted to the hospital. Identification of patients with AHF who have a low risk of adverse events and are suitable for discharge from the ED is difficult, and an objective tool would be useful. The highly sensitive Troponin T Rules Out Acute Cardiac Insufficiency Trial (TACIT) will enroll ED patients being treated for AHF. Patients will undergo standard ED evaluation and treatment. High-sensitivity troponin T (hsTnT) will be drawn at the time of enrollment and 3 hours after the initial draw. The initial hsTnT draw will be no more than 3 hours after initiation of therapy for AHF (vasodilator, loop diuretic, noninvasive ventilation). Treating clinicians will be blinded to hsTnT results. We will assess whether hsTnT, as a single measurement or in series, can accurately predict patients at low risk of short-term adverse events. TACIT will explore the value of hsTnT measurements in isolation, or in combination with other markers of disease severity, for the identification of ED patients with AHF who are at low risk of short-term adverse events.

  7. Developing cardiac and skeletal muscle share fast-skeletal myosin heavy chain and cardiac troponin-I expression.

    Directory of Open Access Journals (Sweden)

    Kelly C Clause

    Full Text Available Skeletal muscle derived stem cells (MDSCs transplanted into injured myocardium can differentiate into fast skeletal muscle specific myosin heavy chain (sk-fMHC and cardiac specific troponin-I (cTn-I positive cells sustaining recipient myocardial function. We have recently found that MDSCs differentiate into a cardiomyocyte phenotype within a three-dimensional gel bioreactor. It is generally accepted that terminally differentiated myocardium or skeletal muscle only express cTn-I or sk-fMHC, respectively. Studies have shown the presence of non-cardiac muscle proteins in the developing myocardium or cardiac proteins in pathological skeletal muscle. In the current study, we tested the hypothesis that normal developing myocardium and skeletal muscle transiently share both sk-fMHC and cTn-I proteins. Immunohistochemistry, western blot, and RT-PCR analyses were carried out in embryonic day 13 (ED13 and 20 (ED20, neonatal day 0 (ND0 and 4 (ND4, postnatal day 10 (PND10, and 8 week-old adult female Lewis rat ventricular myocardium and gastrocnemius muscle. Confocal laser microscopy revealed that sk-fMHC was expressed as a typical striated muscle pattern within ED13 ventricular myocardium, and the striated sk-fMHC expression was lost by ND4 and became negative in adult myocardium. cTn-I was not expressed as a typical striated muscle pattern throughout the myocardium until PND10. Western blot and RT-PCR analyses revealed that gene and protein expression patterns of cardiac and skeletal muscle transcription factors and sk-fMHC within ventricular myocardium and skeletal muscle were similar at ED20, and the expression patterns became cardiac or skeletal muscle specific during postnatal development. These findings provide new insight into cardiac muscle development and highlight previously unknown common developmental features of cardiac and skeletal muscle.

  8. Myocardial damage in dogs affected by heartworm disease (Dirofilaria immitis): immunohistochemical study of cardiac myoglobin and troponin I in naturally infected dogs.

    Science.gov (United States)

    Carretón, E; Grandi, G; Morchón, R; Simón, F; Passeri, B; Cantoni, A M; Kramer, L; Montoya-Alonso, J A

    2012-10-26

    It has recently been reported that dogs affected by canine heartworm disease (Dirofilaria immitis) can show an increase in plasma levels of myoglobin and cardiac troponin I, two markers of muscle/myocardial injury. In order to determine if this increase is due to myocardial damage, the right ventricle of 24 naturally infected dogs was examined by routine histology and immunohistochemistry with anti-myoglobin and anti-cardiac troponin I antibodies. Microscopic lesions included necrosis and myocyte vacuolization, and were associated with loss of staining for one or both proteins. Results confirm that increased levels of myoglobin and cardiac troponin I are indicative of myocardial damage in dogs affected by heartworm disease.

  9. Perinatal Changes of Cardiac Troponin-I in Normal and Intrauterine Growth-Restricted Pregnancies

    Directory of Open Access Journals (Sweden)

    Nicoletta Iacovidou

    2007-01-01

    Full Text Available Intrauterine growth restriction (IUGR implies fetal hypoxia, resulting in blood flow redistribution and sparing of vital organs (brain, heart. Serum cardiac Troponin-I (cTnI, a well-established marker of myocardial ischaemia, was measured in 40 mothers prior to delivery, the doubly clamped umbilical cords (representing fetal state, and their 20 IUGR and 20 appropriate-for-gestational-age (AGA neonates on day 1 and 4 postpartum. At all time points, no differences in cTnI levels were observed between the AGA and IUGR groups. Strong positive correlations were documented between maternal and fetal/neonatal values (r≥.498, P≤.025 in all cases in the AGA and r≥.615, P≤.009 in all cases in the IUGR group. These results may indicate (a normal heart function, due to heart sparing, in the IUGR group (b potential crossing of the placental barrier by cTnI in both groups

  10. Fabrication of Anti-human Cardiac Troponin I Immunogold Nanorods for Sensing Acute Myocardial Damage

    Science.gov (United States)

    Guo, Z. R.; Gu, C. R.; Fan, X.; Bian, Z. P.; Wu, H. F.; Yang, D.; Gu, N.; Zhang, J. N.

    2009-12-01

    A facile, rapid, solution-phase method of detecting human cardiac troponin I for sensing myocardial damage has been described using gold nanorods-based biosensors. The sensing is demonstrated by the distinct change of the longitudinal surface plasmon resonance wavelength of the gold nanorods to specific antibody-antigen binding events. For a higher sensitivity, the aspect ratio of gold nanorods is increased up to ca 5.5 by simply adding small amount of HCl in seed-mediated growth solution. Experimental results show that the detecting limit of the present method is 10 ng/mL. Contrast tests reveal that these gold nanorods-based plasmonic biosensors hold much higher sensitivity than that of conventionally spherical gold nanoparticles.

  11. Fabrication of Anti-human Cardiac Troponin I Immunogold Nanorods for Sensing Acute Myocardial Damage

    Directory of Open Access Journals (Sweden)

    Fan X

    2009-01-01

    Full Text Available Abstract A facile, rapid, solution-phase method of detecting human cardiac troponin I for sensing myocardial damage has been described using gold nanorods-based biosensors. The sensing is demonstrated by the distinct change of the longitudinal surface plasmon resonance wavelength of the gold nanorods to specific antibody–antigen binding events. For a higher sensitivity, the aspect ratio of gold nanorods is increased up to ca 5.5 by simply adding small amount of HCl in seed-mediated growth solution. Experimental results show that the detecting limit of the present method is 10 ng/mL. Contrast tests reveal that these gold nanorods-based plasmonic biosensors hold much higher sensitivity than that of conventionally spherical gold nanoparticles.

  12. Persistent increase in cardiac troponin I in Fabry disease: a case report

    Directory of Open Access Journals (Sweden)

    Schneider Christian

    2011-01-01

    Full Text Available Abstract Background Hypertrophic cardiomyopathy is a frequent manifestation in Fabry disease (FD - an X-linked lysosomal storage disorder caused by reduced activity of the enzyme α-galactosidase A. In FD an elevation of specific cardiac biomarkers, such as cardiac troponin I (cTNI has been reported in case of clinical manifestation suggestive of myocardial ischemia. In diagnosing acute myocardial infarction cTNI is considered the most reliable parameter. Case Presentation In the referred case we present a 59 years old female patient with the diagnosis of FD presenting with persistently increased cTNI level (lowest value 0.46 ng/ml, highest value 0.69 ng/ml; normal range Conclusions Our case report demonstrates a persistent cTNI release in FD with cardiac involvement. Proving the persistence in a symptom free interval, it might be related to a direct damage of myocytes. In FD cTNI could serve as a beneficial long term parameter providing new perspectives for screening strategies.

  13. NT-ProBNP and cardiac troponin I in virulent canine babesiosis.

    Science.gov (United States)

    Lobetti, Remo; Kirberger, Robert; Keller, Ninette; Kettner, Frank; Dvir, Eran

    2012-12-21

    Although cardiac pathology and consequently elevated serum cardiac troponin I (cTnI) have been reported, clinically it remains difficult to diagnose cardiac involvement in canine babesiosis. Thus the use of cardiac biomarkers would be useful in determining if a dog with babesiosis also has concurrent cardiac dysfunction. The objectives of this study were to determine plasma N terminal brain natriuretic peptide (NT-proBNP) in canine babesiosis and if it is correlated with cTnI. Three groups of dogs with babesiosis were used: mild uncomplicated (Group 1), severe uncomplicated (Group 2), and complicated (Group 3), and a control group (Group 4) with 15 dogs per group. Each animal had the following determined: serum urea and creatinine, urea: creatinine ratio, cystatin-C, cTnI, blood lactate, plasma NT-proBNP, fractional shortening (FS), and blood pressure. The median NT-proBNP value in Groups 1-4 was 246, 650, 638, and 106 pmol/l. All 3 babesiosis groups had a statistically elevated NT-proBNP level compared to the control group and Groups 2 and 3 showed significantly higher values compared to Group 1. Median cTnI in Group 1-3 was 0.39, 0.4, and 1.45 ng/ml, respectively with the control group having concentrations below the detection limit (0.2 ng/ml). There was a significant difference in cTnI concentration between the control group and group 3 but no statistical difference between the other babesiosis groups. The study concluded that dogs with babesiosis showed elevated levels NT-proBNP and the more severe the disease process the greater the elevation. This elevation is earlier or independent of the increased cTnI. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Peri-operative troponin monitoring using a prototype high-sensitivity cardiac troponin I (hs-cTnI) assay: comparisons with hs-cTnT and contemporary cTnI assays.

    LENUS (Irish Health Repository)

    Lee, Graham R

    2013-09-18

    Non-cardiac surgery is associated with major vascular complications and higher incidences of elevated plasma troponin (cTn) concentration. Goal-directed therapy (GDT) is a stroke volume (SV)-guided approach to intravenous (IV) fluid therapy that improves tissue perfusion, oxygenation and reduces post-operative complications. In patients undergoing major gastro-intestinal surgery, we compared high sensitive and contemporary troponin assays and correlated results with patient outcome.

  15. Progressive troponin I loss impairs cardiac relaxation and causes heart failure in mice.

    Science.gov (United States)

    Liu, Jing; Du, Jianfeng; Zhang, Chi; Walker, Jeffery W; Huang, Xupei

    2007-08-01

    Cardiac troponin I (TnI) knockout mice exhibit a phenotype of sudden death at 17-18 days after birth due to a progressive loss of TnI. The objective of this study was to gain insight into the physiological consequences of TnI depletion and the cause of death in these mice. Cardiac function was monitored serially between 12 and 17 days of age by using high-resolution ultrasonic imaging and Doppler echocardiography. Two-dimensional B-mode and anatomical M-mode imaging and Doppler echocardiography were performed using a high-frequency ( approximately 20-45 MHz) ultrasound imaging system on homozygous cardiac TnI mutant mice (cTnI(-/-)) and wild-type littermates. On day 12, cTnI(-/-) mice were indistinguishable from wild-type mice in terms of heart rate, atrial and LV (LV) chamber dimensions, LV posterior wall thickness, and body weight. By days 16 through 17, wild-type mice showed up to a 40% increase in chamber dimensions due to normal growth, whereas cTnI(-/-) mice showed increases in atrial dimensions of up to 97% but decreases in ventricular dimensions of up to 70%. Mitral Doppler analysis revealed prolonged isovolumic relaxation time and pronounced inversion of the mitral E/A ratio (early ventricular filling wave-to-late atrial contraction filling wave) only in cTnI(-/-) mice indicative of impaired LV relaxation. cTnI(-/-) mouse hearts showed clear signs of failure on day 17, characterized by >50% declines in cardiac output, ejection fraction, and fractional shortening. B-mode echocardiography showed a profoundly narrowed tube-like LV and enlarged atria at this time. Our data are consistent with TnI deficiency causing impaired LV relaxation, which leads to diastolic heart failure in this model.

  16. 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.

  17. Utility of high-sensitivity cardiac troponin T in patients receiving anthracycline chemotherapy

    Directory of Open Access Journals (Sweden)

    Blaes AH

    2015-11-01

    Full Text Available Anne H Blaes,1 Aamer Rehman,2 David M Vock,3,4 Xianghua Luo,3,4 Mark Menge,5 Douglas Yee,3 Emil Missov,6 Daniel Duprez6 1Division of Hematology/Oncology/Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, 2Division of Cardiology, University of Louisville, Louisville, KY, 3Masonic Cancer Center, 4Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, 5Park Nicollet Frauenshuh Cancer Center, St Louis Park, 6Division of Cardiology, Department of Medicine, University of Minnesota, Minneapolis, MN, USA Background: Anthracycline chemotherapy remains an integral part of the care for curative intent chemotherapy in breast cancer and non-Hodgkin lymphoma patients. Better tools need to be identified to predict cardiac complications of anthracycline chemotherapy. Materials and methods: We investigated the utility of high-sensitivity cardiac troponin T (hscTnT, N-terminal pro-B-type natriuretic peptide, cardiac troponin T and I, and creatine kinase (CK-MB in cancer patients receiving anthracycline-based chemotherapy, in order to determine whether baseline levels or changes in these biomarkers may help predict the onset of congestive heart failure. Results: Eighteen consecutive patients with a pathologic diagnosis of breast cancer or non-Hodgkin lymphoma were enrolled. The median dose of doxorubicin exposure was 240 mg/m2 (range 240–400 mg/m2. After treatment with doxorubicin, the hscTnT increased to 19.1 pg/mL (P<0.001. CKMB and N-terminal pro-B-type natriuretic peptide levels increased to 1.1 ng/mL and 88.3 pg/mL, respectively (P=0.02. When subjects who had a decline in left ventricular ejection fraction (LVEF by equilibrium radionuclide ventriculography were compared to those who did not have a change in LVEF, there was a suggestion that those subjects with an elevated baseline hscTnT were more likely to have a decline in LVEF (2.7 pg/mL and 0.1 pg/mL, respectively; P=0.07. Spearman

  18. Cardiac troponin T: from diagnosis of myocardial infarction to cardiovascular risk prediction.

    Science.gov (United States)

    Mueller, Matthias; Vafaie, Mehrshad; Biener, Moritz; Giannitsis, Evangelos; Katus, Hugo A

    2013-01-01

    Cardiac troponins (cTns) T and I are exclusively expressed at high concentrations in cardiac muscle and have emerged as the preferred biomarker in the universal definition of myocardial infarction (MI). With the recent introduction of high-sensitivity (hs) assays, diagnostic sensitivity for earlier detection of MI has substantially improved. However, lowering the diagnostic cut-off has increased the detection of myocardial injuries in various non-acute coronary syndrome (ACS) conditions, which are not related to myocardial ischemia, leading to rising difficulties in diagnosing MI in clinical situations. Several approaches, such as serial sampling and incorporation of relative or absolute δ-changes, have been proposed to overcome the limitation of decreased sensitivity for MI diagnosis with hs-cTn assays. Current consensus for rapid rule-in proposes a 20% increase within 3 or 6h when baseline cTn levels are elevated. In the case of negative baseline values, relative increases ≥50% above the 99(th) percentile were found to be adequate to improve accuracy of MI diagnosis. Besides improved diagnostic accuracy for myocardial injury, even minor cTn elevations provide important prognostic information, and increased levels of cTn are associated with adverse outcomes in both the ACS and non-ACS condition, irrespective of whether the underlying cause is an acute or chronic illness. Thus, it is highly likely that lowering the diagnostic cut-off with even more sensitive assays might improve risk stratification in both conditions.

  19. Label-free detection of cardiac troponin I with a photonic crystal biosensor.

    Science.gov (United States)

    Zhang, Bailin; Morales, Andres W; Peterson, Ralph; Tang, Liang; Ye, Jing Yong

    2014-08-15

    A biosensor has been developed with a photonic crystal structure used in a total-internal-reflection (PC-TIR) configuration for label-free detection of a cardiac biomarker: Troponin I (cTnI). In contrast to a conventional optical microcavity that has a closed structure with its cavity layer sandwiched between two high-reflection surfaces, the PC-TIR configuration creates a unique open microcavity, which allows its cavity layer (sensing layer) to be easily functionalized and directly exposed to analyte molecules for bioassays. In this study, a PC-TIR sensor has been used for the label-free measurements of cardiac biomarkers by monitoring the changes in the resonant condition of the cavity due to biomolecular binding processes. Antibodies against cTnI are immobilized on the sensor surface for specific detection of cTnI with a wide range of concentrations. Detection limit of cTnI with a concentration as low as 0.1ngmL(-1) has been achieved.

  20. Cardiac troponin: a critical review of the case for point-of-care testing in the ED.

    Science.gov (United States)

    Bingisser, Roland; Cairns, Charles; Christ, Michael; Hausfater, Pierre; Lindahl, Bertil; Mair, Johannes; Panteghini, Mauro; Price, Christopher; Venge, Per

    2012-10-01

    The measurement of cardiac troponin concentrations in the blood is a key element in the evaluation of patients with suspected acute coronary syndromes, according to current guidelines, and contributes importantly to the ruling in or ruling out of acute myocardial infarction. The introduction of point-of-care testing for cardiac troponin has the potential to reduce turnaround time for assay results, compared with central laboratory testing, optimizing resource use. Although, in general, many point-of-care cardiac troponin tests are less sensitive than cardiac troponin tests developed for central laboratory-automated analyzers, point-of-care systems have been used successfully within accelerated protocols for the reliable ruling out of acute coronary syndromes, without increasing subsequent readmission rates for this condition. The impact of shortened assay turnaround times with point-of-care technology on length of stay in the emergency department has been limited to date, with most randomized evaluations of this technology having demonstrated little or no reduction in this outcome parameter. Accordingly, the point-of-care approach has not been shown to be cost-effective relative to central laboratory testing. Modeling studies suggest, however, that reengineering overall procedures within the emergency department setting, to take full advantage of reduced therapeutic turnaround time, has the potential to improve the flow of patients through the emergency department, to shorten discharge times, and to reduce cost. To properly evaluate the potential contribution of point-of-care technology in the emergency department, including its cost-effectiveness, future evaluations of point-of-care platforms will need to be embedded completely within a local decision-making structure designed for its use.

  1. Nuclear tropomyosin and troponin in striated muscle: new roles in a new locale?

    Science.gov (United States)

    Chase, P Bryant; Szczypinski, Mark P; Soto, Elliott P

    2013-08-01

    Tropomyosin and troponin have well known Ca(2+)-regulatory functions in the striated muscle sarcomere. In this review, we summarize experimental evidence that tropomyosin and troponin are localized, with as yet unidentified functional roles, in the striated muscle cell nucleus. We also apply bioinformatics approaches that predict localization of some tropomyosin and troponin to the nucleus, and that SUMOylation could be a covalent modification that modulates their nuclear localization and function. Further, we provide examples of cardiomyopathy mutations that alter the predicted likelihood of nuclear localization and SUMOylation of tropomyosin. These observations suggest novel mechanisms by which cardiomyopathy mutations in tropomyosin and troponin might alter not only cardiac contractility but also nuclear function.

  2. Classification of high-risk with cardiac troponin and shock index in normotensive patients with pulmonary embolism.

    Science.gov (United States)

    Ozsu, Savas; Erbay, Muge; Durmuş, Zerrin Gürel; Ozlu, Tevfik

    2017-02-01

    Accurate risk stratification of normotensive patients with acute pulmonary embolism (PE) require further investigation. We aimed to develop a simple model using clinical (shock index) and laboratory findings (cardiac Troponin, echocardiography) to assess the risk of 30-day mortality in normotensive patients with acute PE. In this retrospective study, 489 normotensive patients with acute PE diagnosed objectively. The primary end-point was defined as a all cause 30-day mortality. Shock index was calculated on admission. The primary end-point occurred in 67 (13.7%, 95% CI 10.7-16.8) patients with acute PE. Predictors of complications included elevated cardiac troponin (OR 1.7, 95% CI 1.3-2.2) and shock index (OR 1.3, 95% CI 1.1-1.5) by multivariable analysis. Risk index point was created based on OR. The model identified stages (stage I: 0-1 point, stage II: 2 points and stage III: 3 point) with 30-day mortality rates of 4.3, 19 and 38.6 %, respectively. The shock index and cardiac troponin can be safely used in combination to determine intermediate risk in patients with PE in emergency departmant. The study provided observations that will require prospective validation before the proposed risk score is adopted in clinical practice.

  3. Causes of Elevated Cardiac Troponins in the Emergency Department and Their Associated Mortality.

    Science.gov (United States)

    Meigher, Stephen; Thode, Henry C; Peacock, W Frank; Bock, Jay L; Gruberg, Louis; Singer, Adam J

    2016-11-01

    Cardiac troponins (cTn) are structural components of myocardial cells and are expressed almost exclusively in the heart. Elevated cTn levels indicate myocardial cell damage/death but not reflect the underlying etiology. The third universal definition of myocardial infarction (MI) differentiates MI into various types. Type 1 (T1MI) is due to plaque rupture with thrombus, while type 2 (T2MI) is a result of a supply:demand mismatch. Non-MI cTn elevations are also common. We determined the causes of elevated cTn in a tertiary care emergency department (ED) and the associated in-hospital mortality. We performed a structured, retrospective review of all consecutive adult ED patients with elevated troponin I (defined as > 99th percentile of the normal population, as run on the ADVIA Centaur platform; Siemens USA) during 1 year. Causes of elevated cTn were classified based on the third universal definitions. Comparisons between groups were performed using chi-square and Mann-Whitney U-tests. Of 96,612 ED patients presenting from May 2012 to April 2013, a total of 13,502 (14%) had cTn measured, of which 1,310 (9.7%) were elevated. Of these, 340 (26.5%, 95% confidence interval [CI], 24.2% to 29.0%) were T1MI, 452 (35.2%, 95% CI = 32.7% to 37.9%) T2MI, 458 (35.7%, 95% CI = 33.1% to 38.4%) multifactorial, and 33 (2.5%, 95% CI = 1.8% to 3.5%) due to nonischemic injury. Non-T1MI patients were slightly older, more likely female, and had higher blood urea nitrogen and creatinine. Comorbidities were more common in non-T1MI while cardiac risk factors were more common in T1MI. Non-T1MI patients were less likely to have diagnostic ECGs and had lower initial and subsequent cTn levels. In-hospital mortality rates were similarly high for T1MI and non-T1MI (11% [95% CI = 8% to 15%] vs. 10% [95% CI = 8% to 12%], p = 0.48). Of all ED patients with elevated cTn, ~75% have a non-T1MI. The mortality of patients with non-T1MI is similar to the mortality in patients with T1MI.

  4. Prognostic Biomarkers in Acute Coronary Syndromes: Risk Stratification Beyond Cardiac Troponins.

    Science.gov (United States)

    Eggers, K M; Lindahl, B

    2017-04-01

    Cardiac troponin (cTn) plays an essential role for assessment of outcome in acute coronary syndrome (ACS). However, the prognostic value of cTn is not absolute. In this mini-review, we summarize the evidence on the utility of established biomarkers of left-ventricular dysfunction, hemodynamic stress, inflammation, and renal dysfunction for risk prediction beyond cTn in ACS. Only few biomarkers consistently demonstrate additive prognostic value to cTn levels. The B-type natriuretic peptides (NPs) and growth-differentiation factor-15 (GDF-15) are most promising in this regard. However, there are uncertainties regarding the role of these biomarkers for guidance of treatment decisions, and their prognostic increment to cTn levels measured with high-sensitivity assays is largely unknown. The NPs and GDF-15 provide the strongest prognostic increment to cTn levels in ACS. However, the role of these biomarkers for clinical decision-making in contemporary settings has still to be defined.

  5. A polyaniline based ultrasensitive potentiometric immunosensor for cardiac troponin complex detection.

    Science.gov (United States)

    Zhang, Qi; Prabhu, Alok; San, Avdar; Al-Sharab, Jafar F; Levon, Kalle

    2015-10-15

    An ultrasensitive immunosensor based on potentiometric ELISA for the detection of a cardiac biomarker, troponin I-T-C (Tn I-T-C) complex, was developed. The sensor fabrication involves typical sandwich ELISA procedures, while the final signal readout was achieved using open circuit potentiometry (OCP). Glassy carbon (GC) working electrodes were first coated with emulsion-polymerized polyaniline/dinonylnaphthalenesulfonic acid (PANI/DNNSA) and the coated surface was utilized as a transducer layer on which sandwich ELISA incubation steps were performed. An enzymatic reaction between o-phenylenediamine (OPD) and hydrogen peroxide (H2O2) was catalyzed by horseradish peroxidase (HRP) labeled on the secondary antibodies. The polymer transducer charged state was mediated through electron (e(-)) and charge transfers between the transducer and charged species generated by the same enzymatic reaction. Such a change in the polymer transducer led to potential variations against an Ag/AgCl reference electrode as a function of Tn I-T-C complex concentration during incubations. The sequence of OPD and H2O2 additions, electrochemical properties of the PANI/DNNSA layer and non-specific binding prevention were all crucial factors for the assay performance. Under optimized conditions, the assay has a low limit of detection (LOD) ( 6 orders of magnitude), high repeatability (coefficient of variance < 8% for all concentrations higher than 5 pg/mL) and a short detection time (< 10 min).

  6. Human cardiac troponin I sensor based on silver nanoparticle doped microsphere resonator

    Science.gov (United States)

    Saliminasab, Maryam; Bahrampour, Alireza; Zandi, Mohammad Hossein

    2012-12-01

    Human cardiac troponin I (cTnI) is a specific biomarker for diagnosis of acute myocardial infarction (AMI). In this paper, a composite sensing system of an optical microsphere resonator and silver nanoparticles based on surface enhanced Raman scattering (SERS) and stimulated Raman scattering (SRS) techniques towards a point of care diagnostic system for AMI using the cTnI biomarker in HEPES buffered solution (HBS) is proposed. Pump and Raman signals enter the optical fiber coupling into the microsphere, and then SRS occurs in the microsphere. The presence of silver nanoparticles on the microsphere surface provides a tremendous enhancement of the resulting Raman signal through an electromagnetic enhancement of both the laser excitation and Stokes-shifted light of the order of 1010. This enhancement occurs in metals as surface plasmon resonance (SPR), which increases the Raman gain through the SERS effect. Our simulation results show that this sensor presents a linear response for cTnI detection. The calculated enhanced Raman signal can be employed to detect the cTnI molecules around the microsphere.

  7. Clinical significance of serum cardiac troponin T in patients with congestive heart failure

    Institute of Scientific and Technical Information of China (English)

    薛春才; 于宏伟; 李瑞杰; 沃金善; 崔家玉; 程海宾; 王洪云; 管庆华; 索晓霞; 贾荣波

    2003-01-01

    Objective To determine whether the level of serum cardiac troponin T (cTnT) was increased in patients with congestive heart failure (CHF). Methods This study consisted of 265 patients with CHF and 75 healthy people. Serum cTnT was measured by electrochemiluminescence immunoassay using an Elecsys 1010 automatic analyzer. Results cTnT concentration was 0.181±0.536 ng/mL in CHF patients and 0.003±0.001 ng/mL in controls (P35%, cTnT was 0.07±0.0 5ng/mL (P0.05, class Ⅱ vs class Ⅲ P<0.01, class Ⅲ vs class Ⅳ P<0.01). A negative correlation was observed between serum cTnT concentration and LVEF in 265 patients with CHF (r=-0.493, P<0.001).Conclusions This study shows that the level of serum cTnT is increased in patients with CHF and that the increased level indicates the severity of CHF.

  8. Rapid homogeneous immunoassay for cardiac troponin I using switchable lanthanide luminescence.

    Science.gov (United States)

    Päkkilä, Henna; Malmi, Eeva; Lahtinen, Satu; Soukka, Tero

    2014-12-15

    Homogeneous assays are advantageous because of their simplicity and rapid kinetics but typically their performance is severely compromised compared to heterogeneous assay formats. Here, we report a homogeneous immunoassay utilizing switchable lanthanide luminescence for detection and site-specifically labeled recombinant antibody fragments as binders to improve the assay performance. Switchable lanthanide luminescence enabled elimination of assay background due to division of the luminescent lanthanide chelate into two non-luminescent label moieties. Simultaneous biomolecular recognition of model analyte cardiac troponin I by two antibody fragments brought the label moieties together and resulted in self-assembly of luminescent mixed chelate complex. The assay was very rapid as maximal signal-to-background ratios were achieved already after 6 min of incubation. Additionally, the limit of detection was 0.38 ng/mL (16 pM), which was comparable to the limit of detection for the heterogeneous reference assay based on the same binders (0.26 ng/mL or 11 pM). This is the first study to apply switchable lanthanide luminescence in immunoassays and demonstrates the versatile potential of the technology for rapid and sensitive homogeneous assays.

  9. Characterization of Cardiac Troponin Elevation in the Setting of Pediatric Supraventricular Tachycardia.

    Science.gov (United States)

    Moore, Jeremy P; Arcilla, Lisa; Wang, Shuo; Lee, Michael S; Shannon, Kevin M

    2016-02-01

    Cardiac troponin (cTn) is currently considered the gold standard biomarker for detection of myocardial necrosis. Patients with supraventricular tachycardia (SVT) often present with symptoms resulting in cTn assessment; however, there are no data on the results of such testing in childhood. We hypothesized that cTn elevation would be common in the pediatric SVT population and would portend a benign prognosis. A retrospective review of all pediatric patients (≤21 years) presenting with SVT was performed. Clinical and electrocardiographic variables from the emergency department (ED) presentation were reviewed and clinical outcomes during subsequent follow-up assessed. Of 128 patients seen in the ED for SVT, cTn was assessed in 48 (38 %). Of patients with cTn assessment, 14 (29 %) patients demonstrated cTn elevation. Univariate predictors of cTn elevation included presentation with respiratory or gastrointestinal symptoms (50 vs 12 % and 42 vs 9 %; p = 0.008 and p = 0.01, respectively), lower mean arterial blood pressure (73 vs 85 mm Hg, p = 0.009), higher age-adjusted tachycardia rate (z score 9.3 vs 7.2, p < 0.001), and longer tachycardia duration (4.2 vs 1.0 h, p = 0.02). Multivariate logistic regression confirmed the association of age-adjusted tachycardia rate (odds ratio [OR] 3.8 per heart rate z score, confidence interval [CI] 1.9-11.8, p = 0.003) and duration (OR 1.5 per hour, CI 1.1-2.5, p = 0.03). Clinical outcome was excellent with no adverse sequelae during a median of 2.9 years of follow-up. Cardiac Tn elevation is common in the pediatric population presenting with SVT. Episode severity, characterized by respiratory or gastrointestinal symptoms, lower mean blood pressure, and increased tachycardia rate and duration are predictive. Clinical follow-up is favorable.

  10. Utilization of cardiac troponin assays in adult and pediatric populations: Guideline recommendations vs. reality.

    Science.gov (United States)

    Saenger, Amy K; Haymond, Shannon

    2015-12-01

    We hypothesized significant gaps remained for cardiac troponin (cTn) utilization in the United States, despite an emerging evidence base and guideline recommendations. We tested this hypothesis and investigated differences and trends between the use of cTn in adult versus pediatric hospitals. Individuals were identified by a targeted distribution through personal contact and professional society email lists. Participants completed an online survey (Qualtrics) from 07/15/13 to 07/26/13. The 31-item questionnaire used skipped logic and collected data about the respondent and their institutional cTn clinical practices. Data tabulation and analysis were conducted using Qualtrics and Microsoft Excel. A total of 159 unique laboratories responded to the survey, representing primarily adult (81%) versus pediatric (19%) institutions. 59% of laboratories utilize the guideline recommended 99th percentile as the upper reference limit (URL) for cTn, with large variability in reporting practices among users of the same assay. 73% of laboratories reported simultaneous ordering of other cardiac biomarkers with cTn, a majority which included CK-MB. Interpretive comments were used with cTn in 71 laboratories with a significant amount of heterogeneity. Pediatric hospitals reported a lower frequency of cTn orders and were less likely to consider elevated cTn a critical value. Gaps in current utilization and reporting of cTn exist, along with practices inconsistent with clinical guideline recommendations. Implementation of the 99th percentile and serial sampling protocols will be critical to adoption of high-sensitivity cTn assays. Differences in chest pain etiology are the most likely reason for the notable differences between cTn use in adults versus pediatric hospitals. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  11. The impact of obesity on cardiac troponin levels after prolonged exercise in humans.

    Science.gov (United States)

    Eijsvogels, Thijs M H; Veltmeijer, Matthijs T W; George, Keith; Hopman, Maria T E; Thijssen, Dick H J

    2012-05-01

    Elevated cardiac troponin I (cTnI), a marker for cardiac damage, has been reported after high-intensity exercise in healthy subjects. Currently, little is known about the impact of prolonged moderate-intensity exercise on cTnI release, but also the impact of obesity on this response. 97 volunteers (55 men and 42 women), stratified for BMI, performed a single bout of walking exercise (30-50 km). We examined cTnI-levels before and immediately after the exercise bout in lean (BMI obese subjects (BMI ≥ 30 kg/m(2), n = 28, 53 ± 9 years). Walking was performed at a self-selected pace. cTnI was assessed using a high-sensitive cTnI-assay (Centaur; clinical cut-off value ≥ 0.04 μg/L). We recorded subject characteristics (body weight, blood pressure, presence of cardiovascular risk) and examined exercise intensity by recording heart rate. Mean cTnI-levels increased significantly from 0.010 ± 0.006 to 0.024 ± 0.046 μg/L (P exercise-induced increase in cTnI was not different between lean, overweight and obese subjects (two-way ANOVA interaction; P = 0.27). In 11 participants, cTnI was elevated above the clinical cut-off value for myocardial infarction. Logistic regression analysis identified exercise intensity (P exercise results in a comparable increase in cTnI-levels in lean, overweight and obese subjects. Therefore, measures of obesity unlikely relate to the magnitude of the post-exercise elevation in cTnI.

  12. The Corellation Between Serum Ferritin and Cardiac Troponin I in Major Beta Thalassemia Children

    Directory of Open Access Journals (Sweden)

    Muhammad Ali Shodikin

    2016-04-01

    Full Text Available Major beta thalassemia (MBT is a hereditary disease which synthesies defects in beta chains of haemoglobin, it is causes red blood cell destruction and the symptoms of anemia. Red blood cell destruction, frequent blood transfusion and low adherence to routine use of iron chelator lead to iron accumulation in the heart, liver and endocrine organs. Accumulation of iron in the myocard can lead acute myocardial infarction. One of cardiac markers that had been used for the diagnosis of myocardial infarction was cardiac troponin I (cTnI. The aim of this research is find the correlation between serum ferritin levels and cTnI in MBT children. A descriptive analytic research was conducted using a cross sectional design. The subjects were divided into 2 groups, the MBT group and the control group. In both groups, the serum ferritin and cTnI levels ere evaluated. Data were analyzed using t-test and Pearson correlation test. Eleven children in the MBT group and 11 children in the control group were involved in this study. In the MBT group, the mean of serum ferritin and cTnI levels were 4292.5 µg/L and 0.20 ng/mL respectively. The mean of serum ferritin levels in the MBT group were higher than in the control and statistically significant (p= 0.0004. The mean of serum ferritin levels in the MBT group were higher than in the control and statistically significant (p= 0.0004. The mean of serum cTnI in the MBT group were higher than in the control, but statistically not significant (p= 0.82. In the MBT group, there was a weak corellation between serum ferritin and cTnI levels (r= 0.34.

  13. Transitioning high sensitivity cardiac troponin I (hs-cTnI) into routine diagnostic use: More than just a sensitivity issue

    LENUS (Irish Health Repository)

    Lee, Graham R

    2016-04-01

    High sensitivity cardiac troponin T and I (hs-cTnT and hs-cTnI) assays show analytical, diagnostic and prognostic improvement over contemporary sensitive cTn assays. However, given the importance of troponin in the diagnosis of myocardial infarction, implementing this test requires rigorous analytical and clinical verification across the total testing pathway. This was the aim of this study.

  14. Protein kinase D selectively targets cardiac troponin I and regulates myofilament Ca2+ sensitivity in ventricular myocytes.

    Science.gov (United States)

    Cuello, Friederike; Bardswell, Sonya C; Haworth, Robert S; Yin, Xiaoke; Lutz, Susanne; Wieland, Thomas; Mayr, Manuel; Kentish, Jonathan C; Avkiran, Metin

    2007-03-30

    Protein kinase D (PKD) is a serine/threonine kinase with emerging myocardial functions; in skinned adult rat ventricular myocytes (ARVMs), recombinant PKD catalytic domain phosphorylates cardiac troponin I at Ser22/Ser23 and reduces myofilament Ca(2+) sensitivity. We used adenoviral gene transfer to determine the effects of full-length PKD on protein phosphorylation, sarcomere shortening and [Ca(2+)](i) transients in intact ARVMs. In myocytes transduced to express wild-type PKD, the heterologously expressed enzyme was activated by endothelin 1 (ET1) (5 nmol/L), as reflected by PKD phosphorylation at Ser744/Ser748 (PKC phosphorylation sites) and Ser916 (autophosphorylation site). The ET1-induced increase in cellular PKD activity was accompanied by increased cardiac troponin I phosphorylation at Ser22/Ser23; this measured approximately 60% of that induced by isoproterenol (10 nmol/L), which activates cAMP-dependent protein kinase (PKA) but not PKD. Phosphorylation of other PKA targets, such as phospholamban at Ser16, phospholemman at Ser68 and cardiac myosin-binding protein C at Ser282, was unaltered. Furthermore, heterologous PKD expression had no effect on isoproterenol-induced phosphorylation of these proteins, or on isoproterenol-induced increases in sarcomere shortening and relaxation rate and [Ca(2+)](i) transient amplitude. In contrast, heterologous PKD expression suppressed the positive inotropic effect of ET1 seen in control cells, without altering ET1-induced increases in relaxation rate and [Ca(2+)](i) transient amplitude. Complementary experiments in "skinned" myocytes confirmed reduced myofilament Ca(2+) sensitivity by ET1-induced activation of heterologously expressed PKD. We conclude that increased myocardial PKD activity induces cardiac troponin I phosphorylation at Ser22/Ser23 and reduces myofilament Ca(2+) sensitivity, suggesting that altered PKD activity in disease may impact on contractile function.

  15. Diagnostic contributions of cardiac magnetic resonance imaging in patients presenting with elevated troponin, acute chest pain syndrome and unobstructed coronary arteries.

    Science.gov (United States)

    Leurent, Guillaume; Langella, Bernard; Fougerou, Claire; Lentz, Pierre-Axel; Larralde, Antoine; Bedossa, Marc; Boulmier, Dominique; Le Breton, Hervé

    2011-03-01

    Myocardial infarction with unobstructed coronary artery disease represents a serious diagnostic challenge. The role of cardiac magnetic resonance in the management of cardiomyopathies is increasing. We examined the diagnostic contributions of cardiac magnetic resonance in patients presenting with acute chest pain syndrome, elevated serum cardiac troponin concentrations and no significant coronary artery stenoses. Over a 3-year period, 107 consecutive patients (mean age 43.5 years; 62% men) presented to our institution with acute onset of chest pain, elevated serum troponin concentration and unobstructed coronary arteries, and underwent 3-tesla cardiac magnetic resonance at a mean delay of 6.9 days. A diagnosis was made based on: wall motion abnormalities and pericardial effusion on cine mode; myocardial oedema on T2-weighted imaging; abnormalities on first-pass perfusion imaging; and late gadolinium enhancement on T1-weighted imaging. Cardiac magnetic resonance was normal in 10.3% of patients and contributed a diagnosis in 89.7%, including myocarditis in 59.9%, stress cardiomyopathy (takotsubo syndrome) in 14% and myocardial infarction in 15.8%. Patients with normal cardiac magnetic resonance had a significantly lower mean peak troponin concentration (2.6ng/mL) than patients with diagnostic cardiac magnetic resonance (9.7ng/mL; P=0.01). Cardiac magnetic resonance contributed a diagnosis in nearly 90% of patients presenting with acute chest pain, elevated serum troponin and unobstructed coronary arteries. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  16. High-Sensitivity Cardiac Troponin T in Prediction and Diagnosis of Myocardial Infarction and Long-Term Mortality after Non-Cardiac Surgery

    Science.gov (United States)

    Nagele, Peter; Brown, Frank; Gage, Brian F.; Gibson, David W.; Miller, J. Philip; Jaffe, Allan S.; Apple, Fred S.; Scott, Mitchell G.

    2013-01-01

    Background Perioperative myocardial infarction is a serious complication after non-cardiac surgery. We hypothesized that preoperative cardiac troponin T detected with a novel high-sensitivity (hs-cTnT) assay will identify patients at risk of acute myocardial infarction (AMI) and long-term mortality after major non-cardiac surgery. Methods This was a prospective cohort study within the Vitamins in Nitrous Oxide (VINO) trial (n=608). Patients had been diagnosed with or had multiple risk factors for coronary artery disease and underwent major non-cardiac surgery. Cardiac troponin I (contemporary assay) and troponin T (high-sensitivity assay), and 12-lead electrocardiograms were obtained before and immediately after surgery and on postoperative day 1, 2 and 3. Results At baseline before surgery, 599 patients (98.5%) had a detectable hs-cTnT concentration and 247 (41%) were above 14 ng/L (99th percentile). After surgery, 497 patients (82%) had a rise in hs-cTnT (median Δhs-cTnT +2.7 ng/L [IQR 0.7, 6.8]). During the first three postoperative days, 9 patients (2.5%) with a preoperative hs-cTnT 14 ng/L (odds ratio, 3.67; 95% CI 1.65 – 8.15). During long-term follow-up, 80 deaths occurred. The 3-year mortality rate was 11% in patients with a preoperative hs-cTnT concentration 14 ng/L (adjusted hazard ratio, 2.17; 95% CI 1.19 – 3.96). Conclusions In this cohort of high-risk patients, preoperative hs-cTnT concentrations were significantly associated with postoperative myocardial infarction and long-term mortality after non-cardiac surgery. PMID:23895816

  17. The value of troponin assays in modern medical practice

    OpenAIRE

    Cutajar, Karl

    2016-01-01

    Cardiac troponins – C, I and T – form part of the troponin complex which is involved in the regulation of the calcium-mediated interaction of actin and myosin in myocytes. Each troponin has a different role in the above mentioned complex. Troponin C is involved in binding calcium, troponin I inhibits interaction of actin to myosin, while Troponin T binds to tropomyosin and facilitates muscle contraction. Both skeletal as well as cardiac muscle types express troponin C, ho...

  18. High-sensitivity cardiac troponin assays: From improved analytical performance to enhanced risk stratification.

    Science.gov (United States)

    Kozinski, Marek; Krintus, Magdalena; Kubica, Jacek; Sypniewska, Grazyna

    2017-05-01

    Implementation of cardiac troponin (cTn) assays has revolutionized the diagnosis, risk stratification, triage and management of patients with suspected myocardial infarction (MI). The Universal Definition of MI brought about a shift in the diagnostics of MI, from an approach primarily based on electrocardiography (ECG) to one primarily based on biomarkers. Currently, detection of a rise and/or fall in concentration or activity of myocardial necrosis biomarkers, preferentially cTns, with at least one value above the 99th percentile upper reference limit (URL), is the essential component for the diagnosis of MI. High-sensitivity cardiac troponin (hs-cTn) assays with their superior analytical performance were designed to further facilitate clinical decision making. The ability of hs-cTn assays to detect measurable cTn concentrations in at least 50% of healthy individuals, along with their improved precision (expressed as coefficient of variation ≤10% at the 99th percentile URL) associated with increased recognition of changing values, leads to enhanced risk stratification of patients with suspected MI, and also enables them to be used as prognostic tools potentially useful in other patient subsets. In this comprehensive review, we aim to integrate updated laboratory and clinical knowledge regarding hs-cTn assays in order to promote their optimal use in daily practice. We primarily focus on the role of hs-cTn assays in patients with suspected MI, discussing recommended diagnostic algorithms and result interpretation. Emphasis is also placed on the release of cTns following myocardial injury, the characteristics of antibodies used in available cTn immunoassays, and analytical performance of hs-cTn assays. In this paper, we also review potential challenges related to the selection of a healthy reference population in determining 99th percentile values, biological variation of hs-cTns, inequality between hs-cTn assays, and outline the current status of c

  19. Unstable Angina in the Era of Cardiac Troponin Assays with Improved Sensitivity-A Clinical Dilemma.

    Science.gov (United States)

    Eggers, K M; Jernberg, T; Lindahl, B

    2017-06-21

    There is an expectation that with the adoption of more sensitive cardiac troponin (cTn) assays, unstable angina would become a rarity. However, recent data from the SWEDEHEART registry demonstrated that 15% of patients admitted with non-ST-elevation acute coronary syndrome still were regarded as having unstable angina. We aimed to further investigate the clinical characteristics and outcome of these patients. This was a retrospective, registry-based analysis (SWEDEHEART) including 3204 unstable patients, 18,194 non-ST-elevation myocardial infarction (NSTEMI) patients, and 977 controls without acute cardiovascular disease. All patients had available data on peak cTnT levels (more sensitive assay) and 1-year outcome. The annual proportions of patients with unstable angina (2009-2013) among those with non-ST-elevation acute coronary syndrome ranged from 9.4% to 15.3%. Only 1239 unstable angina patients (39.7%) had a peak cTnT level ≤14 ng/L. Patients with unstable angina tended to be younger than those with NSTEMI but had higher prevalence of most cardiovascular risk factors and more advanced coronary artery disease. Compared with controls, the adjusted hazard ratios (95% confidence interval) regarding major cardiovascular events were 2.97 (1.30-6.78) and 5.44 (2.54-11.65) in unstable angina patients with peak cTnT ≤14 ng/L and >14 ng/L, respectively. The diagnosis of unstable angina is still commonly used, even in the era of more sensitive cTn assays. Minor cTnT elevation is common, which makes unstable angina difficult to distinguish from NSTEMI. Patients with unstable angina have a nonneglectable cardiovascular risk. We suggest that the clinical management of patients presenting with unstable symptoms should depend on their estimated cardiovascular risk rather than on strictly applied diagnostic criteria. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Impact of Sex on Cardiac Troponin Concentrations-A Critical Appraisal.

    Science.gov (United States)

    Eggers, Kai M; Lindahl, Bertil

    2017-09-01

    The use of sex-specific cutoffs for cardiac troponin (cTn) is currently debated. Although endorsed by scientific working groups, concerns have been raised that sex-specific cutoffs may have only a small clinical effect at the cost of increased complexity in decision-making. We reviewed studies investigating the interrelations between high-sensitivity (hs) cTn results and sex, diagnoses, and outcome. Investigated populations included community-dwelling subjects and patients with stable angina, congestive heart failure, or acute chest pain including those with acute coronary syndromes. Men usually have higher hs-cTn concentrations compared with women, regardless of the assessed population or the applied assay. The distribution and prognostic implications of hs-cTn concentrations indicate that women have a broader cardiovascular risk panorama compared with men, particularly at lower hs-cTn concentrations. At higher concentrations, particularly above the 99th percentile, this variation is often attenuated. Sex-specific hs-cTn 99th percentiles have so far shown clinical net benefit in only 1 study assessing patients with chest pain. However, several methodological aspects need to be considered when interpreting study results, e.g., issues related to the determination of the 99th percentiles, the selection bias, and the lack of prospective and sufficiently powered analyses. Available studies do not show a consistent clinical superiority of sex-specific hs-cTn 99th percentiles. This may reflect methodological aspects. However, from a pathobiological perspective, the use of sex-specific hs-cTn 99th percentiles makes sense for the ruling in of myocardial infarction. We propose a new approach to hs-cTn 99th cutoffs taking into account the analytical properties of the used assays. © 2017 American Association for Clinical Chemistry.

  1. CCQM-P58.1: Immunoassay Quantitation of Human Cardiac Troponin I.

    Science.gov (United States)

    Bunk, David; Noble, James; Knight, Alex E.; Wang, Lili; Klauenberg, Katy; Walzel, Monika; Elster, Clemens

    2015-01-01

    The CCQM study P58.1 assessed the equivalence of immunoassay measurements between participating NMIs. The aim of P58.1 was to demonstrate the equivalence of immunoassay measurements to determine the mass concentration of the clinically-relevant protein human cardiac troponin I (cTnI) present at low concentration relative to the protein concentration of the sample matrix. The measurement equivalence was assessed using traceability to a common certified reference material. To quantify cTnI, participants used a homogeneous sandwich-based immunoassay with an enzymatic amplification step. The antibody format consisted of a single capture and single detection antibody (referred to as 1 + 1), both were supplied to study participants. In the previous P58 study, ELISA measurement results were compared between laboratories which all used common ELISA reagents (including 96-well plates), samples, a standard for the production of calibrants, and a detailed ELISA protocol, which were supplied by a single laboratory. The P58.1 study only utilized common samples, a standard of the production of calibrants, and a set of monoclonal antibodies (mAbs). Because much of the experimental procedure for the P58 study was essentially standardized across participating labs, the study primarily highlighted between-laboratory differences in plate sampling designs and in plate reader response. As the participants in the P58.1 study had to produce most of their own analytical reagents and develop their own measurement procedure, the study provides a better evaluation of the equivalence of ELISA measurements between the participating laboratories. Main text. To reach the main text of this paper, click on Final Report The final report has been peer-reviewed and approved for publication by CCQM.

  2. Measuring high-sensitivity cardiac troponin T blood concentration in population surveys

    Science.gov (United States)

    Mindell, Jennifer S.

    2017-01-01

    Introduction The blood test for high-sensitivity cardiac troponin T (HS-CTnT) has been proposed as a marker of cardiovascular risk in the general population, as it is associated with subsequent incidence of cardiovascular events and mortality. We aimed at evaluating the feasibility of HS-CTnT testing within large nationally-representative population surveys in which blood samples are collected during household visits, shipped using the standard civil postal service, and then frozen for subsequent analyses. Methods The Health Survey for England (HSE) consists of a series of annual surveys beginning in 1991. It is designed to provide regular information on various aspects of the nation’s health and risk factors. We measured HS-CTnT in the blood of 200 people from the HSE 2016 wave, then froze and stored their blood samples at -40°C for 5–10 weeks, and then thawed and retested them to appreciate the extent of within-person agreement or test-retest reliability of the two measurements. Results The Cronbach's Alpha (Scale Reliability Coefficient) and the Interclass Correlation Coefficient (two-way mixed-effects model for consistency of agreement at individual level) were 0.97 (95%CI = 0.96–0.99) and 0.95 (95%CI = 0.94–0.96) respectively. The time delay from blood withdrawal to analysis and storage (1–4 days) did not affect the results, nor did the freezing time before the retest (5–10 weeks). Conclusion The measurement of HS-CTnT plasma concentration within large nationally-representative surveys such as the Health Survey for England is feasible. PMID:28141863

  3. Electronic medical record-based performance improvement project to document and reduce excessive cardiac troponin testing.

    Science.gov (United States)

    Love, Sara A; McKinney, Zeke J; Sandoval, Yader; Smith, Stephen W; Kohler, Rebecca; Murakami, MaryAnn M; Apple, Fred S

    2015-03-01

    We assessed the utilization rationale behind provider ordering of cardiac troponin I (cTnI) testing for the diagnosis of myocardial infarction after implementation of a hospital-wide serial order protocol. During 2 months in 2013, any request for additional cTnI testing within 30 days of the initial serial cTnI order prompted an electronic health record best practice alert (BPA), which included clinical decision support that could be bypassed by giving a clinical indication. cTnI orders were not limited (timing, number), and upon BPA, trigger data was collected for clinical indications and actions, patient stay (duration, location), International Classification of Diseases, Revision 9 diagnosis, cTnI orders, and timing of cTnI measurements. The BPA was triggered 1477 times by 423 providers who cared for 702 patients. There were a mean of 3.6 cTnI results per patient, 2.1 BPAs per patient, and 1.2 visits per patient. Providers (42% of whom were residents) acknowledged and overrode the BPA 97% of the time. In response to the BPA, 65% of providers selected a prepared rationale: 64% acute coronary syndrome/ST-elevation myocardial infarction/non-ST-elevation myocardial infarction; 30% demand ischemia; and 6% non-ACS myocardial necrosis. Of the remaining 35% of providers, 71% listed no rationale for their additional cTnI orders. Of patients with a BPA, 93% had non-ACS-related primary International Classification of Diseases, Revision 9 diagnosis, and 58% of the time, patients' cTnI results never increased during their stay. In 53% of cases, BPAs were generated by a request for an additional cTnI series when <2 results were available. Providers largely ignored the BPA that warned of potential overutilization of cTnI testing independent of diagnosis, including ACS. © 2014 American Association for Clinical Chemistry.

  4. Surface plasmon resonance biosensor with high anti-fouling ability for the detection of cardiac marker troponin T.

    Science.gov (United States)

    Liu, Jen Tsai; Chen, Ching Jung; Ikoma, Toshiyuki; Yoshioka, Tomohiko; Cross, Jeffrey S; Chang, Shwu-Jen; Tsai, Jang-Zern; Tanaka, Junzo

    2011-10-03

    Designing a surface recognition layer with high anti-fouling ability, high affinity, and high specificity is an important issue to produce high sensitivity biosensing transducers. In this study, a self-assembled monolayer (SAM) consisting of a homogeneous mixture of oligo(ethylene glycol) (OEG)-terminated alkanethiolate and mercaptohexadecanoic acid (MHDA) on Au was employed for immobilizing troponin T antibody and applied in detecting cardiac troponin T by using surface plasmon resonance (SPR). The mixed SAM showed no phase segregation and exhibited human serum albumin resistance, particularly with an antibody-immobilized surface. X-ray photoemission spectra revealed that the chemical composition ratio of OEG to the mixed SAM was 69% and the OEG packing density was 82%. The specific binding of troponin T on the designed surface indicated a good linear correlation (R=0.991, P<0.0009) at concentrations lower than 50 μgmL(-1) with the limit of detection of 100 ngmL(-1) using a SPR measuring instrument. It is concluded that the mixed SAM functions as designed since it has high detection capability, high accuracy and reproducibility, as well as shows strong potential to be applied in rapid clinical diagnosis for label-free detection within 2 min.

  5. Cardiac troponin and C-reactive protein for predicting all-cause and cardiovascular mortality in patients with chronic kidney disease: a meta-analysis.

    Science.gov (United States)

    Li, Wei-Jie; Chen, Xu-Miao; Nie, Xiao-Ying; Zhang, Jing; Cheng, Yun-Jiu; Lin, Xiao-Xiong; Wu, Su-Hua

    2015-04-01

    Elevated serum levels of cardiac troponin and C-reactive protein are associated with all-cause and cardiovascular mortality in patients with end-stage renal disease. However, the relationship between these two biomarker levels and mortality in patients with chronic kidney disease remains unclear. We conducted a meta-analysis to quantify the association of cardiac troponin and C-reactive protein levels with all-cause and cardiovascular mortality in patients with chronic kidney disease. Relevant studies were identified by searching the MEDLINE database through November 2013. Studies were included in the meta-analysis if they reported the long-term all-cause or cardiovascular mortality of chronic kidney disease patients with abnormally elevated serum levels of cardiac troponin or C-reactive protein. Summary estimates of association were obtained using a random-effects model. Thirty-two studies met our inclusion criteria. From the pooled analysis, cardiac troponin and C-reactive protein were significantly associated with all-cause (HR 2.93, 95% CI 1.97-4.33 and HR 1.21, 95% CI 1.14-1.29, respectively) and cardiovascular (HR 3.27, 95% CI 1.67-6.41 and HR 1.19, 95% CI 1.10-1.28, respectively) mortality. In the subgroup analysis of cardiac troponin and C-reactive protein, significant heterogeneities were found among the subgroups of population for renal replacement therapy and for the proportion of smokers and the C-reactive protein analysis method. Elevated serum levels of cardiac troponin and C-reactive protein are significant associated with higher risks of all-cause and cardiovascular mortality in patients with chronic kidney disease. Further studies are warranted to explore the risk stratification in chronic kidney disease patients.

  6. Prognostic value of high-sensitivity cardiac troponin T in patients with en-domyocardial-biopsy proven cardiac amyloidosis

    Institute of Scientific and Technical Information of China (English)

    Geng QIAN; Chen WU; Yang ZHANG; Yun-Dai CHEN; Wei DONG; Yi-Hong REN

    2014-01-01

    Objective To investigate prognostic predictors of long-term survival of patients with cardiac amyloidosis (CA), and to determine predictive value of high-sensitivity cardiac troponin T (hs-cTnT) in CA patients. Methods We recruited 102 consecutive CA cases and followed these patients for 5 years. We described their clinical characteristics at presentation and used a new, high-sensitivity assay to determine the concentration of cTnT in plasma samples from these patients. Results The patients with poor prognosis showed older age (56 ±12 years vs. 50 ±15 years, P=0.022), higher incidences of heart failure (36.92%vs. 16.22%, P=0.041), pericardial effusion (60.00%vs. 35.14%, P=0.023), greater thickness of interventricular septum (IVS) (15 ±4 mm vs. 13 ±4 mm, P=0.034), higher level of hs-cTnT (0.186 ±0.249 ng/mL vs. 0.044 ±0.055 ng/mL, P=0.001) and higher NT-proBNP (N-terminal pro-B-type natriuretic pep-tide) levels (11,742 ± 10,464 pg/mL vs. 6,031 ± 7,458 pg/mL, P=0.006). At multivariate Cox regression analysis, heart failure (HR:1.78, 95%CI:1.09-2.92, P=0.021), greater wall thickness of IVS (HR:1.44, 95%CI:1.04-3.01, P=0.0375) and higher hs-cTnT level (HR:6.16, 95%CI:2.20-17.24, P=0.001) at enrollment emerged as independent predictors of all-cause mortality. Conclusions We showed that hs-cTnT is associated with a very ominous prognosis, and it is also the strongest predictor of all-cause mortality in multivariate analysis. Examination of hs-cTnT concentrations provides valuable prognostic information concerning long-term outcomes.

  7. Upconverting nanophosphors as reporters in a highly sensitive heterogeneous immunoassay for cardiac troponin I

    Energy Technology Data Exchange (ETDEWEB)

    Sirkka, Nina, E-mail: nkelon@utu.fi; Lyytikäinen, Annika; Savukoski, Tanja; Soukka, Tero

    2016-06-21

    Photon upconverting nanophosphors (UCNPs) have a unique capability to produce anti-Stokes emission at visible wavelengths via sequential multiphoton absorption upon infrared excitation. Since the anti-Stokes emission can be easily spectrally resolved from the Stokes' shifted autofluorescence, the upconversion luminescence (UCL) is a highly attractive reporter technology for optical biosensors and biomolecular binding assays – potentially enabling unprecedented sensitivity in separation-based solid-phase immunoassays. UCL technology has not previously been applied in sensitive detection of cardiac troponin I (cTnI), which requires highly sensitive detection to enable accurate and timely diagnosis of myocardial infarction. We have developed an UCL-based immunoassay for cTnI using NaYF{sub 4}: Yb{sup 3+}, Er{sup 3+} UCNPs as reporters. Biotinylated anti-cTnI monoclonal antibody (Mab) and Fab fragment immobilized to streptavidin-coated wells were used to capture cTnI. Captured cTnI was detected from dry well surface after a 15 min incubation with poly(acrylic acid) coated UCNPs conjugated to second anti-cTnI Mab. UCL was measured with a dedicated UCL microplate reader. The UCL-based immunoassay allowed sensitive detection of cTnI. The limit of detection was 3.14 ng L{sup −1}. The calibration curve was linear up to cTnI concentration 50,000 ng L{sup −1}. Plasma recoveries of added cTnI were 92–117%. Obtained cTnI concentrations from five normal plasma samples were 4.13–10.7 ng L{sup −1} (median 5.06 ng L{sup −1}). There is yet significant potential for even further improved limit of detection by reducing non-specifically bound fraction of the Mab-conjugated UCNPs. The assay background with zero calibrator was over 40-fold compared to the background obtained from wells where the reporter conjugate had been excluded. - Highlights: • Detection of attomole analyte quantity in microwell using upconversion luminescence. • Upconverting

  8. Clinical implications of high-sensitivity cardiac troponin measurements in hospitalized medical patients.

    Directory of Open Access Journals (Sweden)

    Gideon Y Stein

    Full Text Available The increased use of high sensitivity cardiac troponins (hs-cTn, have made the diagnosis of non-ST elevation myocardial infarction (MI challenging, especially in complex medical patients, in whom the clinical presentation of MI is nonspecific and multiple comorbidities as well as non-ischemic acute conditions may account for elevated hs-cTn levels. The aim of this study was to assess the frequency of both elevated hs-cTn levels and dynamic changes in hospitalized patients.We conducted a retrospective study identifying all patients hospitalized in the Internal Medicine Division of Rabin Medical Center, Israel between January 2011 to December 2011, for whom at least one hs-cTn T (hs-cTnT measurement was obtained. Collected data included patient demographics, acute and chronic diagnosis, hs-cTnT and creatinine levels and date of death. Hs-cTnT levels were obtained in 5,696 admissions and was above the 99th percentile (> = 13 ng/L in 61.6% of the measurements. A relative change of 50% or higher was observed in 24% of the admissions. Among those with elevated hs-cTnT levels, acute coronary syndromes (ACS accounted for only 6.1% of acute diagnoses. Maximal hs-cTnT levels above 100 ng/L but not dynamic changes discriminated between ACS and non-ACS conditions (positive and negative predictive values of 12% and 96% respectively. The frequency of elevated hs-cTnT levels was age-dependent and over 75% of patients aged >70 years-old had levels above the 99th percentile. Multivariate analysis identified hs-cTnT levels higher than the 99th percentile, as an independent, strong predictor for 30-day mortality (OR 4.58 [2.8, 7.49], p<0.0001.Elevated hs-cTnT levels together with dynamic changes are frequent findings among hospitalized patients and in most cases, are not related to the ACS diagnosis. These findings highlight the diagnostic challenge of ACS in this complex population. Further studies are needed in order to optimize the use of hs-cTnT measurements

  9. Ultrasensitive and low-volume point-of-care diagnostics on flexible strips – a study with cardiac troponin biomarkers

    Science.gov (United States)

    Shanmugam, Nandhinee Radha; Muthukumar, Sriram; Prasad, Shalini

    2016-09-01

    We demonstrate a flexible, mechanically stable, and disposable electrochemical sensor platform for monitoring cardiac troponins through the detection and quantification of cardiac Troponin-T (cTnT). We designed and fabricated nanostructured zinc oxide (ZnO) sensing electrodes on flexible porous polyimide substrates. We demonstrate ultrasensitive detection is capable at very low sample volumes due to the confinement phenomenon of target species within the ZnO nanostructures leading to enhancement of biomolecular binding on the sensor electrode surface. The performance of the ZnO nanostructured sensor electrode was evaluated against gold and nanotextured ZnO electrodes. The electrochemical sensor functions on affinity based immunoassay principles whereby monoclonal antibodies for cTnT were immobilized on the sensor electrodes using thiol based chemistry. Detection of cTnT in phosphate buffered saline (PBS) and human serum (HS) buffers was achieved at low sample volumes of 20 μL using non-faradaic electrochemical impedance spectroscopy (EIS). Limit of detection (LOD) of 1E-4 ng/mL (i.e. 1 pg/mL) at 7% CV (coefficient of variation) for cTnT in HS was demonstrated on nanostructured ZnO electrodes. The mechanical integrity of the flexible biosensor platform was demonstrated with cyclic bending tests. The sensor performed within 12% CV after 100 bending cycles demonstrating the robustness of the nanostructured ZnO electrochemical sensor platform.

  10. Benefit of combining quantitative cardiac CT parameters with troponin I for predicting right ventricular dysfunction and adverse clinical events in patients with acute pulmonary embolism

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, Mathias, E-mail: mr.meyer.mathias@gmail.com [Department of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); Fink, Christian, E-mail: Christian.Fink@umm.de [Department of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); Roeger, Susanne, E-mail: susanne.roeger@umm.de [1st Department of Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); Apfaltrer, Paul, E-mail: Paul.Apfaltrer@umm.de [Department of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); Haghi, Dariush, E-mail: dariush.haghi@umm.de [1st Department of Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); Kaminski, Wolfgang E., E-mail: wolfgang.kaminski@umm.de [Department of Clinical Chemistry, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); Neumaier, Michael, E-mail: michael.neumaier@medma.uni-heidelberg.de [Department of Clinical Chemistry, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); Schoenberg, Stefan O., E-mail: Stefan.Schoenberg@umm.de [Department of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim (Germany); and others

    2012-11-15

    Objective: To prospectively evaluate the diagnostic accuracy of quantitative cardiac CT parameters alone and in combination with troponin I for the assessment of right ventricular dysfunction (RVD) and adverse clinical events in patients with acute pulmonary embolism (PE). Materials and results: This prospective study had institutional review board approval and was HIPAA compliant. In total 83 patients with confirmed PE underwent echocardiography and troponin I serum level measurements within 24 h. Three established cardiac CT measurements for the assessment of RVD were obtained (RV/LV{sub axial}, RV/LV{sub 4-CH}, and RV/LV{sub volume}). CT measurements and troponin I serum levels were correlated with RVD found on echocardiography and adverse clinical events according to Management Strategies and Prognosis in Pulmonary Embolism Trial-3 (MAPPET-3 criteria. 31 of 83 patients with PE had RVD on echocardiography and 39 of 83 patients had adverse clinical events. A RV/LV{sub volume} ratio > 1.43 showed the highest area under the curve (AUC) (0.65) for the prediction of adverse clinical events when compared to RV/LV{sub axial}, RV/LV{sub 4Ch} and troponin I. The AUC for the detection of RVD of RV/LV{sub axial}, RV/LV{sub 4Ch}, RV/LV{sub volume}, and troponin I were 0.86, 0.86, 0.92, and 0.69, respectively. Combination of RV/LV{sub axial}, RV/LV{sub 4Ch}, RV/LV{sub volume} with troponin I increased the AUC to 0.87, 0.87 and 0.93, respectively. Conclusion: A combination of cardiac CT parameters and troponin I measurements improves the diagnostic accuracy for detecting RVD and predicting adverse clinical events if compared to either test alone.

  11. Protein Structure-Function Relationship at Work: Learning from Myopathy Mutations of the Slow Skeletal Muscle Isoform of Troponin T

    Science.gov (United States)

    Mondal, Anupom; Jin, J.-P.

    2016-01-01

    Troponin T (TnT) is the sarcomeric thin filament anchoring subunit of the troponin complex in striated muscles. A nonsense mutation in exon 11 of the slow skeletal muscle isoform of TnT (ssTnT) gene (TNNT1) was found in the Amish populations in Pennsylvania and Ohio. This single nucleotide substitution causes a truncation of the ssTnT protein at Glu180 and the loss of the C-terminal tropomyosin (Tm)-binding site 2. As a consequence, it abolishes the myofilament integration of ssTnT and the loss of function causes an autosomal recessive nemaline myopathy (NM). More TNNT1 mutations have recently been reported in non-Amish ethnic groups with similar recessive NM phenotypes. A nonsense mutation in exon 9 truncates ssTnT at Ser108, deleting Tm-binding site 2 and a part of the middle region Tm-binding site 1. Two splicing site mutations result in truncation of ssTnT at Leu203 or deletion of the exon 14-encoded C-terminal end segment. Another splicing mutation causes an internal deletion of the 39 amino acids encoded by exon 8, partially damaging Tm-binding site 1. The three splicing mutations of TNNT1 all preserve the high affinity Tm-binding site 2 but still present recessive NM phenotypes. The molecular mechanisms for these mutations to cause myopathy provide interesting models to study and understand the structure-function relationship of TnT. This focused review summarizes the current knowledge of TnT isoform regulation, structure-function relationship of TnT and how various ssTnT mutations cause recessive NM, in order to promote in depth studies for further understanding the pathogenesis and pathophysiology of TNNT1 myopathies toward the development of effective treatments. PMID:27790152

  12. Discordant diagnoses of acute myocardial infarction due to the different use of assays and cut-off points of cardiac troponins

    DEFF Research Database (Denmark)

    Lyck Hansen, Maria; Saaby, Lotte; Nybo, Mads

    2012-01-01

    Objectives: Several assays for the measurement of cardiac troponin (cTn) are available, but differences in their analytical performances may affect the diagnosis of acute myocardial infarction (MI). Methods: A survey was conducted at all Danish departments of clinical biochemistry at hospitals...

  13. Precocious appearance of cardiac troponin T pre-mRNAs during early avian embryonic skeletal muscle development in ovo.

    Science.gov (United States)

    Swiderski, R E; Solursh, M

    1990-07-01

    Cardiac troponin T (cTNT), a component of the muscle contractile apparatus, is transiently expressed in skeletal muscle during avian limb development. While cTNT was first detected immunohistochemically in limb buds undergoing overt myogenic differentiation (Hamburger and Hamilton stage 26, about 5 days in ovo), RNA blot analyses of early, predifferentiated wing buds have revealed the presence of cTNT transcripts in limb buds as early as stage 23 (4 days in ovo). Steady-state cTNT poly(A) RNAs of stage 22 through stage 37 fore- and hindlimbs were compared using both cTNT cDNA and cTNT intron-specific probes. In the predifferentiated state, two incompletely processed RNAs (3.8 and 2.4 kb) were expressed in the absence of the mature cTNT transcript, while a third pre-mRNA (3.5 kb) appeared concomitantly with the mature mRNA as differentiation and development proceeded. In addition, a population of unique cTNT transcripts were expressed in a proximal to distal manner in wing buds which had undergone initial overt myogenic differentiation (stage 26). Some of the cTNT pre-mRNAs observed in premyogenic limbs appeared to accumulate stably in a tissue-specific manner, based on their absence from the cardiac poly(A) RNA population. These results suggest that the appearance of cardiac troponin T mRNA, as well as the polypeptide, may be regulated at multiple levels including RNA processing, stability, and/or translation during early skeletal muscle myogenesis.

  14. Troponin elevations after non-cardiac, non-vascular surgery are predictive of major adverse cardiac events and mortality

    DEFF Research Database (Denmark)

    Ekeloef, S; Alamili, M; Devereaux, P J

    2016-01-01

    -analysis was conducted in January 2016 according to the Meta-analysis Of Observational Studies in Epidemiology guidelines. Both interventional and observational studies measuring troponin within the first 4 days after surgery were eligible. A systematic search was performed in PubMed, EMBASE, Scopus, and the Cochrane...

  15. 扩张型心肌病患者肌钙蛋白I和心功能的关系%The relationship between cardiac troponin I and cardiac function in patients with dilated cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    王一伟

    2014-01-01

    Objective:To investigate the relationship between cardiac troponin I and cardiac function in patients with dilated cardiomyopathy.Methods:65 patients who were diagnosed with dilated cardiomyopathy were selected from 2011 to 2012.They were classified according to different function,and determined the level of serum cardiac troponin I,and analyzed the relationship between cardiac troponin I and cardiac function.Results:When we measured the serum troponin I in 65 patients,we found that the levels of serum cardiac troponin I had obviously differences in different cardiac function groups,the higher of the grade,the higher of the level of troponin I.Conclusion:The worse of the cardiac function in patients with dilated cardiomyopathy,the higher of the level of troponin I,so we can concluded that cardiac troponin I is an important index that can react cardiac function decreased.%目的:探讨扩张型心肌病患者肌钙蛋白 I 和心功能的关系。方法:2011-2012年收治扩张型心肌病患者65例,对患者按照不同心功能进行分级后血清肌钙蛋白I的水平情况进行测定,并分析肌钙蛋白I与心功能的关系。结果:对65例患者的血清肌钙蛋白 I 进行测定后发现,在不同的心功能组的肌钙蛋白 I 的水平有明显的差异,分级越高,肌钙蛋白I水平越高。结论:扩张型心肌病患者的心功能越差,肌钙蛋白I水平就越高,肌钙蛋白I是反应患者心功能下降的重要指标。

  16. Concentrations of cardiac Troponin I before and after ovariohysterectomy in 46 female dogs with pyometra.

    Science.gov (United States)

    Pelander, Lena; Hagman, Ragnvi; Häggström, Jens

    2008-09-11

    Canine pyometra is a common disease in countries where routine spaying of young dogs is not common practice. This disease is known to lead to systemic inflammation potentially affecting multiple organs in the body, including the heart. Cardiac-specific Troponin I (cTnI) is a sensitive marker of myocardial cell damage, which can result from ischemia, trauma, toxins or inflammation. Dogs with pyometra are also exposed to anaesthesia which can potentially result in myocardial cell damage. The aims of the study were 1) to evaluate the occurrence of myocardial cell damage as indicated by increased serum concentrations of cTnI in dogs with pyometra and relate these to presence of systemic inflammation and 2) to evaluate the change in cTnI-concentrations after anaesthesia and surgery. Serum cTnI concentration was measured preoperatively and one day after surgery in 46 female dogs with pyometra and 15 female dogs that underwent surgery for other reasons (ovariohysterectomy and mammary tumours). Forty-six female dogs of different breeds diagnosed with pyometra were included. The dogs had a median age of 8.5 years (IQR 7.5-10) and a median weight of 29 kg (IQR 9-32). Of the 46 dogs, 37 (80%) fulfilled the chosen criteria for systemic inflammatory response syndrome (SIRS) at inclusion. Thirteen (28%) of the dogs had increased cTnI concentrations (> 0.2 microg/l) before surgery and 18 (39%) had increased cTnI-concentrations the day after surgery. The cTnI concentrations in the 13 dogs with increased preoperative cTnI concentrations decreased in 8 dogs, increased in 4 dogs, and was unchanged in one dog. Seven dogs with nondetectable preoperative cTnI concentrations had increased postoperative concentrations. The only significant association between the studied laboratory or clinical variables (including SIRS) and cTnI concentration was preoperative percentage band neutrophils (PBN) and postoperative cTnI concentration (P = 0.016). In total, 20 dogs (43%) had increased pre- or

  17. Concentrations of cardiac Troponin I before and after ovariohysterectomy in 46 female dogs with pyometra

    Science.gov (United States)

    Pelander, Lena; Hagman, Ragnvi; Häggström, Jens

    2008-01-01

    Background Canine pyometra is a common disease in countries where routine spaying of young dogs is not common practice. This disease is known to lead to systemic inflammation potentially affecting multiple organs in the body, including the heart. Cardiac-specific Troponin I (cTnI) is a sensitive marker of myocardial cell damage, which can result from ischemia, trauma, toxins or inflammation. Dogs with pyometra are also exposed to anaesthesia which can potentially result in myocardial cell damage. The aims of the study were 1) to evaluate the occurrence of myocardial cell damage as indicated by increased serum concentrations of cTnI in dogs with pyometra and relate these to presence of systemic inflammation and 2) to evaluate the change in cTnI-concentrations after anaesthesia and surgery. Methods Serum cTnI concentration was measured preoperatively and one day after surgery in 46 female dogs with pyometra and 15 female dogs that underwent surgery for other reasons (ovariohysterectomy and mammary tumours). Results Forty-six female dogs of different breeds diagnosed with pyometra were included. The dogs had a median age of 8.5 years (IQR 7.5–10) and a median weight of 29 kg (IQR 9–32). Of the 46 dogs, 37 (80%) fulfilled the chosen criteria for systemic inflammatory response syndrome (SIRS) at inclusion. Thirteen (28%) of the dogs had increased cTnI concentrations (> 0.2 μg/l) before surgery and 18 (39%) had increased cTnI-concentrations the day after surgery. The cTnI concentrations in the 13 dogs with increased preoperative cTnI concentrations decreased in 8 dogs, increased in 4 dogs, and was unchanged in one dog. Seven dogs with nondetectable preoperative cTnI concentrations had increased postoperative concentrations. The only significant association between the studied laboratory or clinical variables (including SIRS) and cTnI concentration was preoperative percentage band neutrophils (PBN) and postoperative cTnI concentration (P = 0.016). In total, 20 dogs

  18. Concentrations of cardiac Troponin I before and after ovariohysterectomy in 46 female dogs with pyometra

    Directory of Open Access Journals (Sweden)

    Hagman Ragnvi

    2008-09-01

    Full Text Available Abstract Background Canine pyometra is a common disease in countries where routine spaying of young dogs is not common practice. This disease is known to lead to systemic inflammation potentially affecting multiple organs in the body, including the heart. Cardiac-specific Troponin I (cTnI is a sensitive marker of myocardial cell damage, which can result from ischemia, trauma, toxins or inflammation. Dogs with pyometra are also exposed to anaesthesia which can potentially result in myocardial cell damage. The aims of the study were 1 to evaluate the occurrence of myocardial cell damage as indicated by increased serum concentrations of cTnI in dogs with pyometra and relate these to presence of systemic inflammation and 2 to evaluate the change in cTnI-concentrations after anaesthesia and surgery. Methods Serum cTnI concentration was measured preoperatively and one day after surgery in 46 female dogs with pyometra and 15 female dogs that underwent surgery for other reasons (ovariohysterectomy and mammary tumours. Results Forty-six female dogs of different breeds diagnosed with pyometra were included. The dogs had a median age of 8.5 years (IQR 7.5–10 and a median weight of 29 kg (IQR 9–32. Of the 46 dogs, 37 (80% fulfilled the chosen criteria for systemic inflammatory response syndrome (SIRS at inclusion. Thirteen (28% of the dogs had increased cTnI concentrations (> 0.2 μg/l before surgery and 18 (39% had increased cTnI-concentrations the day after surgery. The cTnI concentrations in the 13 dogs with increased preoperative cTnI concentrations decreased in 8 dogs, increased in 4 dogs, and was unchanged in one dog. Seven dogs with nondetectable preoperative cTnI concentrations had increased postoperative concentrations. The only significant association between the studied laboratory or clinical variables (including SIRS and cTnI concentration was preoperative percentage band neutrophils (PBN and postoperative cTnI concentration (P = 0.016. In

  19. Measurement of troponin in cardiomyopathies

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    Andrew Connelly

    2016-12-01

    Full Text Available Troponins are thin myofilament proteins that regulate the contraction of cardiac and skeletal muscle. The cardio-specific troponin I (TnI and T (TnT proteins are sensitive and specific biomarkers of myocardial injury which over the past twenty years have revolutionised the diagnosis and management of myocardial infarction. With the advent of high sensitivity assays the role for cardiac troponins is possibly expanding. Elevated levels are associated with adverse cardiovascular events and mortality in heart failure and the general population. Studies in cardiomyopathies are generally small with <200 patients, but serum troponin levels can be chronically raised and detect subclinical myocyte damage. This review examines all major published studies of cardiac troponin measurement in cardiomyopathies. There is considerable variability among studies regarding assays used and definitions of abnormal results but elevated troponin levels are almost invariably related to poor prognosis and their negative predictive value is important.

  20. The diagnostic utility of High-Sensitivity Cardiac Troponin T in acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Manal Mohsen

    2016-03-01

    Conclusion: Our study demonstrated highly significant absolute and relative kinetic changes in hs-TnT levels in patients with AMI. The hs-TnT can be used for early rule in patients with MI as it could detect 97% of cases with MI whose Troponin I was negative and could detect 100% of cases of MI after 6–8 h compared to Troponin I which could detect only 21.2% of cases. This can be of great importance in the future introduction and use of the new high sensitive assay as a non-invasive reliable diagnostic tool to replace the currently used invasive diagnostic techniques for patients with ACS.

  1. Effect of preoperative Mg sulfate infusion on serum cardiac troponin (cTn in moderate preeclamptic undergoing elective cesarean section under spinal anesthesia

    Directory of Open Access Journals (Sweden)

    Nashwa S. Elzayyat

    2014-07-01

    Full Text Available This study was designed to investigate and compare the effect of preoperative Mg sulfate infusion on serum cardiac troponin (cTn in moderate preeclampsia undergoing elective cesarean section. A total of fifty parturients having moderate preeclampsia scheduled for elective cesarean section were included. They were randomly allocated into two equal groups 25 each, magnesium group (GMg received preoperative magnesium sulfate infusion and control group (GC then both received spinal anesthesia, serum troponin measured preoperative then at 6, 12 and 24 h postoperative. Mean arterial pressure and heart rate were also recorded. Baseline serum cardiac troponin was higher above normal and was comparable at the rest of times in both groups. Mean arterial pressure readings were significantly lower in GMg compared to GC at induction of spinal, skin incision and skin closure (P < 0.05 and were comparable at the rest of times. Serum cardiac troponin (cTn levels were comparable in parturients received magnesium sulfate infusion preoperatively with those did not receive magnesium sulfate.

  2. Brief Myocardial Ischemia Produces Cardiac Troponin I Release and Focal Myocyte Apoptosis in the Absence of Pathological Infarction in Swine

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    Brian R. Weil, PhD

    2017-04-01

    Full Text Available In a porcine model of brief ischemia leading to reversible stunning in the absence of tissue necrosis, we demonstrated delayed release of cardiac troponin I (cTnI that exceeded the 99th percentile for normal animals 60 min after reperfusion and rose to readily detectable levels 24 h later. Although tissue analysis at 60 min showed no evidence of infarction, TUNEL staining demonstrated isolated myocytes undergoing apoptosis, which was absent after 24 h. These results demonstrate that cTnI elevations occur after ischemia of a duration that is insufficient to produce myocyte necrosis and reflect myocyte injury associated with apoptosis in the absence of pathological evidence of infarction.

  3. High-sensitivity cardiac troponin T is associated with cognitive decline in older adults at high cardiovascular risk

    DEFF Research Database (Denmark)

    Wijsman, Liselotte W; de Craen, Anton JM; Trompet, Stella

    2016-01-01

    AIMS: Cardiac troponin T (cTnT), measured with a high-sensitivity (hs) assay, is associated with cognitive decline, but the underlying mechanism is unknown. We investigated the association of hs-cTnT with cognitive function and decline, and studied whether this association was independent....... Participants with pre-existent advanced clinical heart failure were excluded. Hs-cTnT and NT-proBNP obtained after 6 months of follow-up were related with cognitive function, tested repeatedly during a mean follow-up of 3.2 years. Participants with higher hs-cTnT performed worse at baseline on Stroop test...... diseases risk factors or Apolipoprotein E genotype. Further adjusting for NT-proBNP levels revealed the same results. CONCLUSIONS: Higher levels of hs-cTnT associate with worse cognitive function and steeper cognitive decline in older adults independent of cardiovascular diseases, risk factors and NT-proBNP....

  4. A cis-regulatory mutation in troponin-I of Drosophila reveals the importance of proper stoichiometry of structural proteins during muscle assembly.

    Science.gov (United States)

    Firdaus, Hena; Mohan, Jayaram; Naz, Sarwat; Arathi, Prabhashankar; Ramesh, Saraf R; Nongthomba, Upendra

    2015-05-01

    Rapid and high wing-beat frequencies achieved during insect flight are powered by the indirect flight muscles, the largest group of muscles present in the thorax. Any anomaly during the assembly and/or structural impairment of the indirect flight muscles gives rise to a flightless phenotype. Multiple mutagenesis screens in Drosophila melanogaster for defective flight behavior have led to the isolation and characterization of mutations that have been instrumental in the identification of many proteins and residues that are important for muscle assembly, function, and disease. In this article, we present a molecular-genetic characterization of a flightless mutation, flightless-H (fliH), originally designated as heldup-a (hdp-a). We show that fliH is a cis-regulatory mutation of the wings up A (wupA) gene, which codes for the troponin-I protein, one of the troponin complex proteins, involved in regulation of muscle contraction. The mutation leads to reduced levels of troponin-I transcript and protein. In addition to this, there is also coordinated reduction in transcript and protein levels of other structural protein isoforms that are part of the troponin complex. The altered transcript and protein stoichiometry ultimately culminates in unregulated acto-myosin interactions and a hypercontraction muscle phenotype. Our results shed new insights into the importance of maintaining the stoichiometry of structural proteins during muscle assembly for proper function with implications for the identification of mutations and disease phenotypes in other species, including humans.

  5. Ischemia-modified albumin is not better than creatine kinase-MB and cardiac troponin I in predicting a cardiac injury in nontraumatic subarachnoid hemorrhage.

    Science.gov (United States)

    Baydin, Ahmet; Amanvermez, Ramazan; Tuncel, Özgür Korhan; Ocak, Metin; Meric, Murat; Cokluk, Cengiz

    2015-04-01

    The aims were to investigate the role of serum ischemia-modified albumin (IMA), tumor necrosis factor α (TNF-α), and myeloperoxidase (MPO) and to evaluate the relationship between IMA and cardiac markers (creatine kinase myocardial isoenzyme [CK-MB] and cardiac troponin I [cTnI]) related to cardiac abnormalities in adult patients after nontraumatic subarachnoid hemorrhage (SAH). Twenty-nine patients with nontraumatic SAH admitted to the emergency department and 20 healthy adults as the control group were included in the study. Ischemia-modified albumin, TNF-α, MPO, CK-MB, cTnI, and leukocyte count (white blood cell [WBC]) in the circulation were measured on admission. Ischemia-modified albumin, TNF-α, and MPO levels were higher by mean values of 11.6%, 9.5%, and 2.9%, respectively, in patients with SAH compared with control group. However, levels of these parameters were not statistically different between the groups (P > .05). However, WBC, CK-MB, and cTnI values were significantly higher in patients with SAH compared with healthy control (P MB, and cTnI tests to differentiate between patients after SAH and controls according to receiver operating characteristic curve. The results suggest that IMA is not better than CK-MB and cTnI in predicting a cardiac injury in patients after nontraumatic SAH. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Functional effects of the DCM mutant Gly159Asp troponin C in skinned muscle fibres

    DEFF Research Database (Denmark)

    Preston, Laura C; Lipscomb, Simon; Robinson, Paul

    2006-01-01

    We recently reported a dilated cardiomyopathy (DCM) causing mutation in a novel disease gene, TNNC1, which encodes cardiac troponin C (TnC). We have determined how this mutation, Gly159Asp, affects contractile regulation when incorporated into muscle fibres. Endogenous troponin in rabbit skinned...... psoas fibres was partially replaced by recombinant human cardiac troponin containing either wild-type or Gly159Asp TnC. We measured both the force-pCa relationship of these fibres and the activation rate using the caged-Ca(2+) compound nitrophenyl-EGTA. Gly159Asp TnC had no significant effect on either...... the Ca(2+) sensitivity or cooperativity of force generation when compared to wild type. However, the mutation caused a highly significant (ca. 50%) decrease in the rate of activation. This study shows that whilst not affecting the force-pCa relationship, the mutation Gly159Asp causes a significant...

  7. Comparative Evaluation of 2-Hour Rapid Diagnostic Algorithms for Acute Myocardial Infarction Using High-Sensitivity Cardiac Troponin T.

    Science.gov (United States)

    McRae, Andrew D; Innes, Grant; Graham, Michelle; Lang, Eddy; Andruchow, James E; Yang, Hong; Ji, Yunqi; Vatanpour, Shabnam; Southern, Danielle A; Wang, Dongmei; Seiden-Long, Isolde; DeKoning, Lawrence; Kavsak, Peter

    2017-08-01

    Symptoms of acute coronary syndrome account for a large proportion of emergency department (ED) visits and hospitalizations. High-sensitivity troponin can rapidly rule out or rule in acute myocardial infarction (AMI) within a short time of ED arrival. We sought to validate test characteristics and classification performance of 2-hour high-sensitivity troponin T (hsTnT) algorithms for the rapid diagnosis of AMI. We included consecutive patients from 4 academic EDs with suspected cardiac chest pain who had hsTnT assays performed 2 hours apart (± 30 minutes) as part of routine care. The primary outcome was AMI at 7 days. Secondary outcomes included major adverse cardiac events (mortality, AMI, and revascularization). Test characteristics and classification performance for multiple 2-hour algorithms were quantified. Seven hundred twenty-two patients met inclusion criteria. Seven-day AMI incidence was 10.9% and major adverse cardiac event incidence was 13.7%. A 2-hour rule-out algorithm proposed by Reichlin and colleagues ruled out AMI in 59.4% of patients with 98.7% sensitivity and 99.8% negative predictive value (NPV). The 2-hour rule-out algorithm proposed by the United Kingdom National Institute for Health and Care Excellence ruled out AMI in 50.3% of patients with similar sensitivity and NPV. Other exploratory algorithms had similar sensitivity but marginally better classification performance. According to Reichlin et al., the 2-hour rule-in algorithm ruled in AMI in 16.5% of patients with 92.4% specificity and 58.5% positive predictive value. Two-hour hsTnT algorithms can rule out AMI with very high sensitivity and NPV. The algorithm developed by Reichlin et al. had superior classification performance. Reichlin and colleagues' 2-hour rule-in algorithm had poor positive predictive value and might not be suitable for early rule-in decision-making. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Cardiac troponin I is associated with severity of myxomatous mitral valve disease, age, and C-reactive protein in dogs

    DEFF Research Database (Denmark)

    Ljungvall, L.; Höglund, K.; Tidholm, A.;

    2010-01-01

    BACKGROUND: Concentrations of cardiac troponin I (cTnI) and C-reactive protein (CRP) might be associated with cardiac remodeling in dogs with myxomatous mitral valve disease (MMVD). Age- and sex-dependent variations in cTnI concentration have been described. OBJECTIVE: To investigate whether plasma...... according to severity of MMVD. Plasma cTnI was analyzed by a high sensitivity cTnI assay with a lower limit of detection of 0.001 ng/mL, and plasma CRP was analyzed by a canine-specific CRP ELISA. RESULTS: Higher cTnI concentrations were detected in dogs with moderate (0.014 [interquartile range 0...... associations of age, CRP, heart rate, and left ventricular end-diastolic diameter, on cTnI concentration C-reactive protein did not differ among severity groups, but was significantly associated with cTnI, breed, and systolic blood pressure on CRP concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: Analysis...

  9. Troponin T in patients with traumatic chest injuries with and without cardiac involvement: Insights from an observational study

    Directory of Open Access Journals (Sweden)

    Ismail Mahmood

    2016-01-01

    Full Text Available Background: Serum troponin T (TnT is a common marker of myocardial injury. However, its implication in the absence of clinical evidence of cardiac reason is not well established. Aims: The aim of this study was to identify the implications of positive TnT in traumatic chest injury (TCI patients regardless of the cardiac involvement. Materials and Methods: We conducted a retrospective analysis of all TCI patients admitted to level 1 trauma center between 2008 and 2011. Patients who underwent TnT testing were divided into two groups: Group 1 (positive TnT and Group 2 (negative TnT. The two groups were analyzed and compared, and multivariate regression analyses were performed to identify predictors of TnT positivity and mortality. Results: Out of 993 blunt TCI patients, 19.3% had positive TnT (Group 1. On comparison to Group 2, patients in Group 1 were 5 years younger and more likely to have head, cardiac, hepatic, splenic, and pelvic injuries, in addition to lung contusion. Positive TnT was associated with higher Injury Severity Score (ISS (P = 0.001, higher chest Abbreviated Injury Score (AIS (P = 0.001, and longer hospital stay (P = 0.03. In addition, Group 1 patients were more likely to undergo chest tube insertion, exploratory laparotomy, mechanical ventilation, and tracheostomy. Twenty patients had cardiac involvement, and of them 14 had positive TnT. Among 973 patients who showed no evidence of cardiac involvement, 178 had positive TnT (18.3%. There were 104 deaths (60% in Group 1. On multivariate regression analysis, the predictors of hospital mortality were positive TnT, head injury, and high ISS, whereas, the predictors of TnT positivity were cardiac, hepatic, and pelvic injuries; higher ISS; and age. Conclusions: Positive TnT in blunt TCI patients is a common challenge, particularly in polytrauma cases. Patients with positive TnT tend to have the worst outcome even in the absence of clinical evidence of acute cardiac involvement

  10. Cardiac troponin I in isoproterenol-induced cardiac injury in the Hanover Wistar rat: studies on low dose levels and routes of administration.

    Science.gov (United States)

    Brady, Sally; York, Malcolm; Scudamore, Cheryl; Williams, Thomas; Griffiths, William; Turton, John

    2010-02-01

    The current studies demonstrate the effect of low-dose intraperitoneal (IP) administration of isoprotenerol (ISO) and subcutaneous (SC) versus IP routes of administration of ISO on serum cardiac troponin I (cTnI) levels in female Hanover Wistar rats, providing additional evidence to support acceptance of cTnI as a cardiac biomarker. At 2 hr postdosing with 0-500 microg/kg ISO, mean serum cTnI levels were increased in a dose-related fashion at > or =10 microg/kg with no evidence of cardiac pathology. At 24 h, cTnI concentrations were generally at control levels, but histologic cardiomyocyte injury was evident in a proportion of the animals given > or =10 microg/kg. In a second experiment, rats given SC ISO at 5,000 microg/kg and necropsied at 0, 1, 2, and 4 hr postdosing had higher levels of serum cTnI than animals given the same dose IP.

  11. Improving Prediction of Postoperative Myocardial Infarction With High-Sensitivity Cardiac Troponin T and NT-proBNP.

    Science.gov (United States)

    Kopec, Michael; Duma, Andreas; Helwani, Mohammad A; Brown, Jamie; Brown, Frank; Gage, Brian F; Gibson, David W; Miller, J Philip; Novak, Eric; Jaffe, Allan S; Apple, Fred S; Scott, Mitchell G; Nagele, Peter

    2017-02-01

    This study sought to determine whether preoperatively measured high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) improve cardiac risk prediction in patients undergoing major noncardiac surgery compared with the standard risk indices. In this ancillary study to the Vitamins in Nitrous Oxide trial, patients were included who had preoperative hs-cTnT and NT-proBNP measured (n = 572). Study outcome was the incidence of postoperative myocardial infarction (MI) within the first 3 postoperative days. hs-cTnT was considered elevated if >14 ng/L and NT-proBNP if >300 ng/L. Additional cutoff values were investigated on the basis of receiver operating characteristic statistics. Biomarker risk prediction was compared with Lee's Revised Cardiac Risk Index (RCRI) with the use of standard methods and net reclassification index. The addition of hs-cTnT (>14 ng/L) and NT-proBNP (>300 ng/L) to RCRI significantly improved the prediction of postoperative MI (event rate 30/572 [5.2%], Area under the receiver operating characteristic curve increased from 0.590 to 0.716 with a 0.66 net reclassification index [95% confidence interval 0.32-0.99], P sensitivity compared with 300 ng/L (0.87 vs 0.53). Sensitivity, specificity, positive, and negative predictive value for hs-cTnT were 0.70, 0.60, 0.09, and 0.97 and for NT-proBNP were 0.53, 0.68, 0.08, and 0.96. The addition of cardiac biomarkers hs-cTnT and NT-proBNP to RCRI improves the prediction of adverse cardiac events in the immediate postoperative period after major noncardiac surgery. The high negative predictive value of preoperative hs-cTnT and NT-proBNP suggest usefulness as a "rule-out" test to confirm low risk of postoperative MI.

  12. Economic Considerations of Early Rule-In/Rule-Out Algorithms for The Diagnosis of Myocardial Infarction in The Emergency Department Using Cardiac Troponin and Glycemic Biomarkers.

    Science.gov (United States)

    Shortt, Colleen; Xie, Feng; Whitlock, Richard; Ma, Jinhui; Clayton, Natasha; Sherbino, Jonathan; Hill, Stephen A; Pare, Guillaume; McQueen, Matthew; Mehta, Shamir R; Devereaux, P J; Worster, Andrew; Kavsak, Peter

    2017-02-01

    We have previously demonstrated the utility of a rule-in/rule-out strategy for myocardial infarction (MI) using glycemic biomarkers in combination with cardiac troponin in the emergency department (ED). Given that the cost of assessing patients with possible MI in the ED is increasing, we sought to compare the health services cost of our previously identified early rule-in/rule-out approaches for MI among patients who present to the ED with symptoms suggestive of acute coronary syndrome (ACS). We compared the cost differences between different rule-in/rule-out strategies for MI using presentation cardiac troponin I (cTnI), high-sensitivity cTnI (hs-cTnI), high-sensitivity cardiac troponin T (hs-cTnT), glucose, and/or hemoglobin A1c (Hb A1c) in 1137 ED patients (7-day MI n = 133) as per our previously defined algorithms and compared them with the European Society of Cardiology (ESC) 0-h algorithm-cutoffs. Costs associated with each decision model were obtained from site-specific sources (length of stay) and provincial sources (Ontario Case Costing Initiative). Algorithms incorporating cardiac troponin and glucose for early rule-in/rule-out were the most cost effective and clinically safest methods (i.e., ≤1 MI missed) for early decision making, with hs-cTnI and glucose yielding lower costs compared to cTnI and glucose, despite the higher price for the hs-cTnI test. The addition of Hb A1c to the algorithms increased the cost of these algorithms but did not miss any additional patients with MI. Applying the ESC 0-h algorithm-cutoffs for hs-cTnI and hs-cTnT were the most costly. Rule-in/rule-out algorithms incorporating presentation glucose with high-sensitivity cardiac troponin are the safest and most cost-effective options as compared to the ESC 0-h algorithm-cutoffs. © 2016 American Association for Clinical Chemistry.

  13. A critical appraisal of experimental factors influencing the definition of the 99th percentile limit for cardiac troponins.

    Science.gov (United States)

    Panteghini, Mauro

    2009-01-01

    The recently released document by the Global Task Force on the "universal" definition of myocardial infarction (MI) recommends a single decision limit for cardiac troponin (cTn) corresponding to the 99th percentile limit of the reference value distribution [99th upper reference limit (URL)] for the diagnosis of patients presenting with suspected MI. However, use of this cut-off concentration posed a problem because most assays do not have the sensitivity to consistently measure cTn in the blood of apparently healthy individuals, with a high proportion of the values being below the method's detection limit. In addition to the influence of assay sensitivity, the 99th URL for cTn can vary depending on the reference population used, and its sample size. A marked difference can also be observed between the 99th URL obtained using plasma vs. that obtained with serum. Finally, some interferences with cTn measurement (e.g., by heterophile antibodies) may become more noticeable using assays that have increased analytical sensitivity that measure lower concentrations of these markers. In conclusion, a number of issues can markedly influence the definition of the 99th URL for cTn, which most clinicians are unaware of and may markedly condition the clinical performance of the test in routine practice.

  14. MIPs-graphene nanoplatelets-MWCNTs modified glassy carbon electrode for the determination of cardiac troponin I.

    Science.gov (United States)

    Ma, Ya; Shen, Xiao-Lei; Wang, Hai-Shui; Tao, Jia; Huang, Jian-Zhi; Zeng, Qiang; Wang, Li-Shi

    2017-03-01

    An electrochemical sensor with high selectivity in addition to sensitivity was developed for the determination of cardiac troponin I (cTnI), based on the modification of cTnI imprinted polymer film on a glassy carbon electrode (GCE). The sensor was fabricated by layer-by-layer assembled graphene nanoplatelets (GS), multiwalled carbon nanotubes (MWCNTs), chitosan (CS), glutaraldehyde (GA) composites, which can increase the electronic transfer rate and the active surface area to capture a larger number of antigenic proteins. MWCNTs/GS based imprinted polymers (MIPs/MWCNTs/GS) were synthesized by means of methacrylic acid (MAA) as the monomer, ethylene glycol dimethacrylate (EGDMA) as the cross linker α,α'-azobisisobutyronitrile (AIBN) as the initiator and cTnI as the template. In comparison with conventional methods, the proposed electrochemical sensor is highly sensitive for cTnI, providing a better linear response range from 0.005 to 60 ng cm(-3) and a lower limit of detection (LOD) of 0.0008 ng cm(-3) under optimal experimental conditions. In addition, the electrochemical sensor exhibited good specificity, acceptable reproducibility and stability. Moreover, satisfactory results were obtained in real human serum samples, indicating that the developed method has the potential to find application in clinical detection of cTnI as an alternative approach.

  15. Multiplex detection of B-type natriuretic peptide, cardiac troponin I and C-reactive protein with photonic suspension array.

    Directory of Open Access Journals (Sweden)

    Wenbin Lu

    Full Text Available A novel photonic suspension array has been developed for multiplex immunoassay. The carriers of this array were silica colloidal crystal beads (SCCBs. The codes of these carriers have characteristic reflection peaks originating from their structural periodicity; therefore they do not suffer from fading, bleaching, quenching or chemical instability. In addition, the fluorescence background of SCCBs is negligible because no fluorescence materials or dyes are involved. With a sandwich method, the proposed suspension array was used for simultaneous multiplex detection of heart failure (HF and coronary heart disease (CAD biomarkers in one test tube. The results showed that the three biomarkers: cardiac troponin I (cTnI, C-reactive protein (CRP and B-type natriuretic peptide (BNP could be assayed in the ranges of 0.1-500 ng/ml, 1-500 mg/L and 0.02-50 ng/ml with detection limits of 0.01 ng/ml, 0.36 mg/L and 0.004 ng/ml at 3σ, respectively. There were no significant differences between the photonic suspension array and traditional parallel single-analyte test. This novel method demonstrated acceptable accuracy, high detection sensitivity and reproducibility and excellent storage stability. This technique provides a new strategy for low cost, automated, and simultaneous multiplex immunoassays of bio-markers.

  16. A High-Performance Fluorescence Immunoassay Based on the Relaxation of Quenching, Exemplified by Detection of Cardiac Troponin I

    Directory of Open Access Journals (Sweden)

    Seung-Wan Kim

    2016-05-01

    Full Text Available The intramolecular fluorescence self-quenching phenomenon is a major drawback in developing high-performance fluorometric biosensors which use common fluorophores as signal generators. We propose two strategies involving liberation of the fluorescent molecules by means of enzymatic fragmentation of protein or dehybridization of double-stranded DNA. In the former, bovine serum albumin (BSA was coupled with the fluorescent BODIPY dye (Red BSA, and then immobilized on a solid surface. When the insolubilized Red BSA was treated with proteinase K (10 units/mL for 30 min, the fluorescent signal was significantly increased (3.5-fold compared to the untreated control. In the second case, fluorophore-tagged DNA probes were linked to gold nanoparticles by hybridization with capture DNA strands densely immobilized on the surface. The quenched fluorescence signal was recovered (3.7-fold by thermal dehybridization, which was induced with light of a specific wavelength (e.g., 530 nm for less than 1 min. We next applied the Red BSA self-quenching relaxation technique employing enzymatic fragmentation to a high-performance immunoassay of cardiac troponin I (cTnI in a microtiter plate format. The detection limit was 0.19 ng/mL cTnI, and the fluorescent signal was enhanced approximately 4.1-fold compared with the conventional method of direct measurement of the fluorescent signal from a non-fragmented fluorophore-labeled antibody.

  17. A centrifugally actuated point-of-care testing system for the surface acoustic wave immunosensing of cardiac troponin I.

    Science.gov (United States)

    Lee, Woochang; Jung, Jaeyeon; Hahn, Young Ki; Kim, Sang Kyu; Lee, Yeolho; Lee, Joonhyung; Lee, Tae-Han; Park, Jin-Young; Seo, Hyejung; Lee, Jung Nam; Oh, Jin Ho; Choi, Youn-Suk; Lee, Soo Suk

    2013-05-07

    A fully automated point-of-care testing (POCT) system with a surface acoustic wave (SAW) immunosensor was developed for rapid and sensitive detection of cardiac troponin I (cTnI) in body fluid (plasma and whole blood). The assay, based on gold nanoparticle sandwich immunoassay and subsequent gold staining, was performed on the SAW immunosensor packaged inside a disposable microfluidic cartridge. The entire fluidic process, including plasma separation, reagent transport, metering, and mixing, was carried out by controlling the centrifugal force acting on the rotating cartridge and laser-irradiated ferrowax microvalves. On investigation of sensor response to various cTnI concentrations, the system exhibited a high performance with a detection limit of 6.7 pg mL(-1), and the coefficient of variation was less than 10% over the entire test range (10 pg mL(-1) to 25 ng mL(-1)). On comparing this POCT system with a clinically utilized system in a physical laboratory (Centaur® XP; Siemens), a correlation coefficient of 0.998 was found, validating the diagnostic capability of the SAW immunosensor.

  18. Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death

    DEFF Research Database (Denmark)

    Nyegaard, Mette; Overgaard, Michael Toft; Søndergaard, Mads

    2012-01-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a devastating inherited disorder characterized by episodic syncope and/or sudden cardiac arrest during exercise or acute emotion in individuals without structural cardiac abnormalities. Although rare, CPVT is suspected to cause...... calmodulin-binding-domain peptide at low calcium concentrations. We conclude that calmodulin mutations can cause severe cardiac arrhythmia and that the calmodulin genes are candidates for genetic screening of individual cases and families with idiopathic ventricular tachycardia and unexplained sudden cardiac...

  19. Cardiac Troponin Elevation Predicts Mortality in Patients Undergoing Orthotopic Liver Transplantation

    Directory of Open Access Journals (Sweden)

    David Snipelisky

    2013-01-01

    Full Text Available Introduction. While patients undergoing orthotopic liver transplantation (OLT have high cardiovascular event rates, preoperative risk stratification may not necessarily predict those susceptible patients. Troponin T (TnT may help predict patients at risk for cardiovascular complications. Methods. Consecutive patients undergoing OLT at Mayo Clinic in Florida between 1998 and 2010 who had TnT obtained within 10 days following surgery were included. Three groups were compared based on TnT level: (1 normal (TnT ≤0.01 ng/mL, (2 intermediate (TnT 0.02–0.11 ng/mL, and (3 elevated (TnT >0.11 ng/mL. Overall and cardiovascular mortality was assessed. Results. Of the 78 patients included, there was no difference in age, gender, severity of liver disease, and echocardiographic findings. Patients in the normal and intermediate TnT groups had a lower overall mortality rate (14.3% and 0%, resp. when compared with those with elevated TnT (50%; P=0.001. Patients in the elevated TnT group had a cardiovascular mortality rate of 37.5% compared with 1.4% in the other groups combined (P<0.01. The elevated TnT group had a much higher mortality rate when compared with those in the intermediate group (P<0.0001. Conclusion. TnT may accurately help risk stratify patients in the early postoperative setting to better predict cardiovascular complications.

  20. Preparation of Anti—Cardiac Troponin I Monoclonal Antibodies and Their Characterization with Surface Plasmon Resonance Biosensor

    Institute of Scientific and Technical Information of China (English)

    WEIJing-yan; LIUXia; SONGDa-qian; BULi-sha; HUXing; MUYing

    2003-01-01

    Cardiac troponin I(cTuI)was separated and purified from human left ventricular tissue by affinity chromatographic method and used to immunize Balb/c mice by intraperitoneal injection and four hybridoma cell lines,which secreted monoclonal antibody(mAb)against buman cTnI,were obtained by cell fusion,identification and cloning twice.Three mAbs(9F5,2F11,8C12)were produced from the ascites of Balb/c mice injected intraperitoneally the hybridoma cells and characterized by means of a surface plasmon resonance(SPR) biosensor.An optimal and specific sensing membrane for troponin I was prepared with staphylococcal protein A(SPA) as the intermediate layer and mAb against human cTnI as the capture antibody.On the basis of the sensing membrane,two modes of operation of the SPR biosensor were developed,i.e..a direct detection of antigen-antibody affinity and a sandwich assay.In the sandwich assay deteciton mode,the mAbs competition was measured by monitoring whether the secondary antibody had been attached to the cTnI alresdy captured by the first antibody on the sensor surface.The SPR biosensor was shown to be able to directly daptured by the first antibody on the sensor surface.The SPR biosensor was shown to be abloe to directly detect the antigen-antibody affinity and the order of the affinity was found to be 9F5>2F11>8C12.In the sandwich detection mode,it was found that the different epitopes on the cTnI molecules were recognized by the three mAbs respectively,but the asymmetrical competition was shown between 2F11 and 8C12 and no competition was found between 9F5 and 2F11 or 8c12.Based on these results,a double monoclonal sandwich immunoassay for cTnI was developed by using the optmal antibody pair of 9F5 and 2F11 and the SPR biosensor with SPA substrate membrane,which showed an excellent sensitivity of 0.8μg/L for both the buffer and the serum samples compared with the direct detection of cTnI for the buffer with the lowest detection limit of 4μg/L and conventional

  1. Preparation of Anti-cardiac Troponin I Monoclonal Antibodies and Their Characterization with Surface Plasmon Resonance Biosensor

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Cardiac troponin I(cTnI) was separated and purified from human left ventricular tissue by affinity chromatographic method and used to immunize Balb/c mice by intraperitoneal injection and four hybridoma cell lines, which secreted monoclonal antibody(mAb) against human cTnI, were obtained by cell fusion, identification and cloning twice. Three mAbs(9F5, 2F11, 8C12) were produced from the ascites of Balb/c mice injected intraperitoneally the hybridoma cells and characterized by means of a surface plasmon resonance(SPR) biosensor. An optimal and specific sensing membrane for troponin I was prepared with staphylococcal protein A(SPA) as the intermediate layer and mAb against human cTnI as the capture antibody. On the basis of the sensing membrane, two modes of operation of the SPR biosensor were developed, i.e., a direct detection of antigen-antibody affinity and a sandwich assay. In the sandwich assay detection mode, the mAbs competition was measured by monitoring whether the secondary antibody had been attached to the cTnI already captured by the first antibody on the sensor surface. The SPR biosensor was shown to be able to directly detect the antigen-antibody affinity and the order of the affinity was found to be 9F5>2F11>8C12. In the sandwich detection mode, it was found that the different epitopes on the cTnI molecules were recognized by the three mAbs respectively, but the asymmetrical competition was shown between 2F11 and 8C12 and no competition was found between 9F5 and 2F11 or 8c12. Based on these results, a double monoclonal sandwich immunoassay for cTnI was developed by using the optimal antibody pair of 9F5 and 2F11 and the SPR biosensor with SPA substrate membrane, which showed an excellent sensitivity of 0.8 μg/L for both the buffer and the serum samples compared with the direct detection of cTnI for the buffer with the lowest detection limit of 4 μg/L and conventional ELISA with the sensitivity of 1.9 μg/L.

  2. Functional Basis of Three New Recessive Mutations of Slow Skeletal Muscle Troponin T Found in Non-Amish TNNT1 Nemaline Myopathies.

    Science.gov (United States)

    Amarasinghe, Chinthaka; Hossain, M Moazzem; Jin, J-P

    2016-08-16

    Troponin T (TnT) is the tropomyosin (Tm)-binding and thin filament-anchoring subunit of troponin and plays a central role in striated muscle contraction. A nonsense mutation in exon 11 of the TNNT1 gene encoding slow skeletal muscle troponin T (ssTnT) truncating the polypeptide chain at Glu(180) causes a lethal recessive nemaline myopathy (NM) in the Amish (ANM). More TNNT1 NM mutations have been reported recently with similar recessive phenotypes. A nonsense mutation in exon 9 causes truncation at Ser(108), and a splicing site mutation causes truncation at Leu(203). Another splicing site mutation causes an internal deletion of the 39 exon 8-encoded amino acids. We engineered and characterized these ssTnT mutants to demonstrate that the Ser(108) truncation exhibits a Tm binding affinity lower than that of the ANM Glu(180) truncation, indicating a partial loss of Tm-binding site 1. Despite the presence of Tm-binding sites 1 and 2, ssTnT truncated at Leu(203) binds Tm with decreased affinity, consistent with its recessive NM phenotype and the requirement of troponin complex formation for high-affinity binding of TnT to Tm. The exon 8-deleted ssTnT has a partial loss of Tm-binding site 1 but retains high-affinity Tm-binding site 2. However, exon 8-deleted ssTnT exhibits a dramatically diminished Tm binding affinity, indicating a long-range conformational effect of this middle region deletion. Predicted from the TnT structure-function relationship, removal of the N-terminal variable region partially rescued this negative impact. These novel findings lay a foundation for understanding the pathogenesis of TNNT1 myopathies and provide insights into the development of targeted treatment.

  3. Immediate hypothermia reduces cardiac troponin I after hypoxic-ischemic encephalopathy in newborn pigs.

    Science.gov (United States)

    Liu, Xun; Tooley, James; Løberg, Else M; Suleiman, M Saadeh; Thoresen, Marianne

    2011-10-01

    Neonatal hypoxic-ischemic encephalopathy (HIE) is a clinically defined neurological condition after lack of oxygen and often associated with cardiac dysfunction in term infants. Therapeutic hypothermia (HT) after birth is neuroprotective in infants with HIE. However, it is not known whether HT is also cardioprotective. Four newborn pigs were used in the pilot study and a further 18 newborn pigs [randomly assigned to 72 h normothermia (NT) or 24 h HT followed by 48 h NT] were subjected to global HIE insults. Serum cTnI was measured before and post the HIE insult. Blood pressure, inotropic support, blood gases, and heart rate (HR) were recorded throughout. Cardiac pathology was assessed from histological sections. Cooling reduced serum cTnI levels significantly in HT pigs by 6 h (NT, 1.36 ± 0.67; HT, 0.34 ± 0.23 ng/mL; p = 0.0009). After rewarming, from 24 to 30 h postinsult, HR and cTnI increased in the HT group; from HR[24 h] = 117 ± 22 to HR[30 h] = 218 ± 32 beats/min (p = 0.0002) and from cTnI[24 h] = 0.23 ± 0.12 to cTnI[30 h] = 0.65 ± 0.53 ng/mL, (p = 0.05). There were fewer ischemic lesions on cardiac examination (37%) in the HT group compared with the NT group (70%). HT (24 h) pigs did not have the postinsult cTnI increase seen in NT-treated pigs. There was a trend that HT improved cardiac pathology in this 3-d survival model.

  4. A new immunochemistry platform for a guideline-compliant cardiac troponin T assay at the point of care: proof of principle.

    Science.gov (United States)

    Lopez-Calle, Eloisa; Espindola, Pamela; Spinke, Juergen; Lutz, Sascha; Nichtl, Alfons; Tgetgel, Armin; Herbert, Nicolas; Marcinowski, Moritz; Klepp, Juergen; Fischer, Thomas; Brueckner, Thorsten; Boehm, Christoph; Keller, Thomas

    2017-04-04

    A multitude of troponin assays for the point-of-care (POC) have been developed showing a lack of analytical sensitivity and precision. We present a new platform solution for the high-sensitivity detection of cardiac troponin T (cTnT) in a 30 μL whole blood sample with a turnaround time of 11 min. The immunoassay was completely run in a ready-to-use plastic disposable, a centrifugal microfluidic disc with fully integrated reagents. After the sample application, the assay was automatically processed by separating the cellular blood components via centrifugation, followed by incubation of a defined volume from the generated plasma with the immunoreagents. The fluorescence in the signal zone of a membrane was measured after its washing for the cTnT quantitation. A calibration curve, measured in whole blood samples spiked with native human cTnT, was generated covering a range up to a concentration of approximately 8300 ng/L. The lower detection limit was determined to be 3.0 ng/L. At a concentration of 14 ng/L, the 99th percentile value from the high-sensitivity cardiac troponin T (hs-cTnT) assay in the Elecsys® system, the imprecision (CV) was 3.8%. A CV profile indicated that the functional sensitivity for a CV <10% was 6.8 ng/L. The assay did not show any significant cross-reaction with human skeletal troponin T. We observed an excellent correlation with the hs-TnT Elecsys® assay for 49 clinical plasma samples (r=0.9744). The described technology shows that an analytical performance for a highly sensitive determination of cTnT can be achieved in a POC setting.

  5. Elevated plasma levels of cardiac troponin-I predict left ventricular systolic dysfunction in patients with myotonic dystrophy type 1: A multicentre cohort follow-up study

    Science.gov (United States)

    Robb, Yvonne; Cumming, Sarah; Gregory, Helen; Duncan, Alexis; Rahman, Monika; McKeown, Anne; McWilliam, Catherine; Dean, John; Wilcox, Alison; Farrugia, Maria E.; Cooper, Anneli; McGhie, Josephine; Adam, Berit; Petty, Richard; Longman, Cheryl; Findlay, Iain; Japp, Alan; Monckton, Darren G.; Denvir, Martin A.

    2017-01-01

    Objective High sensitivity plasma cardiac troponin-I (cTnI) is emerging as a strong predictor of cardiac events in a variety of settings. We have explored its utility in patients with myotonic dystrophy type 1 (DM1). Methods 117 patients with DM1 were recruited from routine outpatient clinics across three health boards. A single measurement of cTnI was made using the ARCHITECT STAT Troponin I assay. Demographic, ECG, echocardiographic and other clinical data were obtained from electronic medical records. Follow up was for a mean of 23 months. Results Fifty five females and 62 males (mean age 47.7 years) were included. Complete data were available for ECG in 107, echocardiography in 53. Muscle Impairment Rating Scale score was recorded for all patients. A highly significant excess (p = 0.0007) of DM1 patients presented with cTnI levels greater than the 99th centile of the range usually observed in the general population (9 patients; 7.6%). Three patients with elevated troponin were found to have left ventricular systolic dysfunction (LVSD), compared with four of those with normal range cTnI (33.3% versus 3.7%; p = 0.001). Sixty two patients had a cTnI level < 5ng/L, of whom only one had documented evidence of LVSD. Elevated cTnI was not predictive of severe conduction abnormalities on ECG, or presence of a cardiac device, nor did cTnI level correlate with muscle strength expressed by Muscle Impairment Rating Scale score. Conclusions Plasma cTnI is highly elevated in some ambulatory patients with DM1 and shows promise as a tool to aid cardiac risk stratification, possibly by detecting myocardial involvement. Further studies with larger patient numbers are warranted to assess its utility in this setting. PMID:28323905

  6. Ca2+-induced PRE-NMR changes in the troponin complex reveal the possessive nature of the cardiac isoform for its regulatory switch.

    Science.gov (United States)

    Cordina, Nicole M; Liew, Chu K; Potluri, Phani R; Curmi, Paul M; Fajer, Piotr G; Logan, Timothy M; Mackay, Joel P; Brown, Louise J

    2014-01-01

    The interaction between myosin and actin in cardiac muscle, modulated by the calcium (Ca2+) sensor Troponin complex (Tn), is a complex process which is yet to be fully resolved at the molecular level. Our understanding of how the binding of Ca2+ triggers conformational changes within Tn that are subsequently propagated through the contractile apparatus to initiate muscle activation is hampered by a lack of an atomic structure for the Ca2+-free state of the cardiac isoform. We have used paramagnetic relaxation enhancement (PRE)-NMR to obtain a description of the Ca2+-free state of cardiac Tn by describing the movement of key regions of the troponin I (cTnI) subunit upon the release of Ca2+ from Troponin C (cTnC). Site-directed spin-labeling was used to position paramagnetic spin labels in cTnI and the changes in the interaction between cTnI and cTnC subunits were then mapped by PRE-NMR. The functionally important regions of cTnI targeted in this study included the cTnC-binding N-region (cTnI57), the inhibitory region (cTnI143), and two sites on the regulatory switch region (cTnI151 and cTnI159). Comparison of 1H-15N-TROSY spectra of Ca2+-bound and free states for the spin labeled cTnC-cTnI binary constructs demonstrated the release and modest movement of the cTnI switch region (∼10 Å) away from the hydrophobic N-lobe of troponin C (cTnC) upon the removal of Ca2+. Our data supports a model where the non-bound regulatory switch region of cTnI is highly flexible in the absence of Ca2+ but remains in close vicinity to cTnC. We speculate that the close proximity of TnI to TnC in the cardiac complex is favourable for increasing the frequency of collisions between the N-lobe of cTnC and the regulatory switch region, counterbalancing the reduction in collision probability that results from the incomplete opening of the N-lobe of TnC that is unique to the cardiac isoform.

  7. Ca2+-induced PRE-NMR changes in the troponin complex reveal the possessive nature of the cardiac isoform for its regulatory switch.

    Directory of Open Access Journals (Sweden)

    Nicole M Cordina

    Full Text Available The interaction between myosin and actin in cardiac muscle, modulated by the calcium (Ca2+ sensor Troponin complex (Tn, is a complex process which is yet to be fully resolved at the molecular level. Our understanding of how the binding of Ca2+ triggers conformational changes within Tn that are subsequently propagated through the contractile apparatus to initiate muscle activation is hampered by a lack of an atomic structure for the Ca2+-free state of the cardiac isoform. We have used paramagnetic relaxation enhancement (PRE-NMR to obtain a description of the Ca2+-free state of cardiac Tn by describing the movement of key regions of the troponin I (cTnI subunit upon the release of Ca2+ from Troponin C (cTnC. Site-directed spin-labeling was used to position paramagnetic spin labels in cTnI and the changes in the interaction between cTnI and cTnC subunits were then mapped by PRE-NMR. The functionally important regions of cTnI targeted in this study included the cTnC-binding N-region (cTnI57, the inhibitory region (cTnI143, and two sites on the regulatory switch region (cTnI151 and cTnI159. Comparison of 1H-15N-TROSY spectra of Ca2+-bound and free states for the spin labeled cTnC-cTnI binary constructs demonstrated the release and modest movement of the cTnI switch region (∼10 Å away from the hydrophobic N-lobe of troponin C (cTnC upon the removal of Ca2+. Our data supports a model where the non-bound regulatory switch region of cTnI is highly flexible in the absence of Ca2+ but remains in close vicinity to cTnC. We speculate that the close proximity of TnI to TnC in the cardiac complex is favourable for increasing the frequency of collisions between the N-lobe of cTnC and the regulatory switch region, counterbalancing the reduction in collision probability that results from the incomplete opening of the N-lobe of TnC that is unique to the cardiac isoform.

  8. Comparison of serum cardiac troponin-I and creatine kinase MB isoenzyme concentrations in asphyxiated neonates

    Institute of Scientific and Technical Information of China (English)

    Nouran F.Hussien; Eman A.Abdel Ghany; Amany E.Elwan; Yasser H.Kamel; Dina K.Ali

    2009-01-01

    Objective:To assess the correlation of signs of myocardial damage to serum cardiac tmponin I(cTnI)and creatine kinase MB isoenzyme(CK-MB)concentrations.Methods:Blood samples were collected from 25 term asphyxiated neonates and 25 controls at 12 h of age by immunoassay.The asphyxiated neonates were followed up until discharge or death.Results:Asphyxiated neonates had significanfly higher concentrations of cTnI and CK-MB than controls(P<0.001).Serum cTnI concentrations were significantly higher in asphyxiated neonates who developed hypotension,heart failure or those had low ejection fraction(P<0.01).Serum cTnI concentrations were significantly higher in asphyxiated who died than those who survived(P<0.01).There was no significant difference in selMnl CK-MB mass concentrations between asphyxiated neonates with and without these complications.Conclusion:Unlike CK-MB,serum cTnI concentrations are significantly higher in asphyxiated neonates who died or developed cardiac dysfunction.

  9. Cardiac troponin I concentration is commonly increased in nondialysis patients with CKD: experience with a sensitive assay.

    Science.gov (United States)

    Lamb, Edmund J; Kenny, Claire; Abbas, Nasir A; John, R Ian; Webb, Michelle C; Price, Christopher P; Vickery, Susan

    2007-04-01

    Cardiac troponin (cTn) concentrations commonly are increased in patients with chronic kidney disease (CKD) in the absence of an acute coronary syndrome. cTn T (cTnT) concentration reportedly is increased more commonly than cTn I (cTnI). Using a sensitive cTnI assay, we studied cTnI concentrations in predialysis patients with CKD who did not have an acute coronary event. Observational cohort study. Nondialysis patients with CKD attending an outpatient clinic. Plasma cTnI was measured using the cTnI-Ultra assay (Bayer HealthCare LLC, Diagnostics Division, Tarrytown, NY), the same manufacturer's standard cTnI assay, and a cTnT assay (Roche Diagnostics PLC, East Sussex, UK). Prevalence of increased cTn concentration, effect of clinical variables on cTnI-Ultra concentration, and independent associations between cTn assays and all-cause mortality by using multiple regression modeling. Plasma cTnI-Ultra concentration exceeded the upper limit of normal in 33% of patients compared with 18% with the cTnI-standard assay and 43% with the cTnT assay. Age, vascular disease, parathyroid hormone concentration, and left ventricular mass, but not kidney function, had independent effects on plasma cTnI-Ultra concentrations. There were 39 deaths during follow-up. Survival was decreased in patients with baseline cTnI-Ultra concentrations of 0.040 ng/mL or greater (54% versus 83%; P sensitive assay, we found that the prevalence of increased cTnI concentrations in patients with CKD is similar to that observed for cTnT. cTnT concentration, but not cTnI, was independently associated with death.

  10. Evaluation of C-reactive protein, Haptoglobin and cardiac troponin 1 levels in brachycephalic dogs with upper airway obstructive syndrome

    Directory of Open Access Journals (Sweden)

    Planellas Marta

    2012-08-01

    Full Text Available Abstract Background Brachycephalic dogs have unique upper respiratory anatomy with abnormal breathing patterns similar to those in humans with obstructive sleep apnea syndrome (OSAS. The objective of this study was to evaluate the correlation between anatomical components, clinical signs and several biomarkers, used to determine systemic inflammation and myocardial damage (C-reactive protein, CRP; Haptoglobin, Hp; cardiac troponin I, cTnI, in dogs with brachycephalic upper airway obstructive syndrome (BAOS. Results Fifty brachycephalic dogs were included in the study and the following information was studied: signalment, clinical signs, thoracic radiographs, blood work, ECG, components of BAOS, and CRP, Hp and cTnI levels. A high proportion of dogs with BAOS (88% had gastrointestinal signs. The prevalence of anatomic components of BAOS was: elongated soft palate (100%, stenotic nares (96%, everted laryngeal saccules (32% and tracheal hypoplasia (29.1%. Increased serum levels of biomarkers were found in a variable proportion of dogs: 14% (7/50 had values of CRP > 20 mg/L, 22.9% (11/48 had values of Hp > 3 g/L and 47.8% (22/46 had levels of cTnI > 0.05 ng/dl. Dogs with everted laryngeal saccules had more severe respiratory signs (p Conclusions According to the low percentage of patients with elevated levels of CRP and Hp, BAOS does not seem to cause an evident systemic inflammatory status. Some degree of myocardial damage may occur in dogs with BAOS that can be detected by cTnI concentration.

  11. Establishment of a reference interval for high-sensitivity cardiac troponin I in healthy adults from the Sichuan area.

    Science.gov (United States)

    Li, Shunjun; Zuo, Yue; Huang, Wenfang

    2017-04-01

    High-sensitivity cardiac troponin I (hs-cTnI) has been used in the diagnosis and risk stratification of acute myocardial infarction. However, there is no common consensus on an hs-cTnI reference interval for the Chinese population. The aim of this study was to describe the distribution of hs-TnI and establish the 99th percentile reference interval for hs-cTnI in healthy adults from the Sichuan area.Serum specimens were collected from 1485 healthy adults (731 men and 754 women ranging in age from 18 to 85 years) in Sichuan Provincial People's Hospital. All specimens were divided into 4 groups according to age distribution: 18 to 35 years, 36 to 50 years, 51 to 65 years, and ≥66 years. Specimens were further divided into younger/middle and older-aged groups based on a cut-off age of 50 years. The serum hs-cTnI concentration was determined using the Abbott ARCHITECT STAT hs-cTnI assay.The serum hs-cTnI concentration increased with age (P 51 to 65 years, and 27.9 versus 32.2 pg/mL for ≥66 years.The 99th percentile reference interval for hs-cTnI in healthy adults from the Sichuan area was similar to the manufacturer's recommendation. Men had a higher 99th percentile hs-cTnI value than women in the age range of 18 to 65 years.

  12. A sodium-channel mutation causes isolated cardiac conduction disease

    NARCIS (Netherlands)

    Tan, HL; Bink-Boelkens, MTE; Bezzina, CR; Viswanathan, PC; Beaufort-Krol, GCM; van Tintelen, PJ; van den Berg, MP; Wilde, AAM; Balser, [No Value

    2001-01-01

    Cardiac conduction disorders slow the heart rhythm and cause disability in millions of people worldwide. Inherited mutations in SCN5A, the gene encoding the human cardiac sodium (Na+) channel, have been associated with rapid heart rhythms that occur suddenly and are life-threatening(1-3); however, a

  13. A non-ischaemic cause of elevated troponin.

    Science.gov (United States)

    Lefort, Guy; D'Antonio, Claude; Caffery, Terrell

    2014-04-04

    A 27-year-old woman with chest pain was admitted for elevated troponin levels. Troponin remained mildly elevated upon repeat testing, and a review of the medical record revealed that she had had an elevated troponin level in the past. She had a cardiac catheterisation that revealed angiographically normal coronary arteries. Repeat troponin testing with and without ethylene glycol revealed a negative troponin level after addition of ethylene glycol, suggesting antibodies were interfering with the assay.

  14. Nemaline body myopathy caused by a novel mutation in troponin T1 (TNNT1).

    Science.gov (United States)

    Abdulhaq, Ulla Najwa; Daana, Mohannad; Dor, Talia; Fellig, Yakov; Eylon, Sharon; Schuelke, Markus; Shaag, Avraham; Elpeleg, Orly; Edvardson, Simon

    2016-04-01

    Nemaline myopathy is a rare disorder characterized by skeletal muscle weakness of varying severity and onset, with the presence of nemaline rods on muscle biopsy. Congenital nemaline body myopathy due to mutations in TNNT1 has hitherto only been described as a result of a single founder mutation in patients of Amish origin and in 2 other individuals with different recessive mutations. Autozygosity mapping and whole exome sequencing were applied after we identified 9 Palestinian patients from 7 unrelated families who have nemaline myopathy. All patients were homozygous for a novel complex rearrangement of the TNNT1 gene (c.574_577delinsTAGTGCTGT | NM_003283) leading to C-terminal truncation of the protein (p.L203* | NP_003274.3). Their clinical course was remarkable for early respiratory failure and striking stiffness of the cervical spine. This report exemplifies the utility of combining autozygosity mapping and whole exome sequencing and expands the phenotype associated with TNNT1 mutations. © 2015 Wiley Periodicals, Inc.

  15. Is periprocedural CK-MB a better indicator of prognosis after emergency and elective percutaneous coronary intervention compared with post-procedural cardiac troponins?

    Science.gov (United States)

    Gollop, Nicholas D; Dhullipala, Anumita; Nagrath, Nalin; Myint, Phyo K

    2013-11-01

    A best evidence topic in interventional cardiac surgery was written according to a structured protocol. The question we addressed related to the elevation of markers of cardiac damage associated with percutaneous coronary intervention (PCI). We explored and compared the clinical and prognostic relevance of the elevation of creatinine kinase-myocardial band (CK-MB) and cardiac troponin (cTn) levels during the periprocedural period and the post-procedural period, respectively, following an emergency or elective PCI. We found in excess of 390 papers after a systematic literature search, of which 10 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. From the best evidence available it appears that the monitoring of cardiac biomarkers following a PCI can provide important clinical information about the health of the myocardium, as well as prognostic information on short to mid-term outcomes of mortality up to 3 years. The narrow evidence base advocates the use of periprocedural CK-MB monitoring, recommending that an elevation in CK-MB is a significant predictor of adverse events. Troponins remain a precise and reliable marker of cardiac damage; however, current evidence argues that cTn holds little prognostic relevance until the degree of elevation is almost five times the upper limit of normal (ULN). Thus, the best evidence recommends the use of periprocedural CK-MB routinely during PCI to provide clinical and prognostic information about the degree of myocardial injury and risk of post-procedural morbidity and mortality.

  16. Channelopathies from mutations in the cardiac sodium channel protein complex.

    Science.gov (United States)

    Adsit, Graham S; Vaidyanathan, Ravi; Galler, Carla M; Kyle, John W; Makielski, Jonathan C

    2013-08-01

    The cardiac sodium current underlies excitability in heart, and inherited abnormalities of the proteins regulating and conducting this current cause inherited arrhythmia syndromes. This review focuses on inherited mutations in non-pore forming proteins of sodium channel complexes that cause cardiac arrhythmia, and the deduced mechanisms by which they affect function and dysfunction of the cardiac sodium current. Defining the structure and function of these complexes and how they are regulated will contribute to understanding the possible roles for this complex in normal and abnormal physiology and homeostasis. This article is part of a Special Issue entitled "Na(+) Regulation in Cardiac Myocytes". Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. High-sensitivity cardiac troponin T in prediction and diagnosis of myocardial infarction and long-term mortality after noncardiac surgery.

    Science.gov (United States)

    Nagele, Peter; Brown, Frank; Gage, Brian F; Gibson, David W; Miller, J Philip; Jaffe, Allan S; Apple, Fred S; Scott, Mitchell G

    2013-08-01

    Perioperative myocardial infarction (MI) is a serious complication after noncardiac surgery. We hypothesized that preoperative cardiac troponin T detected with a novel high-sensitivity (hs-cTnT) assay will identify patients at risk for acute MI and long-term mortality after major noncardiac surgery. This was a prospective cohort study within the VINO trial (n = 608). Patients had been diagnosed with or had multiple risk factors for coronary artery disease and underwent major noncardiac surgery. Cardiac troponin I (contemporary assay) and troponin T (high-sensitivity assay) and 12-lead electrocardiograms were obtained before and immediately after surgery and on postoperative days 1, 2, and 3. At baseline before surgery, 599 patients (98.5%) had a detectable hs-cTnT concentration, and 247 (41%) were >14 ng/L (99th percentile). After surgery, 497 patients (82%) had a rise in hs-cTnT (median change in hs-cTnT +2.7 ng/L [interquartile range 0.7-6.8]). During the first 3 postoperative days, there were 9 patients (2.5%) with a preoperative hs-cTnT 14 ng/L (odds ratio 3.67, 95% CI 1.65-8.15). During long-term follow-up, 80 deaths occurred. The 3-year mortality rate was 11% in patients with a preoperative hs-cTnT concentration 14 ng/L (adjusted hazard ratio 2.17, 95% CI 1.19-3.96). In this cohort of high-risk patients, preoperative hs-cTnT concentrations were significantly associated with postoperative MI and long-term mortality after noncardiac surgery. Copyright © 2013 Mosby, Inc. All rights reserved.

  18. Elevated CK-MB with a normal troponin does not predict 30-day adverse cardiac events in emergency department chest pain observation unit patients.

    Science.gov (United States)

    Safdar, Basmah; Bezek, Sarah K; Sinusas, Albert J; Russell, Raymond R; Klein, Matthew R; Dziura, James D; D'Onofrio, Gail

    2014-03-01

    Prior studies indicate that an elevated creatinine kinase (CK)-MB imparts poor prognosis in patients with acute coronary syndrome despite a normal troponin. Its prognosis in the undifferentiated chest pain observation unit (CPU) population remains undefined. To compare rates and predictors of 30-day adverse cardiac events in 2 cohorts (CK ±/MB+ vs. normal [CK ±/MB-]) in low-moderate-risk CPU patients. Consecutive CPU patients were followed in a retrospective cohort study for primary outcome (acute coronary syndrome, percutaneous transluminal coronary angioplasty, coronary artery bypass graft, abnormal stress test, cardiac hospitalization, or death within 30 days) by using standardized chart reviews and national death registry. Exclusions were: those aged 30 years or younger, positive troponin, ischemic electrocardiogram, hemodynamic instability, heart failure, or dialysis. Between January 2006 and April 2009, 2979 patients were eligible, of which 350 excluded and 2629 analyzed. MB+ compared with normal patients were more likely to be: older (mean, 53.4 ± 14 vs. 51.5 ± 12 years; P = 0.04); male (71% vs. 40%; P = 0.01); renal insufficient (5% vs. 2%; P = 0.01); hypertensive (50% vs. 44%; P = 0.04); dyslipidemic (44% vs. 33%; P = 0.01) obese (55% vs. 43%; P = 0.01); and with known coronary artery disease (14% vs. 5%; P MB+ vs. normal (9.1%, 8.0%; odds ratio, 1.1, 0.7-1.9) or serial MB+ vs. normal (7.5%, 7.4%; odds ratio, 1.0, 0.5-1.8). In a multiple logistic regression model, male sex, diabetes, and prior CAD predicted adverse events, whereas CK-MB along with race, hypertension, smoking, dyslipidemia, family history, and obesity did not. Elevated CK-MB does not add value to serial troponin testing in low-moderate-risk CPU patients.

  19. Population pharmacokinetic modelling of doxorubicin and doxorubicinol in children with cancer: is there a relationship with cardiac troponin profiles?

    Science.gov (United States)

    Kunarajah, Kuhan; Hennig, Stefanie; Norris, Ross L G; Lobb, Michael; Charles, Bruce G; Pinkerton, Ross; Moore, Andrew S

    2017-07-01

    Anthracyclines are a mainstay of the treatment of several childhood malignancies, but their utility is limited by dose-related cardiotoxicity. This study is aimed to explore the link between exposure of paediatric cancer patients to doxorubicin and its metabolite doxorubicinol, and cardiac troponin I (cTnI). In a prospective pilot study plasma doxorubicin, doxorubicinol, and cTnI concentrations were measured in samples from children undergoing cancer chemotherapy. A mixed-effects population pharmacokinetic model for doxorubicin and doxorubicinol and in combination with a turn-over model for cTnI were developed. Seventeen patients, aged 3.4-14.7 year, treated for a variety of cancers had 99 doxorubicin and 119 doxorubicinol concentrations analysed from samples drawn between 0.5 and 336 h after the start of the infusion. Eleven patients had received previous doses of anthracyclines, with a median cumulative prior dose of 90 mg/m(2) (range 0-225 mg/m(2)). The median administered doxorubicin dose was 30 mg/m(2) (range 25-75 mg/m(2)). Doxorubicin disposition was described by a three-compartment model with first-order elimination and metabolism to doxorubicinol. Body surface area was related to all clearance and distribution parameters and age further influenced clearance (CL, 58.7 L/h/1.8 m(2) for an average 8.4-year-old patient). Combined doxorubicin and metabolite exposure stimulated a temporary increase in cTnI in plasma, with a concentration of 11.8 µg/L required to achieve half-maximal effect. Prior cumulative anthracycline dosage received by patients was predictive of an increased cTnI baseline prior to a new doxorubicin dose. Prior anthracycline exposure increased baseline cTnI in a dose-dependent manner, consistent with the known cumulative risk of anthracycline exposure-induced cardiotoxicity.

  20. Association Between High-Sensitivity Cardiac Troponin Levels and Myocardial Ischemia During Mental Stress and Conventional Stress.

    Science.gov (United States)

    Hammadah, Muhammad; Al Mheid, Ibhar; Wilmot, Kobina; Ramadan, Ronnie; Alkhoder, Ayman; Obideen, Malik; Abdelhadi, Naser; Fang, Shuyang; Ibeanu, Ijeoma; Pimple, Pratik; Mohamed Kelli, Heval; Shah, Amit J; Pearce, Brad; Sun, Yan; Garcia, Ernest V; Kutner, Michael; Long, Qi; Ward, Laura; Bremner, J Douglas; Esteves, Fabio; Raggi, Paolo; Sheps, David; Vaccarino, Viola; Quyyumi, Arshed A

    2017-03-10

    This study sought to investigate whether patients with mental stress-induced myocardial ischemia will have high resting and post-mental stress high-sensitivity cardiac troponin I (hs-cTnI). Hs-cTnI is a marker of myocardial necrosis, and its elevated levels are associated with adverse outcomes. Hs-cTnI levels may increase with exercise in patients with coronary artery disease. Mental stress-induced myocardial ischemia is also linked to adverse outcomes. In this study, 587 patients with stable coronary artery disease underwent technetium Tc 99m sestamibi-single-photon emission tomography myocardial perfusion imaging during mental stress testing using a public speaking task and during conventional (pharmacologic/exercise) stress testing as a control condition. Ischemia was defined as new/worsening impairment in myocardial perfusion using a 17-segment model. The median hs-cTnI resting level was 4.3 (interquartile range [IQR]: 2.9 to 7.3) pg/ml. Overall, 16% and 34.8% of patients developed myocardial ischemia during mental and conventional stress, respectively. Compared with those without ischemia, median resting hs-cTnI levels were higher in patients who developed ischemia either during mental stress (5.9 [IQR: 3.9 to 8.3] vs. 4.1 [IQR: 2.7 to 7.0] pg/ml; p stress (5.4 [IQR: 3.9 to 9.3] vs. 3.9 [IQR: 2.5 to 6.5] pg/ml; p stress-induced ischemia. Although there was a significant increase in 45-min post-treadmill exercise hs-cTnI levels in those who developed ischemia, there was no significant increase after mental or pharmacological stress test. In patients with coronary artery disease, myocardial ischemia during either mental stress or conventional stress is associated with higher resting levels of hs-cTnI. This suggests that hs-cTnI elevation is an indicator of chronic ischemic burden experienced during everyday life. Whether elevated hs-cTnI levels are an indicator of adverse prognosis beyond inducible ischemia or whether it is amenable to intervention requires

  1. Evaluation of copper concentration in subclinical cases of white muscle disease and its relationship with cardiac troponin I.

    Directory of Open Access Journals (Sweden)

    Forough Ataollahi

    Full Text Available The present study aims to evaluate the serum level of copper (Cu in lambs suffering from subclinical forms of white muscle disease (WMD and its relationship with cardiac troponin I (cTn-I as a novel biomarker of cardiovascular disorders. Ten milliliters of jugular blood were taken from 200 lambs less than one year old to measure serum concentrations of Cu, selenium (Se, and cTn-I. The subjects were divided into 2 groups, namely, the deficient group which included 36 lambs, and the control group which included 164 lambs according to the reference serum Se concentration (50 ng/mL. Serum Se levels in the deficient group were lower than 50 ng/mL. By contrast, the control group showed Se levels higher than 50 ng/mL. Differences among the serum Cu and cTn-I levels were determined in both groups. The mean ±SD and median of serum Cu and cTn-I levels in the deficient group were lower and higher than those in the control group, respectively. A significant positive correlation was observed between serum Cu and Se levels, and also serum Cu and Se levels showed a negative correlation with serum cTn-I concentrations. Stepwise linear regression analysis showed that serum Cu levels were correlated positively with serum Se levels (p<0.05. Receiver operating characteristic (ROC curve analysis indicated that the area under curve (AUC of Cu was significantly higher than that of cTn-I based on the reference diagonal line. It is important to keep in mind that the value of AUC for the ROC curve is between 0.5 and 1.00, in which the lowest accuracy is related to the reference diagonal line with AUC of 0.5. A cut-off was determined to indicate which Cu level can discriminate between affected and healthy lambs. The cut-off level, sensitivity, and specificity of Cu in this study were 144.5 ng/mL, 74%, and 61%, respectively.

  2. Alanine or aspartic acid substitutions at serine23/24 of cardiac troponin I decrease thin filament activation, with no effect on crossbridge detachment kinetics

    Science.gov (United States)

    Mamidi, Ranganath; Gollapudi, Sampath K.; Mallampalli, Sri Lakshmi; Chandra, Murali

    2012-01-01

    Ala/Asp substitutions at Ser23/24 have been employed to investigate the functional impact of cardiac troponin I (cTnI) phosphorylation by protein kinase A (PKA). Some limitations of previous studies include the use of heterologous proteins and confounding effects arising from phosphorylation of cardiac myosin binding protein-C. Our goal was to probe the effects of cTnI phosphorylation using a homologous assay, so that altered function could be solely attributed to changes in cTnI. We reconstituted detergent-skinned rat cardiac papillary fibers with homologous rat cardiac troponin subunits to study the impact of Ala and Asp substitutions at Ser23/24 of rat cTnI (RcTnI S23A/24A and RcTnI S23D/24D). Both RcTnI S23A/24A and RcTnI S23D/24D showed a ~36% decrease in Ca2+-activated maximal tension. Both RcTnI S23A/24A and RcTnI S23D/24D showed a ~18% decrease in ATPase activity. Muscle fiber stiffness measurements suggested that the decrease in thin filament activation observed in RcTnI S23A/24A and RcTnI S23D/24D was due to a decrease in the number of strongly-bound crossbridges. Another major finding was that Ala and Asp substitutions in cTnI did not affect crossbridge detachment kinetics. PMID:22684024

  3. Protein Structure-Function Relationship at Work:Learning from Myopathy Mutations of the Slow Skeletal Muscle Isoform of Troponin T

    Directory of Open Access Journals (Sweden)

    Anupom Mondal

    2016-10-01

    Full Text Available Troponin T (TnT is the sarcomeric thin filament anchoring subunit of the troponin complex in striated muscles. A nonsense mutation in exon 11 of the slow skeletal muscle isoform of TnT (ssTnT gene (TNNT1 was found in the Amish populations in Pennsylvania and Ohio. This single nucleotide substitution causes a truncation of the ssTnT protein at Glu180 and the loss of the C-terminal tropomyosin (Tm-binding site 2. As a consequence, it abolishes the myofilament integration of ssTnT and the loss of function causes an autosomal recessive nemaline myopathy (NM. More TNNT1 mutations have recently been reported in non-Amish ethnic groups with similar recessive NM phenotypes. A nonsense mutation in exon 9 truncates ssTnT at Ser108, deleting Tm-binding site 2 and a part of the middle region Tm-binding site 1. Two splicing site mutations result in truncation of ssTnT at Leu203 or deletion of the exon 14-encoded C-terminal end segment. Another splicing mutation causes an internal deletion of the 39 amino acids encoded by exon 8, partially damaging Tm-binding site 1. The three splicing mutations of TNNT1 all preserve the high affinity Tm-binding site 2 but still present recessive NM phenotypes. The molecular mechanisms for these mutations to cause myopathy provide interesting models to study and understand the structure-function relationship of TnT. This focused review summarizes the current knowledge of TnT isoform regulation, structure-function relationship of TnT and how various ssTnT mutations cause recessive NM, in order to promote in depth studies for further understanding the pathogenesis and pathophysiology of TNNT1 myopathies toward the development of effective treatments.□

  4. Channelopathies from Mutations in the Cardiac Sodium Channel Protein Complex

    Science.gov (United States)

    Adsit, Graham S.; Vaidyanathan, Ravi; Galler, Carla M.; Kyle, John W.; Makielski, Jonathan C.

    2013-01-01

    The cardiac sodium current underlies excitability in heart, and inherited abnormalities of the proteins regulating and conducting this current cause inherited arrhythmia syndromes. This review focuses on inherited mutations in non-pore forming proteins of sodium channel complexes that cause cardiac arrhythmia, and the deduced mechanisms by which they affect function and dysfunction of the cardiac sodium current. Defining the structure and function of these complexes and how they are regulated will contribute to understanding the possible roles for this complex in normal and abnormal physiology and homeostasis. PMID:23557754

  5. Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death

    DEFF Research Database (Denmark)

    Nyegaard, Mette; Overgaard, Michael Toft; Søndergaard, Mads

    2012-01-01

    a substantial part of sudden cardiac deaths in young individuals. Mutations in RYR2, encoding the cardiac sarcoplasmic calcium channel, have been identified as causative in approximately half of all dominantly inherited CPVT cases. Applying a genome-wide linkage analysis in a large Swedish family with a severe...... dominantly inherited form of CPVT-like arrhythmias, we mapped the disease locus to chromosome 14q31-32. Sequencing CALM1 encoding calmodulin revealed a heterozygous missense mutation (c.161A>T [p.Asn53Ile]) segregating with the disease. A second, de novo, missense mutation (c.293A>G [p.Asn97Ser......]) was subsequently identified in an individual of Iraqi origin; this individual was diagnosed with CPVT from a screening of 61 arrhythmia samples with no identified RYR2 mutations. Both CALM1 substitutions demonstrated compromised calcium binding, and p.Asn97Ser displayed an aberrant interaction with the RYR2...

  6. Cardiac troponin-I concentration, myocardial arteriosclerosis, and fibrosis in dogs with congestive heart failure because of myxomatous mitral valve disease.

    Science.gov (United States)

    Falk, T; Ljungvall, I; Zois, N E; Höglund, K; Olsen, L H; Pedersen, H D; Häggström, J

    2013-01-01

    Few previous studies have investigated the association between biomarkers and cardiac disease findings in dogs with naturally occurring myxomatous mitral valve disease (MMVD). To investigate if histopathological changes at necropsy could be reflected by in vivo circulating concentrations of cTnI and aldosterone, and renin activity, in dogs with naturally occurring congestive heart failure because of MMVD. Fifty privately owned dogs with MMVD and heart failure. Longitudinal Study. Dogs were prospectively recruited and examined by clinical and echocardiographical examination twice yearly until time of death. Blood was stored for batched analysis of concentrations of cTnI and aldosterone, and renin activity. All dogs underwent a standardized necropsy protocol. cTnI were associated with echocardiographic left ventricular end-diastolic dimension (P fibrosis (P fibrosis in the papillary muscles (P disease variables investigated. Cardiac fibrosis and arteriosclerosis in dogs with MMVD are reflected by circulating cTnI concentration, but not by aldosterone concentration or renin activity. Cardiac troponin I could be a valuable biomarker for myocardial fibrosis in dogs with chronic cardiac diseases. Copyright © 2013 by the American College of Veterinary Internal Medicine.

  7. 肌钙蛋白测定在急性冠脉综合征中的应用%Applications of cardiac troponin measurement in acute coronary syndrome

    Institute of Scientific and Technical Information of China (English)

    马虹; 罗初凡

    2004-01-01

    @@ 心肌肌钙蛋白(Cardiac Troponins,cTn)作为心肌损伤的非酶学指标,在急性心肌梗死的诊断中因其敏感性高、特异性强、在血液中出现早、持续时间长、对微小心肌损伤具有诊断价值等优点近年备受重视,目前已作为新的"金标准"而逐渐取代肌酸激酶同功酶MB(CK-MB)的地位,并广泛应用于急性冠状动脉综合征(acute coronary syndrome,ACS)的诊断、治疗、危险分层及预后评价等各个方面.

  8. Label-free detection of cardiac troponin-I using gold nanoparticles functionalized single-walled carbon nanotubes based chemiresistive biosensor

    Science.gov (United States)

    Rajesh, Sharma, Vikash; Puri, Nitin K.; Singh, Rajiv K.; Biradar, Ashok M.; Mulchanadani, Ashok

    2013-11-01

    We report a specific and ultrasensitive, label-free chemiresistive biosensor based on mercaptopropionic acid capped gold nanoparticles (GNP) functionalized single walled carbon nanotube (SWNT) hybrid for the detection of cardiac specific biomarker troponin-I (cTnI). GNPs were attached to SWNTs through a molecular linker 1-pyrenemethylamine. The highly specific cTnI antibody was covalently immobilized on GNPs through capping agent using carbodiimide coupling reaction. The cTnI interaction to its corresponding antibody was studied with respect to changes in conductance in SWNTs channel, and a detailed field-effect transistor characteristic was delineated. The device exhibited a linear response to cTnI from 0.01 to 10 ng ml-1.

  9. 心肌肌钙蛋白T与急性冠状动脉综合征%Cardiac Troponin T and Acute Coronary Syndromes

    Institute of Scientific and Technical Information of China (English)

    齐志宏; 刘振元

    2001-01-01

    @@急性冠状动脉综合征代表冠状动脉病变程度不同的一组疾病,其临床表现为不稳定性心绞痛,急性心肌梗死和猝死。其共同的病理生理基础为急性粥样斑块破裂、血小板激活、血栓形成导致血管腔不同程度的阻塞[1]。其结局和治疗措施不同,但是其临床诊断和预后分级常很困难。心肌肌钙蛋白T(cardiac troponin T,cTnT)是心肌细胞肌钙蛋白复合物的亚单位。

  10. Influence of age and renal function on high-sensitivity cardiac troponin T diagnostic accuracy for the diagnosis of acute myocardial infarction.

    Science.gov (United States)

    Chenevier-Gobeaux, Camille; Meune, Christophe; Freund, Yonathan; Wahbi, Karim; Claessens, Yann-Erick; Doumenc, Benoit; Zuily, Stéphane; Riou, Bruno; Ray, Patrick

    2013-06-15

    Concerns have been raised about the performance of highly sensitive cardiac troponin assays to accurately detect acute myocardial infarction (AMI), particularly in non-ST segment elevation (NSTEMI), in elderly patients, and in patients with renal failure. We evaluated whether increased age and low estimated glomerular filtration rate (eGFR) alter diagnostic performance of high-sensitivity cardiac troponin T (HScTnT). In a prospective multicentric study, HScTnT levels were measured blindly at presentation in patients with acute chest pain. Three hundred and sixty-seven patients were enrolled, including 84 patients ≥70 years. Final diagnosis was AMI for 57 patients (16%) and NSTEMI for 43 patients (12%). NSTEMI was more frequent in elderly patients (p = 0.008). Sensitivity and specificity of HScTnT >14 ng/L at admission for AMI were 96% and 51% in patients ≥70 years versus 91% (NS) and 88% (p 53.5 ng/L for the diagnosis of AMI and NSTEMI, respective sensitivities were 87% and 84% and respective specificities were 87% and 87% in elderly patients. Using a cutoff at 35.8 ng/L (for AMI) or 43.2 ng/L (for NSTEMI), sensitivities were 94% and 92%, and specificities were 86% and 88% in patients with low eGFR. Older age, but not low eGFR, was an independent predictive factor of an elevated HScTnT at admission (odds ratio 2.2 [1.2-3.9], p = 0.007). In conclusion, adapted thresholds of HScTnT are required for an accurate diagnosis of AMI/NSTEMI in patients aged ≥70 and in those with low eGFR.

  11. The problems in detection and clinical application of high-sensitivity cardiac troponin%高敏肌钙蛋白检测及临床应用有待解决的问题

    Institute of Scientific and Technical Information of China (English)

    贾克刚

    2014-01-01

    肌钙蛋白是急性冠状动脉综合征重要生物标志物.尤其是近年来兴起的高敏肌钙蛋白在心肌梗死早期诊断和预后评估中起着重要作用.一些国家也发布指南推荐高敏肌钙蛋白的应用.但临床医生和实验室工作人员在使用中仍有许多问题.本文就高敏肌钙蛋白测定和临床应用中的问题,以及国际组织的建议包括统一使用高敏肌钙蛋白名称、单位、确立健康人群选择指南以确定正确的第99百分位值,加以介绍并提出看法.%Troponin is an important biomarker of acute coronary syndrome.Especially highsensitivity cardiac troponin in recent years played an important role for the early diagnosis and prognosis of myocardial infarction.Recommendations for the use of high-sensitivity cardiac troponin have been issued in some guidelines.But the clinical doctors and laboratory workers still have many problems in practice.Some problems in high-sensitivity cardiac troponin assay and the clinical application were introduced here.Suggestions were also put up from international organizations,including unified high-sensitivity cardiac troponin name,unit,establish healthy population,selection guidelines to identify the 99th percentile value.

  12. Abnormal splicing in the N-terminal variable region of cardiac troponin T impairs systolic function of the heart with preserved Frank-Starling compensation.

    Science.gov (United States)

    Feng, Han-Zhong; Chen, Guozhen; Nan, Changlong; Huang, Xupei; Jin, Jian-Ping

    2014-09-01

    Abnormal splice-out of the exon 7-encoded segment in the N-terminal variable region of cardiac troponin T (cTnT-ΔE7) was found in turkeys and, together with the inclusion of embryonic exon (eTnT), in adult dogs with a correlation with dilated cardiomyopathy. Overexpression of these cTnT variants in transgenic mouse hearts significantly decreased cardiac function. To further investigate the functional effect of cTnT-ΔE7 or ΔE7+eTnT in vivo under systemic regulation, echocardiography was carried out in single and double-transgenic mice. No atrial enlargement, ventricular hypertrophy or dilation was detected in the hearts of 2-month-old cTnT-ΔE7 and ΔE7+eTnT mice in comparison to wild-type controls, indicating a compensated state. However, left ventricular fractional shortening and ejection fraction were decreased in ΔE7 and ΔE7+eTnT mice, and the response to isoproterenol was lower in ΔE7+eTnT mice. Left ventricular outflow tract velocity and gradient were decreased in the transgenic mouse hearts, indicating decreased systolic function. Ex vivo working heart function showed that high afterload or low preload resulted in more severe decreases in the systolic function and energetic efficiency of cTnT-ΔE7 and ΔE7+eTnT hearts. On the other hand, increases in preload demonstrated preserved Frank-Starling responses and minimized the loss of cardiac function and efficiency. The data demonstrate that the N-terminal variable region of cardiac TnT regulates systolic function of the heart.

  13. Outliers affecting cardiac troponin I measurement: comparison of a new high sensitivity assay with a contemporary assay on the Abbott ARCHITECT analyser.

    Science.gov (United States)

    Sawyer, Nicola; Blennerhassett, John; Lambert, Ramon; Sheehan, Paul; Vasikaran, Samuel D

    2014-07-01

    False-positive cardiac troponin (Tn) results caused by outliers have been reported on various analytical platforms. We have compared the precision profile and outlier rate of the Abbott Diagnostics contemporary troponin I (TnI) assay with their high sensitivity (hs) TnI assay. Three studies were conducted over a 10-month period using routine patients' samples. TnI was measured in duplicate using the contemporary TnI assay in Study 1 and Study 2 (n = 7011 and 7089) and the hs-TnI assay in Study 3 (n = 1522). Critical outliers were defined as duplicate results whose absolute difference exceeded a critical difference (CD = z x √2 x SDAnalytical) at a probability level of 0.0005, with one of the results on the opposite side of the decision limit to its partner. The TnI concentration at 10% imprecision (coefficient of variation) for the contemporary TnI assay was 0.034 µg/L (Study 1) and 0.042 µg/L (Study 2), and 0.006 µg/L (6 ng/L) for the hs-TnI assay. The critical outlier rates for the contemporary TnI assay were 0.51% (Study 1) and 0.37% (Study 2) using a cut-off of 0.04 µg/L, and 0% for the hs-TnI assay using gender-specific cut-offs. The significant number of critical outliers detected using the contemporary TnI assay may pose a risk for misclassification of patients. By contrast, no critical outliers were detected using the hs-TnI assay. However, the total outlier rates for both assays were significantly higher than the expected variability of either assay. The cause of these outliers remains unclear. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  14. Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death.

    Science.gov (United States)

    Mohler, Peter J; Schott, Jean-Jacques; Gramolini, Anthony O; Dilly, Keith W; Guatimosim, Silvia; duBell, William H; Song, Long-Sheng; Haurogné, Karine; Kyndt, Florence; Ali, Mervat E; Rogers, Terry B; Lederer, W J; Escande, Denis; Le Marec, Herve; Bennett, Vann

    2003-02-06

    Mutations in ion channels involved in the generation and termination of action potentials constitute a family of molecular defects that underlie fatal cardiac arrhythmias in inherited long-QT syndrome. We report here that a loss-of-function (E1425G) mutation in ankyrin-B (also known as ankyrin 2), a member of a family of versatile membrane adapters, causes dominantly inherited type 4 long-QT cardiac arrhythmia in humans. Mice heterozygous for a null mutation in ankyrin-B are haploinsufficient and display arrhythmia similar to humans. Mutation of ankyrin-B results in disruption in the cellular organization of the sodium pump, the sodium/calcium exchanger, and inositol-1,4,5-trisphosphate receptors (all ankyrin-B-binding proteins), which reduces the targeting of these proteins to the transverse tubules as well as reducing overall protein level. Ankyrin-B mutation also leads to altered Ca2+ signalling in adult cardiomyocytes that results in extrasystoles, and provides a rationale for the arrhythmia. Thus, we identify a new mechanism for cardiac arrhythmia due to abnormal coordination of multiple functionally related ion channels and transporters.

  15. Ca++-sensitizing mutations in troponin, P(i), and 2-deoxyATP alter the depressive effect of acidosis on regulated thin-filament velocity.

    Science.gov (United States)

    Longyear, Thomas J; Turner, Matthew A; Davis, Jonathan P; Lopez, Joseph; Biesiadecki, Brandon; Debold, Edward P

    2014-05-01

    Repeated, intense contractile activity compromises the ability of skeletal muscle to generate force and velocity, resulting in fatigue. The decrease in velocity is thought to be due, in part, to the intracellular build-up of acidosis inhibiting the function of the contractile proteins myosin and troponin; however, the underlying molecular basis of this process remains poorly understood. We sought to gain novel insight into the decrease in velocity by determining whether the depressive effect of acidosis could be altered by 1) introducing Ca(++)-sensitizing mutations into troponin (Tn) or 2) by agents that directly affect myosin function, including inorganic phosphate (Pi) and 2-deoxy-ATP (dATP) in an in vitro motility assay. Acidosis reduced regulated thin-filament velocity (VRTF) at both maximal and submaximal Ca(++) levels in a pH-dependent manner. A truncated construct of the inhibitory subunit of Tn (TnI) and a Ca(++)-sensitizing mutation in the Ca(++)-binding subunit of Tn (TnC) increased VRTF at submaximal Ca(++) under acidic conditions but had no effect on VRTF at maximal Ca(++) levels. In contrast, both Pi and replacement of ATP with dATP reversed much of the acidosis-induced depression of VRTF at saturating Ca(++). Interestingly, despite producing similar magnitude increases in VRTF, the combined effects of Pi and dATP were additive, suggesting different underlying mechanisms of action. These findings suggest that acidosis depresses velocity by slowing the detachment rate from actin but also by possibly slowing the attachment rate.

  16. Ca++-sensitizing mutations in troponin, Pi, and 2-deoxyATP alter the depressive effect of acidosis on regulated thin-filament velocity

    Science.gov (United States)

    Longyear, Thomas J.; Turner, Matthew A.; Davis, Jonathan P.; Lopez, Joseph; Biesiadecki, Brandon

    2014-01-01

    Repeated, intense contractile activity compromises the ability of skeletal muscle to generate force and velocity, resulting in fatigue. The decrease in velocity is thought to be due, in part, to the intracellular build-up of acidosis inhibiting the function of the contractile proteins myosin and troponin; however, the underlying molecular basis of this process remains poorly understood. We sought to gain novel insight into the decrease in velocity by determining whether the depressive effect of acidosis could be altered by 1) introducing Ca++-sensitizing mutations into troponin (Tn) or 2) by agents that directly affect myosin function, including inorganic phosphate (Pi) and 2-deoxy-ATP (dATP) in an in vitro motility assay. Acidosis reduced regulated thin-filament velocity (VRTF) at both maximal and submaximal Ca++ levels in a pH-dependent manner. A truncated construct of the inhibitory subunit of Tn (TnI) and a Ca++-sensitizing mutation in the Ca++-binding subunit of Tn (TnC) increased VRTF at submaximal Ca++ under acidic conditions but had no effect on VRTF at maximal Ca++ levels. In contrast, both Pi and replacement of ATP with dATP reversed much of the acidosis-induced depression of VRTF at saturating Ca++. Interestingly, despite producing similar magnitude increases in VRTF, the combined effects of Pi and dATP were additive, suggesting different underlying mechanisms of action. These findings suggest that acidosis depresses velocity by slowing the detachment rate from actin but also by possibly slowing the attachment rate. PMID:24651988

  17. 高敏心肌肌钙蛋白Ⅰ与心肌肌钙蛋白T预测心血管事件的对比研究%Compare the values of high-sensitivity cardiac troponin I versus cardiac troponin T for prediction of cardiovascular events in acute coronary syndrome

    Institute of Scientific and Technical Information of China (English)

    曹志林

    2012-01-01

    目的 比较高敏心肌肌钙蛋白(high-sensitivity cardiac troponin Ⅰ,hs-cTnI)与心肌肌钙蛋白(cardiac troponin T,cTnT)对非ST段抬高型急性冠状动脉综合征(急性冠脉综合征)患者心血管事件的预测价值.方法 采集103例连续的不稳定型心绞痛和非ST段抬高型急性心肌梗死患者的血浆样品,分别采用电化学发光免疫法和VITROS化学发光免疫分析法检测cTnT和hs-cTnI.采用工作者特征曲线评估心血管事件的发生率,确定hs-cTnI与cTnT的最佳预测值.结果 hs-cTnI与cTnT均能显著预测心血管事件,两者差异无统计学意义(P=0.75).两种心脏标志物的最佳预测值分别为hs-cTnI>0.055μg/L和cTnT>0.010μg/L,敏感度均为90%,特异度均为52%;hs-cTnI阳性患者的心血管事件发生率为17%,而hs-cTnI阴性患者的心血管事件发生率为2%,两者差异有统计学意义(P=0.02).结论 hs-cTnI与cTnT对非ST段抬高型急性冠脉综合征患者心血管事件有相似的预测诊断价值.%Objective To compare the value of high-sensitivity cardiac troponin I(hs-cTnI)versus cardiac troponin T(cTnT) for prediction of cardiovascular evenls in acute coronary syndromes. Methods The plasma samples were collected from 103 patients with unstable angina or non-ST elevation acute myocardial infarction, cTnT and hs-cTnI levels were detected by electrochemilumines-cence immunoassay and VITROS chemiluminescence immunoassay respectively. The prognostic value was compared to the occurrence of cardiovascular events during hospitalization. Results Both hs-cTnI and cTnT could significantly predict cardiovascular events and existed no significant difference(P = 0. 75). The best predictive value of the two cardiac markers were hs-cTnI> 0. 055 μg/L and cTnT> 0. 010 μg/L,the sensitivity and specificity of these two markers were 90% and 52% respectively. The incidence of cardiovascular e-vents was 17% for hs-cTnI-positive patients and 2% for hs-cTnI-negative patients( P

  18. Comparison of the Results of Sentive Cardiac Troponin I Detected by Two Different Detection Methods%两种不同方法检测敏感心肌肌钙蛋白Ⅰ结果比较

    Institute of Scientific and Technical Information of China (English)

    宋金萍; 孟晓辉; 达仁别克·苏利坦拜

    2012-01-01

      Objective:To comparise results of serum cardiac troponin I by Beckman-Coulter Access Immunoassay analyzer and Johnson VITROS-5600 fully automated dry chemistry analyzer,and exploring the differences as well as the linear relationship and correlation between the two. Method:45 serum samples were collected from patients presenting symptoms suggestive of acute myocardial infarction. The concentrations of serum cardiac troponin I were measured with Beckman-Coulter Access Immunoassay analyzer and Johnson VITROS-5600 fully automated dry chemistry analyzer. Data were processed by SPSS13.0 statistical analysis software.Result:Results of serum cardiac troponin I using the two methods showed no significant difference(P>0.05),while analysis shows the significant relation between the two methods(P0.05),组存在显著相关性(P<0.05).结论:本实验室采用的这两种敏感cTnI的检测结果一致性较好.

  19. 高敏心脏肌钙蛋白在冠状动脉粥样硬化性心脏病的研究进展%Summary of Advancements of High Sensitive Cardiac Troponin in Coronary Artery Disease

    Institute of Scientific and Technical Information of China (English)

    孙伟峰

    2012-01-01

    Cardiac troponin is one of the primary biochemical markers used to identify myocardial injury. It is one of the easiest markers to identify because troponin-I and T are specific to cardiac muscle. The identification and measurement of cardiac troponin levels using a high sensitive assay plays an important role in the early diagnosis and prognostic evaluation of coronary artery disease. This article summarizes current research in this field.%心脏肌钙蛋白是心肌损伤的主要生物标志物之一.近年来推出的高敏心脏肌钙蛋白检测法因其更好的检验性能及更高的敏感性,在冠状动脉粥样硬化性心脏病,尤其是急性冠状动脉综合征早期诊断、预后判断等方面发挥非常重要的作用,现就其在冠状动脉粥样硬化性心脏病领域的研究进展做一综述.

  20. Predictive Values of N-Terminal Pro-B-Type Natriuretic Peptide and Cardiac Troponin I for Myocardial Fibrosis in Hypertrophic Obstructive Cardiomyopathy.

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    Changlin Zhang

    Full Text Available Both high-sensitivity cardiac troponin T and B-type natriuretic peptide are useful in detecting myocardial fibrosis, as determined by late gadolinium enhancement (LGE cardiovascular magnetic resonance (CMR, in patients with non-obstructive hypertrophic cardiomyopathy. However, their values to predict myocardial fibrosis in hypertrophic obstructive cardiomyopathy (HOCM remain unclear. We investigated the role of N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP and cardiac troponin I (cTnI to identify LGE-CMR in patients with HOCM.Peripheral concentrations of NT-proBNP and cTnI were determined in patients with HOCM (n = 163; age = 47.2 ± 10.8 years; 38.7% females. Contrast-enhanced CMR was performed to identify and quantify myocardial fibrosis.LGE was detected in 120 of 163 patients (73.6%. Patients with LGE had significantly higher levels of NT-proBNP and cTnI than those without LGE (1386.2 [904.6-2340.8] vs. 866.6 [707.2-1875.2] pmol/L, P = 0.003; 0.024 [0.010-0.049] vs. 0.010 [0.005-0.021] ng/ml, P <0.001, respectively. The extent of LGE was positively correlated with log cTnI (r = 0.371, P <0.001 and log NT-proBNP (r = 0.211, P = 0.007. On multivariable analysis, both log cTnI and maximum wall thickness (MWT were independent predictors of the presence of LGE (OR = 3.193, P = 0.033; OR = 1.410, P < 0.001, respectively, whereas log NT-proBNP was not. According to the ROC curve analysis, combined measurements of MWT ≥21 mm and/or cTnI ≥0.025 ng/ml indicated good diagnostic performance for the presence of LGE, with specificity of 95% or sensitivity of 88%.Serum cTnI is an independent predictor useful for identifying myocardial fibrosis, while plasma NT-proBNP is only associated with myocardial fibrosis on univariate analysis. Combined measurements of serum cTnI with MWT further improve its value in detecting myocardial fibrosis in patients with HOCM.

  1. Low clinical penetrance in causal mutation carriers for cardiac channelopathies.

    Science.gov (United States)

    Jiménez-Jáimez, Juan; Álvarez, Miguel; Algarra, María; Macías Ruíz, Rosa; Peñas, Rocío; Valverde, Francisca; Tortajada, Gustavo; Lorente, Jose Antonio; Melgares, Rafael; Tercedor, Luis

    2013-04-01

    Cardiac channelopathies are genetic alterations that can cause sudden death. Long QT syndrome and Brugada syndrome are 2 such conditions. Both are diagnosed according to previously published criteria. Our objective was to determine the sensitivity of these criteria in a consecutive series of patients carrying the mutations that cause them. We enrolled 15 families and 31 causal mutation carriers with a high pathogenic probability of having long QT syndrome and Brugada syndrome. We conducted clinical and electrocardiographic studies to analyze the extent to which these patients fulfilled the diagnostic criteria. Statistical analysis was with SPSS 17.0. Some 48.3% of the subjects met the criteria indicating a high probability of long QT syndrome or Brugada syndrome. Among those with the mutation for long QT syndrome, only 10 out of 21 had a Schwartz index score ≥ 4. Both the median Schwartz score and the cQT interval were lower in relatives than in probands. Of those with the mutation for Brugada syndrome, 60% failed to meet current diagnostic criteria, which were more frequently fulfilled in relatives. Pharmacological tests with epinephrine and flecainide helped establish the diagnosis in 2 mutation carriers with negative phenotype. Current diagnostic criteria for long QT syndrome and Brugada syndrome had low sensitivity in our sample of genetic carriers. Genetic tests supported by pharmacological tests can increase diagnostic sensitivity, especially in asymptomatic relatives. Copyright © 2012 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  2. Analysis of the Indicating Value of Cardiac Troponin I, Tumor Necrosis Factor-α, Interleukin-18, Mir-1 and Mir-146b for Viral Myocarditis among Children

    Directory of Open Access Journals (Sweden)

    Dahui Wang

    2016-12-01

    Full Text Available Background/Aims: The primary objective of this study is to evaluate the diagnosis effect of serum protein factors and microRNAs for children suffering from viral myocarditis (VMC. Methods: The expression levels of serum cardiac troponin I (cTnI, interleukin-18 (IL-18 and tumor necrosis factor-α (TNF-α in both VMC and control groups were examined by using the Elisa Kit. The expression levels of miR-1 and miR-146b were measured through RT-PCR. Subsequently, the Receiver Operating Characteristic (ROC curves were drawn based on the diagnostic results of VMC. Moreover, the Spearman correlation analysis was carried out to unveil the association between the indicator expression levels and the ultrasonic cardiogram results, including the left ventricular fractional shortening (FS and left ventricular ejection fraction (EF. Results: It is found that the expression levels between the VMC and control group portrait significant differences with respect to cTnI, IL-18, TNF-α, miR-1 and mIR-146b (P Conclusions: The expression levels of the TNF-α, IL-18 and cTnI and the expression levels of the miR-1 and miR-146b could be used to predict VMC among children and this approach may reinforce the diagnosis of VMC in clinical practices.

  3. Nanocomposites of gold nanoparticles and graphene oxide towards an stable label-free electrochemical immunosensor for detection of cardiac marker troponin-I.

    Science.gov (United States)

    Liu, Guozhen; Qi, Meng; Zhang, Yin; Cao, Chaomin; Goldys, Ewa M

    2016-02-25

    A stable label-free amperometric immunosensor is presented based on gold nanoparticles and graphene oxide nanocomposites for detection of cardiac troponin-I in the early diagnosis of myocardial infarction. For designing of the sensing platform, firstly the nanocomposites based on GO and AuNPs were prepared and anchored on electrode surfaces. The formed nanocomposites provided a platform with big surface area for loading anti-cTnI capture antibody, and worked as a bridge for fast electron transfer subsequently increased the sensitivity. Moreover, the linkages between AuNP, GO, and electrodes were based on covalent bonding by aryldiazonium salt coupling chemistry, which favors the stability of the sensing interface. Finally, the anti-cTnI detection antibody was immobilized on GO tailored with ferrocene molecules, functioning as the signal reporter for the detection of cTnI. The modification process was monitored using electrochemistry, SEM, XPS. The herein immunosensor demonstrates a good selectivity and high sensitivity against human-cTnI, and is capable of detecting cTnI at concentrations as low as 0.05 ng mL(-1), which is 100 times lower than that possible by conventional methods. It is potential to design the portable sensing platform based on AuNPs and GO nanocomposites for future point-of-care diagnostics.

  4. Limited proteolysis combined with isotope labeling and quantitative LC-MALDI MS for monitoring protein conformational changes: a study on calcium-binding sites of cardiac Troponin C

    Energy Technology Data Exchange (ETDEWEB)

    McDonald, Chris; Li Liang

    2005-04-04

    Studies of protein-protein and protein-ligand interactions are important for understanding biological functions of proteins. A new technique based on the partial proteolysis of proteins combined with quantitative mass spectrometry is developed as a means of tracking structural changes after the formation of a protein-ligand complex. In this technique, a protein of interest with and without the binding of a ligand is digested with an enzyme to generate a set of peptides, followed by separation of the peptides by liquid chromatography. Matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS) is used to identify chromatographically separated peptides, and locate their sequence alignments in the parent protein. Using an isotopically labeled protein as a sample against an unlabeled protein standard, quantitative information can be gathered. This overcomes the inherent lack of quantitative capability of MALDI MS. The utility of the technique to investigate protein-ligand interactions is demonstrated in a model system involving calcium binding to cardiac Troponin C (cTnC). Using this technique, the general location of the three calcium-binding sites of cTnC can be determined by using several different enzymes to generate overlapping peptide maps of cTnC.

  5. Direct Comparison of Four Very Early Rule-Out Strategies for Acute Myocardial Infarction Using High-Sensitivity Cardiac Troponin I.

    Science.gov (United States)

    Boeddinghaus, Jasper; Nestelberger, Thomas; Twerenbold, Raphael; Wildi, Karin; Badertscher, Patrick; Cupa, Janosch; Bürge, Tobias; Mächler, Patrick; Corbière, Sydney; Grimm, Karin; Rubini Giménez, Maria; Puelacher, Christian; Shrestha, Samyut; Flores Widmer, Dayana; Fuhrmann, Jakob; Hillinger, Petra; Sabti, Zaid; Honegger, Ursina; Schaerli, Nicolas; Kozhuharov, Nikola; Rentsch, Katharina; Miró, Òscar; López Barbeito, Beatriz; Martin-Sanchez, F Javier; Rodriguez-Adrada, Esther; Morawiec, Beata; Kawecki, Damian; Ganovská, Eva; Parenica, Jiri; Lohrmann, Jens; Kloos, Wanda; Buser, Andreas; Geigy, Nicolas; Keller, Dagmar I; Osswald, Stefan; Reichlin, Tobias; Müller, Christian

    2017-03-10

    Background -Four strategies for very early rule-out of acute myocardial infarction (AMI) using high-sensitivity cardiac troponin I (hs-cTnI) have been identified. It remains unclear which strategy is most attractive for clinical application. Methods -We prospectively enrolled unselected patients presenting to the emergency department (ED) with symptoms suggestive of AMI. The final diagnosis was adjudicated by two independent cardiologists. Hs-cTnI levels were measured at presentation and after 1h in a blinded fashion. We directly compared all four hs-cTnI-based rule-out strategies: limit of detection (LOD, hs-cTnIstrategies. Two-year survival was 100% with LOD and 98.1% with the other strategies (pstrategies). Conclusions -All four rule-out strategies balance effectiveness and safety equally well. The single cut-off should not be applied in early presenters, while the three other strategies seem to perform well also in this challenging subgroup. Clinical Trial Registration -https://clinicaltrials.gov/ Identifier: NCT00470587.

  6. High-sensitivity cardiac troponin T levels and risk of cerebral microbleeds in acute ischemic stroke patients with atrial fibrillation and/or rheumatic heart disease.

    Science.gov (United States)

    Liu, Junfeng; Wang, Deren; Xiong, Yao; Liu, Bian; Wei, Chenchen; Ma, Zhenxing; Wu, Bo; Tang, Hehan; Liu, Ming

    2016-10-15

    Elevated high-sensitivity cardiac troponin T (hs-cTnT) levels are associated with coronary disease and small-vessel ischemic stroke through their associations with atherosclerosis. Considering the relationship between atherosclerosis and cerebral microbleeds (CMBs), the purpose of this study was to examine associations between serum hs-cTnT levels and risk of CMBs in acute ischemic stroke patients. This prospective study involved consecutively recruited acute ischemic stroke patients with atrial fibrillation and/or rheumatic heart disease treated at a large tertiary care hospital in southwestern China. Clinico-demographic data were collected and analyzed by logistic regression to identify the relationship between serum hs-cTnT levels and CMB occurrence and location. In the final analysis, of 66 patients (27 males; mean age, 68.7years), 39 (59.1%) had CMBs. Hs-cTnT levels were not associated with risk of strictly lobar CMBs. However, after adjusting age, sex, current alcohol consumption, total cholesterol, hypertension, diabetes mellitus, prior antithrombotic therapy and NIHSS on admission, patients in the higher tertile were more likely to have CMBs and deep or infratentorial CMBs (PCMBs, particularly of deep or infratentorial CMBs. This finding justifies further research into how hs-cTnT levels may contribute to CMBs and potentially other subclinical small-vessel diseases. Copyright © 2016. Published by Elsevier B.V.

  7. A Drosophila Melanogaster Model of Diastolic Dysfunction and Cardiomyopathy Based on Impaired Troponin-T Function

    Science.gov (United States)

    Viswanathan, Meera Cozhimuttam; Kaushik, Gaurav; Engler, Adam J.; Lehman, William; Cammarato, Anthony

    2015-01-01

    Rationale Regulation of striated muscle contraction is achieved by Ca2+-dependent steric modulation of myosin cross-bridge cycling on actin by the thin filament troponin-tropomyosin complex. Alterations in the complex can induce contractile dysregulation and disease. For example, mutations between or near residues 112–136 of cardiac troponin-T, the crucial N-terminal TnT1 tropomyosin-binding region, cause cardiomyopathy. The Drosophila up101 Glu/Lys amino acid substitution lies C-terminally adjacent to this phylogenetically conserved sequence. Objective Using a highly integrative approach, we sought to determine the molecular trigger of up101 myofibrillar degeneration, to evaluate contractile performance in the mutant cardiomyocytes, and to examine the effects of the mutation on the entire Drosophila heart to elucidate regulatory roles for conserved TnT1 regions and provide possible mechanistic insight into cardiac dysfunction. Methods and Results Live video imaging of Drosophila cardiac tubes revealed the troponin-T mutation prolongs systole and restricts diastolic dimensions of the heart, due to increased numbers of actively cycling myosin cross-bridges. Elevated resting myocardial stiffness, consistent with up101 diastolic dysfunction, was confirmed by an atomic force microscopy-based nanoindentation approach. Direct visualization of mutant thin filaments via electron microscopy and three-dimensional reconstruction resolved destabilized tropomyosin positioning and aberrantly exposed myosin binding sites under low Ca2+ conditions. Conclusions As a result of troponin-tropomyosin dysinhibition, up101 hearts exhibit cardiac dysfunction and remodeling comparable to that observed during human restrictive cardiomyopathy. Thus, reversal of charged residues about the conserved tropomyosin-binding region of TnT1 may perturb critical intermolecular associations required for proper steric regulation, which likely elicits myopathy in our Drosophila model. PMID:24221941

  8. 肌钙蛋白对心脏外科手术后急性心肌梗死的诊断价值%Discussing the diagnostic value of troponin in the acute myocardial infarction after cardiac surgery

    Institute of Scientific and Technical Information of China (English)

    梁林宝; 程国栋; 朱春磊; 陈国锋; 陈乃颖; 黄伟

    2014-01-01

    Objective To research the diagnostic value of troponin in the acute myocardial infarction after cardiac surgery.Methods The prospective study method was used.One hundred and thirtyfour patients of cardiac surgery were selected as observation group,36 patients of thoracic surgery were selected as control group.All the patients were given continuous electrocardiogram monitoring and measured troponin I,and the results were compared between the 2 groups.Results There was no statistical difference in the troponin I before anesthesia between the 2 groups (P > 0.05).The troponin I 4 h after surgery was (13.010 ± 14.829) μg/L in observation group,(0.019 ± 0.007) μg/L in control group,there was statistical difference (P < 0.05).One case of observation group happened the acute myocardial infarction after cardiac surgery,the troponin I was > 40.000 μ g/L.Conclusions The troponin is obviously increased in the early stage in most patients of cardiac surgery,the false positive rate in diagnostic acute myocardial infarction is higher according to the troponin.For troponin,it will need the more evidence of evidence-based medicine to establish the diagnosis of acute myocardial infarction after cardiac surgery.%目的 探讨肌钙蛋白对心脏外科手术后急性心肌梗死的诊断价值.方法 采用前瞻性研究方法,选择134例心脏手术患者作为观察组,同期36例胸科手术患者作为对照组,两组患者术后持续心电监护,检测肌钙蛋白I,并对结果进行比较.结果 两组麻醉前肌钙蛋白I比较差异无统计学意义(P>0.05).观察组术后4h肌钙蛋白I为(13.010±14.829) μg,/L,与对照组的(0.019±0.007) μg/L比较差异有统计学意义(P<0.05).观察组发生急性心肌梗死1例,其肌钙蛋白Ⅰ>40.000 μg/L.结论 心脏外科手术后早期绝大部分患者的肌钙蛋白明显增高,根据肌钙蛋白诊断术后急性心肌梗死的假阳性率较高,有待更多循证医学证据制定肌钙蛋白对

  9. Time course characterization of serum cardiac troponins, heart fatty acid-binding protein, and morphologic findings with isoproterenol-induced myocardial injury in the rat.

    Science.gov (United States)

    Clements, Peter; Brady, Sally; York, Malcolm; Berridge, Brian; Mikaelian, Igor; Nicklaus, Rosemary; Gandhi, Mitul; Roman, Ian; Stamp, Clare; Davies, Dai; McGill, Paul; Williams, Thomas; Pettit, Syril; Walker, Dana; Turton, John

    2010-08-01

    We investigated the kinetics of circulating biomarker elevation, specifically correlated with morphology in acute myocardial injury. Male Hanover Wistar rats underwent biomarker and morphologic cardiac evaluation at 0.5 to seventy-two hours after a single subcutaneous isoproterenol administration (100 or 4000 microg/kg). Dose-dependent elevations of serum cardiac troponins I and T (cTnI, cTnT), and heart fatty acid-binding protein (H-FABP) occurred from 0.5 hour, peaked at two to three hours, and declined to baseline by twelve hours (H-FABP) or forty-eight to seventy-two hours (Serum cTns). They were more sensitive in detecting cardiomyocyte damage than other serum biomarkers. The Access 2 platform, an automated chemiluminescence analyzer (Beckman Coulter), showed the greatest cTnI fold-changes and low range sensitivity. Myocardial injury was detected morphologically from 0.5 hour, correlating well with loss of cTnI immunoreactivity and serum biomarker elevation at early time points. Ultrastructurally, there was no evidence of cardiomyocyte death at 0.5 hour. After three hours, a clear temporal disconnect occurred: lesion scores increased with declining cTnI, cTnT, and H-FABP values. Serum cTns are sensitive and specific markers for detecting acute/active cardiomyocyte injury in this rat model. Heart fatty acid-binding protein is a good early marker but is less sensitive and nonspecific. Release of these biomarkers begins early in myocardial injury, prior to necrosis. Assessment of cTn merits increased consideration for routine screening of acute/ongoing cardiomyocyte injury in rat toxicity studies.

  10. Structural Dynamics of Troponin I during Ca2+-Activation of Cardiac Thin Filaments: A Multi-Site Förster Resonance Energy Transfer Study

    Science.gov (United States)

    Wang, Hui; Chalovich, Joseph M.; Marriott, Gerard

    2012-01-01

    A multi-site, steady-state Förster resonance energy transfer (FRET) approach was used to quantify Ca2+-induced changes in proximity between donor loci on human cardiac troponin I (cTnI), and acceptor loci on human cardiac tropomyosin (cTm) and F-actin within functional thin filaments. A fluorescent donor probe was introduced to unique and key cysteine residues on the C- and N-termini of cTnI. A FRET acceptor probe was introduced to one of three sites located on the inner or outer domain of F-actin, namely Cys-374 and the phalloidin-binding site on F-actin, and Cys-190 of cTm. Unlike earlier FRET analyses of protein dynamics within the thin filament, this study considered the effects of non-random distribution of dipoles for the donor and acceptor probes. The major conclusion drawn from this study is that Ca2+ and myosin S1-binding to the thin filament results in movement of the C-terminal domain of cTnI from the outer domain of F-actin towards the inner domain, which is associated with the myosin-binding. A hinge-linkage model is used to best-describe the finding of a Ca2+-induced movement of the C-terminus of cTnI with a stationary N-terminus. This dynamic model of the activation of the thin filament is discussed in the context of other structural and biochemical studies on normal and mutant cTnI found in hypertrophic cardiomyopathies. PMID:23227172

  11. Structural dynamics of troponin I during Ca2+-activation of cardiac thin filaments: a multi-site Forster resonance energy transfer study.

    Directory of Open Access Journals (Sweden)

    Hui Wang

    Full Text Available A multi-site, steady-state Förster resonance energy transfer (FRET approach was used to quantify Ca(2+-induced changes in proximity between donor loci on human cardiac troponin I (cTnI, and acceptor loci on human cardiac tropomyosin (cTm and F-actin within functional thin filaments. A fluorescent donor probe was introduced to unique and key cysteine residues on the C- and N-termini of cTnI. A FRET acceptor probe was introduced to one of three sites located on the inner or outer domain of F-actin, namely Cys-374 and the phalloidin-binding site on F-actin, and Cys-190 of cTm. Unlike earlier FRET analyses of protein dynamics within the thin filament, this study considered the effects of non-random distribution of dipoles for the donor and acceptor probes. The major conclusion drawn from this study is that Ca(2+ and myosin S1-binding to the thin filament results in movement of the C-terminal domain of cTnI from the outer domain of F-actin towards the inner domain, which is associated with the myosin-binding. A hinge-linkage model is used to best-describe the finding of a Ca(2+-induced movement of the C-terminus of cTnI with a stationary N-terminus. This dynamic model of the activation of the thin filament is discussed in the context of other structural and biochemical studies on normal and mutant cTnI found in hypertrophic cardiomyopathies.

  12. Cardiac troponin I phosphorylation and heart failure%心脏肌钙蛋白I的磷酸化调控与心衰

    Institute of Scientific and Technical Information of China (English)

    王晓建; 惠汝太

    2011-01-01

    心脏肌钙蛋白I(cTnI)是心肌收缩/舒张的关键性调控蛋白.多种激酶调控的cTnI磷酸化通过改变心肌纤维性状影响心脏功能.生理条件下,PKA依赖的cTnI Ser23/24磷酸化与PKC依赖的Ser43/45磷酸化相互拮抗,相互制衡,共同调控心脏的功能.心衰时,动态平衡被打破,cTnI出现磷酸化紊乱,Ser23/24"磷酸化不足"而Ser43/45则"磷酸化过度",肌纤维性状改变,心脏功能受损.除了PKA和PKC,PKG,PKD和PAK3等激酶亦对cTnI的磷酸化起调控作用.本文就cTnI磷酸化调控的分子机制及其对心衰作用研究的最新进展进行综述.%Cardiac troponin I (cTnI) is a key regulatory protein involved in cardiac muscle contraction and relaxation,Phosphorylation of specific serine and threonine residues on cTnI by several different kinases has profound effects on modulation of myofilament properties and cardiac function. Under physiological conditions,the cardiac contractile function achieves optimal performance by PKA-dependent Ser23/24 phosphorylation and PKC-dependent Ser43/45 phosphorylation.In pathological states,this fine balance is disrupted.The Ser23/24 is "hypo-phosphorylation" whereas the Ser43/45 is "hyper-phosphorlaed".The alternationsin cTnI phosphorylation may contribute to impaired contractile function.Besides PKA and PKC,cTnI may also be specifically modified by PKD,PKG and PAK3.This review summarized recent advances in understanding the mechanisms of cTnI modification and the consequent functional effects both under physiological conditions and in heart failure.

  13. High-sensitivity cardiac troponin-I is elevated in patients with rheumatoid arthritis, independent of cardiovascular risk factors and inflammation.

    Directory of Open Access Journals (Sweden)

    William S Bradham

    Full Text Available OBJECTIVES: We examined the hypothesis that cardiac-specific troponin-I (cTn-I, a biomarker of myocardial injury, is elevated in patients with rheumatoid arthritis (RA. BACKGROUND: RA patients have an increased incidence of heart failure (HF. Chronic myocardial injury in RA may be a mechanism for the development of HF. METHODS: We compared cTn-I concentrations measured by high-sensitivity immunoassay in 164 patients with RA and 90 controls, excluding prior or active heart failure. We examined the relationship between cTn-I concentrations and cardiovascular risk factors, inflammation, and coronary artery calcium score (CACS, a measure of coronary atherosclerosis. RESULTS: cTn-I concentrations were 49% higher in patients with RA (median 1.15 pg/mL [IQR 0.73-1.92] than controls (0.77 pg/mL [0.49-1.28](P<0.001. The difference remained statistically significant after adjustment for demographic characteristics (P = 0.002, further adjustment for cardiovascular (CV risk factors (P = 0.004, inflammatory markers (P = 0.008, and in a comprehensive model of CV risk factors and inflammatory markers (P = 0.03. In patients with RA, cTn-I concentrations were positively correlated with age (rho = 0.359, Framingham risk score (FRS (rho = 0.366, and systolic blood pressure (rho = 0.248 (all P values ≤ 0.001, but not with measures of inflammation or RA drug therapies. cTn-I was significantly correlated with CACS in RA in univariate analysis, but not after adjustment for age, race, sex and FRS (P = 0.79. Further model adjustments for renal function and coronary artery disease confirmed the significance of the findings. CONCLUSION: High-sensitivity cTn-I concentrations are elevated in patients with RA without heart failure, independent of cardiovascular risk profile and inflammatory markers. Elevated troponin concentrations in RA may indicate subclinical, indolent myocardial injury.

  14. Q10 supplementation effects on cardiac enzyme CK-MB and troponin in patients undergoing coronary artery bypass graft: a randomized, double-blinded, placebo-controlled clinical trial.

    Science.gov (United States)

    Moludi, Jalal; Keshavarz, Seyedali; Tabaee, Ali Sadeghpour; Safiri, Saeid; Pakzad, Reza

    2016-01-01

    Coronary artery bypass surgery (CABG) is associated with ischemia-reperfusion injury and tissue damage. CoQ10 as an antioxidant has an important role and may have cardio-protective effects after myocardial dysfunction and CABG. We aimed to evaluate whether CoQ10 has a myocardial cardio protective impact on cardiac biomarkers after CABG. In this double-blind study, 80 patients with coronary artery disease (CAD) who underwent CABG surgery were divided into intervention and control groups and received Q10 supplement or placebo, respectively. The surgical characteristics of the patients in the two groups were similar. The intervention group received 150 mg of Q10 supplement per day for 7 days before the surgery. The control group received placebo capsule. After operation the inter- and intra-group blood levels of CK-MB and troponin, before and after supplementation and 12 hours after the CABG, and postoperative outcomes such as intensive care unit (ICU) stay and hospital stay were compared. In this study, 40 subjects were located in each group. The participation rate was 97.5% and men and women accounted for 52.5% and 47.5% respectively. The mean age of the subjects was 58.17 ± 8.55. The two groups were not significantly different in terms of basic variables. Within-group comparison showed a significant increase in the level of troponin enzymes over time (P MB (P MB (P = 0.384) and troponin (P = 0.115). In the end, no interaction was observed between the intervention and time on CK-MB (P = 0.095) and troponin (P = 0.198) variables. Q10 supplementation 7 days before surgery was not effective in reducing CK-MB and troponin after CABG.

  15. Role of Troponins I and T and N-Terminal Prohormone of Brain Natriuretic Peptide in Monitoring Cardiac Safety of Patients With Early-Stage Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Receiving Trastuzumab: A Herceptin Adjuvant Study Cardiac Marker Substudy.

    Science.gov (United States)

    Zardavas, Dimitrios; Suter, Thomas M; Van Veldhuisen, Dirk J; Steinseifer, Jutta; Noe, Johannes; Lauer, Sabine; Al-Sakaff, Nedal; Piccart-Gebhart, Martine J; de Azambuja, Evandro

    2017-03-10

    Purpose Women receiving trastuzumab with chemotherapy are at risk for trastuzumab-related cardiac dysfunction (TRCD). We explored the prognostic value of cardiac markers (troponins I and T, N-terminal prohormone of brain natriuretic peptide [NT-proBNP]) to predict baseline susceptibility to develop TRCD. We examined whether development of cardiac end points or significant left ventricular ejection fraction (LVEF) drop was associated with markers' increases. Patients and Methods Cardiac marker assessments were coupled with LVEF measurements at different time points for 533 patients from the Herceptin Adjuvant (HERA) study who agreed to participate in this study. Patients with missing marker assessments were excluded, resulting in 452 evaluable patients. A primary cardiac end point was defined as symptomatic congestive heart failure of New York Heart Association class III or IV, confirmed by a cardiologist, and a significant LVEF drop, or death of definite or probable cardiac causes. A secondary cardiac end point was defined as a confirmed significant asymptomatic or mildly symptomatic LVEF drop. Results Elevated baseline troponin I (> 40 ng/L) and T (> 14 ng/L), occurring in 56 of 412 (13.6%) and 101 of 407 (24.8%) patients, respectively, were associated with an increased significant LVEF drop risk (univariate analysis: hazard ratio, 4.52; P < .001 and hazard ratio, 3.57; P < .001, respectively). Few patients had their first elevated troponin value recorded during the study (six patients for troponin I and 25 patients for troponin T). Two patients developed a primary and 31 patients a secondary cardiac end point (recovery rate of 74%, 23 of 31). For NT-proBNP, higher increases from baseline were seen in patients with significant LVEF drop. Conclusion Elevated troponin I or T before trastuzumab is associated with increased risk for TRCD. A similar conclusion for NT-proBNP could not be drawn because of the lack of a well-established elevation threshold; however

  16. Troponin elevation in subarachnoid hemorrhage

    Institute of Scientific and Technical Information of China (English)

    Ioannis N Mavridis; Maria Meliou; Efstratios-Stylianos Pyrgelis

    2015-01-01

    Troponin (tr) elevation in aneurysmal subarachnoid hemorrhage (SAH) patients is often difficult to be appropriately assessed by clinicians, causing even disagreements regarding its management between neurosurgeons and cardiologists. The purpose of this article was to review the literature regarding the clinical interpretation of tr elevation in SAH. We searched for articles in PubMed using the key words:“troponin elevation”and“subarachnoid hemorrhage”. All of them, as well as relative neurosurgical books, were used for this review. Some type of cardiovascular abnormality develops in most SAH patients. Neurogenic stunned myocardium is a frequent SAH complication, due to catecholamine surge which induces cardiac injury, as evidenced by increased serum tr levels, electrocardiographic (ECG) changes and cardiac wall motion abnormalities. Tr elevation, usually modest, is an early and specific marker for cardiac involvement after SAH and its levels peak about two days after SAH. Cardiac tr elevation predictors include poor clinical grade, intraventricular hemorrhage, loss of consciousness at ictus, global cerebral edema, female sex, large body surface area, lower systolic blood pressure, higher heart rate and prolonged Q-Tc interval. Elevated tr levels are associated with disability and death (especially tr>1μg/L), worse neurological grade, systolic and diastolic cardiac dysfunction, pulmonary congestion, longer intensive care unit stay and incidence of vasospasm. Tr elevation is a common finding in SAH patients and constitutes a rightful cause of worry about the patients’ cardiac function and prognosis. It should be therefore early detected, carefully monitored and appropriately managed by clinicians.

  17. Myosin heavy chain and cardiac troponin T damage is associated with impaired myofibrillar ATPase activity contributing to sarcomeric dysfunction in Ca(2+)-paradox rat hearts.

    Science.gov (United States)

    Kovács, Árpád; Kalász, Judit; Pásztor, Enikő T; Tóth, Attila; Papp, Zoltán; Dhalla, Naranjan S; Barta, Judit

    2017-06-01

    This study aimed to explore the potential contribution of myofibrils to contractile dysfunction in Ca(2+)-paradox hearts. Isolated rat hearts were perfused with Krebs-Henseleit solution (Control), followed by Ca(2+)-depletion, and then Ca(2+)-repletion after Ca(2+)-depletion (Ca(2+)-paradox) by Langendorff method. During heart perfusion left ventricular developed pressure (LVDP), end-diastolic pressure (LVEDP), rate of pressure development (+ dP/dt), and pressure decay (-dP/dt) were registered. Control LVDP (127.4 ± 6.1 mmHg) was reduced during Ca(2+)-depletion (9.8 ± 1.3 mmHg) and Ca(2+)-paradox (12.9 ± 1.3 mmHg) with similar decline in +dP/dt and -dP/dt. LVEDP was increased in both Ca(2+)-depletion and Ca(2+)-paradox. Compared to Control, myofibrillar Ca(2+)-stimulated ATPase activity was decreased in the Ca(2+)-depletion group (12.08 ± 0.57 vs. 8.13 ± 0.19 µmol Pi/mg protein/h), besides unvarying Mg(2+) ATPase activity, while upon Ca(2+)-paradox myofibrillar Ca(2+)-stimulated ATPase activity was decreased (12.08 ± 0.57 vs. 8.40 ± 0.22 µmol Pi/mg protein/h), but Mg(2+) ATPase activity was increased (3.20 ± 0.25 vs. 7.21 ± 0.36 µmol Pi/mg protein/h). In force measurements of isolated cardiomyocytes at saturating [Ca(2+)], Ca(2+)-depleted cells had lower rate constant of force redevelopment (k tr,max, 3.85 ± 0.21) and unchanged active tension, while those in Ca(2+)-paradox produced lower active tension (12.12 ± 3.19 kN/m(2)) and k tr,max (3.21 ± 23) than cells of Control group (25.07 ± 3.51 and 4.61 ± 22 kN/m(2), respectively). In biochemical assays, α-myosin heavy chain and cardiac troponin T presented progressive degradation during Ca(2+)-depletion and Ca(2+)-paradox. Our results suggest that contractile impairment in Ca(2+)-paradox partially resides in deranged sarcomeric function and compromised myofibrillar ATPase activity as a result of myofilament protein degradation, such

  18. Improving the diagnostic accuracy of acute myocardial infarction with the use of high-sensitive cardiac troponin T in different chronic kidney disease stages

    Science.gov (United States)

    Yang, Hongliu; Liu, Jing; Luo, Han; Zeng, Xiaoxi; Tang, Xi; Ma, Liang; Mai, Hongxia; Gou, Shenju; Liu, Fang; Fu, Ping

    2017-01-01

    High-sensitive cardiac troponin T (hs-TnT) is a critical biomarker in diagnosis of acute myocardial infarction (AMI). However, CKD individuals usually have elevated hs-TnT even in the absence of AMI. Our study aimed to explore the optimal cutoff-value of hs-TnT and further to improve diagnostic accuracy of AMI in CKD patients. Clinical data of 489 patients were collected from the maintained database between September 2010 and June 2014. CKD patients with AMI were assigned to CKD+AMI group and CKD patients without AMI were assigned to CKD group. Receiver operating characteristic curves were utilized to derive the optimal cutoff-value. In CKD+STEMI and CKD group, hs-TnT was increased with descending eGFR. In CKD+NSTEMI group, hs-TnT showed an upward trend with increasing SYNTAX Score. In patients with CKD+STEMI, hs-TnT was significantly correlated with SYNTAX Score in CKD stage 2, stage 4 and in total. In CKD patients, the optimal cutoff-value of hs-TnT for diagnosis of AMI was 129.45 ng/l with 75.2% sensitivity and 83.2% specificity. The cutoff-value appeared to be hs-TnT level of 99.55ng/l in CKD stage 3, 129.45 ng/l in CKD stage 4, 105.50 ng/l in CKD stage 5 and 149.35 ng/l in dialysis patients, respectively. In different stages of CKD, eGFR-range-specific optimal cutoff-values should be considered. PMID:28145489

  19. Comparison of Abbott AxSYM, Behring Opus Plus, DPC Immulite and Ortho-Clinical Diagnostics Vitros ECi for measurement of cardiac troponin I.

    Science.gov (United States)

    Kao, J T; Wong, I L; Lee, J Y; Chen, R C

    2001-03-01

    Myocardial infarction is a common cause of morbidity and mortality in patients with chest pain. The presence of human cardiac troponin I (cTnI) in serum is considered to be a highly specific biochemical marker of acute myocardial infarction. In this study we compare the performances of the Abbott AxSYM, Behring Opus Plus, DPC Immulite and Ortho-Clinical Diagnostics Vitros ECi for the measurement of cTnI. The first two methods use a fluorogenic enzyme-linked immunoassay. whereas the last two use chemiluminescent immunometric assays. All procedures are completely automated. Total percentage coefficients of variation using pooled sera ranged from 5.9 to 6.5% for the AxSYM, 14.4 to 25.6% for the Opus, 6.9 to 9.8% for the Immulite and 4.5 to 5.2% for the Vitros ECi method. The closest correlation between methods, obtained from 120 fresh serum samples, was observed between the Vitros ECi and the Immulite methods, with r=0.99, and the regression line was Immulite cTnI 1.505 (95% confidence interval 1.474-1.536) x Vitros cTnI--0.154 (-0.702 to 0.394). Receiver operating characteristic curves were nearly identical for all assays, and the areas under the curves were 0.972, 0.927, 0.967 and 0.969 for the AxSYM, Opus, Immulite and Vitros ECi methods, respectively. There was a significant difference between the AxSYM and Opus methods (P= 0.036).

  20. Sensitive cardiac troponins and N-terminal pro-B-type natriuretic peptide in stable coronary artery disease: correlation with left ventricular function as assessed by myocardial strain.

    Science.gov (United States)

    Smedsrud, Marit Kristine; Gravning, Jørgen; Omland, Torbjørn; Eek, Christian; Mørkrid, Lars; Skulstad, Helge; Aaberge, Lars; Bendz, Bjørn; Kjekshus, John; Edvardsen, Thor

    2015-06-01

    N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponins (cTns) measured with sensitive assays provide strong prognostic information in patients with stable coronary artery disease. However, the relationship between these biomarkers and myocardial contractile function, as well as infarct size, in this patient group, remains to be defined. The study population consisted of 160 patients referred to a follow-up echocardiography scheduled 1 year after coronary revascularization. Concentrations of NT-proBNP, high-sensitive cTnT (hs-cTnT) and sensitive cTnI assays were assessed. Left ventricular function was measured as global peak systolic longitudinal strain by speckle tracking echocardiography and infarct size was assessed by late-enhancement MRI. NT-proBNP and sensitive cTnI levels were significantly associated with left ventricular function by peak systolic strain (R-values 0.243 and 0.228, p = 0.002 and 0.004) as well as infarct size (R-values 0.343 and 0.366, p = 0.014 and p = 0.008). In contrast, hs-cTnT did not correlate with left ventricular function (R = 0.095, p = 0.231) and only marginally with infarct size (R = 0.237, p = 0.094). NT-proBNP and sensitive cTnI levels correlate with left ventricular function and infarct size in patients with stable coronary artery disease after revascularization. As opposed to hs-cTnT, NT-proBNP and cTnI seem to be indicators of incipient myocardial dysfunction and the extent of myocardial necrosis.

  1. The prognostic use of serum concentrations of cardiac troponin-I, CK-MB and myoglobin in patients with idiopathic dilated cardiomyopathy.

    Science.gov (United States)

    Li, Xiaoping; Luo, Rong; Jiang, Rongjian; Kong, Hong; Tang, Yijia; Shu, Yan; Hua, Wei

    2014-01-01

    To examine the association between survival and serum concentrations of cTnI, CK-MB, and myoglobin in patients with idiopathic dilated cardiomyopathy (IDC). It has been suggested that elevated circulating biomarkers of myocardial damage such as cardiac troponin-I (cTnI), creatine kinase MB (CK-MB) and myoglobin are independent risk factors for mortality in patients with heart failure, and recent studies, although limited, showed that there was a potential association between cTnI and the prognosis of patients with dilated cardiomyopathy (DCM). A cohort study was undertaken in 310 patients with IDC. Standard demographic information, transthoracic echocardiography, and routine blood tests were obtained shortly after hospital admission. Outcome was assessed with all-cause mortality. Among the 310 patients studied, 61 (19.7%) died during a mean follow-up of 2.2 years. There was a significant difference in the all-cause mortality rate between patients with serum cTnI >0.05 ng/mL and with cTnI ≤ 0.05 ng/mL (37.5% vs 15%, log-rank χ(2) = 18.423, P 0.05 ng/mL, QRS duration, NYHA functional class and systolic blood pressure predicted all-cause mortality in patients with IDC. There was no association between circulating CK-MB and myoglobin levels and all-cause mortality in the studied IDC patients. Serum concentrations of cTnI but not CK-MB or myoglobin are an independent predictor of all-cause mortality in patients with IDC. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Mechanism of the Frank-Starling law--a simulation study with a novel cardiac muscle contraction model that includes titin and troponin I.

    Science.gov (United States)

    Schneider, Natalie S; Shimayoshi, Takao; Amano, Akira; Matsuda, Tetsuya

    2006-09-01

    A stretch-induced increase of active tension is one of the most important properties of the heart, known as the Frank-Starling law. Although a variation of myofilament Ca(2+) sensitivity with sarcomere length (SL) change was found to be involved, the underlying molecular mechanisms are not fully clarified. Some recent experimental studies indicate that a reduction of the lattice spacing between thin and thick filaments, through the increase of passive tension caused by the sarcomeric protein titin with an increase in SL within the physiological range, promotes formation of force-generating crossbridges (Xbs). However, the mechanism by which the Xb concentration determines the degree of cooperativity for a given SL has so far evaded experimental elucidation. In this simulation study, a novel, rather simple molecular-based cardiac contraction model, appropriate for integration into a ventricular cell model, was designed, being the first model to introduce experimental data on titin-based radial tension to account for the SL-dependent modulation of the interfilament lattice spacing and to include a conformational change of troponin I (TnI). Simulation results for the isometric twitch contraction time course, the length-tension and the force-[Ca(2+)] relationships are comparable to experimental data. A complete potential Frank-Starling mechanism was analyzed by this simulation study. The SL-dependent modulation of the myosin binding rate through titin's passive tension determines the Xb concentration which then alters the degree of positive cooperativity affecting the rate of the TnI conformation change and causing the Hill coefficient to be SL-dependent.

  3. The cardiac biomarkers troponin I and CK-MB in nonpregnant and pregnant goats, goats with normal birth, goats with prolonged birth, and goats with pregnancy toxemia.

    Science.gov (United States)

    Tharwat, M; Al-Sobayil, F; Al-Sobayil, K

    2012-10-15

    This study was designed to establish the reference range for the cardiac biomarkers cardiac troponin I (cTnI) and creatine kinase myocardial band (CK-MB) in nonpregnant and pregnant goats, goats with normal birth, goats with prolonged birth associated with dystocia, and goats with pregnancy toxemia. Fifty-seven does, categorized into three groups (G1 to G3), were used. These groups were comprised of 20 healthy does (G1), 19 does with prolonged birth (G2), and 18 does with pregnancy toxemia (G3). Six blood samples (T0 to T5) were collected from G1. The first blood sample (T0) was taken before insemination, the second (T1) at the first trimester, the third (T2) at the second trimester, the fourth (T3) at the last trimester, the fifth (T4) within 12 h of parturition, and the sixth blood sample (T5) was taken 10 days after parturition. A sample of blood was obtained from G2 and G3 upon admission to the hospital. At T0 to T3, no cTnI was detected in any of the 20 does in G1. At parturition (T4), seven of the 20 goats (35%) exhibited slightly elevated cTnI concentrations (range, 0.01 to 0.04 ng/mL). Ten days after parturition (T5), cTnI was not detected in any of the 20 goats. In 10 of the 19 goats (53%) with prolonged birth (G2), the cTnI was significantly elevated to a mean value of 0.094 ± 0.155 ng/mL, with a maximum value of 0.61 ng/mL. In 16 of the 18 goats (89%) with pregnancy toxemia (G3), the cTnI was significantly elevated to a value of 0.852 ± 1.472 ng/mL, with a maximum value of 5.219 ng/mL. Comparing the values of CK-MB in G1 (T0 to T5), G2 and G3 revealed nonsignificant differences. Only a slight elevation in the CK-MB levels in goats with prolonged birth (G2) was noted. We concluded that in healthy does, the cardiac biomarker cTnI is not elevated during normal pregnancy. The serum cTnI concentration may be elevated in a number of goats at normal vaginal or cesarean delivery. Finally, cTnI is significantly elevated in does with pregnancy toxemia and could

  4. Implications of troponin testing in clinical medicine

    Directory of Open Access Journals (Sweden)

    Meinertz Thomas

    2001-04-01

    Full Text Available Abstract During the past decade considerable research has been conducted into the use of cardiac troponins, their diagnostic capability and their potential to allow risk stratification in patients with acute chest pain. Determination of risk in patients with suspected myocardial ischaemia is known to be as important as retrospective confirmation of a diagnosis of myocardial infarction (MI. Therefore, creatine kinase (CK-MB - the former 'gold standard' in detecting myocardial necrosis - has been supplanted by new, more accurate biomarkers.Measurement of cardiac troponin levels constitute a substantial determinant in assessment of ischaemic heart disease, the presentations of which range from silent ischaemia to acute MI. Under these conditions, troponin release is regarded as surrogate marker of thrombus formation and peripheral embolization, and therefore new therapeutic strategies are focusing on potent antithrombotic regimens to improve long-term outcomes. Although elevated troponin levels are highly sensitive and specific indicators of myocardial damage, they are not always reflective of acute ischaemic coronary artery disease; other processes have been identified that cause elevations in these biomarkers. However, because prognosis appears to be related to the presence of troponins regardless of the mechanism of myocardial damage, clinicians increasingly rely on troponin assays when formulating individual therapeutic plans.

  5. Clinical Characteristics and Outcomes of Patients with Myocardial Infarction, Myocardial Injury, and Nonelevated Troponins

    DEFF Research Database (Denmark)

    Sarkisian, Laura; Saaby, Lotte; Poulsen, Tina S

    2015-01-01

    was diagnosed in cases of a cardiac troponin I increase or decrease pattern with at least 1 value >30 ng/L (99th percentile) together with myocardial ischemia. Myocardial injury was defined as cardiac troponin I values >30 ng/L, but without signs or symptoms indicating overt cardiac ischemia. Patients with peak...

  6. Depressed Frank-Starling mechanism in the left ventricular muscle of the knock-in mouse model of dilated cardiomyopathy with troponin T deletion mutation ΔK210.

    Science.gov (United States)

    Inoue, Takahiro; Kobirumaki-Shimozawa, Fuyu; Kagemoto, Tatsuya; Fujii, Teruyuki; Terui, Takako; Kusakari, Yoichiro; Hongo, Kenichi; Morimoto, Sachio; Ohtsuki, Iwao; Hashimoto, Kazuhiro; Fukuda, Norio

    2013-10-01

    It has been reported that the Frank-Starling mechanism is coordinately regulated in cardiac muscle via thin filament "on-off" equilibrium and titin-based lattice spacing changes. In the present study, we tested the hypothesis that the deletion mutation ΔK210 in the cardiac troponin T gene shifts the equilibrium toward the "off" state and accordingly attenuate the sarcomere length (SL) dependence of active force production, via reduced cross-bridge formation. Confocal imaging in isolated hearts revealed that the cardiomyocytes were enlarged, especially in the longitudinal direction, in ΔK210 hearts, with striation patterns similar to those in wild type (WT) hearts, suggesting that the number of sarcomeres is increased in cardiomyocytes but the sarcomere length remains unaltered. For analysis of the SL dependence of active force, skinned muscle preparations were obtained from the left ventricle of WT and knock-in (ΔK210) mice. An increase in SL from 1.90 to 2.20μm shifted the mid-point (pCa50) of the force-pCa curve leftward by ~0.21pCa units in WT preparations. In ΔK210 muscles, Ca(2+) sensitivity was lower by ~0.37pCa units, and the SL-dependent shift of pCa50, i.e., ΔpCa50, was less pronounced (~0.11pCa units), with and without protein kinase A treatment. The rate of active force redevelopment was lower in ΔK210 preparations than in WT preparations, showing blunted thin filament cooperative activation. An increase in thin filament cooperative activation upon an increase in the fraction of strongly bound cross-bridges by MgADP increased ΔpCa50 to ~0.21pCa units. The depressed Frank-Starling mechanism in ΔK210 hearts is the result of a reduction in thin filament cooperative activation.

  7. Is general anesthesia a risk for myocardium? Effect of anesthesia on myocardial function as assessed by cardiac troponin-i in two different groups (isofluran+N2O inhalation and propofol+fentanyl iv anesthesia

    Directory of Open Access Journals (Sweden)

    Demet Dogan Erol

    2007-11-01

    Full Text Available Demet Dogan Erol1, Ibrahim Ozen21Department of Anaesthesiology and Reanimation, School of Medicine, Kocatepe University, Afyonkarahisar, Turkey; 2Department of Anaesthesiology and Reanimation, Karadeniz Technical University Faculty of Medicine, Trabzon, TurkeyBackground and objectives: Peroperative myocardial infarction (MI is the most common cause of morbidity and mortality. What is the role of general anesthesia in this process? Is general anesthesia a risk for myocardial infarction? The present study was designed to determine whether the measurement of serum levels of cardiac troponin I (cTnI, a highly sensitive and specific marker for cardiac injury, would help establish the diagnosis of myocardial infarction in two different types of anesthesia.Method: Elective abdominal hysterectomy was planned with the permission of the ethic committee in 40 patients who were 20–45 years range, in ASA-I group, and have a Goldman Cardiac Risk Index-0. The patients were divided into two groups. Isoflurane + N2O was administrated to first group, and Propofol + Fentanyl to second group. cTnI levels were determined before anesthesia, after induction before surgery and 9 hours after the second period respectively.Results: There was no significant difference between the groups by the means of demographic properties, hemodynamic parameters and cTnI levels, and the cTnI levels were determined under the basal levels in all samples.Conclusion: General anesthesia is not a risk for myocardial infarction to state eliminating risk factors and protection hemodynamia cardiac.Keywords: cardiac troponin-I, myocardial infarction, isofluran + N2O inhalation anesthesia, propofol + fentanyl intravenous anesthesia.

  8. Motor neurone disease presenting with raised serum Troponin T.

    Science.gov (United States)

    Mamo, Jonathan P

    2015-05-01

    Myocardial damage indicated by a rise in cardiac Troponin may not necessarily be due to a cardiac event. Many diseases such as sepsis, pulmonary embolism, heart and renal failure can also be associated with an elevated cardiac Troponin level. This brief report discusses the rare event of a patient with motor neurone disease, where the possible diagnosis of acute myocardial infarction arose due to an elevated cardiac Troponin. A 69-year-old gentleman presented with a history of a central chest ache of mild intensity, lasting a total of 2 h prior to complete resolution. Multiple cardiac Troponin assays were elevated, and echocardiography did not show any acute changes of myocardial damage. His electrocardiogram was also normal. This patient's raised cardiac Troponin was therefore explained on the basis of his active motor neurone disease. This rare case outlines the importance of considering motor neurone disease as a cause of elevated cardiac Troponin in the absence of clinical evidence of an acute coronary event.

  9. Troponin and anti-troponin autoantibody levels in patients with ventricular noncompaction.

    Directory of Open Access Journals (Sweden)

    Hatice Betül Erer

    Full Text Available Ventricular hypertrabeculation/noncompaction is a morphologic and functional anomaly of myocardium characterized by prominent trabeculae accompanied by deep recessus. Dilated cardiomyopathy with left ventricular failure is observed in these patients, while the cause or pathophysiologic nature of this complication is not known. Anti-troponin antibodies are formed against circulating cardiac troponins after an acute coronary event or conditions associated with chronic myocyte necrosis, such as dilated cardiomyopathy. In present study, we aimed to investigate cardiac troponins and anti troponin autoantibodies in ventricular noncompaction/hypertrabeculation patients with/without reduced ejection fraction. A total of 50 patients with ventricular noncompaction and 23 healthy volunteers were included in this study. Noncompaction/hypertrabeculation was diagnosed with two-dimensional echocardiography using appropriate criteria. Depending on ejection fraction, patients were grouped into noncompaction with preserved EF (LVEF >50%, n = 24 and noncompaction with reduced EF (LVEF <35%, n = 26 groups. Troponin I, troponin T, anti-troponin I IgM and anti-troponin T IgM were measured with sandwich immunoassay method using a commercially available kit. Patients with noncompaction had significantly higher troponin I (28.98±9.21 ng/ml in NCNE group and 28.11±10.42 ng/ml in NCLE group, troponin T (22.17±6.97 pg/ml in NCNE group and 22.78±7.76 pg/ml in NCLE group and antitroponin I IgM (1.92±0.43 µg/ml in NCNE group and 1.79±0.36 µg/ml in NCLE group levels compared to control group, while antitroponin T IgM and IgG were only elevated in patients with noncompaction and reduced EF (15.81±6.52 µg/ml for IgM and 16.46±6.25 µg/ml for IgG. Elevated cardiac troponins and anti-troponin I autoantibodies were observed in patients with noncompaction preceding the decline in systolic function and could indicate ongoing myocardial damage in these patients.

  10. Troponin and anti-troponin autoantibody levels in patients with ventricular noncompaction.

    Science.gov (United States)

    Erer, Hatice Betül; Güvenç, Tolga Sinan; Kemik, Ahu Sarbay; Yılmaz, Hale Yaka; Kul, Şeref; Altay, Servet; Sayar, Nurten; Kaya, Yüksel; Eren, Mehmet

    2013-01-01

    Ventricular hypertrabeculation/noncompaction is a morphologic and functional anomaly of myocardium characterized by prominent trabeculae accompanied by deep recessus. Dilated cardiomyopathy with left ventricular failure is observed in these patients, while the cause or pathophysiologic nature of this complication is not known. Anti-troponin antibodies are formed against circulating cardiac troponins after an acute coronary event or conditions associated with chronic myocyte necrosis, such as dilated cardiomyopathy. In present study, we aimed to investigate cardiac troponins and anti troponin autoantibodies in ventricular noncompaction/hypertrabeculation patients with/without reduced ejection fraction. A total of 50 patients with ventricular noncompaction and 23 healthy volunteers were included in this study. Noncompaction/hypertrabeculation was diagnosed with two-dimensional echocardiography using appropriate criteria. Depending on ejection fraction, patients were grouped into noncompaction with preserved EF (LVEF >50%, n = 24) and noncompaction with reduced EF (LVEF <35%, n = 26) groups. Troponin I, troponin T, anti-troponin I IgM and anti-troponin T IgM were measured with sandwich immunoassay method using a commercially available kit. Patients with noncompaction had significantly higher troponin I (28.98±9.21 ng/ml in NCNE group and 28.11±10.42 ng/ml in NCLE group), troponin T (22.17±6.97 pg/ml in NCNE group and 22.78±7.76 pg/ml in NCLE group) and antitroponin I IgM (1.92±0.43 µg/ml in NCNE group and 1.79±0.36 µg/ml in NCLE group) levels compared to control group, while antitroponin T IgM and IgG were only elevated in patients with noncompaction and reduced EF (15.81±6.52 µg/ml for IgM and 16.46±6.25 µg/ml for IgG). Elevated cardiac troponins and anti-troponin I autoantibodies were observed in patients with noncompaction preceding the decline in systolic function and could indicate ongoing myocardial damage in these patients.

  11. High-sensitive cardiac Troponin T is superior to echocardiography in predicting 1-year mortality in patients with SIRS and shock in intensive care

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    Bergenzaun Lill

    2012-09-01

    Full Text Available Abstract Background Left ventricular (LV dysfunction is well documented in the critically ill. We assessed 1-year mortality in relation to cardiac biomarkers and LV function parameters by echocardiography in patients with shock. Methods A prospective, observational, cohort study of 49 patients. B-natriuretic peptide (BNP, high-sensitive troponin T (hsTNT and transthoracic echocardiography (TTE were assessed within 12 h of study inclusion. LV systolic function was measured by ejection fraction (LVEF, mean atrioventricular plane displacement (AVPDm, peak systolic tissue Doppler velocity imaging (TDIs and velocity time integral in the LV outflow tract (LVOT VTI. LV diastolic function was evaluated by transmitral pulsed Doppler (E, A, E/A, E-deceleration time, tissue Doppler indices (é, á, E/é and left atrial volume (La volume. APACHE II (Acute Physiology and Chronic Health Evaluation and SOFA (Sequential Organ Failure Assessment scores were calculated. Results hsTNT was significantly higher in non-survivors than in survivors (60 [17.0-99.5] vs 168 [89.8-358] ng/l, p = 0.003. Other univariate predictors of mortality were APACHE II (p = 0.009, E/é (p = 0.023, SOFA (p = 0.024 and age (p = 0.031. Survivors and non-survivors did not differ regarding BNP (p = 0.26 or any LV systolic function parameter (LVEF p = 0.87, AVPDm p = 0.087, TDIs p = 0.93, LVOT VTI p = 0.18. Multivariable logistic regression analysis identified hsTNT (p = 0.010 as the only independent predictor of 1-year mortality; adjusted odds ratio 2.0 (95% CI 1.2- 3.5. Conclusions hsTNT was the only independent predictor of 1-year mortality in patients with shock. Neither BNP nor echocardiographic parameters had an independent prognostic value. Further studies are needed to establish the clinical significance of elevated hsTNT in patients in shock.

  12. Nanocomposites of gold nanoparticles and graphene oxide towards an stable label-free electrochemical immunosensor for detection of cardiac marker troponin-I

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Guozhen, E-mail: gzliu@mail.ccnu.edu.cn [Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079 (China); ARC Centre of Excellence in Nanoscale Biophotonics (CNBP), Department of Physics and Astronomy, Macquarie University, North Ryde 2109 (Australia); Qi, Meng; Zhang, Yin; Cao, Chaomin [Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079 (China); Goldys, Ewa M. [ARC Centre of Excellence in Nanoscale Biophotonics (CNBP), Department of Physics and Astronomy, Macquarie University, North Ryde 2109 (Australia)

    2016-02-25

    A stable label-free amperometric immunosensor is presented based on gold nanoparticles and graphene oxide nanocomposites for detection of cardiac troponin-I in the early diagnosis of myocardial infarction. For designing of the sensing platform, firstly the nanocomposites based on GO and AuNPs were prepared and anchored on electrode surfaces. The formed nanocomposites provided a platform with big surface area for loading anti-cTnI capture antibody, and worked as a bridge for fast electron transfer subsequently increased the sensitivity. Moreover, the linkages between AuNP, GO, and electrodes were based on covalent bonding by aryldiazonium salt coupling chemistry, which favors the stability of the sensing interface. Finally, the anti-cTnI detection antibody was immobilized on GO tailored with ferrocene molecules, functioning as the signal reporter for the detection of cTnI. The modification process was monitored using electrochemistry, SEM, XPS. The herein immunosensor demonstrates a good selectivity and high sensitivity against human-cTnI, and is capable of detecting cTnI at concentrations as low as 0.05 ng mL{sup −1}, which is 100 times lower than that possible by conventional methods. It is potential to design the portable sensing platform based on AuNPs and GO nanocomposites for future point-of-care diagnostics. - Highlights: • Nanocomposites based on GO and AuNPs were prepared and anchored on the electrode surfaces covalently to form a stable sensing interface. • The anti-cTnI detection antibody was immobilized on GO tailored with ferrocene molecules, functioning as the signal reporter for the detection of cTnI. • The detectable concentration of cTnI is 0.05 ng mL{sup -1} in buffer with the assay time of less than 5 min. • The herein simple and novel approach for fabrication of AuNP and graphene based platform is promising for future fabrication of point-of-care devices.

  13. Association of glomerular filtration rate with high-sensitivity cardiac troponin T in a community-based population study in Beijing.

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    Fan Wang

    Full Text Available BACKGROUND: Reduced renal function is an independent risk factor for cardiovascular disease mortality, and persistently elevated cardiac troponin T (cTnT is frequently observed in patients with end-stage renal disease. In the general population the relationship between renal function and cTnT levels may not be clear because of the low sensitivity of the assay. In this study, we investigated the level of cTnT using a highly sensitive assay (hs-cTnT and evaluated the association of estimated glomerular filtration rate (eGFR with detectable hs-cTnT levels in a community-based population. METHODS: The serum hs-cTnT levels were measured in 1365 community dwelling population aged ≥45 years in Beijing, China. eGFR was determined by the Chinese modifying modification of diet in renal disease (C-MDRD equation. RESULTS: With the highly sensitive assay, cTnT levels were detectable (≥3pg/mL in 744 subjects (54.5%. The result showed that eGFR was associated with Log hs-cTnT (r = -0.14, P20% and other prognostic indicators, moderate to severe reduced eGFR was independently associated with detectable hs-cTnT, whereas normal to mildly reduced eGFR was not independently associated with detectable hs-cTnT. In addition, after adjustment for other risk factors, the high predicted Framingham CHD risk was associated with detectable hs-cTnT in the subjects with different quartile levels of eGFR. CONCLUSION: The levels of hs-cTnT are detectable in a community-based Chinese population and low eGFR is associated with detectable hs-cTnT. Moreover, eGFR and high predicted Framingham CHD risk are associated with detectable hs-cTnT in subjects with moderate-to-severe reduced renal function.

  14. Association between high-sensitivity cardiac troponin T and N-terminal pro-brain natriuretic peptide in a community based population

    Institute of Scientific and Technical Information of China (English)

    Xu Ruyi; Ye Ping; Luo Leiming; Sheng Li; Wu Hongmei; Xiao Wenkai; Zheng Jin

    2014-01-01

    Background N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) are excellent biomarkers for detecting heart failure and subclinical myocardial injury.However,it remains unclear whether subclinical myocardial injury is associated with NT-proBNP elevation in a community based population.Methods In a community based study,levels of hs-cTnT and of NT-proBNP were determined in 1 497 participants older than 45 years.The lower detection limit of the hs-cTnT assay used in the present study was 0.003 ng/ml.The association of hs-cTnT levels and NT-proBNP levels was analyzed.Results When the subjects with undetectable (<0.003 ng/ml),intermediate (0.003-0.014 ng/ml),and elevated (≥0.014 ng/ml) levels of hs-cTnT were compared (r=0.175,P <0.001),a strong association between the hs-cTnT levels and NT-proBNP levels was observed (β=-0.206,P <0.001; β=-0.118,P <0.001,respectively).In multivariable analyses,older age and hs-cTnT were positively and independently associated with NT-proBNP levels (β=0.341,P <0.001; β=0.143,P <0.001,respectively),and male gender and the levels of eGFR were inversely and independently associated with NT-proBNP levels.When the subjects with normal or elevated NT-proBNP were analyzed separately,the hs-cTnT level was not an independent predictor for the NT-proBNP level in the normal NT-proBNP group,whereas the hs-cTnT level was the only independent predictor for NT-proBNP level in the elevated NT-proBNP group (β=0.399,P <0.01).Conclusions In this community based population,NT-proBNP elevation was common.In addition to female gender and older age,subclinical myocardial injury indicated by the hs-cTnT level was another important factor in NT-proBNP elevation.

  15. Avaliação dos valores séricos de troponina I cardíaca em crianças menores de 1 ano de idade Evaluation of serum cardiac troponin I values in children less than 1 year of age

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    Antonio Carlos Arruda Souto

    2008-09-01

    Full Text Available OBJETIVO: Verificar os valores séricos para troponina I cardíaca em crianças abaixo de um ano de idade, sem disfunção cardíaca clínica. MÉTODOS: Os níveis séricos de troponina I cardíaca foram determinados em 99 crianças com idade abaixo de um ano, incluindo-se recém-nascidos a termo, sem doenças relacionadas a comprometimento da função cardíaca identificável clinicamente, por meio do kit específico Opus T Troponin I (cTn (Dade Behring Inc. - Newalk, DE 19714, USA. RESULTADOS: A dosagem sérica de troponina I cardíaca apresentou, em todos os pacientes, valor menor que 0,1 ng/ml. CONCLUSÃO: Verificamos que o valor da dosagem sérica de troponina I cardíaca é menor do que 0,1 ng/ml para pacientes pediátricos, sem disfunção cardíaca, desde recém-nascidos a termo até um ano de idade, quando realizada por meio do kit Opus T Troponin I (cTn test modules.OBJECTIVE: The objective is to verify the cardiac troponin I values in children less than 1 year of age without clinical cardiac dysfunction. METHODS: The cardiac troponin I values were determined in 99 children less than 1 year of age, including term infants without diseases related to cardiac dysfunction using the specific kit Opus T Troponin I (cTn (Dade Behring Inc. -Newalk, DE 19714, USA. RESULTS: All children have values of cardiac troponin I less than 0.1 ng/ml. CONCLUSION: We verified that the cardiac troponin I value is less than 0.1 ng/ml in children less than 1 year, including term infants without cardiac dysfunction, when analized by the kit Opus T Troponin I (cTn test modules.

  16. Mutations in the Kv1.5 channel gene KCNA5 in cardiac arrest patients

    DEFF Research Database (Denmark)

    Nielsen, Nathalie H; Winkel, Bo G; Kanters, Jørgen K

    2007-01-01

    identified the point mutations P91L and E33V in the KCNA5 gene encoding the Kv1.5 potassium channel that has not previously been associated with arrhythmia. We functionally characterized the mutations in HEK293 cells. The mutated channels behaved similarly to the wild-type with respect to biophysical......Mutations in one of the ion channels shaping the cardiac action potential can lead to action potential prolongation. However, only in a minority of cardiac arrest cases mutations in the known arrhythmia-related genes can be identified. In two patients with arrhythmia and cardiac arrest, we...... characteristics and drug sensitivity. Both patients also carried a D85N polymorphism in KCNE1, which was neither found to influence the Kv1.5 nor the Kv7.1 channel activity. We conclude that although the two N-terminal Kv1.5 mutations did not show any apparent electrophysiological phenotype, it is possible...

  17. Genetic variation in exon 5 of troponin - I gene in hypertrophic cardiomyopathy cases

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    Annapurna S

    2007-01-01

    Full Text Available Background: Cardiomyopathies are a heterogeneous group of heart muscle disorders and are classified as 1 Hypertrophic Cardiomyopathy (HCM 2 Dilated cardiomyopathy (DCM 3 Restrictive cardiomyopathy (RCM and 4 Arrhythmogenic right ventricular dysplasia (ARVD as per WHO classification, of which HCM and DCM are common. HCM is a complex but relatively common form of inherited heart muscle disease with prevalence of 1 in 500 individuals and is commonly associated with sarcomeric gene mutations. Cardiac muscle troponin I (TNNI-3 is one such sarcomeric protein and is a subunit of the thin filament-associated troponin-tropomyosin complex involved in calcium regulation of skeletal and cardiac muscle contraction. Mutations in this gene were found to be associated with a history of sudden cardiac death in HCM patients. Aim: Therefore the present study aims to identify for mutations associated with troponin I gene in a set of HCM patients from Indian population. Materials and Methods: Mutational analyses of 92 HCM cases were carried out following PCR based SSCP analysis. Results: The study revealed band pattern variation in 3 cases from a group of 92 HCM patients. This band pattern variation, on sequencing revealed base changes, one at nt 2560 with G>T transversion in exon-5 region with a wobble and others at nt 2479 and nt 2478 with G>C and C>G transversions in the intronic region upstream of the exon 5 on sequencing. Further analysis showed that one of the probands showed apical form of hypertrophy, two others showing asymmetric septal hypertrophy. Two of these probands showed family history of the condition. Conclusions: Hence, the study supports earlier reports of involvement of TNNI-3 in the causation of apical and asymmetrical forms of hypertrophy.

  18. Inherited Cardiac Diseases Caused by Mutations in the Nav1.5 Sodium Channel

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Jacob; Winkel, Bo Gregers; Grunnet, Morten

    2009-01-01

    Cardiac Diseases Caused by SCN5A Mutations. A prerequisite for a normal cardiac function is a proper generation and propagation of electrical impulses. Contraction of the heart is obtained through a delicate matched transmission of the electrical impulses. A pivotal element of the impulse propaga......-QT syndrome, Brugada syndrome, and AF, reported to be associated with mutations in SCN5A, are thoroughly described. (J Cardiovasc Electrophysiol, Vol. pp. 1-9)....

  19. Cardiac ryanodine receptor gene (hRyR2) mutation underlying catecholaminergic polymorphic ventricular tachycardia in a Chinese adolescent presenting with sudden cardiac arrest and cardiac syncope

    Institute of Scientific and Technical Information of China (English)

    Ngai-Shing Mok; Ching-Wan Lam; Nai-Chung Fong; Yim-Wo Hui; Yuen-Choi Choi; Kwok-Yin Chan

    2006-01-01

    @@ Sudden cardiac death (SCD) in children and adolescents is uncommon and yet it is devastating for both victim's family and the society.Recently, it was increasingly recognized that SCD in young patients with structurally normal heart may be caused by inheritable primary electrical diseases due to the malfunction of cardiac ion channels, a disease entity known as the ion channelopathies.Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a specific form of ion channelopathy which can cause cardiac syncope or SCD in young patients by producing catecholamine-induced bi-directional ventricular tachycardia (BiVT), polymorphic VT and ventricular fibrillation (VF) during physical exertion or emotion.1-7 We reported here an index case of CPVT caused by cardiac ryanodine receptor gene (hRyR2)mutation which presented as cardiac syncope and sudden cardiac arrest in a Chinese adolescent female.

  20. Troponin elevation in subarachnoid hemorrhage

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    Ioannis N. Mavridis

    2015-03-01

    Full Text Available Troponin (tr elevation in aneurysmal subarachnoid hemorrhage (SAH patients is often difficult to be appropriately assessed by clinicians, causing even disagreements regarding its management between neurosurgeons and cardiologists. The purpose of this article was to review the literature regarding the clinical interpretation of tr elevation in SAH. We searched for articles in PubMed using the key words: “troponin elevation” and “subarachnoid hemorrhage”. All of them, as well as relative neurosurgical books, were used for this review. Some type of cardiovascular abnormality develops in most SAH patients. Neurogenic stunned myocardium is a frequent SAH complication, due to catecholamine surge which induces cardiac injury, as evidenced by increased serum tr levels, electrocardiographic (ECG changes and cardiac wall motion abnormalities. Tr elevation, usually modest, is an early and specific marker for cardiac involvement after SAH and its levels peak about two days after SAH. Cardiac tr elevation predictors include poor clinical grade, intraventricular hemorrhage, loss of consciousness at ictus, global cerebral edema, female sex, large body surface area, lower systolic blood pressure, higher heart rate and prolonged Q-Tc interval. Elevated tr levels are associated with disability and death (especially tr >1 μg/L, worse neurological grade, systolic and diastolic cardiac dysfunction, pulmonary congestion, longer intensive care unit stay and incidence of vasospasm. Tr elevation is a common finding in SAH patients and constitutes a rightful cause of worry about the patients' cardiac function and prognosis. It should be therefore early detected, carefully monitored and appropriately managed by clinicians.

  1. 老年2型糖尿病患者血清心肌肌钙蛋白水平与心血管事件的相关性研究%Correlation of serum cardiac troponin levels and cardiovascular events in elderly type 2 diabetes patients

    Institute of Scientific and Technical Information of China (English)

    李天艺; 李华

    2016-01-01

    目的 探讨老年2型糖尿病患者血清心肌肌钙蛋白水平与心血管事件的相关性,为2型糖尿病并发心血管疾病的预防和诊治提供依据.方法 回顾性分析,选择我院老年2型糖尿病患者200例,根据患者的血清心肌肌钙蛋白水平分为肌钙蛋白阳性组(30例)和肌钙蛋白阴性组(170例).比较两组患者的心血管事件及心血管事件死亡的发生情况.结果 心肌肌钙蛋白阳性组的果糖胺、血红蛋白水平低于心肌肌钙蛋白阴性组(P<0.05),C反应蛋白水平高于心肌肌钙蛋白阴性组(P<0.05).心肌肌钙蛋白阳性组的心血管事件发生率63.3% (19/30)和心血管事件病死率26.7%(8/30)均高于心肌肌钙蛋白阴性组的4.1%(7/170)、1.2%(2/170),差异有统计学意义(x2值分别为73.45、28.44,均P<0.05).结论 心肌肌钙蛋白水平高的患者的血清果糖胺和血红蛋白水平较低,C反应蛋白水平较高.糖尿病患者的血清心肌肌钙蛋白水平与心血管事件的发生有关.%Objective To study the correlation of serum cardiac troponin levels and cardiovascular events in elderly type 2 diabetes patients,and provide the basis for prevention and treatment of cardiovascular disease combined with type 2 diabetes mellitus.Methods Totally 200 elderly type 2 diabetes patients were selected in the First Affiliated Hospital of Zhengzhou University,and divided into cardiac troponin-positive and negative groups according to serum cardiac troponin levels.The incidence of cardiovascular events and mortality was compared between the two groups.Results The levels of fructosamine and hemoglobin in cardiac troponin-positive group were significantly lower than those of cardiac troponin-negative group (P<0.05).The C-reactive protein levels were increased in cardiac troponin-positive versus negative group (P <0.05).The incidences of cardiovascular events and mortality in cardiac troponin-positive group showed higher than those of

  2. Troponin elevation in conditions other than acute coronary syndromes

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    Tanindi A

    2011-09-01

    Full Text Available Asli Tanindi, Mustafa CemriGazi University Faculty of Medicine, Department of Cardiology, Ankara, TurkeyAbstract: Acute coronary syndromes comprise a large spectrum of clinical conditions ranging from unstable angina pectoris to acute ST-elevation myocardial infarction. Chest pain is usually the major symptom of atherosclerotic heart disease; however, it may be challenging to diagnose correctly, especially in the emergency department, because of the ambiguous way that pain is characterized by some patients. Cardiac troponins are sensitive and specific biomarkers used in the diagnosis of myocardial infarction that are released into the bloodstream when cardiac myocytes are damaged by acute ischemia or any other mechanism. They are the cornerstone for the diagnosis, risk assessment, prognosis, and determination of antithrombotic and revascularization strategies. However, troponin elevation indicates the presence, not the mechanism, of myocardial injury. There are many clinical conditions other than myocardial infarction that cause troponin elevation; thus, the physician should be aware of the wide spectrum of disease states that may result in troponin elevation and have a clear understanding of the related pathophysiology to effectively make a differential diagnosis. This review focuses on causes of troponin elevation other than acute coronary syndromes.Keywords: cardiac troponin, troponin elevation without acute coronary syndrome, differential diagnosis

  3. Missense mutations in desmin associated with familial cardiac and skeletal myopathy.

    Science.gov (United States)

    Goldfarb, L G; Park, K Y; Cervenáková, L; Gorokhova, S; Lee, H S; Vasconcelos, O; Nagle, J W; Semino-Mora, C; Sivakumar, K; Dalakas, M C

    1998-08-01

    Desmin-related myopathy (OMIM 601419) is a familial disorder characterized by skeletal muscle weakness associated with cardiac conduction blocks, arrhythmias and restrictive heart failure, and by intracytoplasmic accumulation of desmin-reactive deposits in cardiac and skeletal muscle cells. The underlying molecular mechanisms are unknown. Involvement of the desmin gene (DES) has been excluded in three families diagnosed with desmin-related myopathy. We report two new families with desmin-related cardioskeletal myopathy associated with mutations in the highly conserved carboxy-terminal end of the desmin rod domain. A heterozygous A337P mutation was identified in a family with an adult-onset skeletal myopathy and mild cardiac involvement. Compound heterozygosity for two other mutations, A360P and N393I, was detected in a second family characterized by childhood-onset aggressive course of cardiac and skeletal myopathy.

  4. A primary cardiac leiomyosarcoma with mutation at H-ras codon 12.

    Science.gov (United States)

    Parissis, J; Arvanitis, D; Sourvinos, G; Spandidos, D

    1997-01-01

    The presence of activating ras mutations in a cardiac leiomyosarcoma which occurred in the right atrium of the heart of a female patient was examined. The tumor had the appearance of leiomyosarcoma in rutine histopathological examination and the definite diagnosis was confirmed by a positive immunohistochemical reaction to smooth muscle actin. Molecular analysis by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) technique showed a point mutation of H-ras gene at codon 12. To the best of our knowledge, this is the first report describing ras gene mutation in a cardiac leiomyosarcoma implying a role for the ras oncogenes in the development of this tumor.

  5. Making sense of high sensitivity troponin assays and their role in clinical care.

    Science.gov (United States)

    Daniels, Lori B

    2014-04-01

    Cardiac troponin assays have an established and undisputed role in the diagnosis and risk stratification of patients with acute myocardial infarction. As troponin assays gets more sensitive and more precise, the number of potential uses has rapidly expanded, but the use of this test has also become more complicated and controversial. Highly sensitive troponin assays can now detect troponin levels in most individuals, but accurate interpretation of these levels requires a clear understanding of the assay in the context of the clinical scenario. This paper provides a practical and up-to-date overview of the uses of highly sensitive troponin assays for diagnosis, prognosis, and risk stratification in clinical practice.

  6. Proposal for the use in emergency departments of cardiac troponins measured with the latest generation methods in patients with suspected acute coronary syndrome without persistent ST-segment elevation

    Directory of Open Access Journals (Sweden)

    Ivo Casagranda

    2013-10-01

    Full Text Available The purpose of this document is to develop recommendations on the use of the latest generation of cardiac troponins in emergency room settings for the diagnosis of myocardial infarction in patients with suspected acute coronary syndrome without persistent ST-segment elevation (NSTE-ACS. The main points which have been addressed reaching a consensus are: i suitability and appropriateness of the terminology; ii appropriateness of the request; iii confirmation of the diagnosis of myocardial infarction (rule-in; iv exclusion of the diagnosis of myocardial infarction (rule-out. Each point has been analyzed by taking into account the evidence presented in medical publications. Recommendations were developed using the criteria adopted by the European Society of Cardiology and the American Heart Association/American College of Cardiology. Each point of the recommendation was submitted for validation to an external audit by a Group of Experts (named above.

  7. Incremental value of a combination of cardiac troponin T, N-terminal pro-brain natriuretic peptide and C-reactive protein for prediction of mortality in end-stage renal disease

    DEFF Research Database (Denmark)

    Hallén, Jonas; Madsen, Lene Helleskov; Ladefoged, Søren

    2011-01-01

    Abstract Objective. To determine the relative prognostic merits of C-reactive protein (CRP), cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) for prediction of all-cause death in patients with end-stage renal disease (ESRD) receiving haemodialysis. Material...... were predictive of death in univariate analysis. In multivariable analysis, elevated cTnT (> 0.01 µg/l) and CRP (> 1.0 mg/dl) remained significantly associated with mortality [hazard ratio (95% confidence interval), 3.2 (1.2-8.5), p = 0.017 for cTnT; 2.0 (1.0-3.8), p = 0.032 for CRP], while NT...

  8. Cardiospecific troponins in non-ischemic cardiological pathologies

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    Giuseppe Lippi

    2006-10-01

    Full Text Available Cardiospecific troponin T (TnT and I (TnI are low-molecularweight proteins that form part of the troponin complex and are integral components of the myofibrillar contractile apparatus of the heart. Loss of integrity of cardiac myocyte membranes causes release of cardiac troponins into the circulation, which can be detected by highly sensitive assays for cTnT and cTnI developed to the stat diagnosis of acute coronary syndrome. Regardless of preanalytical and analytical sources (incorrect collection or handling of the specimen, malfunctioning of the analyzer, heterophilic antibodies, a diagnostic troponin value is expression of myocardial damage, though it does not provide definitive clue on the nature of such an increment. In fact, increases in serum cardiac troponins also occur in the absence of cardiac ischemia and may sometimes led to an inappropriate or unjustified clinical decision making. Abnormal troponin values in plasma are frequently observed in various clinical contexts independent from the acute coronary disease, like myocarditis, pulmonary embolism, acute heart failure, septic shock, and as a result of cardiotoxic drugs as well as after therapeutic procedures like coronary angioplasty, electrophysiological ablations, or electrical cardioversion. Awareness of this issue is essential to either prevent unjustified alarmism or underestimation of clinical situations that may finally compromise the patient’s health.

  9. Troponins Biomarkers Of Miocardic Injury

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    Ana Consuelo González Patiño

    2011-12-01

    Full Text Available Biomarkers or Biological markers are tools that for their availability, economy, specificity and sensitivity are useful in the diagnosis, prognosis and monitoring of canine and feline patients with cardiovascular alterations; widely used and standardized in human cardiology, presented as an excellent complement, of easy access, for specialized tests such as Doppler ultrasound and electrocardiography that, sometimes, are not available in everyday clinical practice. The cardiac troponins are sensitive and specific biomarkers in the detection of different abnormalities that affect the integrity of the myocardium, these are minimally invasive tests, inexpensive and would provide valuable information in the treatment of cardiac patients; therefore, the possibility of making these part of the protocol in the routine evaluation of patients, with suspect of heart disease should be considered.

  10. Beta-catenin mutations do not contribute to cardiac fibroma pathogenesis.

    Science.gov (United States)

    Miller, Dylan V; Wang, Huamin; Wang, Hua; Fealey, Michael E; Tazelaar, Henry D

    2008-01-01

    Cardiac fibromas are the 2nd most common benign cardiac tumor occurring in children and bear a striking morphologic resemblance to soft tissue or desmoid fibromatosis. Since activating mutations in beta-catenin are common in desmoid fibromatosis as well as other spindle cell proliferations, the aim of our study was to determine if such mutations could be identified in cardiac fibroma. Nine cardiac fibromas from patients with surgical resection were examined for beta-catenin mutations by immunoperoxidase staining for beta-catenin protein and DNA sequencing of a region in exon 3 of the beta-catenin gene, where relatively conserved mutations have been described in desmoid fibromatosis. The mean age of the patients was 7.6 years (range: 10 weeks to 27 years), and 6 of the patients were male. No nuclear staining for beta-catenin was seen in the fibroma cells by immunoperoxidase methods. The beta-catenin exon 3 sequence data showed no mutations in any of the 9 tumors. We conclude that despite their morphologic similarity, cardiac fibroma and desmoid fibromatosis do not share this common molecular pathway of neoplastic growth.

  11. Interpretation of positive troponin results among patients with and without myocardial infarction

    Science.gov (United States)

    Tecson, Kristen M.; Arnold, William; Barrett, Tyler; Birkhahn, Robert; Daniels, Lori B.; DeFilippi, Christopher; Headden, Gary; Peacock, W. Frank; Reed, Michael; Singer, Adam J.; Schussler, Jeffrey M.; Smith, Stephen; Than, Martin P.

    2017-01-01

    Measuring cardiac troponins is integral to diagnosing acute myocardial infarction (AMI); however, troponins may be elevated without AMI, and the use of multiple different assays confounds comparisons. We considered characteristics and serial troponin values in emergency department chest pain patients with and without AMI to interpret troponin excursions. We compared serial troponin in 124 AMI and non-AMI patients from the observational Performance of Triage Cardiac Markers in the Clinical Setting (PEARL) study who presented with chest pain and had at least one troponin value exceeding the 99th percentile of normal. Because 8 assays were used during data collection, we employed a method of scaling the troponin value to the corresponding assay's 99th percentile upper reference limit to standardize the results. In 81 AMI patients, 96% had elevated troponin at the first test following initial elevation, compared to 73% of the 43 non-AMI patients (P < 0.001). Scaling troponin to the 99th percentile of normal yielded a median value that was 4.8 [2.2, 14.1] times higher than the 99th percentile cutpoint among AMI patients, compared to 2.3 [1.5, 6.5] times higher among non-AMI patients (P = 0.04). The rise in serial scaled troponin values distinguished the AMI patients. Scaling to the 99th percentile was useful for comparing troponin when different assays were utilized. PMID:28127121

  12. Mitochondrial DNA deletion mutations in adult mouse cardiac side population cells

    Energy Technology Data Exchange (ETDEWEB)

    Lushaj, Entela B., E-mail: lushaj@surgery.wisc.edu [Division of Cardiothoracic Surgery, Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53792 (United States); Lozonschi, Lucian; Barnes, Maria; Anstadt, Emily; Kohmoto, Takushi [Division of Cardiothoracic Surgery, Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53792 (United States)

    2012-06-01

    We investigated the presence and potential role of mitochondrial DNA (mtDNA) deletion mutations in adult cardiac stem cells. Cardiac side population (SP) cells were isolated from 12-week-old mice. Standard polymerase chain reaction (PCR) was used to screen for the presence of mtDNA deletion mutations in (a) freshly isolated SP cells and (b) SP cells cultured to passage 10. When present, the abundance of mtDNA deletion mutation was analyzed in single cell colonies. The effect of different levels of deletion mutations on SP cell growth and differentiation was determined. MtDNA deletion mutations were found in both freshly isolated and cultured cells from 12-week-old mice. While there was no significant difference in the number of single cell colonies with mtDNA deletion mutations from any of the groups mentioned above, the abundance of mtDNA deletion mutations was significantly higher in the cultured cells, as determined by quantitative PCR. Within a single clonal cell population, the detectable mtDNA deletion mutations were the same in all cells and unique when compared to deletions of other colonies. We also found that cells harboring high levels of mtDNA deletion mutations (i.e. where deleted mtDNA comprised more than 60% of total mtDNA) had slower proliferation rates and decreased differentiation capacities. Screening cultured adult stem cells for mtDNA deletion mutations as a routine assessment will benefit the biomedical application of adult stem cells.

  13. N terminal pro-B-type natriuretic peptide and cardiac troponin in patients with severe coronary artery disease%重症冠心病患者的N末端-前B型脑钠肽与心肌肌钙蛋白的相关性研究

    Institute of Scientific and Technical Information of China (English)

    卢新; 于大勇; 任平香; 李丽; 郭菊秋; 王冬梅

    2013-01-01

    目的 研究重症冠心病患者N末端-前B型钠尿肽与心肌肌钙蛋白的相关性.方法 收集2012年1-12月在唐山市丰润区人民医院ICU及CCU住院的282例重症冠心病患者临床数据,根据诊断分为急性心肌梗死组(104例)、急性心力衰竭组(60例)和不稳定型心绞痛组(118例).采用非参数Spearman检验进行数值相关性分析.结果 N末端-前B型钠尿肽与心肌肌钙蛋白呈中度正相关(P<0.01),其中心肌梗死组的N末端-前B型钠尿肽与心肌肌钙蛋白T的相关系数r=0.569(P<0.01),与心肌肌钙蛋白I的相关系数r =0.568(P <0.01).心肌肌钙蛋白T与心肌肌钙蛋白I的相关系数r=0.999(P <0.01),它们之间具有良好的线性关系.结论 N末端-前B型钠尿肽与心肌肌钙蛋白呈中度正相关.心肌肌钙蛋白T与心肌肌钙蛋白I呈高度正相关.%Objective To study the correlation between N terminal pro-B-type natriuretic peptide and cardiac troponin in patients with severe coronary artery disease.Methods The clinical data of 282 hospitalized patients in ICU and CCU with severe coronary artery disease were retrospectively observed from January to December 2012.The patients were divided into acute myocardial infarction group (AMI,104),acute heart failure group (AHF,60) and acute coronary syndrome group (ACS,118).The correlations were analyzed through the nonparametric Spearman test.Results The correlations between N terminal pro-B-type natriuretic peptide and cardiac troponin was positively moderate(P <0.01),while correlation coefficient of N terminal pro-B-type natriuretic peptide and cardiac troponin T was 0.569 (P < 0.01),correlation coefficients of N terminal pro-B-type natriuretic peptide and cardiac troponin I was 0.568 (P < 0.01) in acute myocardial infarction group.Correlation coefficient of cardiac troponin T and cardiac troponin I was 0.999 (P < 0.01).There was a good linear relation between them.Conclusions There is a moderately positive

  14. Multiple biomarkers including cardiac troponins T and I measured by high-sensitivity assays, as predictors of long-term mortality in patients with chronic renal failure who underwent dialysis.

    Science.gov (United States)

    Hickman, Peter E; McGill, Darryl; Potter, Julia M; Koerbin, Gus; Apple, Fred S; Talaulikar, Girish

    2015-06-01

    There is a high cardiac mortality in patients on long-term renal dialysis. No studies have reported long-term outcomes relating to both high-sensitivity cardiac troponin T (hs-cTnT) and high-sensitivity cardiac troponin I (hs-cTnI) in these patients. Patients who underwent long-term dialysis at the Canberra Hospital had blood samples collected for both cardiac and other biomarkers. Samples were stored at -80°C until analysis. Mortality data were collected at 5 years, and univariate and multivariate analyses were performed to identify which biomarkers were predictive of mortality at 5 years. After multivariate analysis, albumin, C-reactive protein (CRP), and hs-cTnT remained independently predictive of all-cause mortality, with hs-cTnT having the highest hazard ratio. If hs-cTnT was excluded from the analysis, then hs-cTnI was independently predictive of mortality. For hs-cTnT, for both genders, the ninety-ninth percentile, derived from a population with subjects with subclinical disease excluded, served as an excellent partition between survivors and nonsurvivors. Receiver-operating characteristic curve analysis for hs-cTnT had area under the curve of 0.798 and for hs-cTnI of 0.774. Kaplan-Meier curves for the aggregation of albumin, CRP, and hs-cTnT showed a stronger predictive power with receiver-operating characteristic area under the curve of 0.805. The addition of echocardiographic data in an analysis of all patients who had an echocardiogram for clinical reasons (n = 105) did not alter the final observations in this subgroup. In conclusion, hs-cTnT retains a superior predictive power in a dialysis-dependent population for identifying those at risk for death and when aggregated with albumin and CRP also has substantial additive value for identifying mortality risk in a renal-dialysis population.

  15. 人心肌TnⅠ的测定及临床意义的探讨%Clinical Significance of Cardiac Troponin -Ⅰ

    Institute of Scientific and Technical Information of China (English)

    张季; 刘春; 宋晓菲; 朱清

    2003-01-01

    @@ 肌钙蛋白Ⅰ(troponin Ⅰ,TnI)和TnC、TnT组成复合物,在肌肉收缩和舒张过程中起重要调节作用.大量临床研究证实,心肌TnI(cTnⅠ)为心肌损伤最特异、最敏感的血清标志物之一,被广泛应用于临床诊断.本文就cTnⅠ的临床应用进展作一综述.

  16. Troponin in Cardiovascular Disease Prevention: Updates and Future Direction.

    Science.gov (United States)

    Hoff, Jason; Wehner, William; Nambi, Vijay

    2016-03-01

    Cardiac troponin has been well described as the preferred biomarker for diagnosis of myocardial infarction due to the high sensitivity and specificity for myocardial injury. Numerous other conditions apart from acute coronary syndrome can also lead to small elevations in troponin levels. However, the use of cTn as prognostic biomarker for the primary assessment of cardiovascular risk in asymptomatic patient has only recently been described. And with the development of newer generations of high-sensitivity cardiac troponin assays that can detect 10-fold lower concentrations of troponin, the potential value cTn in the prevention and management of asymptomatic cardiovascular disease has come to the fore. This review provides an overview of the transition of cardiac troponin as a marker of acute myocardial injury to one that detects sub-clinical injury. Evidence continues to show that high-sensitivity troponin is emerging as one of the most powerful prognostic biomarkers for the assessment of cardiovascular risk in the general population.

  17. Sick sinus syndrome, progressive cardiac conduction disease, atrial flutter and ventricular tachycardia caused by a novel SCN5A mutation

    DEFF Research Database (Denmark)

    Holst, Anders G; Liang, Bo; Jespersen, Thomas

    2010-01-01

    Mutations in the cardiac sodium channel encoded by the gene SCN5A can result in a wide array of phenotypes. We report a case of a young male with a novel SCN5A mutation (R121W) afflicted by sick sinus syndrome, progressive cardiac conduction disorder, atrial flutter and ventricular tachycardia. His...

  18. A novel LQT3 mutation implicates the human cardiac sodium channel domain IVS6 in inactivation kinetics

    NARCIS (Netherlands)

    Groenewegen, WA; Bezzina, CR; van Tintelen, JP; Hoorntje, TM; Mannens, MMAM; Wilde, AAM; Jongsma, HJ; Rook, MB

    2003-01-01

    The Long QT3 syndrome is associated with mutations in the cardiac sodium channel gene SCN5A. Objective: The aim of the present study was the identification and functional characterization of a mutation in a family with the long QT3 syndrome. Methods: The human cardiac sodium channel gene SCN5A was s

  19. Short-term prognostic value of perioperative coronary sinus-derived-serum cardiac troponin-I, creatine kinase-MB, lactate, pyruvate, and lactate-pyruvate ratio in adult patients undergoing open heart surgery

    Directory of Open Access Journals (Sweden)

    Ujjwal Kumar Chowdhury

    2016-01-01

    Full Text Available Objectives: To investigate the release pattern of different cardiac metabolites and biomarkers directly from the coronary sinus (CS and to establish the diagnostic discrimination limits of each marker protein and metabolites to evaluate perioperative myocardial injury in patients undergoing cardiac surgery under cardiopulmonary bypass (CPB. Patients and Methods: Sixty-eight patients undergoing first mitral and/or aortic valve replacements with/without coronary artery bypass grafting and Bentall procedure under CPB and blood cardioplegic arrest were studied. All cardiac metabolites and biomarkers were measured in serial CS-derived blood samples at pre-CPB, immediate post aortic declamping, 10 minutes post-CPB and 12 hrs post-CPB. Results: Receiver operating characteristic curve analysis of cardiac biomarkers indicated lactate-pyruvate ratio as the superior diagnostic discriminator of myocardial injury with an optimal "cut-off" value >10.8 immediately after aortic declamping (AUC, 0.92; 95% CI: 0.85-0.98. Lactate was the second best diagnostic discriminator of myocardial injury with an optimal "cut-off" value >2mmol/l at immediately after aortic declamping (AUC, 0.89; 95% CI: 0.80-0.96. Cardiac troponin-I was the third best diagnostic discriminator of myocardial injury with an optimal "cut-off" value >2.1ng/ml at immediately after aortic declamping (AUC, 0.88; 95% CI: 0.80-0.95. Creatine kinase-MB was the fourth best diagnostic discriminator of myocardial injury with an optimal "cut-off" value >58 log units/ml prior to decanulation (AUC, 0.85; 95% CI: 0.78-0.94. Conclusions: Measurable cardiac damage exists in all patients undergoing cardiac surgery under cardioplegic arrest. The degree of myocardial injury is more in patients with poor ventricular function and those requiring longer aortic clamp time. CS-derived lactate-pyruvate ratio, lactate, cTn-I served as superior diagnostic discriminators of peri-operative myocardial damage.

  20. Cardiac sodium channelopathy associated with SCN5A mutations: electrophysiological, molecular and genetic aspects.

    Science.gov (United States)

    Remme, Carol Ann

    2013-09-01

    Over the last two decades, an increasing number of SCN5A mutations have been described in patients with long QT syndrome type 3 (LQT3), Brugada syndrome, (progressive) conduction disease, sick sinus syndrome, atrial standstill, atrial fibrillation, dilated cardiomyopathy, and sudden infant death syndrome (SIDS). Combined genetic, electrophysiological and molecular studies have provided insight into the dysfunction and dysregulation of the cardiac sodium channel in the setting of SCN5A mutations identified in patients with these inherited arrhythmia syndromes. However, risk stratification and patient management is hindered by the reduced penetrance and variable disease expressivity in sodium channelopathies. Furthermore, various SCN5A-related arrhythmia syndromes are known to display mixed phenotypes known as cardiac sodium channel overlap syndromes. Determinants of variable disease expressivity, including genetic background and environmental factors, are suspected but still largely unknown. Moreover, it has become increasingly clear that sodium channel function and regulation is more complicated than previously assumed, and the sodium channel may play additional, as of yet unrecognized, roles in cardiac structure and function. Development of cardiac structural abnormalities secondary to SCN5A mutations has been reported, but the clinical relevance and underlying mechanisms are unclear. Increased insight into these issues would enable a major next step in research related to cardiac sodium channel disease, ultimately enabling improved diagnosis, risk stratification and treatment strategies.

  1. Use of cardiac biomarkers in neonatology.

    Science.gov (United States)

    Vijlbrief, Daniel C; Benders, Manon J N L; Kemperman, Hans; van Bel, Frank; de Vries, Willem B

    2012-10-01

    Cardiac biomarkers are used to identify cardiac disease in term and preterm infants. This review discusses the roles of natriuretic peptides and cardiac troponins. Natriuretic peptide levels are elevated during atrial strain (atrial natriuretic peptide (ANP)) or ventricular strain (B-type natriuretic peptide (BNP)). These markers correspond well with cardiac function and can be used to identify cardiac disease. Cardiac troponins are used to assess cardiomyocyte compromise. Affected cardiomyocytes release troponin into the bloodstream, resulting in elevated levels of cardiac troponin. Cardiac biomarkers are being increasingly incorporated into clinical trials as indicators of myocardial strain. Furthermore, cardiac biomarkers can possibly be used to guide therapy and improve outcome. Natriuretic peptides and cardiac troponins are potential tools in the diagnosis and treatment of neonatal disease that is complicated by circulatory compromise. However, clear reference ranges need to be set and validation needs to be carried out in a population of interest.

  2. Mutation analysis and evaluation of the cardiac localization of TMEM43 in arrhythmogenic right ventricular cardiomyopathy

    DEFF Research Database (Denmark)

    Christensen, A H; Andersen, C B; Tybjærg-Hansen, A;

    2011-01-01

    Christensen AH, Andersen CB, Tybjærg-Hansen A, Haunso S, Svendsen JH. Mutation analysis and evaluation of the cardiac localization of TMEM43 in arrhythmogenic right ventricular cardiomyopathy. A single report has associated mutations in TMEM43 (LUMA) with a distinctive form of arrhythmogenic right...... with anti-TMEM43, anti-plakoglobin, anti-plakophilin-2, anti-connexin-43, and anti-emerin antibodies was performed on myocardium from TMEM43-positive patients (n = 3) and healthy controls (n = 3). The genetic screening identified heterozygous variants in two families: one reported mutation (c.1073C> T...

  3. Rescue of mutated cardiac ion channels in inherited arrhythmia syndromes.

    Science.gov (United States)

    Balijepalli, Sadguna Y; Anderson, Corey L; Lin, Eric C; January, Craig T

    2010-08-01

    Inherited arrhythmia syndromes comprise an increasingly complex group of diseases involving mutations in multiple genes encoding ion channels, ion channel accessory subunits and channel interacting proteins, and various regulatory elements. These mutations serve to disrupt normal electrophysiology in the heart, leading to increased arrhythmogenic risk and death. These diseases have added impact as they often affect young people, sometimes without warning. Although originally thought to alter ion channel function, it is now increasingly recognized that mutations may alter ion channel protein and messenger RNA processing, to reduce the number of channels reaching the surface membrane. For many of these mutations, it is also known that several interventions may restore protein processing of mutant channels to increase their surface membrane expression toward normal. In this article, we reviewed inherited arrhythmia syndromes, focusing on long QT syndrome type 2, and discuss the complex biology of ion channel trafficking and pharmacological rescue of disease-causing mutant channels. Pharmacological rescue of misprocessed mutant channel proteins, or their transcripts providing appropriate small molecule drugs can be developed, has the potential for novel clinical therapies in some patients with inherited arrhythmia syndromes.

  4. The Cardiac Phenotype in Patients With a CHD7 Mutation

    NARCIS (Netherlands)

    Corsten-Janssen, Nicole; Kerstjens-Frederikse, Wilhelmina S.; du Marchie Sarvaas, Gideon J.; Baardman, Maria E.; Bakker, Marian K.; Bergman, Jorieke E. H.; Hove, Hanne D.; Heimdal, Ketil R.; Rustad, Cecilie F.; Hennekam, Raoul C. M.; Hofstra, Robert M. W.; Hoefsloot, Lies H.; Van Ravenswaaij-Arts, Conny M. A.; Kapusta, Livia

    2013-01-01

    Background- Loss-of-function mutations in CHD7 cause Coloboma, Heart Disease, Atresia of Choanae, Retardation of Growth and/or Development, Genital Hypoplasia, and Ear Abnormalities With or Without Deafness (CHARGE) syndrome, a variable combination of multiple congenital malformations including hear

  5. The cardiac phenotype in patients with a CHD7 mutation

    DEFF Research Database (Denmark)

    Corsten-Janssen, Nicole; Kerstjens-Frederikse, Wilhelmina S; du Marchie Sarvaas, Gideon J

    2013-01-01

    Loss-of-function mutations in CHD7 cause Coloboma, Heart Disease, Atresia of Choanae, Retardation of Growth and/or Development, Genital Hypoplasia, and Ear Abnormalities With or Without Deafness (CHARGE) syndrome, a variable combination of multiple congenital malformations including heart defects...

  6. Troponin I in acute decompensated heart failure : insights from the ASCEND-HF study

    NARCIS (Netherlands)

    Felker, G. Michael; Hasselblad, Vic; Tang, W. H. Wilson; Hernandez, Adrian F.; Armstrong, Paul W.; Fonarow, Gregg C.; Voors, Adriaan A.; Metra, Marco; McMurray, John J. V.; Butler, Javed; Heizer, Gretchen M.; Dickstein, Kenneth; Massie, Barry M.; Atar, Dan; Troughton, Richard W.; Anker, Stefan D.; Califf, Robert M.; Starling, Randall C.; O'Connor, Christopher M.

    2012-01-01

    We examined the prognostic importance of cardiac troponin I (cTnI) in a cohort of patients enrolled in the ASCEND-HF study of nesiritide in acute decompensated heart failure (ADHF). Circulating troponins are a prognostic marker in patients with ADHF. Contemporary assays with greater sensitivity requ

  7. Markedly Elevated Troponin in Diabetic Ketoacidosis without Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    Demet Menekşe Gerede

    2016-06-01

    Full Text Available Troponin gives excellent accuracy in the identification of myocardial necrosis, however, it may elevate also in a series of non-atherosclerotic heart diseases. We report the case of a 58-year-old woman with diabetic ketoacidosis (DKA. She had markedly increased levels (90 fold of cardiac biomarkers (troponin I and CK-MB and initial electrocardiography changes compatible with myocardial infarction. She had normal a coronary angiogram. This case shows that nonspecific myocardial injury may occur in DKA with the findings mimicking myocardial infarction including increased level of cardiac biomarkers and electrocardiography changes.

  8. Usefulness of positive troponin-T and negative creatine kinase levels in identifying high-risk patients with unstable angina pectoris.

    Science.gov (United States)

    Pettijohn, T L; Doyle, T; Spiekerman, A M; Watson, L E; Riggs, M W; Lawrence, M E

    1997-08-15

    Troponin-T was measured in patients with chest pain and negative creatine phosphokinase-MB isoenzymes. Patients with elevated troponin-T had a significantly greater risk of cardiac events over the next 6 months than patients with normal troponin-T.

  9. An explicitly solvated full atomistic model of the cardiac thin filament and application on the calcium binding affinity effects from familial hypertrophic cardiomyopathy linked mutations

    Science.gov (United States)

    Williams, Michael; Schwartz, Steven

    2015-03-01

    The previous version of our cardiac thin filament (CTF) model consisted of the troponin complex (cTn), two coiled-coil dimers of tropomyosin (Tm), and 29 actin units. We now present the newest revision of the model to include explicit solvation. The model was developed to continue our study of genetic mutations in the CTF proteins which are linked to familial hypertrophic cardiomyopathies. Binding of calcium to the cTnC subunit causes subtle conformational changes to propagate through the cTnC to the cTnI subunit which then detaches from actin. Conformational changes propagate through to the cTnT subunit, which allows Tm to move into the open position along actin, leading to muscle contraction. Calcium disassociation allows for the reverse to occur, which results in muscle relaxation. The inclusion of explicit TIP3 water solvation allows for the model to get better individual local solvent to protein interactions; which are important when observing the N-lobe calcium binding pocket of the cTnC. We are able to compare in silica and in vitro experimental results to better understand the physiological effects from mutants, such as the R92L/W and F110V/I of the cTnT, on the calcium binding affinity compared to the wild type.

  10. Troponin T3 expression in skeletal and smooth muscle is required for growth and postnatal survival: Characterization of Tnnt3tm2a(KOMP)Wtsi mice

    OpenAIRE

    Ju, Yawen; Li, Jie; Xie, Chao; Ritchlin, Christopher T.; Xing, Lianping; Hilton, Matthew J.; Schwarz, Edward M.

    2013-01-01

    The troponin complex, which consists of three regulatory proteins (troponin C, troponin I and troponin T), is known to regulate muscle contraction in skeletal and cardiac muscle, but its role in smooth muscle remains controversial. Troponin T3 (TnnT3) is a fast skeletal muscle troponin believed to be expressed only in skeletal muscle cells. To determine the in vivo function and tissue specific expression of Tnnt3, we obtained the heterozygous Tnnt3+/flox/lacZ mice from Knockout Mouse Project ...

  11. CUGBP2 directly interacts with U2 17S snRNP components and promotes U2 snRNA binding to cardiac troponin T pre-mRNA.

    Science.gov (United States)

    Goo, Young-Hwa; Cooper, Thomas A

    2009-07-01

    CUGBP2 (ETR-3/NAPOR/BRUNOL3) promotes inclusion of cardiac troponin T (cTNT) exon 5 via binding between positions 21 and 74 of the downstream intron. The molecular mechanism by which CUGBP2 activates cTNT exon 5 inclusion is unknown. Our results suggest that CUGBP2 promotes exon inclusion by a novel mechanism in which CUGBP2 directly interacts with components of the activated U2 snRNP and enhances binding of U2 snRNP to the branch site located upstream of the exon. Using an in vitro splicing assay, we show that recombinant CUGBP2 enhances complex A formation of a cTNT pre-mRNA. Enhanced complex A assembly requires both the upstream and downstream introns consistent with dual requirements for the downstream CUGBP2-binding site and an upstream branch site for U2 snRNP binding. We also show that CUGBP2 enhances binding of U2 snRNA to the cTNT pre-mRNA consistent with enhanced complex A assembly. Purification of CUGBP2-interacting proteins using tandem affinity purification leads to the demonstration that the core 17S U2 snRNP components, SF3b145 and SF3b49 bind directly to CUGBP2. We conclude that CUGBP2 activates exon inclusion by forming direct interactions with components of the 17S snRNP complex and recruits and/or stabilizes binding of U2 snRNP.

  12. Elevated troponin T after acute ischemic stroke: Association with severity and location of infarction.

    Directory of Open Access Journals (Sweden)

    Siamak Abdi

    2015-03-01

    Full Text Available Serum troponin elevation, characteristic of ischemic myocardial injury, has been observed in some acute ischemic stroke (AIS patients. Its cause and significance are still controversial. The purpose of this study is to find determinants of troponin elevation and its relationship with stroke severity and location.Between January 2013 and August 2013, 114 consecutive AIS patients confirmed by diffusion-weighted magnetic resonance imaging were recruited in this study. Serum troponin T level was measured as part of routine laboratory testing on admission. Ten lead standard electrocardiogram (ECG was performed and stoke severity was assessed based on National Institutes of Health Stroke Scale (NIHSS.Troponin T was elevated in 20 (17.6% of 114 patients. Patients with elevated troponin were more likely to have higher age, higher serum creatinine and ischemic ECG changes. Troponin levels were higher in patients with more severe stroke measured by NIHSS [7.96 (6.49-9.78 vs. 13.59 (10.28-18.00]. There was no association between troponin and locations of stroke and atrial fibrillation. There were 6 (5% patients with elevated troponin in the presence of normal creatinine and ECG.Stroke severity, not its location, was associated with higher troponin levels. Abnormal troponin levels are more likely, but not exclusively, to be due to cardiac and renal causes than cerebral ones.

  13. Diagnosis of Unstable Angina Pectoris Has Declined Markedly with the Advent of More Sensitive Troponin Assays

    DEFF Research Database (Denmark)

    D'Souza, Maria; Sarkisian, Laura; Saaby, Lotte

    2015-01-01

    in unselected hospital patients. METHODS: During 2010 we evaluated all patients in whom cardiac troponin I had been measured at a single university hospital. The diagnosis of acute myocardial infarction (ST-elevation myocardial infarction [STEMI] or non-ST-elevation myocardial infarction [NSTEMI......BACKGROUND: Since the arrival of the universal definition of myocardial infarction more sensitive troponin assays have been developed. How these occurrences have influenced the proportions and clinical features of the components of acute coronary syndrome have not been studied prospectively......]) was established in cases of a rise and/or fall of cardiac troponin I together with cardiac ischemic features. Patients with unstable chest discomfort and cardiac troponin I values below the decision limit of myocardial infarction were diagnosed as having unstable angina pectoris. The definition of acute coronary...

  14. Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels.

    NARCIS (Netherlands)

    C.W. Hamm (Christian); C. Heeschen (Christopher); B. Goldmann (Britta); A. Vahanian (Alec); J. Adgey (Jennifer); C.M. Miguel (Carlos); W.R. Rutsch (Wolfgang); J. Berger (Jürgen); J.G. Kootstra (Jille); M.L. Simoons (Maarten)

    1999-01-01

    textabstractBACKGROUND: In patients with refractory unstable angina, the platelet glycoprotein IIb/IIIa-receptor antibody abciximab reduces the incidence of cardiac events before and during coronary angioplasty. We investigated whether serum troponin T levels identify patients most

  15. Evaluation of analytical performance and comparison of clinical results of the new generation method AccuTnI+3 for the measurement of cardiac troponin I using both patients and quality control plasma samples.

    Science.gov (United States)

    Storti, Simona; Masotti, Silvia; Prontera, Concetta; Franzini, Maria; Buzzi, Paola; Casagranda, Ivo; Ciofini, Enrica; Zucchelli, Gian Carlo; Ndreu, Rudina; Passino, Claudio; Clerico, Aldo

    2015-12-07

    The study aims are to evaluate the analytical performance and the clinical results of the chemiluminescent Access AccuTnI+3 immunoassay for the determination of cardiac troponin I (cTnI) with DxI 800 and Access2 platforms and to compare the clinical results obtained with this method with those of three cTnI immunoassays, recently introduced in the European market. The limits of blank (LoB), detection (LoD), and quantitation (LoQ) at 20% CV and 10% CV were 4.5 ng/L and 10.9 ng/L, 17.1 and 30.4 ng/L, respectively. The results of STAT Architect high Sensitive TnI (Abbott Diagnostics), ADVIA Centaur Troponin I Ultra (Siemens Healthcare Diagnostics), ST AIA-Pack cTnI third generation (Tosoh Bioscience), and Access AccuTnI+3 (Beckman Coulter Diagnostics) showed very close correlations (R ranging from 0.901 to 0.994) in 122 samples of patients admitted to the emergency department. However, on average there was a difference up to 2.4-fold between the method measuring the highest (ADVIA method) and lowest cTnI values (AccuTnI+3 method). The consensus mean values between methods ranged from 6.2% to 29.6% in 18 quality control samples distributed in an external quality control study (cTnI concentrations ranging from 29.3 ng/L to 1557.5 ng/L). In conclusion, the results of our analytical evaluation concerning the AccuTnI+3 method, using the DxI platform, are well in agreement with those suggested by the manufacturer as well as those reported by some recent studies using the Access2 platform. Our results confirm that the AccuTnI+3 method for the Access2 and DxI 800 platforms is a clinically usable method for cTnI measurement.

  16. Falsely elevated troponin: rare occurrence or future problem

    Directory of Open Access Journals (Sweden)

    James Nguyen

    2016-12-01

    Full Text Available Introduction: Troponins are known to be released in response to cardiac damage and therefore are the biomarkers of choice for the early diagnosis of acute myocardial infarction (AMI, improving outcome in patients presenting with chest pain. However, false results can occur due to interference from other substances in the blood. Case: A 52-year-old male with a past medical history of alcohol abuse, hypertension, and coronary artery bypass graft at age 34 with normal stress test 2 years before presented to the emergency department (ED complaining of 1 day of non-exertional chest pain with radiation to the neck and left arm. His troponin was elevated to 5 ng/mL in two samples drawn 12 h apart, with normal CK-MB. Renal function was normal. Electrocardiogram (ECG showed normal sinus rhythm with no ST elevations or depressions. He underwent cardiac catheterization which showed no obstructive lesions. Five years later, he returned to the ED with abdominal pain and shortness of breath. Troponin was elevated and showed no signs of downtrend on repeat every 6 h. ECG was unchanged from 5 years before. He was discharged with a follow-up cardiac computed tomography (CT. Troponin was measured on the day of his scan and remained elevated; he was asymptomatic. Cardiac CT showed unremarkable coronaries and bypass grafts. Given persistently positive troponin in the setting of minimal to no symptoms, he was thought to have falsely elevated troponins. Centrifugation and 2:1 dilution of the sample resulted in the same general value, respectively. Rheumatoid factor and heterophile antibodies were negative. When his blood sample was sent to a different hospital utilizing a three-site immunoassay method, the value was found zero. Discussion: Cardiac troponins (cTn are structural proteins unique to the heart, not expressed outside of cardiac tissue and have high sensitivity and specificity for myocardial damage. Therefore, it is the test of choice for the diagnosis of

  17. Sick sinus syndrome, progressive cardiac conduction disease, atrial flutter and ventricular tachycardia caused by a novel SCN5A mutation

    DEFF Research Database (Denmark)

    Holst, Anders G; Liang, Bo; Jespersen, Thomas

    2010-01-01

    Mutations in the cardiac sodium channel encoded by the gene SCN5A can result in a wide array of phenotypes. We report a case of a young male with a novel SCN5A mutation (R121W) afflicted by sick sinus syndrome, progressive cardiac conduction disorder, atrial flutter and ventricular tachycardia. His...... the spectrum of SCN5A loss-of-function associated disease entities should be viewed as one syndrome....

  18. Correlation between lipid profile and troponin I test results in patients with chest pain in Nepal

    Institute of Scientific and Technical Information of China (English)

    Arun Kumar; Brijesh Sathian

    2013-01-01

    To study the usefulness of traditional lipid profile levels in screening subjects who had developed chest pain due to cardiac event as indicated by a positive troponin I test. Methods: In this retrospective study data of the 430 patients presented to the emergency department with symptoms of cardiac ischemia who underwent both troponin and lipid profiles tests were compared with the lipid profiles of 165 normal healthy subjects (controls). The troponin was detected qualitatively when a specimen contains troponin I (cTnI) above the 99th percentile (TnI>0.5 ng/mL). The total cholesterol, high density lipoproteins cholesterol, very low density lipoproteins and triacyl glycerol levels were also analyzed and low density lipoprotein level was calculated using Friedewald’s formula. Results: Patients with chest pain and positive troponin test (with confirmed cardiac event) were found to have significantly elevated levels of total cholesterol, triacyl glycerol levels, low density lipoprotein level and significantly reduced high density lipoproteins cholesterol levels when compared to the patients who experienced only chest pain (negative troponin) and healthy controls. Conclusions: Traditional lipid profile levels is still can be used in screening populations to identify the subjects with high risk of developing cardiac event in case if the laboratory set up has not troponin test facilities.

  19. 快速检测心肌肌钙蛋白T在急性心肌梗死诊断中的应用研究%The research of application for rapid detection of cardiac troponin T in the diagnosis of acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    李琳; 王龙安; 朱娟; 刘晓宇; 楚英杰

    2013-01-01

    目的 探讨快速检测心急肌钙蛋白T在急性心肌梗死患者诊断中的价值.方法 选取2010年7月份~2011年10月份因急性心肌梗死就诊于某院急诊医学部心血管病区进行治疗的患者180例为研究对象,随机分为观察组A(采用快速免疫层析法检测心肌肌钙蛋白T)和观察组B组(采用化学发光免疫分析法检测心肌肌钙蛋白T),同时检测两组患者的心肌肌钙蛋白Ⅰ和CK—M,再选取同期在该院行健康体检的70人分别采用两种方法检测其心肌肌钙蛋白T情况,同时采用化学发光免疫分析法检测其心肌肌钙蛋白Ⅰ和CK—M情况.比较上述三组人员的检测结果并分析.结果 观察组B较观察组A检测心肌肌钙蛋白T阳性的准确率明显高,准确率比较,组间差异有统计学意义(P<0.05);急性心肌急性心肌梗死患者心肌肌钙蛋白T检测阳性率高于CK-MB,但是低于心肌肌钙蛋白Ⅰ;不同浓度范围,cTnT与CK-MB的敏感性不同,但是cTnT的敏感性均显著高于CK-MB的敏感性.结论 心肌肌钙蛋白T检测阳性对急性心肌梗死患者具有较高的特异性和敏感性,并且检测方法较简单,所需时间较短,值得临床推广使用.%OBJECTIVE To investigate the value for rapid detection of cardiac troponin T in the diagnosis of acute myocardial infarction. METHODS 180 patients with acute myocardial infarction treatment in cardiovascular ward of emergency department in hospital for the treatment from July 2010 to October 2011 were chosen as the research objects. They were randomly divided into the observation group of A (using rapid immunochromatography assay in detection of cardiac troponin T) and observation group of B (using chemiluminescenee immunoassay in detection of cardiac troponin T). The cardiac troponin I and CK-M of the two groups were detected. 70 patients selected at the same period in our hospital for health medical examination were used two methods to detect cardiac

  20. Sporadic cardiac and skeletal myopathy caused by a de novo desmin mutation.

    Science.gov (United States)

    Park, K Y; Dalakas, M C; Semino-Mora, C; Lee, H S; Litvak, S; Takeda, K; Ferrans, V J; Goldfarb, L G

    2000-06-01

    Desmin myopathy is a familial or sporadic disorder characterized by intracytoplasmic accumulation of desmin in the muscle cells. We and others have previously identified desmin gene mutations in patients with familial myopathy, but close to 45% of the patients do not report previous family history of the disease. The present study was conducted to determine the cause of desmin myopathy in a sporadic patient presenting with symmetrical muscle weakness and atrophy combined with atrioventricular conduction block requiring a permanent pacemaker. A novel heterozygous R406W mutation in the desmin gene was identified by sequencing cDNA and genomic DNA. Expression of a construct containing the patient's mutant desmin cDNA in SW13 (vim-) cells demonstrated a high pathogenic potential of the R406W mutation. This mutation was not found in the patient's father, mother or sister by sequencing and restriction analysis. Testing with five microsatellite markers and four intragenic single nucleotide polymorphisms excluded alternative paternity. Haplotype analysis indicates that the patient's father was germ-line mosaic for the desmin mutation. We conclude that de novo mutations in the desmin gene may be the cause of sporadic forms of desmin-related cardiac and skeletal myopathy.

  1. Molecular Effects of cTnC DCM Mutations on Calcium Sensitivity and Myofilament Activation-An Integrated Multiscale Modeling Study.

    Science.gov (United States)

    Dewan, Sukriti; McCabe, Kimberly J; Regnier, Michael; McCulloch, Andrew D; Lindert, Steffen

    2016-08-25

    Mutations in cardiac troponin C (D75Y, E59D, and G159D), a key regulatory protein of myofilament contraction, have been associated with dilated cardiomyopathy (DCM). Despite reports of altered myofilament function in these mutants, the underlying molecular alterations caused by these mutations remain elusive. Here we investigate in silico the intramolecular mechanisms by which these mutations affect myofilament contraction. On the basis of the location of cardiac troponin C (cTnC) mutations, we tested the hypothesis that intramolecular effects can explain the altered myofilament calcium sensitivity of force development for D75Y and E59D cTnC, whereas altered cardiac troponin C-troponin I (cTnC-cTnI) interaction contributes to the reported contractile effects of the G159D mutation. We employed a multiscale approach combining molecular dynamics (MD) and Brownian dynamics (BD) simulations to estimate cTnC calcium association and hydrophobic patch opening. We then integrated these parameters into a Markov model of myofilament activation to compute the steady-state force-pCa relationship. The analysis showed that myofilament calcium sensitivity with D75Y and E59D can be explained by changes in calcium binding affinity of cTnC and the rate of hydrophobic patch opening, if a partial cTnC interhelical opening angle (110°) is sufficient for cTnI switch peptide association to cTnC. In contrast, interactions between cTnC and cTnI within the cardiac troponin complex must also be accounted for to explain contractile alterations due to G159D. In conclusion, this is the first multiscale in silico study to elucidate how direct molecular effects of genetic mutations in cTnC translate to altered myofilament contractile function.

  2. 心肌肌钙蛋白检测诊断急性心肌梗死临床应用评价%Comparison between cardiac troponin I and T for detection of acute m-yocardial infarction

    Institute of Scientific and Technical Information of China (English)

    王晋军; 李运乾; 刘卓敏; 王绪太; 薛树仁

    2001-01-01

    Objective To compare the value be tween cardiac troponin I (cTnI) and T (cTnT) for detection of acute myocardial infarction(AMI). Methods In this prospective, double-blind, randomized, parallel controlled study, the subjects were divided into two: AMI g roup and non-AMI group. There were 121 patients with AMI(WHO Criteria). Serum cTnI and cTnT were measured randomly in the two groups. cTnI in 62 patients with AMI and cTnI in 59 patients with AMI were measured. Non-AMI group included 80 normal subjects, patients w ith old myocardial infarction, angina pectoris, renal failure and so on. The monoclonal enzyme immunoassay test was us ed. The normal range for both cTnI and cTnT was 0.2 mg/L and for c reatine kinase isoenzyme MB(CK-MB) was 25 U/L. Results The sensitivity of cTnI was higher in early period and that of cTnT was better in late period. Sen sitivity of cTnI and cTnT was 41.7% and 0.0% (P0.05)。cTnI和cTnT有较高的阴性预测值,它们均可达100% 。血管再通和梗塞部位及有无Q波影响它们在AMI早期的敏感性。结论 cTnI和c TnT是诊断AMI的敏感指标。在AMI早期检测cTnI而中晚期检测cTnT可提高AMI的诊断阳性率。

  3. Observation of {mu}s time-scale protein dynamics in the presence of Ln{sup 3+} ions: application to the N-terminal domain of cardiac troponin C

    Energy Technology Data Exchange (ETDEWEB)

    Eichmueller, Christian [Sandoz GmbH (Austria); Skrynnikov, Nikolai R. [Purdue University, Department of Chemistry (United States)], E-mail: nikolai@purdue.edu

    2007-02-15

    The microsecond time-scale motions in the N-terminal domain of cardiac troponin C (NcTnC) loaded with lanthanide ions have been investigated by means of a {sup 1}H{sup N} off-resonance spin-lock experiment. The observed relaxation dispersion effects strongly increase along the series of NcTnC samples containing La{sup 3+}, Ce{sup 3+}, and Pr{sup 3+} ions. This rise in dispersion effects is due to modulation of long-range pseudocontact shifts by {mu}s time-scale dynamics. Specifically, the motion in the coordination sphere of the lanthanide ion (i.e. in the NcTnC EF-hand motif) causes modulation of the paramagnetic susceptibility tensor which, in turn, causes modulation of pseudocontact shifts. It is also probable that opening/closing dynamics, previously identified in Ca{sup 2+}-NcTnC, contributes to some of the observed dispersions. On the other hand, it is unlikely that monomer-dimer exchange in the solution of NcTnC is directly responsible for the dispersion effects. Finally, on-off exchange of the lanthanide ion does not seem to play any significant role. The amplification of dispersion effects by Ln{sup 3+} ions is a potentially useful tool for studies of {mu}s-ms motions in proteins. This approach makes it possible to observe the dispersions even when the local environment of the reporting spin does not change. This happens, for example, when the motion involves a 'rigid' structural unit such as individual {alpha}-helix. Even more significantly, the dispersions based on pseudocontact shifts offer better chances for structural characterization of the dynamic species. This method can be generalized for a large class of applications via the use of specially designed lanthanide-binding tags.

  4. 钙蛋白酶介导模拟失重大鼠心肌肌钙蛋白抑制亚基的降解%Calpain mediates cardiac troponin Ⅰ degradation in tail-suspended rats

    Institute of Scientific and Technical Information of China (English)

    徐彭涛; 宋振; 李全; 张琳; 王云英; 余志斌

    2010-01-01

    本文旨在观察尾部悬吊模拟失重大鼠心肌钙蛋白酶(calpain)与钙蛋白酶抑素(calpastatin)表达的变化,以探讨心肌肌钙蛋白抑制业基(cardiac troponin Ⅰ,cTnⅠ)降解的可能机制.采用尾部悬吊模拟失重大鼠模型,Western blotting技术观测心肌calpain-1、calpain-2与calpastatin的表达;PD150606抑制calpain活性,分析cTnⅠ降解程度的变化.结果显示:与同步对照组相比,悬吊2周与4周组大鼠心肌calpastatin表达呈显著性降低(P<0.05),calpain-1表达未改变,calpain-2表达略有降低:但是,心肌calpain-1/calpastatin及calpain-2/calpastatin的比值在悬吊2周与4周组明显增高(P<0.05,P<0.01).悬吊4周组cTnⅠ降解显著高于对照组(P<0.01);然而,用calpain非特异件抑制剂PD150606处理后,对照组及悬吊组cTnⅠ的降解均被显著抑制(P<0.01).这些结果提示模拟失重大鼠心肌calpain活性增高可能增加cTnⅠ的降解.

  5. Up-regulation of alpha-smooth muscle actin in cardiomyocytes from non-hypertrophic and non-failing transgenic mouse hearts expressing N-terminal truncated cardiac troponin I

    Directory of Open Access Journals (Sweden)

    Stephanie Kern

    2014-01-01

    Full Text Available We previously reported that a restrictive N-terminal truncation of cardiac troponin I (cTnI-ND is up-regulated in the heart in adaptation to hemodynamic stresses. Over-expression of cTnI-ND in the hearts of transgenic mice revealed functional benefits such as increased relaxation and myocardial compliance. In the present study, we investigated the subsequent effect on myocardial remodeling. The alpha-smooth muscle actin (α-SMA isoform is normally expressed in differentiating cardiomyocytes and is a marker for myocardial hypertrophy in adult hearts. Our results show that in cTnI-ND transgenic mice of between 2 and 3 months of age (young adults, a significant level of α-SMA is expressed in the heart as compared with wild-type animals. Although blood vessel density was increased in the cTnI-ND heart, the mass of smooth muscle tissue did not correlate with the increased level of α-SMA. Instead, immunocytochemical staining and Western blotting of protein extracts from isolated cardiomyocytes identified cardiomyocytes as the source of increased α-SMA in cTnI-ND hearts. We further found that while a portion of the up-regulated α-SMA protein was incorporated into the sarcomeric thin filaments, the majority of SMA protein was found outside of myofibrils. This distribution pattern suggests dual functions for the up-regulated α-SMA as both a contractile component to affect contractility and as possible effector of early remodeling in non-hypertrophic, non-failing cTnI-ND hearts.

  6. Cardiac effects of the c.1583 C→G LMNA mutation in two families with Emery-Dreifuss muscular dystrophy.

    Science.gov (United States)

    Zhang, Li; Shen, Hongrui; Zhao, Zhe; Bing, Qi; Hu, Jing

    2015-10-01

    The present study aimed to examine and analyze cardiac involvement in two Emery‑Dreifuss muscular dystrophy (EDMD) pedigrees caused by the c.1583 C→G mutation of the lamin A/C gene (LMNA). The clinical and genetic characteristics of members of two families with EDMD were evaluated by performing neurological examinations, skeletal muscle biopsies, cardiac evaluations, including electrocardiography, 24 h Holter, ultrasound cardiography and 99TcM‑MIBI‑gated myocardiac perfusion imaging, and genomic DNA sequencing. Family history investigations revealed an autosomal dominant transmission pattern of the disease in Family 1 and a sporadic case in Family 2. The three affected patients exhibited typical clinical features of EDMD, including joint contractures, muscle weakness and cardiac involvement. Muscle histopathological investigation revealed dystrophic features. In addition, each affected individual exhibited either cardiac arrhythmia, which was evident as sinus tachycardia, atrial flutter or complete atrioventricular inhibition. Cardiac imaging revealed dilated cardiomyopathy in two of the individuals, one of whom was presented with heart failure. The second patient presented with no significant abnormalities in cardiac structure or function. The three affected individuals exhibited a heterozygous missense mutation in the LMNA gene (c.1583 C→G), which caused a T528R amino acid change in the LMNA protein. In conclusion, the present study identified three patients with EDMD, exhibiting the same dominant LMNA mutation and presenting with a spectrum of severe cardiac abnormalities, including cardiac conduction system defects, cardiomyopathy and heart failure. As LMNA mutations have been associated with at least six clinical disorders, including EDMD, the results of the present study provide additional mutational and functional data, which may assist in further establishing LMNA mutational variation and disease pathogenesis.

  7. GATA6 mutations cause human cardiac outflow tract defects by disrupting semaphorin-plexin signaling

    Science.gov (United States)

    Kodo, Kazuki; Nishizawa, Tsutomu; Furutani, Michiko; Arai, Shoichi; Yamamura, Eiji; Joo, Kunitaka; Takahashi, Takao; Matsuoka, Rumiko; Yamagishi, Hiroyuki

    2009-01-01

    Congenital heart diseases (CHD) occur in nearly 1% of all live births and are the major cause of infant mortality and morbidity. Although an improved understanding of the genetic causes of CHD would provide insight into the underlying pathobiology, the genetic etiology of most CHD remains unknown. Here we show that mutations in the gene encoding the transcription factor GATA6 cause CHD characteristic of a severe form of cardiac outflow tract (OFT) defect, namely persistent truncus arteriosus (PTA). Two different GATA6 mutations were identified by systematic genetic analysis using DNA from patients with PTA. Genes encoding the neurovascular guiding molecule semaphorin 3C (SEMA3C) and its receptor plexin A2 (PLXNA2) appear to be regulated directly by GATA6, and both GATA6 mutant proteins failed to transactivate these genes. Transgenic analysis further suggests that, in the developing heart, the expression of SEMA3C in the OFT/subpulmonary myocardium and PLXNA2 in the cardiac neural crest contributing to the OFT is dependent on GATA transcription factors. Together, our data implicate mutations in GATA6 as genetic causes of CHD involving OFT development, as a result of the disruption of the direct regulation of semaphorin-plexin signaling. PMID:19666519

  8. ARRHYTHMOGENIC CALMODULIN MUTATIONS AFFECT THE ACTIVATION AND TERMINATION OF CARDIAC RYANODINE RECEPTOR MEDIATED CA2+ RELEASE

    DEFF Research Database (Denmark)

    Søndergaard, Mads Toft; Chazin, Walter J.; Chen, Wayne S.R.;

    We recently identified the first two human missense mutations in a calmodulin (CaM) gene (CALM1) and linked these to catecholaminergic polymorphic ventricular tachycardia (CPVT) and sudden cardiac death in young individuals1. More CaM mutations have since been identified in CALM1 and also......M in the presence of RyR2 CaMBD. The D95V, N97S and D129G mutations lowered the affinity of Ca2+ binding of the C-lobe of CaM, to apparent KDs of ~ 140, 150, and 4000 nM, respectively, consistent with the critical role of these residues in Ca2+ binding to the C-lobe. Thus, we suggest that these mutations may shift...... to an apo-CaM binding state during diastole, leading to dysregulation of RyR2 mediated Ca2+ release. Despite the pronounced impact on RyR2 mediated Ca2+ release, the N-lobe N53I mutation only imposed a small lowering of the N-lobe Ca2+ affinity (KD ~1200 nM). Thus, the RyR2 mediated Ca2+ release is either...

  9. Evidence of a wide spectrum of cardiac involvement due to ACAD9 mutations: Report on nine patients.

    Science.gov (United States)

    Dewulf, Joseph P; Barrea, Catherine; Vincent, Marie-Françoise; De Laet, Corinne; Van Coster, Rudy; Seneca, Sara; Marie, Sandrine; Nassogne, Marie-Cécile

    2016-07-01

    Acyl-CoA dehydrogenase 9 (ACAD9) is a mitochondrial protein involved in oxidative phosphorylation complex I biogenesis. This protein also exhibits acyl-CoA dehydrogenase (ACAD) activity. ACAD9-mutated patients have been reported to suffer from primarily heart, muscle, liver, and nervous system disorders. ACAD9 mutation is suspected in cases of elevated lactic acid levels combined with complex I deficiency, and confirmed by ACAD9 gene analysis. At least 18 ACAD9-mutated patients have previously been reported, usually displaying severe cardiac involvement. We retrospectively studied nine additional patients from three unrelated families with a wide spectrum of cardiac involvement between the families as well as the patients from the same families. All patients exhibited elevated lactate levels. Deleterious ACAD9 mutations were identified in all patients except one for whom it was not possible to recover DNA. To our knowledge, this is one of the first reports on isolated mild ventricular hypertrophy due to ACAD9 mutation in a family with moderate symptoms during adolescence. This report also confirms that dilated cardiomyopathy may occur in conjunction with ACAD9 mutation and that some patients may respond clinically to riboflavin treatment. Of note, several patients suffered from patent ductus arteriosus (PDA), with one exhibiting a complex congenital heart defect. It is yet unknown whether these cardiac manifestations were related to ACAD9 mutation. In conclusion, this disorder should be suspected in the presence of lactic acidosis, complex I deficiency, and any cardiac involvement, even mild.

  10. Beyond the Electrocardiogram: Mutations in Cardiac Ion Channel Genes Underlie Nonarrhythmic Phenotypes

    Directory of Open Access Journals (Sweden)

    Thomas M Roston

    2017-03-01

    Full Text Available Cardiac ion channelopathies are an important cause of sudden death in the young and include long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, idiopathic ventricular fibrillation, and short QT syndrome. Genes that encode ion channels have been implicated in all of these conditions, leading to the widespread implementation of genetic testing for suspected channelopathies. Over the past half-century, researchers have also identified systemic pathologies that extend beyond the arrhythmic phenotype in patients with ion channel gene mutations, including deafness, epilepsy, cardiomyopathy, periodic paralysis, and congenital heart disease. A coexisting phenotype, such as cardiomyopathy, can influence evaluation and management. However, prior to recent molecular advances, our understanding and recognition of these overlapping phenotypes were poor. This review highlights the systemic and structural heart manifestations of the cardiac ion channelopathies, including their phenotypic spectrum and molecular basis.

  11. A novel heterozygous mutation in cardiac calsequestrin causes autosomal dominant catecholaminergic polymorphic ventricular tachycardia

    Science.gov (United States)

    Gray, Belinda; Bagnall, Richard D.; Lam, Lien; Ingles, Jodie; Turner, Christian; Haan, Eric; Davis, Andrew; Yang, Pei-Chi; Clancy, Colleen E.; Sy, Raymond W.; Semsarian, Christopher

    2017-01-01

    Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal inherited arrhythmia syndrome characterized by adrenergically stimulated ventricular tachycardia. Mutations in the cardiac ryanodine receptor gene (RYR2) cause an autosomal dominant form of CPVT, while mutations in the cardiac calsequestrin 2 gene (CASQ2) cause an autosomal recessive form. Objective The aim of this study was to clinically and genetically evaluate a large family with severe autosomal dominant CPVT. Methods Clinical evaluation of family members was performed, including detailed history, physical examination, electrocardiogram, exercise stress test, and autopsy review of decedents. We performed genome-wide linkage analysis in 12 family members and exome sequencing in 2 affected family members. In silico models of mouse and rabbit myocyte electrophysiology were used to predict potential disease mechanisms. Results Severe CPVT with dominant inheritance in 6 members was diagnosed in a large family with 2 sudden deaths, 2 resuscitated cardiac arrests, and multiple appropriate implantable cardioverter-defibrillator shocks. A comprehensive analysis of cardiac arrhythmia genes did not reveal a pathogenic variant. Exome sequencing identified a novel heterozygous missense variant in CASQ2 (Lys180Arg) affecting a highly conserved residue, which cosegregated with disease and was absent in unaffected family members. Genome-wide linkage analysis confirmed a single linkage peak at the CASQ2 locus (logarithm of odds ratio score 3.01; θ = 0). Computer simulations predicted that haploinsufficiency was unlikely to cause the severe CPVT phenotype and suggested a dominant negative mechanism. Conclusion We show for the first time that a variant in CASQ2 causes autosomal dominant CPVT. Genetic testing in dominant CPVT should include screening for heterozygous CASQ2 variants. PMID:27157848

  12. PRKAG2 mutation: An easily missed cardiac specific non-lysosomal glycogenosis

    Directory of Open Access Journals (Sweden)

    Varun Aggarwal

    2015-01-01

    Full Text Available Mutations in PRKAG2 gene that regulates the γ2 subunit of the adenosine monophosphate (AMP dependent protein kinase have been associated with the development of atrioventricular (AV accessory pathways, cardiac hypertrophy, and conduction system abnormalities. These patients can potentially be misdiagnosed as hypertrophic cardiomyopathy (HOCM and/or Wolf-Parkinson White (WPW syndrome due to similar clinical phenotype. Early recognition of this disease entity is very important as ablation of suspected accessory pathways is not effective and the natural history of the disease is very different from HOCM and WPW syndrome.

  13. Clinical utility of natriuretic peptides and troponins in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Kehl, Devin W; Buttan, Anshu; Siegel, Robert J; Rader, Florian

    2016-09-01

    The diagnosis of hypertrophic cardiomyopathy (HCM) is based on clinical, echocardiographic and in some cases genetic findings. However, prognostication remains limited except in the subset of patients with high-risk indicators for sudden cardiac death. Additional methods are needed for risk stratification and to guide clinical management in HCM. We reviewed the available data regarding natriuretic peptides and troponins in HCM. Plasma levels of natriuretic peptides, and to a lesser extent serum levels of troponins, correlate with established disease markers, including left ventricular thickness, symptom status, and left ventricular hemodynamics by Doppler measurements. As a reflection of left ventricular filling pressure, natriuretic peptides may provide an objective measure of the efficacy of a specific therapy. Both natriuretic peptides and troponins predict clinical risk in HCM independently of established risk factors, and their prognostic power is additive. Routine measurement of biomarker levels therefore may be useful in the clinical evaluation and management of patients with HCM.

  14. Search for cardiac calcium cycling gene mutations in familial ventricular arrhythmias resembling catecholaminergic polymorphic ventricular tachycardia

    Directory of Open Access Journals (Sweden)

    Toivonen Lauri

    2009-02-01

    Full Text Available Abstract Background Catecholaminergic polymorphic ventricular tachycardia (CPVT is a severe inherited cardiac disorder caused by mutations predominantly in the ryanodine receptor (RyR2 gene. We sought to identify mutations in genes affecting cardiac calcium cycling in patients with CPVT and in less typical familial exercise-related ventricular arrhythmias. Methods and Results We recruited 33 consecutive patients with frequent ventricular premature complexes (VPCs without structural heart disease and often history of syncope or sudden death in family. Sixteen of the patients featured a phenotype typical of CPVT. In 17 patients, VPCs emerged also at rest. Exercise stress test and echocardiography were performed to each patient and 232 family members. Familial background was evident in 42% of cases (n = 14. We sequenced all the coding exons of the RyR2, FKBP1B, ATP2A2 and SLC8A1 genes from the index patients. Single channel recordings of a mutant RyR2 were performed in planar lipid bilayers. Two novel RyR2 missense mutations (R1051P and S616L and two RyR2 exon 3 deletions were identified, explaining 25% of the CPVT phenotypes. A rare variant (N3308S with open probabilities similar to the wild type channels in vitro, was evident in a patient with resting VPCs. No disease-causing variants were detectable in the FKBP1B, ATP2A2 or SLC8A1 genes. Conclusion We report two novel CPVT-causing RyR2 mutations and a novel RyR2 variant of uncertain clinical significance in a patient with abundant resting VPCs. Our data also strengthen the previous assumption that exon 3 deletions of RyR2 should screened for in CPVT and related phenotypes.

  15. Structure of the inhibitory region of troponin by site directed spin labeling electron paramagnetic resonance

    Science.gov (United States)

    Brown, Louise J.; Sale, Ken L.; Hills, Ron; Rouviere, Clement; Song, Likai; Zhang, Xiaojun; Fajer, Piotr G.

    2002-01-01

    Site-directed spin labeling EPR (SDSL-EPR) was used to determine the structure of the inhibitory region of TnI in the intact cardiac troponin ternary complex. Maeda and collaborators have modeled the inhibitory region of TnI (skeletal 96–112: the structural motif that communicates the Ca2+ signal to actin) as a kinked α-helix [Vassylyev, D., Takeda, S., Wakatsuki, S., Maeda, K. & Maeda, Y. (1998) Proc. Natl. Acad. Sci. USA 95, 4847–4852), whereas Trewhella and collaborators have proposed the same region to be a flexible β-hairpin [Tung, C. S., Wall, M. E., Gallagher, S. C. & Trewhella, J. (2000) Protein Sci. 9, 1312–1326]. To distinguish between the two models, residues 129–145 of cardiac TnI were mutated sequentially to cysteines and labeled with the extrinsic spin probe, MTSSL. Sequence-dependent solvent accessibility was measured as a change in power saturation of the spin probe in the presence of the relaxation agent. In the ternary complex, the 129–137 region followed a pattern characteristic of a regular 3.6 residues/turn α-helix. The following region, residues 138–145, showed no regular pattern in solvent accessibility. Measurements of 4 intradomain distances within the inhibitory sequence, using dipolar EPR, were consistent with an α-helical structure. The difference in side-chain mobility between the ternary (C⋅I⋅T) and binary (C⋅I) complexes revealed a region of interaction of TnT located at the N-terminal end of the inhibitory sequence, residues 130–135. The above findings for the troponin complex in solution do not support either of the computational models of the binary complex; however, they are in very good agreement with a preliminary report of the x-ray structure of the cardiac ternary complex [Takeda, S. Yamashita, A., Maeda, K. & Maeda, Y. (2002) Biophys. J. 82, 832]. PMID:12239350

  16. A proposed mutation, Val781Ile, associated with hyperkalemic periodic paralysis and cardiac dysrhythmia is a benign polymorphism.

    Science.gov (United States)

    Green, D S; Hayward, L J; George, A L; Cannon, S C

    1997-08-01

    Twenty different point mutations have been identified in the gene coding for the alpha subunit of the adult skeletal muscle sodium channel in families with hyperkalemic periodic paralysis, paramyotonia congenita, and the potassium-aggravated myotonias. One novel mutation (Val(781)Ile) was reported in an adopted boy with potassium-sensitive weakness and cardiac dysrhythmia. The confidence in establishing this rare amino acid substitution as a causative mutation was limited by the absence of family members for segregation analysis. Functional expression studies herein show that Val(781)Ile is most likely a benign polymorphism and not a disease-associated mutation.

  17. Clinical considerations in the interpretation of elevated troponin levels

    DEFF Research Database (Denmark)

    Rujic, Dragana; Pareek, Manan; Egholm, Gro

    2015-01-01

    The essential role of cardiac troponin (cTn) in the diagnosis of acute myocardial infarction has led to the development of high-sensitivity assays, which are able to detect very small amounts of myocardial necrosis. However, although elevated blood levels of cTn indicate myocardial injury, they do...... not provide a causal explanation. The differential diagnosis of minor elevations of the cTn-level is broad and includes both acute and chronic cardiac and non-cardiac conditions. The purpose of this paper is to review common causes of elevated cTn-levels in daily clinical practice....

  18. Troponin-T as a biomarker in neonates with perinatal asphyxia.

    Science.gov (United States)

    Abiramalatha, T; Kumar, M; Chandran, S; Sudhakar, Y; Thenmozhi, M; Thomas, N

    2017-08-23

    Troponin-T is a commonly used cardiac biomarker, which could be useful in perinatal asphyxia. We aimed to analyze troponin-T concentrations in asphyxiated neonates and to correlate the concentrations with clinical outcomes. Data were collected from electronic medical records of neonates diagnosed with perinatal asphyxia over a period of four years. There were 63 neonates with moderate to severe encephalopathy, in whom serial troponin-T concentrations had been done on days 1, 3, and 7. 53 (84%) asphyxiated infants had troponin-T concentration >100 pg/ml at 2-4 h of life.The difference in troponin-T concentrations between moderate and severe encephalopathy was not statistically significant (173 vs. 263 pg/ml, p value 0.40). The difference in the concentrations at 72 hours between cooled and non-cooled neonates was not significant (48.5 vs. 62.5 pg/ml, p value 0.22). Troponin-T concentration was significantly higher in babies with hypotensive shock and hepatic injury, but not acute kidney injury. There was no significant correlation between troponin-T and the extent of resuscitation needed.Troponin-T concentration on day 1 of life was significantly higher in babies who died than who survived (407 vs. 168 pg/ml, p value 0.03). ROC curve for troponin-T to predict mortality had an area under the curve (AUC) of 0.803; the best cut-off value (190 pg/ml) had 82% sensitivity and 80% specificity. There was no significant difference in troponin-T concentrations between cooled and non-cooled neonates. Troponin-T concentration had a good predictive accuracy for mortality before discharge.

  19. Troponin elevations in patients with chronic cardiovascular disease: An analysis of current evidence and significance.

    Science.gov (United States)

    Martin, Archer K; Malhotra, Anita K; Sullivan, Breandan L; Ramakrishna, Harish

    2016-01-01

    Serum troponin elevation above the 99th percentile of the upper reference limit in healthy subjects (troponin laboratory assays) is required to establish the diagnosis the diagnosis of myocardial necrosis in acute cardiovascular syndromes, as well as guide prognosis and therapy. In the perioperative period, for patients with cardiac disease undergoing noncardiac surgery, it is a particularly critical biomarker universally used to assess the myocardial damage. The value of troponin testing and elevation (as well as its significance) in patients with chronic cardiac valvular, vascular, and renal disease is relatively less well understood. This evidence-based review seeks to examine the currently available data assessing the significance of troponin elevation in certain chronic valvular and other disease states.

  20. Significance of serum troponin T and Creactive protein in the long-term prognosis of hemodialysis patients

    Institute of Scientific and Technical Information of China (English)

    毛永辉

    2013-01-01

    Objective To investigate the long-term prognostic factors and the significance of serum cardiac troponin T(cTnT) and C-reactive protein(CRP) in maintenance hemodialysis(MHD) patients.Methods Clinical data of

  1. Gain-of-function mutation in TASK-4 channels and severe cardiac conduction disorder.

    Science.gov (United States)

    Friedrich, Corinna; Rinné, Susanne; Zumhagen, Sven; Kiper, Aytug K; Silbernagel, Nicole; Netter, Michael F; Stallmeyer, Birgit; Schulze-Bahr, Eric; Decher, Niels

    2014-07-01

    Analyzing a patient with progressive and severe cardiac conduction disorder combined with idiopathic ventricular fibrillation (IVF), we identified a splice site mutation in the sodium channel gene SCN5A. Due to the severe phenotype, we performed whole-exome sequencing (WES) and identified an additional mutation in the KCNK17 gene encoding the K2P potassium channel TASK-4. The heterozygous change (c.262G>A) resulted in the p.Gly88Arg mutation in the first extracellular pore loop. Mutant TASK-4 channels generated threefold increased currents, while surface expression was unchanged, indicating enhanced conductivity. When co-expressed with wild-type channels, the gain-of-function by G88R was conferred in a dominant-active manner. We demonstrate that KCNK17 is strongly expressed in human Purkinje cells and that overexpression of G88R leads to a hyperpolarization and strong slowing of the upstroke velocity of spontaneously beating HL-1 cells. Thus, we propose that a gain-of-function by TASK-4 in the conduction system might aggravate slowed conductivity by the loss of sodium channel function. Moreover, WES supports a second hit-hypothesis in severe arrhythmia cases and identified KCNK17 as a novel arrhythmia gene.

  2. 心肌肌钙蛋白T和C-反应蛋白与不稳定型心绞痛的关系%Relationship between unstable angina and cardiac troponin T and C-reactive protein

    Institute of Scientific and Technical Information of China (English)

    苗霞

    2013-01-01

    Objective To detect the levels of cardiac troponin T (cTnT),C-reactive protein (CRP),creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase isoenzymes (LDH1) in unstable angina (UA) patients and investigate their clinical value for the diagnosis of UA.Methods The levels of cTnT,CK-MB and LDH1 were detected with biochemical analyzer; CRP was detected with specific protein analyzer.Results The elevated cases of cTnT,CK-MB,LDH1 and CRP were 23 cases(18.3%),26 cases(20.6%),41 cases(32.5%) and 73 cases(57.9%),respectively.Sixteen cases were attacked by acute myocardial infarction (AMI) and 3 cases suffered from sudden cardiac death in the five months.The incidence of AMI in the above elevated groups was significantly higher than that in the normal control group (P <0.01).The elevated levels of three index (cTnT,LDH1 and CRP),old myocardial infarction and numbers of chest pain were independent risk factors by multivariate Logistic regression analysis.Conclusions cTnT,LDH1 and CRP have important clinical significance for the early treatment and prognosis of patients with UA,which may be routine tests for these patients.%目的 检测血清心肌肌钙蛋白T (cTnT)、C-反应蛋白(CRP)、肌酸激酶同工酶(CK-MB)和乳酸脱氢酶同工酶(LDH1)在不稳定型心绞痛(UA)患者中的变化,探讨各指标对UA的诊断价值.方法 126例UA患者分别用生化分析仪检测cTnT、CK-MB和LDH1,特定蛋白分析仪检测CRP.结果 cTnT升高23例(18.3%),CK-MB升高26例(20.6%),LDH1升高41例(32.5%),CRP升高73例(57.9%).5个月内发生急性心肌梗死(AMI) 16例,心源性猝死3例.其中上述各指标升高组AMI发生率明显高于正常对照组(P<0.01).多因素Logistic回归分析cTnT、LDH1、CRP升高、陈旧性心肌梗死和胸痛次数是预测近期AMI和心源性猝死的独立危险因素.结论 cTnT、LDH1和CRP对UA患者的早期治疗和预后判断有重要临床意义,可作为UA患者的常规检测指标.

  3. Cardiac Paraganglioma Arising From the Right Atrioventricular Groove in a Paraganglioma-Pheochromocytoma Family Syndrome With Evidence of SDHB Gene Mutation: An Unusual Presentation.

    Science.gov (United States)

    Del Forno, Benedetto; Zingaro, Carlo; Di Palma, Enza; Capestro, Filippo; Rescigno, Giuseppe; Torracca, Lucia

    2016-09-01

    Primary cardiac paragangliomas are extremely rare. Recently this neoplasm has been associated with a familiar syndrome as a result of mutation of genes that encode proteins in the mitochondrial complex II. We report a case of a 46-year-old woman having cases of vertebral paraganglioma in her family showing an unusual anatomic and clinical presentation of cardiac paraganglioma and expressing a genetic mutation never associated before with cardiac localization of this neoplasm.

  4. [Early invasive strategy no better than a selective invasive strategy for patients with non-ST-segment elevation acute coronary syndromes and elevated cardiac troponin T levels: long-term follow-up results of the ICTUS trial

    NARCIS (Netherlands)

    Windhausen, F.; Hirsch, A.; Tijssen, J.G.P.; Verheugt, F.W.A.; Cornel, J.H.; Winter, R.J. de

    2008-01-01

    OBJECTIVE: To determine whether routine coronary angiography followed by revascularisation where appropriate is better than initial drug treatment in patients with non-ST-segment elevation acute coronary syndromes (nSTE-ACS) and elevated troponin T concentrations. DESIGN: Multicentre randomised

  5. A cardiac myosin binding protein C mutation in the Maine Coon cat with familial hypertrophic cardiomyopathy.

    Science.gov (United States)

    Meurs, Kathryn M; Sanchez, Ximena; David, Ryan M; Bowles, Neil E; Towbin, Jeffrey A; Reiser, Peter J; Kittleson, Judith A; Munro, Marcia J; Dryburgh, Keith; Macdonald, Kristin A; Kittleson, Mark D

    2005-12-01

    Hypertrophic cardiomyopathy (HCM) is one of the most common causes of sudden cardiac death in young adults and is a familial disease in at least 60% of cases. Causative mutations have been identified in several sarcomeric genes, including the myosin binding protein C (MYBPC3) gene. Although numerous causative mutations have been identified, the pathogenetic process is still poorly understood. A large animal model of familial HCM in the cat has been identified and may be used for additional study. As the first spontaneous large animal model of this familial disease, feline familial HCM provides a valuable model for investigators to evaluate pathophysiologic processes and therapeutic (pharmacologic or genetic) manipulations. The MYBPC3 gene was chosen as a candidate gene in this model after identifying a reduction in the protein in myocardium from affected cats in comparison to control cats (P<0.001). DNA sequencing was performed and sequence alterations were evaluated for evidence that they changed the amino acid produced, that the amino acid was conserved and that the protein structure was altered. We identified a single base pair change (G to C) in the feline MYBPC3 gene in affected cats that computationally alters the protein conformation of this gene and results in sarcomeric disorganization. We have identified a causative mutation in the feline MYBPC3 gene that results in the development of familial HCM. This is the first report of a spontaneous mutation causing HCM in a non-human species. It should provide a valuable model for evaluating pathophysiologic processes and therapeutic manipulations.

  6. Familial Evaluation in Catecholaminergic Polymorphic Ventricular Tachycardia Disease Penetrance and Expression in Cardiac Ryanodine Receptor Mutation-Carrying Relatives

    NARCIS (Netherlands)

    van der Werf, Christian; Nederend, Ineke; Hofman, Nynke; van Geloven, Nan; Ebink, Corne; Frohn-Mulder, Ingrid M. E.; Alings, A. Marco W.; Bosker, Hans A.; Bracke, Frank A.; van den Heuvel, Freek; Waalewijn, Reinier A.; Bikker, Hennie; van Tintelen, J. Peter; Bhuiyan, Zahurul A.; van den Berg, Maarten P.; Wilde, Arthur A. M.

    2012-01-01

    Background-Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome associated with mutations in the cardiac ryanodine receptor gene (RYR2) in the majority of patients. Previous studies of CPVT patients mainly involved probands, so current insight into disease

  7. Identifying potential functional impact of mutations and polymorphisms: Linking heart failure, increased risk of arrhythmias and sudden cardiac death.

    Directory of Open Access Journals (Sweden)

    BENOIT eJAGU

    2013-09-01

    Full Text Available Researchers and clinicians have discovered several important concepts regarding the mechanisms responsible for increased risk of arrhythmias, heart failure and sudden cardiac death. One major step in defining the molecular basis of normal and abnormal cardiac electrical behaviour has been the identification of single mutations that greatly increase the risk for arrhythmias and sudden cardiac death by changing channel-gating characteristics. Indeed, mutations in several genes encoding ion channels, such as SCN5A, which encodes the major cardiac Na+ channel, have emerged as the basis for a variety of inherited cardiac arrhythmias such as long QT syndrome, Brugada syndrome, progressive cardiac conduction disorder, sinus node dysfunction or sudden infant death syndrome. In addition, genes encoding ion channel accessory proteins, like anchoring or chaperone proteins, which modify the expression, the regulation of endocytosis and the degradation of ion channel α-subunits have also been reported as susceptibility genes for arrhythmic syndromes. The regulation of ion channel protein expression also depends on a fine-tuned balance among different other mechanisms, such as gene transcription, RNA processing, post-transcriptional control of gene expression by miRNA, protein synthesis, assembly and post-translational modification and trafficking.

  8. A novel lamin A/C gene mutation causing spinal muscular atrophy phenotype with cardiac involvement: report of one case.

    Science.gov (United States)

    Iwahara, Naotoshi; Hisahara, Shin; Hayashi, Takashi; Kawamata, Jun; Shimohama, Shun

    2015-02-20

    Mutations of the lamin A/C gene have been associated with several diseases such as Emery-Dreifuss muscular dystrophy, dilated cardiomyopathy and Charcot-Marie-Tooth disease, referred to as laminopathies. Only one report of spinal muscular atrophy and cardiomyopathy phenotype with lamin A/C gene mutations has been published. The concept that lamin A/C gene mutations cause spinal muscular atrophy has not been established. We report a man aged 65 years who presented with amyotrophy of lower limbs, arrhythmia and cardiac hypofunction. He showed gait disturbance since childhood, and his family showed similar symptoms. Neurological and electrophysiological findings suggested spinal muscular atrophy type 3. Gene analysis of lamin A/C gene showed a novel nonsense mutation p.Q353X (c.1057C > T). Further investigations revealed that he and his family members had cardiac diseases including atrioventricular block. We report the first Japanese case of spinal muscular atrophy phenotype associated with lamin A/C mutation. When a patient presents a spinal muscular atrophy phenotype and unexplained cardiac disease, especially when the family history is positive, gene analysis of lamin A/C gene should be considered.

  9. New intronic splicing mutation in the LMNA gene causing progressive cardiac conduction defects and variable myopathy.

    Science.gov (United States)

    Rogozhina, Y; Mironovich, S; Shestak, A; Adyan, T; Polyakov, A; Podolyak, D; Bakulina, A; Dzemeshkevich, S; Zaklyazminskaya, E

    2016-12-31

    Most of mutations in the LMNA gene are unique and have been found in only a few unrelated families. The clinical interpretation of new genetic variants, especially beyond the coding area and canonical splice sites, is proving to be difficult and requires advanced investigation. This study included patients with progressive cardiac conduction defects with neuromuscular involvement. The clinical evaluation included medical history and 24-h Holter monitoring. The genetic evaluation included mutation screening in the LMNA gene by the Sanger sequence. Sanger sequencing was followed by RT-PCR of the target fragment of cDNA. In silico modeling was performed with CCBulder and Modeller software. The diagnosis of limb-girdle muscular dystrophy type 1B (LGMD1B) was established. The new intronic variant c.513+45T>G was found in the LMNA gene in the proband and affected daughter. The insertion of 45bp was confirmed in the proband's cDNA. The structural and possible functional effects of the aberrant protein were predicted. Variant c.513+45T>G in the LMNA gene likely translates into the longer lamin A/C proteins with additional 15 amino acids. This variant is thought to be pathogenic. Intronic variants in the LMNA gene located beside canonic splice sites may be responsible for some genotype-negative cases with clinical phenotype of laminopathies. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Elevated Troponin I in the Absence of Coronary Artery Disease: A Case Report With Review of Literature

    Science.gov (United States)

    Arshed, Sabrina; Luo, Hong Xiu; Zafar, Shoaib; Regeti, Kalyani; Malik, Nilma; Alam, Mahmood; Yousif, Abdalla

    2015-01-01

    Cardiac troponins are the most sensitive and specific markers of myocardial injury. In fact, the Joint European Society of Cardiology/American College of Cardiology committee for the redefinition of myocardial infarction (MI) states that troponins are the preferred cardiac marker for detecting myocardial injury. For the aforementioned reasons, troponin levels are routinely ordered for patients presenting to the emergency department with chest pain, dyspnea, syncope, or any other possible presentations of MI. While troponin levels do reflect the extent of myocardial damage, they do not necessarily indicate myocardial ischemia in a subset of patients. Elevated troponin levels can be due to a wide array of mechanisms in the absence of myocardial ischemia and injury. Thus, relying solely on troponin levels, in the presence of a normal electrocardiogram (ECG), to diagnose myocardial ischemia can lead to unnecessary and expensive invasive testing. It is therefore important for the clinician to keep in mind the varying causes of troponin elevations in order to provide the highest value care to the patient. We present a case and review of literature regarding patients who present with elevated troponin levels in the absence of any coronary artery disease. PMID:26346942

  11. L30A Mutation of Phospholemman Mimics Effects of Cardiac Glycosides in Isolated Cardiomyocytes.

    Science.gov (United States)

    Himes, Ryan D; Smolin, Nikolai; Kukol, Andreas; Bossuyt, Julie; Bers, Donald M; Robia, Seth L

    2016-11-08

    To determine if mutations introduced into phospholemman (PLM) could increase the level of PLM-Na,K-ATPase (NKA) binding, we performed scanning mutagenesis of the transmembrane domain of PLM and measured Förster resonance energy transfer (FRET) between each mutant and NKA. We observed an increased level of binding to NKA for several PLM mutants compared to that of the wild type (WT), including L27A, L30A, and I32A. In isolated cardiomyocytes, overexpression of WT PLM increased the amplitude of the Ca(2+) transient compared to the GFP control. The Ca(2+) transient amplitude was further increased by L30A PLM overexpression. The L30A mutation also delayed Ca(2+) extrusion and increased the duration of cardiomyocyte contraction. This mimics aspects of the effect of cardiac glycosides, which are known to increase contractility through inhibition of NKA. No significant differences between WT and L30A PLM-expressing myocytes were observed after treatment with isoproterenol, suggesting that the superinhibitory effects of L30A are reversible with β-adrenergic stimulation. We also observed a decrease in the extent of PLM tetramerization with L30A compared to WT using FRET, suggesting that L30 is an important residue for mediating PLM-PLM binding. Molecular dynamics simulations revealed that the potential energy of the L30A tetramer is greater than that of the WT, and that the transmembrane α helix is distorted by the mutation. The results identify PLM residue L30 as an important determinant of PLM tetramerization and of functional inhibition of NKA by PLM.

  12. Distinct functional defect of three novel Brugada syndrome related cardiac sodium channel mutations

    Directory of Open Access Journals (Sweden)

    Juang Jyh-Ming

    2009-02-01

    Full Text Available Abstract The Brugada syndrome is characterized by ST segment elevation in the right precodial leads V1-V3 on surface ECG accompanied by episodes of ventricular fibrillation causing syncope or even sudden death. The molecular and cellular mechanisms that lead to Brugada syndrome are not yet completely understood. However, SCN5A is the most well known responsible gene that causes Brugada syndrome. Until now, more than a hundred mutations in SCN5A responsible for Brugada syndrome have been described. Functional studies of some of the mutations have been performed and show that a reduction of human cardiac sodium current accounts for the pathogenesis of Brugada syndrome. Here we reported three novel SCN5A mutations identified in patients with Brugada syndrome in Taiwan (p.I848fs, p.R965C, and p.1876insM. Their electrophysiological properties were altered by patch clamp analysis. The p.I848fs mutant generated no sodium current. The p.R965C and p.1876insM mutants produced channels with steady state inactivation shifted to a more negative potential (9.4 mV and 8.5 mV respectively, and slower recovery from inactivation. Besides, the steady state activation of p.1876insM was altered and was shifted to a more positive potential (7.69 mV. In conclusion, the SCN5A channel defect related to Brugada syndrome might be diverse but all resulted in a decrease of sodium current.

  13. 尿毒症患者血清肌钙蛋白T测定的临床意义%Study of Cardiac Troponin T Assay in Asymptomatic Patients with Chronic Renal Failure

    Institute of Scientific and Technical Information of China (English)

    陈向东; 彭立人; 刘平

    2001-01-01

    To identify the clinical significance of cardiac troponin T (cTnT) in asymptomatic patients with chronic renal failure (CRF), vein blood was drawn from patients with CRF of no hemodialysis (HD), maintenance HD, the skeletomuscular damage, the acute myocardial infarction and CRF with heart failure patients in proper order. Fullautomatic ELISA assay was used to determine cTnT serum levels, assay serum cretinine (Cr), creatine phosphate kinase-MB (CK-MB), lactic dehydrogenase (LDH) and hydroxybutyric acid dehydrogenase (HBD). The results is that during acute myocardial infarction, the mass density of cTnT increased significantly as a result of myocardial infarction. Blood cTnT was elevated in patients of CRF with heart failure. Blood cTnT fell to normal as soon as the heart failure was cured. But cTnT was not significantly elevated in asymptomatic patients with CRF. There was no clinical specificity for cTnT assay in asymptomatic patients with CRF.%为探讨血清肌钙蛋白T(cTnT)在无症状尿毒症患者中的临床意义,分别抽取尿毒症非血液透析组、血液透析组透析前和透析后、骨骼肌损伤组、急性心肌梗死组和尿毒症合并心功能不全组病人的静脉血,以双抗体夹心法测定cTnT值,同时检测各组血肌酐(Cr)、肌酸磷酸激酶-MB同工酶(CK-MB)、乳酸脱氢酶(LDH)及羟丁酸脱氢酶(HBD)。结果显示:心肌梗死时,由于心肌大面积坏死致cTnT质量浓度明显升高;尿毒症合并心功能不全时cTnT质量浓度升高,但随心功能不全缓解,cTnT质量浓度恢复正常。而尿毒症非透析组、血透组透析前和透析后病人cTnT质量浓度与肾病对照组比较无显著性差异(P>0.01)。提示:测定无症状尿毒症患者的cTnT对判断心肌受损无特殊临床意义。

  14. The change and significance of heart fatty acid-binding protein and cardiac troponin Ⅰ in valve replacement patients%心脏瓣膜置换围手术期H-FABP和cTnI的变化及意义

    Institute of Scientific and Technical Information of China (English)

    陈志军; 王永连; 王忠民

    2011-01-01

    目的 探讨心脏瓣膜置换术后心肌肌钙蛋白I(cTnI)和心型脂肪酸结合蛋白(H-FABP)的变化规律.方法 选本院风湿性心脏病手术患者40例,随机分为晶体停搏液灌注组和冷血停搏液灌注组,选取8个时间点,分析和比较各时点血清cTnI和H-FABP浓度变化规律.结果 晶体停搏液灌注组cTnI组间及交互效应差异均有统计学意义(F组间=2744.397,P<0.01; F交互=125.345,P<0.01),冷血停搏液灌注组cTnI组间及交互效应差异均有统计学意义(F组间=1056.357,P<0.01; F交互 =64.242,P<0.01);晶体停搏液灌注组H- FABP组间及交互效应差异均有统计学意义(F组间=1775.022,P<0.01;F交互=34.297,P<0.01),冷血停搏液灌注组H -FABP组间及交互效应差异均有统计学意义(F组间=3064.451,P<0.01;F交互=60.472,P<0.01).结论 H-FABP心肌的特异性强,有效诊断窗口期短,较符合心肌损伤的理想判定标志物.%Objective To explore change trend of Cardiac Troponin Ⅰ (cTnI) and Heart Fatty Acid-binding Protein(H-FABP) in serum during the perioperation of valve replacement.Methods Forty patients with heumatoid valvular heart disease were selected for this study,and the patients were randomly divided into two groups.Blood samples were taken from center vein,and the serum levels of cTnI and H-FABP were determined.The change of the serum levels of these two markers at different time points was recorded and compared between two groups.Results There were significant differences in the concentration of cTnl in the cold crystalloid cardioplegia group ( F between group =2744.397,P <0.01 ; F interaction =125.345,P <0.01 ).There were significant differences in the concentration of cTnI in the cold blood cardioplegia group ( F between group =1056.357,P < 0.01 ; Finteraction =64.242,P < 0.01 ).There were significant differences in the concentration of H - FABP in the cold crystalloid cardioplegia group ( F between group =1775.022,P <0.01; F

  15. Clinical Significance of Serum Cardiac Troponin T and Serum uric acid levels in Aged Patients with Chronic Congestive Heart Failure%老年慢性心力衰竭患者血清肌钙蛋白T及尿酸检测的临床意义

    Institute of Scientific and Technical Information of China (English)

    李莉

    2011-01-01

    目的 探讨老年慢性心力衰竭(CHF)患者血清肌钙蛋白T(cTnT)及尿酸(UA)水平检测的意义.方法 回顾性分析200例老年慢性心力衰竭患者临床资料,心功能Ⅰ级为对照组,Ⅱ、Ⅲ、Ⅳ级患者为观察组,每组50例.分析血UA、cTnT与慢性心力衰竭的发生是否存在相关性.按cTnT浓度分为正常组和增高组,比较其住院期间及随访2年发生的心脏事件(心力衰竭反复或加重、死亡)的发生情况.结果 观察组cTnT与UA含量明显高于对照组.cTnT增高组患者心脏事件的发生率明显高于正常组(P<0.05).结论 心衰越重,cTnT与UA增高越明显,血尿酸、肌钙蛋白T与充血性心力衰竭密切相关,是充血性心力衰竭发病的危险因素,二者联合可作为评价老年心力衰竭严重程度的指标.cTnT对判断老年慢性心力衰竭患者的预后有较好的预测价值.%Objective To evaluate the correlations of serum cardiac troponin T and serum uric acid levels in in aged patients with chronic congestive heart failure(CHF) and the effect of cardiac troponin T(cTnT) on the prognosis of the CHF. Methods 200 cases of congestive heart failure patients(Cardiac function NYHA class Ⅰ-Ⅳ) were enrolled for retrospective analysis and divided into four groups ,50 cases per group;randomly picked 50 cases of pantients with cardiac function NYHA class Ⅰ as a control group; and analyzed the relationship of serum uric (UA) and cTnT level and the occurrence of CHF. All the patients were arranged into normal group and higher group according to cTnT concentration. Cardiac events, including repeated or aggravated heart failure or cardiac death,in patients with increased cTnT during hospitalization were compared to those without it. Results In congestive heart failure group (Cardiac function NYHA class Ⅱ-Ⅳ) ,the cTnT and UA contents increased significantly than that in control group.Incidence of cardiac events was higher in patients with increased c

  16. Gene mutations in cardiac arrhythmias: a review of recent evidence in ion channelopathies

    Directory of Open Access Journals (Sweden)

    Hsiao PY

    2013-01-01

    Full Text Available Pi-Yin Hsiao,1 Hui-Chun Tien,2 Chu-Pin Lo,2 Jyh-Ming Jimmy Juang,3 Yi-Hsin Wang,2 Ruey J Sung41Institute of Life Sciences, National Central University, Taoyuan, Taiwan; 2Department of Financial and Computational Mathematics, Providence University, Taichung, Taiwan; 3Cardiovascular Center and Department of Cardiology, National Taiwan University, Taipei, Taiwan; 4Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USAAbstract: Over the past 15 years, molecular genetic studies have linked gene mutations to many inherited arrhythmogenic disorders, in particular, "ion channelopathies", in which mutations in genes encode functional units of ion channels and/or their transporter-associated proteins in patients without primary cardiac structural abnormalities. These disorders are exemplified by congenital long QT syndrome (LQTS, short QT syndrome, Brugada syndrome (BrS and catecholaminergic polymorphic ventricular tachycardia (CPVT. Functional and pathophysiological studies have led to better understanding of the clinical spectrum, ion channel structures and cellular electrophysiology involving dynamics of intracellular calcium cycling in many subtypes of these disorders and more importantly, development of potentially more effective pharmacological agents and even curative gene therapy. In this review, we have summarized (1 the significance of unveiling mutations in genes encoding transporter-associated proteins as the cause of congenital LQTS, (2 the technique of catheter ablation applied at the right ventricular outflow tract may be curative for severely symptomatic BrS, (3 mutations with channel function modulated by protein Kinase A-dependent phosphorylation can be the culprit of CPVT mimicry in Andersen-Tawil syndrome (LQT7, (4 ablation of the ion channel anchoring protein may prevent arrhythmogenesis in Timothy syndrome (LQT8, (5 altered intracellular Ca2+ cycling can be the basis of effective targeted

  17. Physical exertion may cause high troponin levels.

    Science.gov (United States)

    Agewall, Stefan; Tjora, Solve

    2011-11-15

    It is important to measure troponin levels when acute myocardial infarct is suspected. Many other factors that affect the heart can cause an increase in troponin levels, for example extreme physical exertion. Recent studies have shown that more normal physical activity can also lead to increase in troponin levels in healthy individuals.

  18. Prevalence and Prognostic Association of Circulating Troponin in the Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Metkus, Thomas S; Guallar, Eliseo; Sokoll, Lori; Morrow, David; Tomaselli, Gordon; Brower, Roy; Schulman, Steven; Korley, Frederick K

    2017-10-01

    Circulating cardiac troponin has been associated with adverse prognosis in the acute respiratory distress syndrome in small and single-center studies; however, comprehensive studies of myocardial injury in acute respiratory distress syndrome using modern high-sensitivity troponin assays, which can detect troponin at much lower circulating concentrations, have not been performed. We performed a prospective cohort study. We included patients enrolled in previously completed trials of acute respiratory distress syndrome. One thousand fifty-seven acute respiratory distress syndrome patients were included. To determine the association of circulating high-sensitivity troponin I (Abbott ARCHITECT), with acute respiratory distress syndrome outcomes, we measured high-sensitivity troponin I within 24 hours of intubation. The primary outcome was 60-day mortality. Detectable high-sensitivity troponin I was present in 94% of patients; 38% of patients had detectable levels below the 99th percentile of a healthy reference population (26 ng/L), whereas 56% of patients had levels above the 99th percentile cut point. After multivariable adjustment, age, cause of acute respiratory distress syndrome, temperature, heart rate, vasopressor use, Sequential Organ Failure Assessment score, creatinine, and PCO2 were associated with higher high-sensitivity troponin I concentration. After adjustment for age, sex, and randomized trial assignment, the hazard ratio for 60-day mortality comparing the fifth to the first quintiles of high-sensitivity troponin I was 1.61 (95% CI, 1.11-2.32; p trend = 0.003). Adjusting for Sequential Organ Failure Assessment score suggested that this association was not independent of disease severity (hazard ratio, 0.95; 95% CI, 0.64-1.39; p = 0.93). Circulating troponin is detectable in over 90% of patients with acute respiratory distress syndrome and is associated with degree of critical illness. The magnitude of myocardial injury correlated with mortality.

  19. Non dominant-negative KCNJ2 gene mutations leading to Andersen-Tawil syndrome with an isolated cardiac phenotype.

    Science.gov (United States)

    Limberg, Maren M; Zumhagen, Sven; Netter, Michael F; Coffey, Alison J; Grace, Andrew; Rogers, Jane; Böckelmann, Doris; Rinné, Susanne; Stallmeyer, Birgit; Decher, Niels; Schulze-Bahr, Eric

    2013-05-01

    Andersen-Tawil syndrome (ATS) is characterized by dysmorphic features, periodic paralyses and abnormal ventricular repolarization. After genotyping a large set of patients with congenital long-QT syndrome, we identified two novel, heterozygous KCNJ2 mutations (p.N318S, p.W322C) located in the C-terminus of the Kir2.1 subunit. These mutations have a different localization than classical ATS mutations which are mostly located at a potential interaction face with the slide helix or at the interface between the C-termini. Mutation carriers were without the key features of ATS, causing an isolated cardiac phenotype. While the N318S mutants regularly reached the plasma membrane, W322C mutants primarily resided in late endosomes. Co-expression of N318S or W322C with wild-type Kir2.1 reduced current amplitudes only by 20-25 %. This mild loss-of-function for the heteromeric channels resulted from defective channel trafficking (W322C) or gating (N318S). Strikingly, and in contrast to the majority of ATS mutations, neither mutant caused a dominant-negative suppression of wild-type Kir2.1, Kir2.2 and Kir2.3 currents. Thus, a mild reduction of native Kir2.x currents by non dominant-negative mutants may cause ATS with an isolated cardiac phenotype.

  20. Chest pain and high-sensitivity troponin: What is the evidence?

    Directory of Open Access Journals (Sweden)

    Daniel Ashmore

    2015-03-01

    Full Text Available The number of attendances and admissions of patients with chest pain to hospitals in England and Wales is increasing. Initial assessment may be unrewarding. Consequently, cardiac troponin has become the mainstay of investigation for non-ST-segment-elevation myocardial infarction and unstable angina, although only a small proportion of patients are eventually diagnosed as such. Current National Institute for Healthcare and Clinical Excellence guidance recommends measuring cardiac troponin levels on presentation and 10–12 h after onset of symptoms. A more effective diagnostic tool is needed. The aims are twofold: to increase accuracy of acute coronary syndrome diagnosis thus implementing the most appropriate management at an earlier stage while reducing costs and to provide a more rapid diagnosis to ease the anxieties of patients. Three key issues have been highlighted. The first is that many current studies do not have a ‘normal/reference’ population, making comparison between two studies difficult to interpret. Second, whether newer ‘high-sensitivity’ cardiac troponin tests can be used to rule out a myocardial infarction in a patient with chest pain is discussed. Third, whether a ‘high-sensitivity’ cardiac troponin has great enough specificity to differentiate between the number of other causes of raised troponin in a single test or whether serial testing is needed is assessed. A strategy for such serial testing is discussed. Finally, use of ‘high-sensitivity’ cardiac troponin in risk stratification of other disease processes is highlighted, which is likely to become common practice, changing the way we manage patients with, and without, chest pain.

  1. The Correlation between Troponin and Ferritin Serum Levels in the Patients with Major Beta-Thalassemia

    Directory of Open Access Journals (Sweden)

    Iraj Shahramian

    2013-06-01

    Full Text Available Background: Thalassemia is a hereditary hemoglobinopathy whose most common complication is cardiac involvement which ends up in these patients’ death. Since troponin is a sensitive and specific marker for the detection of microinfarct, we studied the relationship between troponin and ferritin serum levels for early diagnosis of cardiac involvement in these patients. Materials and Methods: This case-control study was performed on 80 patients, including 40 patients with major thalassemia and normal echocardiography and 40 healthy volunteers ranging from 6 months to 16 years old. All the children were examined and the eligible children who were not infected with known heart disease, iron deficiency anemia, kidney disease, diabetes, fever, and systemic diseases were enrolled into the study after obtaining written informed consents from their parents. At 8:00 A.M. before breakfast, 5cc blood was drawn from these children. After collecting the samples, ferritin and troponin serum levels were evaluated using ELISA and electro- kymonolonsense methods, respectively. The gathered data were analyzed through the SPSS statistical software (v. 20 and T-test. Besides, P value<0.05 was considered as statistically significant. Results: The study results revealed a significant difference between the two groups regarding the mean of the serum levels of troponin (P=0.045 and ferritin (P=0.001. In this study, no significant correlation was observed between serum troponin and ferritin levels and age and BMI in the two groups. Also, no significant relationship was found between serum troponin level and sex (P=0.264. Conclusions: In microinfarct, troponin increases independent of ferritin; therefore, it can be used for early detection of cardiac involvement in thalassemia patients to determine the sub-clinical effects.

  2. Evaluation of the flanking nucleotide sequences of sarcomeric hypertrophic cardiomyopathy substitution mutations.

    Science.gov (United States)

    Meurs, Kathryn M; Mealey, Katrina L

    2008-07-03

    Hypertrophic cardiomyopathy (HCM) is a familial myocardial disease with a prevalence of 1 in 500. More than 400 causative mutations have been identified in 13 sarcomeric and myofilament related genes, 350 of these are substitution mutations within eight sarcomeric genes. Within a population, examples of recurring identical disease causing mutations that appear to have arisen independently have been noted as well as those that appear to have been inherited from a common ancestor. The large number of novel HCM mutations could suggest a mechanism of increased mutability within the sarcomeric genes. The objective of this study was to evaluate the most commonly reported HCM genes, beta myosin heavy chain (MYH7), myosin binding protein C, troponin I, troponin T, cardiac regulatory myosin light chain, cardiac essential myosin light chain, alpha tropomyosin and cardiac alpha-actin for sequence patterns surrounding the substitution mutations that may suggest a mechanism of increased mutability. The mutations as well as the 10 flanking nucleotides were evaluated for frequency of di-, tri- and tetranucleotides containing the mutation as well as for the presence of certain tri- and tetranculeotide motifs. The most common substitutions were guanine (G) to adenine (A) and cytosine (C) to thymidine (T). The CG dinucleotide had a significantly higher relative mutability than any other dinucleotide (pmutation was calculated; none were at a statistically higher frequency than the others. The large number of G to A and C to T mutations as well as the relative mutability of CG may suggest that deamination of methylated CpG is an important mechanism for mutation development in at least some of these cardiac genes.

  3. Mutations in conserved amino acids in the KCNQ1 channel and risk of cardiac events in type-1 long-QT syndrome

    DEFF Research Database (Denmark)

    Jons, Christian; Moss, Arthur J; Lopes, Coeli M

    2009-01-01

    with the highest tertile scores (>0.665; n = 196) showed significantly increased risk of cardiac events (HR = 3.32, P gender, age, and beta......-blocker therapy. CONCLUSIONS: Mutations in highly conserved amino acid residues in the KCNQ1 gene are associated with a significant risk of cardiac events independent of QTc, gender, and beta-blocker therapy Udgivelsesdato: 2009/8...

  4. Compound heterozygosity for mutations (W156X and R225W) in SCN5A associated with severe cardiac conduction disturbances and degenerative changes in the conduction system

    NARCIS (Netherlands)

    Bezzina, CR; Rook, MB; Groenewegen, WA; Herfst, LJ; van der Wal, AC; Lam, J; Jongsma, HJ; Wilde, AAM; Mannens, MMAM

    2003-01-01

    Cardiac conduction defects associate with mutations in SCN5A, the gene encoding the cardiac Na+ channel. In the present study, we characterized a family in which the proband was born in severe distress with irregular wide complex tachycardia. His older sister died at 1 year of age from severe conduc

  5. Research of cardiac troponin I release after transcatheter closure of atrial septal defect in children%房间隔缺损患儿介入治疗前后肌钙蛋白I变化的研究

    Institute of Scientific and Technical Information of China (English)

    陈轶维; 张志芳; 李奋; 周爱卿; 吉炜; 胡晶晶

    2012-01-01

    Objective To investigate whether transcatheter closure of atrial septal defect makes cardiac troponin I(cTnI) realease in children. Methods Clinical data, laboratory tests, imagings, diagnosis, the information of interventional therapy and postoperative follow-up from 146 children with secundum atrial septal defect who were diagnosed and get treatment of interventional were collected. The median age was(5. 87 ± 3. 48) years( range,2. 25-12. 5) with 87 boys and 59 girls. The device size ranged from 8 to 22 mm. These patients were divided to 2 groups according to the level of cTnI after intervention. The cTnI serum concentrations were examined immediately eafter intervention ,6 hours later,24 hours later and 3 days after intervention. Results The level of cTnI were normal before intervention,and the peak level of cTnI was found at 6 hours after intervention(Z = - 3. 410,P =0. 005) . All of the patients had a normal level of cTnI 3 days after operation ( Z = - 0. 332, P = 0. 74 ) . Univariate analysis showed age, height,device size,size/BSA ratio to be contributing factors for level of cTnI. The device size/body surface area ratio was identified by demonstration positive correlation with cTnI elevation by multivariate logistic regression analysis ( r = 0. 31, P =0. 022 ). Conclusions The transcatheter closure of atrial septal defect in children could lead to reversible increase of cTnI or induce minor myocardial lesion, the extent of which depends on the ratio of device size/ body surface area. Interventional therapy of atrial septal defect is safe and effective for children.%目的 总结并分析儿童继发孔型房间隔缺损患者接受介入封堵治疗前后肌钙蛋白I(cTnI)变化的原因及相关因素,提高临床医师对介入封堵技术治疗儿童房间隔缺损相关适应证及手术风险的了解.方法 收集146例2009年9月至2012年4月在上海儿童医学中心心内科介入封堵的继发孔型房间隔缺损患儿的临床资料、辅

  6. 基因重组心肌肌钙蛋白I融合蛋白的抗肿瘤效应%Inhibitory effect of tumor growth of recombinant protein fused with cardiac troponin I and artificial peptide

    Institute of Scientific and Technical Information of China (English)

    雷光强; 刘朝阳; 姜懿纳; 李金萍; 曹勤燕; 李涛; 刘凤鸣

    2015-01-01

    目的:研究基因重组心肌肌钙蛋白I 与人工短肽的融合蛋白( CIS)对肿瘤生长的作用。方法用MTT法观察CIS体外对人脐静脉内皮细胞( HUVEC)生长的作用。利用鸡胚绒毛尿囊膜模型观察CIS对新生血管生长的影响。用6种小鼠肿瘤异位可移植模型观察CIS在体内对肿瘤生长的作用。结果 CIS对HUVEC细胞增殖具有明显抑制作用,并呈剂量依赖关系;鸡胚绒毛尿囊膜实验显示,CIS 浓度为5、10 mg·L-1时,新生血管生成的数量明显减少;荷瘤鼠体内异位移植模型实验显示:CIS(10 mg·kg-1)处理组肿瘤生长缓慢,瘤体明显小于模型对照组,对 S180肿瘤瘤重抑制率85.3%,对Lewis肺癌肿瘤瘤重抑制率87.0%,对H22肝癌肿瘤瘤重抑制率84.2%,对人小细胞肺癌H446肿瘤瘤重抑制率60.42%,对人可移植性肝癌SMMC7721肿瘤瘤重抑制率61.62%,对人胃低分化腺癌BGC823肿瘤瘤重抑制率为41.84%。结论 CIS在体外抑制HUVEC细胞的生长,在鸡胚绒毛尿囊膜实验中,CIS对新生血管生成有明显的抑制作用。在体内,CIS融合蛋白可有效抑制小鼠可移植肿瘤细胞的生长。 CIS抗肿瘤效应很可能是通过抑制肿瘤组织中血管内皮细胞的增殖,进而减少肿瘤组织中新生血管生成的数量而达到的。%Aim To examine the inhibitory effect of re-combinant cardiac troponin fusion protein composed of subunit I and artificial peptide which was called CIS on tumor growth. Methods The CIS ’ s effect on the growth of human umbilical vein endothelial cells ( HU-VEC) was examined using MTT assay in vitro. Chick chorioallantoic membrane model was applied to study the alteration of angiogenesis treated with purified re-combinant CIS protein. The effect of tumor growth trea-ted with CIS was observed using several in vivo mice xenograft models. Results There was a statistically significant reduction in HUVEC cell proliferative rate when the cells were treated

  7. Cardiac abnormalities in diabetic patients with mutation in the mitochondrial tRNA {sup Leu(UUR)}Gene

    Energy Technology Data Exchange (ETDEWEB)

    Ueno, Hiroshi [Hyogo Medical Center for Adults, Akashi (Japan); Shiotani, Hideyuki

    1999-11-01

    An A-to-G transition at position 3243 of the mitochondrial DNA is known to be a pathogenic factor for mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), diabetes and cardiomyopathy. This mutation causes dysfunction of the central nervous system in MELAS. Because the heart, as well as the brain and nervous system, is highly dependent on the energy produced by mitochondrial oxidation, these tissues are more vulnerable to mitochondrial defects. Cardiac abnormalities were assessed in 10 diabetic patients associated with this mutation using echocardiography and {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy, and compared with 19 diabetic patients without the mutation. Duration of diabetes, therapy, control of blood glucose and diabetic complications, such as diabetic retinopathy and nephropathy, were not different between the 2 groups. Diabetic patients with the mutation had a significantly thicker interventricular septum (16.8{+-}3.7 vs 11.0{+-}1.6 mm, p<0.001) than those without the mutation. Fractional shortening was lower in diabetic patients with the mutation than those without it (30.7{+-}7.0 vs 42.5{+-}6.6, p<0.001). MIBG uptake on the delayed MIBG image was significantly lower in diabetic patients with the mutation than in those without the mutation (mean value of the heart to mediastinum ratio: 1.6{+-}0.2 vs 2.0{+-}0.4, p>0.05). In conclusion, left ventricular hypertrophy with or without abnormal wall motion and severely reduced MIBG uptake may be characteristic in diabetic patients with a mutation in the mitochondrial tRNA {sup Leu(UUR)} gene. (author)

  8. [P1208fs mutation in the cardiac myosin binding protein C is associated with hypertrophic cardiomyopathy in a Chinese pedigree].

    Science.gov (United States)

    Li, J; Liu, L W; Na, L S; Zuo, L; Qi, W; Liu, Y; Shao, H; Ma, Z L; Wang, L F

    2016-04-24

    To identify the potential mutations in a Chinese pedigree with hypertrophic cardiomyopathy (HCM), and to analyze the genotype-phenotype relationship in this pedigree. Clinical history and physical examinations, electrocardiography (ECG), echocardiography (UCG), cardiac magnetic resonance (CMR) data were obtained from 10 members of a three-generation Chinese family with HCM. A total of 96 genes related to hereditary cardiomyopathy were detected by exon and boarding intron analyses in the proband using second-generation sequencing. Mutations identified in the proband were confirmed by bi-directional Sanger sequencing in the rest 9 family members and 300 healthy controls. Three mutations, including MYBPC3-P1208fs, ANK2-H556R and ANK2-P1974H, were identified in this pedigree. MYBPC3-P1208fs gene mutation was detected in 3 family members (proband, his mother and son), while this mutation was not detected in the rest family members. HCM was diagnosed in the proband and his mother by ECG, UCG and CMR. Son of the proband demonstrated early phenotype of HCM: although UCG and CMR were normal, ECG showed sinus bradycardia and paroxysmal supraventricular arrhythmias as well as ST segment changes. The onset age of HCM diagnosis of the proband and his mother was 42 and 50 years old, presented with palpitation and chest pain, and myocardial fibrosis sign in CMR. Furthermore, we found that left ventricular myocardial fibrosis is related to ECG changes (increasing r wave, ST segment change) in the proband and his mother. No HCM phenotype was evidenced in the 7 family members carrying ANK2-H556R and ANK2-P1974H mutations. Our results show that MYBPC3-P1208fs gene mutation is associated HCM phenotype in this Chinses pedigree. This mutation is associated with myocardial fibrosis and ST changes in HCM phenotype in this pedigree while ANK2-H556R and ANK2-P1974H mutations are not related to HCM phenotype in this family.

  9. Calmodulin is essential for cardiac IKS channel gating and assembly: impaired function in long-QT mutations

    DEFF Research Database (Denmark)

    Shamgar, Liora; Ma, Lijuan; Schmitt, Nicole;

    2006-01-01

    The slow IKS K+ channel plays a major role in repolarizing the cardiac action potential and consists of the assembly of KCNQ1 and KCNE1 subunits. Mutations in either KCNQ1 or KCNE1 genes produce the long-QT syndrome, a life-threatening ventricular arrhythmia. Here, we show that long-QT mutations...... located in the KCNQ1 C terminus impair calmodulin (CaM) binding, which affects both channel gating and assembly. The mutations produce a voltage-dependent macroscopic inactivation and dramatically alter channel assembly. KCNE1 forms a ternary complex with wild-type KCNQ1 and Ca(2+)-CaM that prevents...... the risk of ventricular arrhythmias. Udgivelsesdato: 2006-Apr-28...

  10. Prevalence of Positive Troponin and Echocardiogram Findings and Association With Mortality in Acute Ischemic Stroke.

    Science.gov (United States)

    Wrigley, Peter; Khoury, Jane; Eckerle, Bryan; Alwell, Kathleen; Moomaw, Charles J; Woo, Daniel; Flaherty, Mathew L; De Los Rios la Rosa, Felipe; Mackey, Jason; Adeoye, Opeolu; Martini, Sharyl; Ferioli, Simona; Kissela, Brett M; Kleindorfer, Dawn O

    2017-05-01

    Acute ischemic stroke (AIS) patients may have raised serum cardiac troponin levels on admission, although it is unclear what prognostic implications this has, and whether elevated levels are associated with cardiac causes of stroke or structural cardiac disease as seen on echocardiogram. We investigated the positivity of cardiac troponin and echocardiogram testing within a large biracial AIS population and any association with poststroke mortality. Within a catchment area of 1.3 million, we screened emergency department admissions from 2010 using International Classification of Diseases, Ninth Edition, discharge codes 430 to 436 and ascertained all physician-confirmed AIS cases by retrospective chart review. Hypertroponinemia was defined as elevation in cardiac troponin above the standard 99th percentile. Multiple logistic regression was performed, controlling for stroke severity, history of cardiac disease, and all other stroke risk factors. Of 1999 AIS cases, 1706 (85.3%) had a cardiac troponin drawn and 1590 (79.5%) had echocardiograms. Hypertroponinemia occurred in 353 of 1706 (20.7%) and 160 of 1590 (10.1%) had echocardiogram findings of interest. Among 1377 who had both tests performed, hypertroponinemia was independently associated with echocardiogram findings (odds ratio, 2.9; 95% confidence interval, 2-4.2). When concurrent myocardial infarctions (3.5%) were excluded, hypertroponinemia was also associated with increased mortality at 1 year (35%; odds ratio, 3.45; 95% confidence interval, 2.1-5.6) and 3 years (60%; odds ratio, 2.91; 95% confidence interval, 2.06-4.11). Hypertroponinemia in the context of AIS without concurrent myocardial infarction was associated with structural cardiac disease and long-term mortality. Prospective studies are needed to determine whether further cardiac evaluation might improve the long-term mortality rates seen in this group. © 2017 American Heart Association, Inc.

  11. Comprehensive clinical evaluation of a large Spanish family with Anderson-Fabry disease, novel GLA mutation and severe cardiac phenotype.

    Science.gov (United States)

    San Román-Monserrat, Irene; Moreno-Flores, Victoria; López-Cuenca, David; Rodríguez-González-Herrero, Elena; Guillén-Navarro, Encarna; Rodríguez-González-Herrero, Beatriz; Alegría-Fernández, Marisol; Poza-Cisneros, Gabriela; Piñero-Fernández, Juan A; Sornichero-Martínez, Javier; Gimeno-Blanes, Juan R

    2014-06-06

    Fabry disease is an X-linked multisystemic lysosomal-storage condition. We describe a large family with a novel GLA mutation: p.M187R/g7219 T>G. Anamnesis/physical-exam, blood/urine analysis, α-Gal-A activity and/or genetic study of at-risk individuals and multidisciplinary evaluation in confirmed cases. 4 males and 13 heterozygous-females displayed the mutation. Cardiac/renal/neurological disease was diagnosed at a mean age of 41/29/39 years in males and 51/56/46 years in females. Onset mean age was 20 years versus 42 years. 9/15 had cardiomyopathy. Delta wave suggestive of accessory pathway was identified in 1 male and 2 females. 1 female had cardiac arrest (ventricular fibrillation, 61 years). 2 females and 1 male died suddenly (63, 64 and 57 years). Cardiac-subscore of Mainz Severity-Score-Index was severe for males and females over 40 years. 4/15(26%) developed early renal disease. 2 males needed dialysis. 1 male died at 69 years in spite of kidney-heart transplant. We describe the largest genetically confirmed Spanish family using multidisciplinary evaluation and MSSI calculation. The novel mutation p.M187R/g7219 T>G is associated with a particularly malignant cardiac phenotype in males and females over 40 years. Severity was higher than that of the largest Spanish FOS-cohort. Short-PR with delta is being reported for the first time. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  12. Elevated Troponin Level with Negative Outcome Was Found in Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Buse Hasırcı

    2013-01-01

    Full Text Available Background. Troponin increment is a highly sensitive and specific marker of myocardial necrosis. The reason of high troponin levels in acute stroke is not clear. The aim of this study was to identify the relationships between cardiac troponin-I (cTnI level and stroke. Methods. This study recruited 868 patients who were admitted to Istanbul Medeniyet University due to acute ischemic stroke, and the diagnosis was confirmed by diffusion magnetic resonance imaging. The patients with the causes increasing troponin level were excluded from the study. A total of 239 patients were finally included in the study. Clinics were evaluated by the modified Rankin Scale (mRS and the National Institutes of Health Stroke Scale (NIHSS. Results. Serum level of troponin was higher in ischemic stroke patients with anterior circulation involvement in comparison to posterior involvement or hemorrhagic stroke (. Higher troponin levels related to increased stroke scale scores at discharge in ischemic stroke (. The level of cTnI was correlated with stroke scale scores at both admission and discharge in posterior stroke patients (. Conclusion. cTnI is a highly specific and sensitive marker of myocardial damage, and its elevation was associated with more severe neurological deficits in acute ischemic stroke.

  13. [High-sensitivity troponin in patients with stable coronary artery disease].

    Science.gov (United States)

    van 't Hof, Arnoud W J

    2015-01-01

    With the introduction of more sensitive markers of myocardial necrosis, it was shown that the diagnosis of (acute) myocardial infarction could be improved. However, many patients without myocardial infarction have elevated troponin levels (low sensitivity), resulting in additional diagnostic testing and longer admission times to find the cause of the troponin rise. Elevated troponin levels in these patients were found to have limited diagnostic but strong prognostic value. This led to studies assessing the value of high-sensitivity troponin in patients with stable disease, e.g. coronary artery disease, or even in patients without apparent (clinical) disease. These studies consistently showed a strong association with long-term (cardiac) mortality. What is the value for the general physician in daily practice? Although troponin levels may help in finding (healthy?) patients at higher risk, it remains unclear whether interventions (medication, lifestyle) are more (cost-)effective in this high-risk subgroup. The role of troponin levels as a prognostic marker in stable patients therefore remains to be determined.

  14. Heart-specific expression of laminopathic mutations in transgenic zebrafish.

    Science.gov (United States)

    Verma, Ajay D; Parnaik, Veena K

    2017-07-01

    Lamins are key determinants of nuclear organization and function in the metazoan nucleus. Mutations in human lamin A cause a spectrum of genetic diseases that affect cardiac muscle and skeletal muscle as well as other tissues. A few laminopathies have been modeled using the mouse. As zebrafish is a well established model for the study of cardiac development and disease, we have investigated the effects of heart-specific lamin A mutations in transgenic zebrafish. We have developed transgenic lines of zebrafish expressing conserved lamin A mutations that cause cardiac dysfunction in humans. Expression of zlamin A mutations Q291P and M368K in the heart was driven by the zebrafish cardiac troponin T2 promoter. Homozygous mutant embryos displayed nuclear abnormalities in cardiomyocyte nuclei. Expression analysis showed the upregulation of genes involved in heart regeneration in transgenic mutant embryos and a cell proliferation marker was increased in adult heart tissue. At the physiological level, there was deviation of up to 20% from normal heart rate in transgenic embryos expressing mutant lamins. Adult homozygous zebrafish were fertile and did not show signs of early mortality. Our results suggest that transgenic zebrafish models of heart-specific laminopathies show cardiac regeneration and moderate deviations in heart rate during embryonic development. © 2017 International Federation for Cell Biology.

  15. A series of West European patients with severe cardiac and skeletal myopathy associated with a de novo R406W mutation in desmin.

    Science.gov (United States)

    Dagvadorj, Ayush; Olivé, Montse; Urtizberea, Jean-Andoni; Halle, Martin; Shatunov, Alexey; Bönnemann, Carsten; Park, Kye-Yoon; Goebel, Hans H; Ferrer, Isidro; Vicart, Patrick; Dalakas, Marinos C; Goldfarb, Lev G

    2004-02-01

    Desminopathy is a familial or sporadic cardiac and skeletal muscular dystrophy associated with mutations in desmin. We have previously characterized a de novo desmin R406W mutation in a patient of European origin with early onset muscle weakness in the lower extremities and atrioventricular conduction block requiring a permanent pacemaker. The disease relentlessly progressed resulting in severe incapacity within 5 years after onset. We have now identified three other patients with early onset rapidly progressive cardiac and skeletal myopathy caused by this same desmin R406W mutation. The mutation was present in each studied patient, but not in their parents or other unaffected family members, indicating that the mutation in all four cases was generated de novo. The patients' mutation-carrying chromosomes showed no similarity, suggesting that the R406W mutation has occurred independently. These observations strongly confirm that the de novo R406W desmin mutation is the genetic basis for early-onset cardiac and skeletal myopathy in patients with sporadic disease and indicate that desmin position 406 is a hot spot for spontaneous mutations. The high pathogenic potential of this mutation can be explained by its location in the highly conserved YRKLLEGEE motif at the C-terminal end of the 2B helix that has a critical role in the process of desmin filament assembly.

  16. High-sensitive Troponin T assay for the diagnosis of acute myocardial infarction: An economic evaluation

    NARCIS (Netherlands)

    A. Vaidya (Anil); J.L. Severens (Hans); B.W.C. Bongaerts (Brenda); C.B.J.M. Cleutjens (Kitty); P. Nelemans (Patricia); L. Hofstra (Leo); M.P. van Dieijen-Visser (Marja); E.A.L. Biessen (Erik)

    2014-01-01

    markdownabstract__Abstract__ Background: Delayed diagnosis and treatment of Acute Myocardial Infarction (AMI) has a major adverse impact on prognosis in terms of both morbidity and mortality. Since conventional cardiac Troponin assays have a low sensitivity for diagnosing AMI in the first hours

  17. High-sensitive Troponin T assay for the diagnosis of acute myocardial infarction: An economic evaluation

    NARCIS (Netherlands)

    A. Vaidya (Anil); J.L. Severens (Hans); B.W.C. Bongaerts (Brenda); C.B.J.M. Cleutjens (Kitty); P. Nelemans (Patricia); L. Hofstra (Leo); M.P. van Dieijen-Visser (Marja); E.A.L. Biessen (Erik)

    2014-01-01

    markdownabstract__Abstract__ Background: Delayed diagnosis and treatment of Acute Myocardial Infarction (AMI) has a major adverse impact on prognosis in terms of both morbidity and mortality. Since conventional cardiac Troponin assays have a low sensitivity for diagnosing AMI in the first hours aft

  18. Detected troponin elevation is associated with high early mortality after lung resection for cancer

    Directory of Open Access Journals (Sweden)

    Van Tornout Fillip

    2006-10-01

    Full Text Available Abstract Background Myocardial infarction can be difficult to diagnose after lung surgery. As recent diagnostic criteria emphasize serum cardiac markers (in particular serum troponin we set out to evaluate its clinical utility and to establish the long term prognostic impact of detected abnormal postoperative troponin levels after lung resection. Methods We studied a historic cohort of patients with primary lung cancer who underwent intended surgical resection. Patients were grouped according to known postoperative troponin status and survival calculated by Kaplan Meier method and compared using log rank. Parametric survival analysis was used to ascertain independent predictors of mortality. Results From 2001 to 2004, a total of 207 patients underwent lung resection for primary lung cancer of which 14 (7% were identified with elevated serum troponin levels within 30 days of surgery, with 9 (64% having classical features of myocardial infarction. The median time to follow up (interquartile range was 22 (1 to 52 months, and the one and five year survival probabilities (95% CI for patients without and with postoperative troponin elevation were 92% (85 to 96 versus 60% (31 to 80 and 61% (51 to 71 versus 18% (3 to 43 respectively (p T stage and postoperative troponin elevation remained independent predictors of mortality in the final multivariable model. The acceleration factor for death of elevated serum troponin after adjusting for tumour stage was 9.19 (95% CI 3.75 to 22.54. Conclusion Patients with detected serum troponin elevation are at high risk of early mortality with or without symptoms of myocardial infarction after lung resection.

  19. Familial Hypertrophic Cardiomyopathy and Troponin T%家族性肥厚型心肌病与肌钙蛋白T

    Institute of Scientific and Technical Information of China (English)

    徐潮; 宋怀东

    2009-01-01

    家族性肥厚型心肌病(familial hypertrophic cardiomyopathy,FHCM)是一种常染色体显性遗传病,是由编码心肌蛋白的基因突变引起,目前已识别出至少13个不同致病基因的200余种突变.目前,阐明FHCM的分子遗传学机制已经成为当前研究的热点之一.肌钙蛋白T通过与原肌凝蛋白结合,在将肌钙蛋白复合体锚钉到细肌丝上起重要作用.肌钙蛋白T(cardiac troponin T,TNNT2)基因突变是导致家族性肥厚型心肌病的主要原因,至今已经发现了大约30个突变,约占所有突变的15%~20%.肌钙蛋白T基因突变所致FHCM有两个主要特征:①心肌肥厚程度较轻,疾病外显率差别较大;②猝死率高.目前所发现的致FHCM突变,主要集中在肌钙蛋白T的T1和T2结构域.对肌钙蛋白T突变致FHCM分子机制的研究将有助于肥厚型心肌病的基因诊断和临床治疗.%Familial hypertrophic cardiomyopathy (FHCM) is an autosomal dominant disorder.More than 200 mutations for thirteen genes are ilnvolved in FHCM,which result from all encoding components of the contractile apparatus of the cardiac myocyte.Troponin T (TnT) is one of the three subunits that form troponin complex which is responsible for the regulation of striated muscle contraction together with tropomyosin.In fact,the TNNT2 gene is the third most common gene responsible for familial hypertrophic cardiomyopathy,accounting for approximately 15%~20% of all cases.The mutations in cardiac tmponin T gene appear to be associated with incomplete penetrance and poor prognosis of the family hypertrophic cardiomyopathy.TNNT2 mutations are clustered in its two domains.The study on the molecular mechanism for hypertrophic cardiomyopathy caused by TnT can lead to improved genetic counseling and better clinical management in families with HCM.

  20. A novel mutation in lamin a/c causing familial dilated cardiomyopathy associated with sudden cardiac death.

    Science.gov (United States)

    Pérez-Serra, Alexandra; Toro, Rocío; Campuzano, Oscar; Sarquella-Brugada, Georgia; Berne, Paola; Iglesias, Anna; Mangas, Alipio; Brugada, Josep; Brugada, Ramon

    2015-03-01

    Dilated cardiomyopathy (DCM), a cardiac heterogeneous pathology characterized by left ventricular or biventricular dilatation, is a leading cause of heart failure and heart transplantation. The genetic origin of DCM remains unknown in most cases, but >50 genes have been associated with DCM. We sought to identify the genetic implication and perform a genetic analysis in a Spanish family affected by DCM and sudden cardiac death. Clinical assessment and genetic screening were performed in the index case as well as family members. Of all relatives clinically assessed, nine patients showed clinical symptoms related to the pathology. Genetic screening identified 20 family members who carried a novel mutation in LMNA (c.871 G>A, p.E291K). Family segregation analysis indicated that all clinically affected patients carried this novel mutation. Clinical assessment of genetic carriers showed that electrical dysfunction was present previous to mechanical and structural abnormalities. Our results report a novel pathogenic mutation associated with DCM, supporting the benefits of comprehensive genetic studies of families affected by this pathology. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. New mutation of the desmin gene identified in an extended Indian pedigree presenting with distal myopathy and cardiac disease

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    Atchayaram Nalini

    2013-01-01

    Full Text Available In this report, we describe a new mutation located in the coiled 1B domain of desmin and associated with a predominant cardiac involvement and a high degree of cardiac sudden death in a large Indian pedigree with 12 affected members. The index cases was 38-year-old man who presented with progressive difficulty in gripping footwear of 5 years duration with the onset in the left lower limb followed by right lower limb in 6 months. 3 years from onset, he developed lower limb proximal and truncal muscle weakness. There was mild atrophy of the shoulder girdle muscles with grade 3 weakness, moderate wasting of thigh and anterior leg muscles with proximal muscle weakness and foot drop. At 40 years, he had a pacemaker implanted. The 9 exons and intronic boundaries of the desmin gene were sequenced and a heterozygous nucleotide change c. 734A > G in exon 3 was identified.

  2. Two rare human mitofusin 2 mutations alter mitochondrial dynamics and induce retinal and cardiac pathology in Drosophila.

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    William H Eschenbacher

    Full Text Available Mitochondrial fusion is essential to organelle homeostasis and organ health. Inexplicably, loss of function mutations of mitofusin 2 (Mfn2 specifically affect neurological tissue, causing Charcot Marie Tooth syndrome (CMT and atypical optic atrophy. As CMT-linked Mfn2 mutations are predominantly within the GTPase domain, we postulated that Mfn2 mutations in other functional domains might affect non-neurological tissues. Here, we defined in vitro and in vivo consequences of rare human mutations in the poorly characterized Mfn2 HR1 domain. Human exome sequencing data identified 4 rare non-synonymous Mfn2 HR1 domain mutations, two bioinformatically predicted as damaging. Recombinant expression of these (Mfn2 M393I and R400Q in Mfn2-null murine embryonic fibroblasts (MEFs revealed incomplete rescue of characteristic mitochondrial fragmentation, compared to wild-type human Mfn2 (hMfn2; Mfn2 400Q uniquely induced mitochondrial fragmentation in normal MEFs. To compare Mfn2 mutation effects in neurological and non-neurological tissues in vivo, hMfn2 and the two mutants were expressed in Drosophila eyes or heart tubes made deficient in endogenous fly mitofusin (dMfn through organ-specific RNAi expression. The two mutants induced similar Drosophila eye phenotypes: small eyes and an inability to rescue the eye pathology induced by suppression of dMfn. In contrast, Mfn2 400Q induced more severe cardiomyocyte mitochondrial fragmentation and cardiac phenotypes than Mfn2 393I, including heart tube dilation, depressed fractional shortening, and progressively impaired negative geotaxis. These data reveal a central functional role for Mfn2 HR1 domains, describe organ-specific effects of two Mfn2 HR1 mutations, and strongly support prospective studies of Mfn2 400Q in heritable human heart disease of unknown genetic etiology.

  3. Recurrent Muscle Weakness with Rhabdomyolysis, Metabolic Crises, and Cardiac Arrhythmia Due to Bi-allelic TANGO2 Mutations.

    Science.gov (United States)

    Lalani, Seema R; Liu, Pengfei; Rosenfeld, Jill A; Watkin, Levi B; Chiang, Theodore; Leduc, Magalie S; Zhu, Wenmiao; Ding, Yan; Pan, Shujuan; Vetrini, Francesco; Miyake, Christina Y; Shinawi, Marwan; Gambin, Tomasz; Eldomery, Mohammad K; Akdemir, Zeynep Hande Coban; Emrick, Lisa; Wilnai, Yael; Schelley, Susan; Koenig, Mary Kay; Memon, Nada; Farach, Laura S; Coe, Bradley P; Azamian, Mahshid; Hernandez, Patricia; Zapata, Gladys; Jhangiani, Shalini N; Muzny, Donna M; Lotze, Timothy; Clark, Gary; Wilfong, Angus; Northrup, Hope; Adesina, Adekunle; Bacino, Carlos A; Scaglia, Fernando; Bonnen, Penelope E; Crosson, Jane; Duis, Jessica; Maegawa, Gustavo H B; Coman, David; Inwood, Anita; McGill, Jim; Boerwinkle, Eric; Graham, Brett; Beaudet, Art; Eng, Christine M; Hanchard, Neil A; Xia, Fan; Orange, Jordan S; Gibbs, Richard A; Lupski, James R; Yang, Yaping

    2016-02-01

    The underlying genetic etiology of rhabdomyolysis remains elusive in a significant fraction of individuals presenting with recurrent metabolic crises and muscle weakness. Using exome sequencing, we identified bi-allelic mutations in TANGO2 encoding transport and Golgi organization 2 homolog (Drosophila) in 12 subjects with episodic rhabdomyolysis, hypoglycemia, hyperammonemia, and susceptibility to life-threatening cardiac tachyarrhythmias. A recurrent homozygous c.460G>A (p.Gly154Arg) mutation was found in four unrelated individuals of Hispanic/Latino origin, and a homozygous ∼34 kb deletion affecting exons 3-9 was observed in two families of European ancestry. One individual of mixed Hispanic/European descent was found to be compound heterozygous for c.460G>A (p.Gly154Arg) and the deletion of exons 3-9. Additionally, a homozygous exons 4-6 deletion was identified in a consanguineous Middle Eastern Arab family. No homozygotes have been reported for these changes in control databases. Fibroblasts derived from a subject with the recurrent c.460G>A (p.Gly154Arg) mutation showed evidence of increased endoplasmic reticulum stress and a reduction in Golgi volume density in comparison to control. Our results show that the c.460G>A (p.Gly154Arg) mutation and the exons 3-9 heterozygous deletion in TANGO2 are recurrent pathogenic alleles present in the Latino/Hispanic and European populations, respectively, causing considerable morbidity in the homozygotes in these populations.

  4. [Mutation screening for the causative gene in a four-generation Chinese pedigree with progressive cardiac conduction defect].

    Science.gov (United States)

    Tan, X J; Huang, H; He, F; Zhu, L; Li, H; Jiang, Y S; Li, H; Huang, X H; Sun, Z S; Li, Z H

    2016-05-24

    To define the potential causative gene mutation in a Chinese pedigree with progressive cardiac conduction defect (PCCD). Sanger sequencing was performed to define potential causative gene mutation in a four-generation family with 68 members including seven PCCD patients (5 male) from 2010 to 2015.No causative gene was detected by screening known candidate genes related to PCCD including SCN5A, NKX2.5 and LMNA.High-throughput sequencing technology on exon-enriched DNA was then used to search the causative genes in 2 patients and one normal family member. Eight new non-synonymous single nucleotide variants including AQP7 gene (exon5: c.T343C: p.Y115H), CACNA1B gene (NM_001243812: exon19: c.A2986G: p.T996A), CATSPERB gene (exon27: c.C3254G: p.P1085R), CLCA2 gene (exon11: c.G1725T: p.W575C), CLCA3P gene (ncRNA_intronic), MYLK-AS1 gene (ncRNA_intronic), TTN gene (ncRNA_UTR3), LMNA gene (LMNA: NM_170708: exon5: c.C922T: p.Q308X) were identified by comparing and filtering the results with known public databases.Then, more detailed biological analysis on these 8 genes was conducted.Traditional Sanger sequencing validated the exome sequencing results, and found that the mutation c. 1725G﹥T in gene CLCA2 segregated with the phenotype of this PCCD pedigree.The mutation c. 1725G﹥T in gene CLCA2 was thus be considered as the causative PCCD gene in this pedigree from the perspective of genetics and genomics. The heterozygote mutation c. 1725G﹥T in gene CLCA2 might be causative gene in this PCCD pedigree.This finding adds new gene mutation variant responsible for PCCD.

  5. PKCα-specific phosphorylation of the troponin complex in human myocardium: a functional and proteomics analysis.

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    Viola Kooij

    Full Text Available Protein kinase Cα (PKCα is one of the predominant PKC isoforms that phosphorylate cardiac troponin. PKCα is implicated in heart failure and serves as a potential therapeutic target, however, the exact consequences for contractile function in human myocardium are unclear. This study aimed to investigate the effects of PKCα phosphorylation of cardiac troponin (cTn on myofilament function in human failing cardiomyocytes and to resolve the potential targets involved.Endogenous cTn from permeabilized cardiomyocytes from patients with end-stage idiopathic dilated cardiomyopathy was exchanged (∼69% with PKCα-treated recombinant human cTn (cTn (DD+PKCα. This complex has Ser23/24 on cTnI mutated into aspartic acids (D to rule out in vitro cross-phosphorylation of the PKA sites by PKCα. Isometric force was measured at various [Ca(2+] after exchange. The maximal force (Fmax in the cTn (DD+PKCα group (17.1±1.9 kN/m(2 was significantly reduced compared to the cTn (DD group (26.1±1.9 kN/m(2. Exchange of endogenous cTn with cTn (DD+PKCα increased Ca(2+-sensitivity of force (pCa50 = 5.59±0.02 compared to cTn (DD (pCa50 = 5.51±0.02. In contrast, subsequent PKCα treatment of the cells exchanged with cTn (DD+PKCα reduced pCa50 to 5.45±0.02. Two PKCα-phosphorylated residues were identified with mass spectrometry: Ser198 on cTnI and Ser179 on cTnT, although phosphorylation of Ser198 is very low. Using mass spectrometry based-multiple reaction monitoring, the extent of phosphorylation of the cTnI sites was quantified before and after treatment with PKCα and showed the highest phosphorylation increase on Thr143.PKCα-mediated phosphorylation of the cTn complex decreases Fmax and increases myofilament Ca(2+-sensitivity, while subsequent treatment with PKCα in situ decreased myofilament Ca(2+-sensitivity. The known PKC sites as well as two sites which have not been previously linked to PKCα are phosphorylated in human cTn complex treated

  6. Value of detection of myocardial enzymes, troponin T, liver and renal function in children with severe pneumonia

    Institute of Scientific and Technical Information of China (English)

    Zhen Wang; Bin Wang; Lin Fu; Xue Ren

    2016-01-01

    Objective:To analyze the significance of myocardial enzymes, cardiac troponin T (Troponin T, cTnT), liver and renal function in children with severe pneumonia. Methods:A total of 164 children with pneumonia who were admitted in our hospital from March, 2014 to March, 2015 were included in the study and divided into the severe pneumonia group (n=82) and the common pneumonia group (n=82). The myocardial enzymes (AST,α-HBDH, LD, CK-MB), troponin T, and liver and renal function indicators (UCr, Alb, ALT) in the two groups were observed and compared. According to the arterial partial pressure of oxygen, the children with severe pneumonia were divided into the varying degrees of hypoxia groups, i.e. mild hypoxia group, moderate hypoxia group, and severe hypoxia group. The myocardial enzymes, troponin T, and liver and renal function in the three groups were compared. The correlation of partial pressure of blood oxygen with myocardial enzymes, troponin T, and liver and renal function was analyzed. Results:In the severe pneumonia group, the myocardial enzymes AST, LD, CK, HBDH, CK-MB was significantly higher than that in the ordinary pneumonia group;UCr, Alb ALT troponin T was significantly higher than that in the ordinary pneumonia group;With the increasing hypoxia degree, the levels of myocardial enzymes, troponin T, and liver and renal function indicators in the mild hypoxia group, moderate hypoxia group, and severe hypoxia group were elevated. In the severe pneumonia group, the partial pressure of blood oxygen was negatively correlated with myocardial enzymes, troponin T, and liver and renal function. Conclusions:Timely monitoring of the levels of myocardial enzymes, troponin T, and liver and renal function indicators in the clinic is extremely crucial to evaluate the progression in children with severe pneumonia.

  7. Conformation of the troponin core complex in the thin filaments of skeletal muscle during relaxation and active contraction.

    Science.gov (United States)

    Knowles, Andrea C; Irving, Malcolm; Sun, Yin-Biao

    2012-08-03

    Contraction of skeletal and cardiac muscles is regulated by Ca(2+) binding to troponin in the actin-containing thin filaments, leading to an azimuthal movement of tropomyosin around the filament that uncovers the myosin binding sites on actin. Here, we use polarized fluorescence to determine the orientation of the C-terminal lobe of troponin C (TnC) in skeletal muscle cells as a step toward elucidating the molecular mechanism of troponin-mediated regulation. Assuming, as shown by X-ray crystallography, that this lobe of TnC is part of a well-defined troponin domain called the IT arm, we show that the coiled coil formed by troponin components I and T makes an angle of about 55° with the thin filament axis in relaxed muscle, in contrast with previous models based on electron microscopy in which this angle is close to 0°. The E helix of TnC makes an angle of about 45° with the thin filament axis. Both the IT coiled coil and the TnC E helix tilt by about 10° on muscle activation. By combining in situ measurements of the orientation of the IT arm and regulatory domain of troponin, which together form the troponin core complex, with published intermolecular distances between thin filament components, we derive models of thin filament structure in which the IT arm of troponin holds its regulatory domain close to the actin surface. Although the structure and function of troponin regions outside the core complex remain to be characterized, the present results provide useful constraints for molecular models of the mechanism of muscle regulation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Troponin elevations after electroconvulsive therapy: the need for caution.

    Science.gov (United States)

    Martinez, Matthew W; Rasmussen, Keith G; Mueller, Paul S; Jaffe, Allan S

    2011-03-01

    Electroconvulsive therapy is used to treat patients with severe or resistant depression. Troponin elevations are associated with an adverse prognosis, and it is well known that central nervous system insults can cause biochemical evidence of cardiac injury. No study previously has studied this with electroconvulsive therapy. Patients scheduled for electroconvulsive therapy were enrolled. Clinical information, an electrocardiogram, and a baseline sample for cardiac troponin I and T (cTnI and cTnT) were obtained. Electroconvulsive therapy was done with standard techniques. Subsequently, electrocardiograms and additional samples were obtained. cTnT was measured with the Roche assay and cTnI with the Dade Stratus equipment. Values above the 99th percentile were considered abnormal. Seventy patients completed the study. Four patients had elevated levels of cTn before treatment. In 3 patients, the elevations persisted. Four additional patients developed elevated cTn levels during electroconvulsive therapy. Two of the patients with cTn elevations died. No other events occurred during follow-up. Elevations of cTn occurred in 11.5% of patients treated with electroconvulsive therapy. Some of the elevations preceded therapy and some occurred during treatment. Given the adverse prognostic importance of cTn elevations in general, in addition to additional studies, an increased degree of medical scrutiny may be appropriate for this group of patients and for those receiving electroconvulsive therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. 快速检测心肌肌钙蛋白T在急性心肌梗死诊断中的临床应用%Clinical application of rapid determination of cardiac troponin T in diagnosis of acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    李晓冬

    2016-01-01

    Objective To investigate the value of rapid determination of cardiac troponin T (cTnT) in the diagnosis of acute myocardial infarction. Methods A total of 110 patients with acute myocardial infarction were selected, and cTnT and serum myocardial enzyme were determined. Results There were no significant differences in positive rate, sensitivity, specificity, and positive predictive value between cTnT and serum myocardial enzyme (P>0.05);determination of cTnT combined with serum myocardial enzyme had a significantly higher positive rate than electrocardiography (P0.05);cTnT联合心肌酶检测阳性率检出显著高于心电图检查(P<0.05). 结论 快速检测cTnT可及时诊断急性心肌梗死,该方法具有准确度好、灵敏度高等优点,联合心电图进行检测能够有效提高急性心肌梗死诊断率,值得在临床中推广应用.

  10. Study of Plasma Malondialdehyde, Troponin I and C - Reactive protein in Acute Coronary Syndromes Patients

    Directory of Open Access Journals (Sweden)

    S. Shams

    2006-04-01

    Full Text Available Introduction & Objective: Ischemic injury of endothelium is associated with prostaglandin synthesis and platelet adhesion and aggregation, which may be associated with the release of aldehydes such as malondialdehyde (MDA. C-reactive protein and cardiac troponin I have been proposed as diagnostic markers of acute coronary syndromes. In this study, we compared the usefulness of plasma MDA as a marker of acute coronary syndromes with that of C-reactive protein and troponin I.Material & Methods: The study population contained 50 patients with unstable angina and 50 patients with acute myocardial infarction admitted to the hearth department of the Ekbatan Hospital of Hamadan. The subjects were matched according to age and sex. Total cholesterol, LDL and HDL cholesterol, triglycerides, plasma MDA, troponin I and C-reactive protein levels were determined in all patients. Results: Results showed that the plasma MDA levels were significantly higher in patients with acute myocardial infarction than in individuals with unstable angina (P<0.001 and were associated with increased levels of troponin I and C-reactive protein (P<0.001.Conclusion: The combination of the plasma MDA levels, which reflect endothelial injury, and troponin I and C-reactive protein levels may allow better discrimination in acute coronary syndromes patients.

  11. Dosagem única de troponina cardíaca T prediz risco adverso na insuficiência cardíaca descompensada Dosificación única de troponina cardíaca T predice riesgo adverso en la insuficiencia cardiaca descompensada Single cardiac troponin T measurement predicts risk for adverse outcome in decompensated heart failure

    Directory of Open Access Journals (Sweden)

    Manoel D. C. Oliveira

    2010-04-01

    Full Text Available FUNDAMENTO: O aumento discreto de troponina cardíaca no sangue de pacientes com insuficiência cardíaca (IC sugere que miofibrilas são degradadas no miocárdio e liberadas na circulação, refletindo um processo contínuo e progressivo de lesão do aparato contrátil. OBJETIVO: Correlacionar o nível sérico da troponina cardíaca-T (TnTc à admissão hospitalar de pacientes com IC descompensada e o prognóstico. MÉTODOS: Foram incluídos 79 pacientes consecutivos, internados por IC descompensada, com FEVE 2,5 mg%, insuficiência hepática ou doenças neuromusculares. RESULTADOS: Detectou-se TnTc elevada (>0,02 ng/ml em 37 pacientes (46,84%. A mortalidade global foi de 35,4%. Nos grupos TnTc elevada e TnTc baixa (FUNDAMENTO: El aumento discreto de troponina cardíaca en la sangre de pacientes con insuficiencia cardiaca (IC sugiere que miofibrillas se degraden en el miocardio y se liberen en la circulación, lo que refleja un proceso continuo y progresivo de lesión del aparato contráctil. OBJETIVO: Correlacionar el nivel sérico de la troponina cardíaca-T (TnTc al ingreso hospitalario de pacientes con IC descompensada y el pronóstico. MÉTODOS: Se incluyó a 79 pacientes consecutivos, internados por IC descompensada, con FEVI 2,5 mg%, insuficiencia hepática o enfermedades neuromusculares. RESULTADOS: Se detectó TnTc elevada (> 0,02 ng/ml en 37 pacientes (46,84%. La mortalidad global fue del 35,4%. En los grupos TnTc elevada y TnTc baja (BACKGROUND: The slight increase in cardiac troponin in the blood of patients with heart failure (HF suggests that myofibrils are degraded in the myocardium and released in the circulation, reflecting a continuous and progressive injury process in the contractile system. OBJECTIVE: To correlate the serum levels of cardiac troponin T (TnT at the hospital admission of patients with decompensated HF and prognosis. METHODS: A total of 79 consecutive patients, hospitalized due to decompensated HF, with LVEF 2

  12. Predicting Effects of Tropomyosin Mutations on Cardiac Muscle Contraction through Myofilament Modeling

    Directory of Open Access Journals (Sweden)

    Lorenzo Rakesh Sewanan

    2016-10-01

    Full Text Available Point mutations to the human gene TPM1 have been implicated in the development of both hypertrophic and dilated cardiomyopathies. Such observations have led to studies investigating the link between single residue changes and the biophysical behavior of the tropomyosin molecule. However, the degree to which these molecular perturbations explain the performance of intact sarcomeres containing mutant tropomyosin remains uncertain. Here, we present a modeling approach that integrates various aspects of tropomyosin’s molecular properties into a cohesive paradigm representing their impact on muscle function. In particular, we considered the effects of tropomyosin mutations on (1 persistence length, (2 equilibrium between thin filament blocked and closed regulatory states, and (3 the crossbridge duty cycle. After demonstrating the ability of the new model to capture Ca-dependent myofilament responses during both dynamic and steady-state activation, we used it to capture the effects of hypertrophic cardiomyopathy (HCM related E180G and D175N mutations on skinned myofiber mechanics. Our analysis indicates that the fiber-level effects of the two mutations can be accurately described by a combination of changes to the three tropomyosin properties represented in the model. Subsequently, we used the model to predict mutation effects on muscle twitch. Both mutations led to increased twitch contractility as a consequence of diminished cooperative inhibition between thin filament regulatory units. Overall, simulations suggest that a common twitch phenotype for HCM-linked tropomyosin mutations includes both increased contractility and elevated diastolic tension.

  13. Gambaran Kadar Troponin T dan Creatinin Kinase Myocardial Band pada Infark Miokard Akut

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    Rendi Dwi Prasetyo

    2014-09-01

    Full Text Available AbstrakInfark Miokard Akut (IMA adalah kematian sel miokardium akibat terlepasnya plak aterosklerotik dari salah satu arteri koroner yang mencetuskan terjadinya agregasi trombosit, pembentukan trombus, dan spasme koroner. Diagnosis IMA dapat dilakukan dengan cara: anamnesis, abnormalitas Elektrokardiogram (EKG, peningkatan Creatinin Kinase Myocardial Band (CKMB, dan cardiac specific troponin (cTnT. Diagnosis IMA dapat ditegakkan jika terdapat minimal dua dari tiga kriteria yang harus dipenuhi, yaitu: anamnesis, abnormalitas EKG, dan peningkatan aktivitas enzim jantung. Tujuan penelitian ini adalah untuk mengetahui gambaran kadar troponin T dan CKMB pada pasien IMA di RS. Dr. M. Djamil Padang periode 1 Januari 2012 - 31 Desember 2012. Penelitian dilakukan secara retrospektif deskriptif terhadap 54 sampel rekam medik pasien IMA yang dirawat inap di bagian penyakit dalam dan jantung RS. Dr. M. Djamil Padang periode 1 Januari 2012 - 31 Desember 2012. Kadar troponin T diperiksa dengan metode chemiluminescent dan CKMB diperiksa dengan metode enzymatic immunoassay with serum start. Hasil penelitian ini menunjukkan umur terbanyak pasien IMA adalah 40-60 tahun berjumlah 30 orang (55,56%. Jenis kelamin terbanyak pasien IMA adalah laki-laki berjumlah 39 orang (72,22%. Pasien IMA yang memiliki kadar CKMB ≥24 U/L berjumlah 35 orang (64,82%. Pasien IMA yang memiliki kadar troponin T ≥0,1 ng/mL berjumlah 44 orang (81,48%. Didapatkan peningkatan kadar troponin T dan CKMB pada pasien IMA.Kata kunci: infark miokard akut, troponin t, CKMBAbstractAcute Myocardial Infarction (AMI is a muscle necrosis of the heart caused by rupture atherosclerotic plaque from one of coronary artery that cause platelet aggregation, thrombus formation, and coronary spasm. Diagnosis of AMI can be made by some way : anamnesis, electrocardiogram (ECG abnormalities, increase levels of creatinine kinase myocardial band (CKMB and cardiac specific troponin (cTnT. Diagnosis of AMI can be

  14. Clinical and functional characterization of a novel mutation in lamin a/c gene in a multigenerational family with arrhythmogenic cardiac laminopathy.

    Science.gov (United States)

    Forleo, Cinzia; Carmosino, Monica; Resta, Nicoletta; Rampazzo, Alessandra; Valecce, Rosanna; Sorrentino, Sandro; Iacoviello, Massimo; Pisani, Francesco; Procino, Giuseppe; Gerbino, Andrea; Scardapane, Arnaldo; Simone, Cristiano; Calore, Martina; Torretta, Silvia; Svelto, Maria; Favale, Stefano

    2015-01-01

    Mutations in the lamin A/C gene (LMNA) were associated with dilated cardiomyopathy (DCM) and, recently, were related to severe forms of arrhythmogenic right ventricular cardiomyopathy (ARVC). Both genetic and phenotypic overlap between DCM and ARVC was observed; molecular pathomechanisms leading to the cardiac phenotypes caused by LMNA mutations are not yet fully elucidated. This study involved a large Italian family, spanning 4 generations, with arrhythmogenic cardiomyopathy of different phenotypes, including ARVC, DCM, system conduction defects, ventricular arrhythmias, and sudden cardiac death. Mutation screening of LMNA and ARVC-related genes PKP2, DSP, DSG2, DSC2, JUP, and CTNNA3 was performed. We identified a novel heterozygous mutation (c.418_438dup) in LMNA gene exon 2, occurring in a highly conserved protein domain across several species. This newly identified variant was not found in 250 ethnically-matched control subjects. Genotype-phenotype correlation studies suggested a co-segregation of the LMNA mutation with the disease phenotype and an incomplete and age-related penetrance. Based on clinical, pedigree, and molecular genetic data, this mutation was considered likely disease-causing. To clarify its potential pathophysiologic impact, functional characterization of this LMNA mutant was performed in cultured cardiomyocytes expressing EGFP-tagged wild-type and mutated LMNA constructs, and indicated an increased nuclear envelope fragility, leading to stress-induced apoptosis as the main pathogenetic mechanism. This study further expands the role of the LMNA gene in the pathogenesis of cardiac laminopathies, suggesting that LMNA should be included in mutation screening of patients with suspected arrhythmogenic cardiomyopathy, particularly when they have ECG evidence for conduction defects. The combination of clinical, genetic, and functional data contribute insights into the pathogenesis of this form of life-threatening arrhythmogenic cardiac laminopathy.

  15. Clinical and functional characterization of a novel mutation in lamin a/c gene in a multigenerational family with arrhythmogenic cardiac laminopathy.

    Directory of Open Access Journals (Sweden)

    Cinzia Forleo

    Full Text Available Mutations in the lamin A/C gene (LMNA were associated with dilated cardiomyopathy (DCM and, recently, were related to severe forms of arrhythmogenic right ventricular cardiomyopathy (ARVC. Both genetic and phenotypic overlap between DCM and ARVC was observed; molecular pathomechanisms leading to the cardiac phenotypes caused by LMNA mutations are not yet fully elucidated. This study involved a large Italian family, spanning 4 generations, with arrhythmogenic cardiomyopathy of different phenotypes, including ARVC, DCM, system conduction defects, ventricular arrhythmias, and sudden cardiac death. Mutation screening of LMNA and ARVC-related genes PKP2, DSP, DSG2, DSC2, JUP, and CTNNA3 was performed. We identified a novel heterozygous mutation (c.418_438dup in LMNA gene exon 2, occurring in a highly conserved protein domain across several species. This newly identified variant was not found in 250 ethnically-matched control subjects. Genotype-phenotype correlation studies suggested a co-segregation of the LMNA mutation with the disease phenotype and an incomplete and age-related penetrance. Based on clinical, pedigree, and molecular genetic data, this mutation was considered likely disease-causing. To clarify its potential pathophysiologic impact, functional characterization of this LMNA mutant was performed in cultured cardiomyocytes expressing EGFP-tagged wild-type and mutated LMNA constructs, and indicated an increased nuclear envelope fragility, leading to stress-induced apoptosis as the main pathogenetic mechanism. This study further expands the role of the LMNA gene in the pathogenesis of cardiac laminopathies, suggesting that LMNA should be included in mutation screening of patients with suspected arrhythmogenic cardiomyopathy, particularly when they have ECG evidence for conduction defects. The combination of clinical, genetic, and functional data contribute insights into the pathogenesis of this form of life-threatening arrhythmogenic

  16. High prevalence of Arginine to Glutamine Substitution at 98, 141 and 162 positions in Troponin I (TNNI3 associated with hypertrophic cardiomyopathy among Indians

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    Rani Deepa

    2012-08-01

    Full Text Available Abstract Background Troponin I (TNNI3 is the inhibitory subunit of the thin filament regulatory complex Troponin, which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. Mutations (2-7% in this gene had been reported in hypertrophic cardiomyopathy patients (HCM. However, the frequencies of mutations and associated clinical presentation have not been established in cardiomyopathy patients of Indian origin, hence we have undertaken this study. Methods We have sequenced all the exons, including the exon-intron boundaries of TNNI3 gene in 101 hypertrophic cardiomyopathy patients (HCM, along with 160 healthy controls, inhabited in the same geographical region of southern India. Results Our study revealed a total of 16 mutations. Interestingly, we have observed Arginine to Glutamine (R to Q mutation at 3 positions 98, 141 and 162, exclusively in HCM patients with family history of sudden cardiac death. The novel R98Q was observed in a severe hypertrophic obstructive cardiomyopathy patient (HOCM. The R141Q mutation was observed in two familial cases of severe asymmetric septal hypertrophy (ASH++. The R162Q mutation was observed in a ASH++ patient with mean septal thickness of 29 mm, and have also consists of allelic heterogeneity by means of having one more synonymous (E179E mutation at g.4797: G → A: in the same exon 7, which replaces a very frequent codon (GAG: 85% with a rare codon (GAA: 14%. Screening for R162Q mutation in all the available family members revealed its presence in 9 individuals, including 7 with allelic heterogeneity (R162Q and E179E of which 4 were severely affected. We also found 2 novel SNPs, (g.2653; G → A and g.4003 C → T exclusively in HCM, and in silico analysis of these SNPs have predicted to cause defect in recognition/binding sites for proteins responsible for proper splicing. Conclusion Our study has provided valuable information regarding the prevalence of TNNI3 mutations in

  17. Phenotypical Manifestations of Mutations in the Genes Encoding Subunits of the Cardiac Sodium Channel

    NARCIS (Netherlands)

    Wilde, Arthur A. M.; Brugada, Ramon

    2011-01-01

    Variations in the gene encoding for the major sodium channel (Na(v)1.5) in the heart, SCN5A, has been shown to cause a number of arrhythmia syndromes (with or without structural changes in the myocardium), including the long-QT syndrome (type 3), Brugada syndrome, (progressive) cardiac conduction di

  18. 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 d

  19. 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

  20. [Should the patient with myocardial bridge be advised not to performe extreme sport effort? Case of a patient with troponin I elevation after exercise].

    Science.gov (United States)

    Jankowski, Krzysztof; Ożdżeńska-Milke, Ewa; Jankowski, Łukasz; Rzewuska, Ewa; Dul, Przemysław; Ilnicka, Edyta; Kobylecka, Małgorzata; Pruszczyk, Piotr

    2012-01-01

    Elevated levels of cardiac troponins are an established method of diagnosis of heart muscle necrosis. A case of a long distance amateur-marathon runner, who showed significant elevation of plasma troponin I after extreme physical effort is reported. The diagnostic examinations did not reveal atherosclerosis burden, but myocardial bridging of coronary artery. The authors describe the significance of the pathology in the view of extreme sport effort performed by the described patient.

  1. Prognostic assessment of elderly patients with symptoms of heart failure by combining high-sensitivity troponin T and N-terminal pro-B-type natriuretic peptide measurements

    DEFF Research Database (Denmark)

    Alehagen, Urban; Dahlström, Ulf; Rehfeld, Jens F.

    2010-01-01

    N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a useful biomarker in heart failure assessment, whereas measurement of cardiac troponin is central in the diagnosis of patients with acute coronary syndromes. This report examined the prognostic use of combining high-sensitivity cardiac...

  2. 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 ...

  3. The Role of Bedside Troponin T Test for Identification of High Risk Patients With Acute Chest Pain

    Institute of Scientific and Technical Information of China (English)

    Guo xiaobi; Feng Jianzhan; Guo Hengshan

    2005-01-01

    Objectives Evaluation of patients with acute chest pain when they admitted is time-consuming. We prospectively investigated the role of bedside troponin T test for predicting the risk of death and acute heart failure of patients with acute chest pain. Methods and Results 502 consecutive patients with chest pain for less than 24 hours were determined by troponin T test at bedside and quantitative troponin I test in lab. For bedside troponin T tests, there were 160 patients in positive and 323 in negative. During 30 days of followed-up. Myocardial infarction evolved in 139 patients among 160 patients in positive troponin T test, only 7 patients in negative one. Acute heart failure occurred in 51 patients among the positive group, but 37 occurred it at negative group.The odds ratio of acute heart failure of positive group vs.negative group was 3.6. Patients died 39 in positive group, 15 in negative group, the all-cause death odds ratio of positive group vs. negative group was 6.7; 31patients died with cardiac event in positive group, 5 in negative group only. Conclusions Bedside Troponin T test is a powerful and independent predictor of death and acute heart failure for patients with acute chest pain.

  4. Comparison of ARCHITECT chemiluminiscent microparticle immunoassay for determination of Troponin I in serum with AXYM MEIA technology

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    Nafija Serdarević

    2011-12-01

    Full Text Available Introduction: The aim of this study was determination of troponin I at serum using Architect (Abbott and AxSYM System (Abbott. Troponin is regulatory subunit of the troponin complex associate with actin filament within muscle cells and it is a marker for diagnosis of myocardial damage.Methods: We used Architect STAT chemiluminescent microparticle immunoassay (CMIA and AxSYM microparticle Enzyme Immunoassay (MEIA, techniques for quantitative determination of cardiac TnI in human serum or plasma. At our study we have proved precision, reproducibility and accuracy from both methods. The investigation included patients (n=119 who have myocardial infarction or ischemic heart damage and were treated at cardiology, emergency, internal medicine and neurology unit in Clinical Center University in Sarajevo.Results: The precision for three controls using Architect STAT TnI asssay technology were 3.6 – 5.2 % and reproducibility was 3.7 to 5.6 %. The AxSYM STAT TnI has precision for three controls 4.3–6.6 % and reproducibilitywas from 4.8 to 7.8 %. We have got very good correlation between Architect and AxSYM technology r = 0.999 in the investigation of troponin I in serum.Conclusions: We can conclude that chemiluminescent troponin assay I (Architect showed good analytical performance and gave new possibility at troponin I determination.

  5. Early cardiac involvement in children carrying the A3243G mtDNA mutation.

    NARCIS (Netherlands)

    Wortmann, S.B.; Rodenburg, R.J.T.; Backx, A.P.C.M.; Schmitt, E.; Smeitink, J.A.M.; Morava, E.

    2007-01-01

    The phenotypic spectrum of the mitochondrial A3243G DKA mutation is highly variable, particularly when occuring in childhood. In contrast to the classical presentation in adulthood (MELAS syndrome; mitochondria! myopathy, encephalopathy, lactic acidosis and stroke-like episodes) children show a diff

  6. 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.)

  7. Titin and Troponin: Central Players in the Frank-Starling Mechanism of the Heart

    OpenAIRE

    Fukuda, Norio; Terui, Takako; Ohtsuki, Iwao; Ishiwata, Shin’ichi; Kurihara, Satoshi

    2009-01-01

    The basis of the Frank-Starling mechanism of the heart is the intrinsic ability of cardiac muscle to produce greater active force in response to stretch, a phenomenon known as length-dependent activation. A feedback mechanism transmitted from cross-bridge formation to troponin C to enhance Ca2+ binding has long been proposed to account for length-dependent activation. However, recent advances in muscle physiology research technologies have enabled the identification of other factors involved ...

  8. Characterization of N-terminally mutated cardiac Na+ channels associated with long QT syndrome 3 and Brugada syndrome

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    Christian eGütter

    2013-06-01

    Full Text Available Mutations in SCN5A, the gene encoding the cardiac voltage-gated Na+ channel hNav1.5, can result in life-threatening arrhythmias including long QT syndrome 3 (LQT3 and Brugada syndrome (BrS. Numerous mutant hNav1.5 channels have been characterized upon heterologous expression and patch-clamp recordings during the last decade. These studies revealed functionally important regions in hNav1.5 and provided insight into gain-of-function or loss-of-function channel defects underlying LQT3 or BrS, respectively. The N-terminal region of hNav1.5, however, has not yet been investigated in detail, although several mutations were reported in the literature. In the present study we investigated three mutant channels, previously associated with LQT3 (G9V, R18W, V125L, and six mutant channels, associated with BrS (R18Q, R27H, G35S, V95I, R104Q, K126E. We applied both the two-microelectrode voltage clamp technique, using cRNA-injected Xenopus oocytes, and the whole-cell patch clamp technique using transfected HEK293 cells. Surprisingly, four out of the nine mutations did not affect channel properties. Gain-of-function, as typically observed in LQT3 mutant channels, was observed only in R18W and V125L, whereas loss-of-function, frequently found in BrS mutants, was found only in R27H, R104Q, and K126E. Our results indicate that the hNav1.5 N-terminus plays an important role for channel kinetics and stability. At the same time, we suggest that additional mechanisms, as e.g. disturbed interactions of the Na+ channel N-terminus with other proteins, contribute to severe clinical phenotypes.

  9. A de novo novel cardiac ryanodine mutation (Ser4155Tyr) associated with catecholaminergic polymorphic ventricular tachycardia.

    Science.gov (United States)

    Mantziari, Lilian; Vassilikos, Vassilios; Anastasakis, Aris; Kotsaka, Xanthippi; Paraskevaidis, Stelios; Styliadis, Ioannis H; Luria, David

    2013-11-01

    We describe the case of a 14-year-old girl with a history of syncopal episodes triggered by stress or exercise. Catecholaminergic polymorphic ventricular tachycardia was diagnosed with the aid of an implantable loop recorder. The genetic testing of the patient and her family revealed a de novo novel missense mutation (Ser4155Tyr) in the exon 90 of the ryanodine receptor gene. This mutation affects a highly conserved residue (S4155) and results to replacement of serine (S) with tyrosine (Y) leading to change in physical and chemical properties. The girl was treated with an implantable defibrillator, metoprolol and flecainide. Over 1 year of follow-up she had no recurrence of ventricular tachycardia. ©2013 Wiley Periodicals, Inc.

  10. The effect of sevoflurane versus propofol anesthesia on troponin I after congenital heart surgery, a randomized clinical trial

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    Leila Mahdavi

    2015-01-01

    Full Text Available Background : The ischemic preconditioning phenomenon can save myocardium against move severe ischemic damages and reduce infarction size and furthermore a heart rhythm disturbance. In this study we examine relationship between troponin I (as a structural myocardial protein level and anesthetic agents in the children. Materials and Methods: In this study 84 children under 12 years age before cardiac surgery were divided randomly into two groups of 42 each. For anesthetic maintenance sevoflurane with dose of 0.5-1 MAC was used in Group 1 and 100-150 mg/kg/min of intravenous propofol in Group 2 for maintenance of anesthesia. Troponin I level was assessed 2 before and 1 hour after anesthetic induction. Outcome measures included the serum cardiac troponin I level in children before and after surgery in two study groups. Results: There was no significant difference between two groups in indices and both groups were homogenous in this point of view. The troponin I level after surgery was significantly increased in two groups. In the sevoflurane group it was 0.04 ± 0.12 to 0.05 ± 0.09 ng/ml (P value = 0.003 and the propofol group was 0.12 ± 0.26 to 0.19 ± 0.38 ng/ml (P value = 0.001. Conclusions: In this study two Anesthetic regimens were compared to assess the mean troponin I level before and after pediatric closed heart surgery, and it was shown that mean troponin level before and after surgery in the sevoflurane group was less than the propofol group. But this result was not statistically significant. These results indicate that although more protective effects of sevoflurane on myocardial injuries during pediatric cardiac surgery is predominant but this effect has no significant difference in the propofol group.

  11. Molecular and Functional Effects of a Splice Site Mutation in the MYL2 Gene Associated with Cardioskeletal Myopathy and Early Cardiac Death in Infants.

    Science.gov (United States)

    Zhou, Zhiqun; Huang, Wenrui; Liang, Jingsheng; Szczesna-Cordary, Danuta

    2016-01-01

    The homozygous appearance of the intronic mutation (IVS6-1) in the MYL2 gene encoding for myosin ventricular/slow-twitch skeletal regulatory light chain (RLC) was recently linked to the development of slow skeletal muscle fiber type I hypotrophy and early cardiac death. The IVS6-1 (c403-1G>C) mutation resulted from a cryptic splice site in MYL2 causing a frameshift and replacement of the last 32 codons by 19 different amino acids in the RLC mutant protein. Infants who were IVS6-1(+∕+)-positive died between 4 and 6 months of age due to cardiomyopathy and heart failure. In this report we have investigated the molecular mechanism and functional consequences associated with the IVS6-1 mutation using recombinant human cardiac IVS6-1 and wild-type (WT) RLC proteins. Recombinant proteins were reconstituted into RLC-depleted porcine cardiac muscle preparations and subjected to enzymatic and functional assays. IVS6-1-RLC showed decreased binding to the myosin heavy chain (MHC) compared with WT, and IVS6-1-reconstituted myosin displayed reduced binding to actin in rigor. The IVS6-1 myosin demonstrated a significantly lower Vmax of the actin-activated myosin ATPase activity compared with WT. In stopped-flow experiments, IVS6-1 myosin showed slower kinetics of the ATP induced dissociation of the acto-myosin complex and a significantly reduced slope of the kobs-[MgATP] relationship compared to WT. In skinned porcine cardiac muscles, RLC-depleted and IVS6-1 reconstituted muscle strips displayed a significant decrease in maximal contractile force and a significantly increased Ca(2+) sensitivity, both hallmarks of hypertrophic cardiomyopathy-associated mutations in MYL2. Our results showed that the amino-acid changes in IVS6-1 were sufficient to impose significant conformational alterations in the RLC protein and trigger a series of abnormal protein-protein interactions in the cardiac muscle sarcomere. Notably, the mutation disrupted the RLC-MHC interaction and the steady

  12. B-type natriuretic peptide is a long-term predictor of all-cause mortality, whereas high-sensitive C-reactive protein predicts recurrent short-term troponin T positive cardiac events in chest pain patients: a prognostic study

    Directory of Open Access Journals (Sweden)

    Staines Harry

    2008-11-01

    Full Text Available Abstract Background Few studies have addressed whether the combined use of B-type natriuretic peptide (BNP and high-sensitive C-reactive protein (hsCRP improves risk stratification for mortality and cardiovascular events in a population with chest pain and suspected acute coronary syndromes (ACS. Therefore, we wanted to assess the incremental prognostic value of these biomarkers with respect to long-term all-cause mortality and recurrent troponin T (TnT positive cardiac events in 871 patients admitted to the emergency department. Methods Blood samples were obtained immediately following admission. Results After a follow-up period of 24 months, 129 patients had died. The BNP levels were significantly higher among patients dying than in long-term survivors (401 (145–736 versus 75 (29–235 pq/mL [median, 25 and 75% percentiles], p = 0.000. In a multivariable Cox regression model for death within 2 years, the hazard ratio (HR for BNP in the highest quartile (Q4 was 5.13 (95% confidence interval (CI, 1.97–13.38 compared to the lowest quartile (Q1 and was associated with all-cause mortality above and beyond age, congestive heart failure and the index diagnosis ST-segment elevation myocardial infarction. HsCRP rendered no prognostic information for all-cause mortality. However, within 30 days, the adjusted HR for patients with recurrent TnT cardiac positive events hsCRP in Q4 was 14.79 (95% CI, 1.89–115.63 compared with Q1 and was associated with recurrent ischemic events above and beyond age, hypercholesterolemia and TnT values at admission. Conclusion BNP may act as a clinically useful biomarker when obtained at admission in an unselected patient population following hospitalization with chest pain and potential ACS, and may provide complementary prognostic information to established risk determinants at long-term follow-up. Our data do not support the hypothesis that the additional assessment of hsCRP will lead to better risk stratification

  13. Deficiency of ataxia telangiectasia mutated kinase modulates cardiac remodeling following myocardial infarction: involvement in fibrosis and apoptosis.

    Directory of Open Access Journals (Sweden)

    Cerrone R Foster

    Full Text Available Ataxia telangiectasia mutated kinase (ATM is a cell cycle checkpoint protein activated in response to DNA damage. We recently reported that ATM plays a protective role in myocardial remodeling following β-adrenergic receptor stimulation. Here we investigated the role of ATM in cardiac remodeling using myocardial infarction (MI as a model.Left ventricular (LV structure, function, apoptosis, fibrosis, and protein levels of apoptosis- and fibrosis-related proteins were examined in wild-type (WT and ATM heterozygous knockout (hKO mice 7 days post-MI. Infarct sizes were similar in both MI groups. However, infarct thickness was higher in hKO-MI group. Two dimensional M-mode echocardiography revealed decreased percent fractional shortening (%FS and ejection fraction (EF in both MI groups when compared to their respective sham groups. However, the decrease in %FS and EF was significantly greater in WT-MI vs hKO-MI. LV end systolic and diastolic diameters were greater in WT-MI vs hKO-MI. Fibrosis, apoptosis, and α-smooth muscle actin staining was significantly higher in hKO-MI vs WT-MI. MMP-2 protein levels and activity were increased to a similar extent in the infarct regions of both groups. MMP-9 protein levels were increased in the non-infarct region of WT-MI vs WT-sham. MMP-9 protein levels and activity were significantly lower in the infarct region of WT vs hKO. TIMP-2 protein levels similarly increased in both MI groups, whereas TIMP-4 protein levels were significantly lower in the infarct region of hKO group. Phosphorylation of p53 protein was higher, while protein levels of manganese superoxide dismutase were significantly lower in the infarct region of hKO vs WT. In vitro, inhibition of ATM using KU-55933 increased oxidative stress and apoptosis in cardiac myocytes.

  14. Troponin T3 expression in skeletal and smooth muscle is required for growth and postnatal survival: characterization of Tnnt3(tm2a(KOMP)Wtsi) mice.

    Science.gov (United States)

    Ju, Yawen; Li, Jie; Xie, Chao; Ritchlin, Christopher T; Xing, Lianping; Hilton, Matthew J; Schwarz, Edward M

    2013-09-01

    The troponin complex, which consists of three regulatory proteins (troponin C, troponin I, and troponin T), is known to regulate muscle contraction in skeletal and cardiac muscle, but its role in smooth muscle remains controversial. Troponin T3 (TnnT3) is a fast skeletal muscle troponin believed to be expressed only in skeletal muscle cells. To determine the in vivo function and tissue-specific expression of Tnnt3, we obtained the heterozygous Tnnt3+/flox/lacZ mice from Knockout Mouse Project (KOMP) Repository. Tnnt3(lacZ/+) mice are smaller than their WT littermates throughout development but do not display any gross phenotypes. Tnnt3(lacZ/lacZ) embryos are smaller than heterozygotes and die shortly after birth. Histology revealed hemorrhagic tissue in Tnnt3(lacZ/lacZ) liver and kidney, which was not present in Tnnt3(lacZ/+) or WT, but no other gross tissue abnormalities. X-gal staining for Tnnt3 promoter-driven lacZ transgene expression revealed positive staining in skeletal muscle and diaphragm and smooth muscle cells located in the aorta, bladder, and bronchus. Collectively, these findings suggest that troponins are expressed in smooth muscle and are required for normal growth and breathing for postnatal survival. Moreover, future studies with this mouse model can explore TnnT3 function in adult muscle function using the conditional-inducible gene deletion approach

  15. Troponin elevation in patients with heart failure: on behalf of the third Universal Definition of Myocardial Infarction Global Task Force: Heart Failure Section.

    Science.gov (United States)

    Januzzi, James L; Filippatos, Gerasimos; Nieminen, Markku; Gheorghiade, Mihai

    2012-09-01

    Cardiac troponin testing is commonly performed in patients with heart failure (HF). Despite being strongly linked to spontaneous (Type I) acute myocardial infarction (MI)--a common cause of acute HF syndromes--it is well recognized that concentrations of circulating troponins above the 99 th percentile of a normal population in the context of both acute and chronic HF are highly prevalent, and frequently unrelated to Type I MI. Other mechanism(s) leading to troponin elevation in HF syndromes remain elusive in many cases but prominently includes supply-demand inequity (Type II MI), which may be associated with coronary artery obstruction and endothelial dysfunction, or may occur in the absence of coronary obstruction due to increased oxygen demand related to increased wall tension, anaemia, or other factors provoking subendocardial injury. Non-coronary triggers, such as cellular necrosis, apoptosis, or autophagy in the context of wall stress may explain the troponin release in HF, as can toxic effects of circulating neurohormones, toxins, inflammation, and infiltrative processes, among others. Nonetheless, across a wide spectrum of HF syndromes, when troponin elevation occurs, independent of mechanism, it is strongly predictive of an adverse outcome. Clinicians should be aware of the high frequency of troponin elevation when measuring the marker in patients with HF, should keep in mind the possible causes of this phenomenon, and, independent of a diagnosis of 'acute MI', should recognize the considerable ramifications of troponin elevation in this setting.

  16. Stop-codon and C-terminal nonsense mutations are associated with a lower risk of cardiac events in patients with long QT syndrome type 1

    DEFF Research Database (Denmark)

    Ruwald, Martin H; Xu Parks, Xiaorong; Moss, Arthur J;

    2016-01-01

    BACKGROUND: In long QT syndrome type 1 (LQT1), the location and type of mutations have been shown to affect the clinical outcome. Although haploinsufficiency, including stop-codon and frameshift mutations, has been associated with a lower risk of cardiac events in patients with LQT1, nonsense...... on mutation type and location: missense not located in the high-risk cytoplasmic loop (c-loop) (n = 698), which is used as reference; missense c-loop (n = 192); stop-codon (n = 67); frameshift (n = 39); and others (n = 94). The primary outcome was a composite end point of syncope, aborted cardiac arrest...... in patients with stop-codon mutations (hazard ratio [HR] 0.57; 95% confidence interval [CI] 0.34-0.96; P = .035), but not in patients with frameshift mutations (HR 1.01; 95% CI 0.58-1.77; P = .97). Our data suggest that currents of the most common stop-codon mutant channel (Q530X) were larger than those...

  17. Atrial fibrillation associated with exogenous subclinical hyperthyroidism, changing axis deviation, troponin-I positive and without acute coronary syndrome.

    Science.gov (United States)

    Patanè, Salvatore; Marte, Filippo

    2011-08-04

    Changing axis deviation has been rarely reported also during atrial fibrillation or atrial flutter. Changing axis deviation has been also rarely reported during acute myocardial infarction associated with atrial fibrillation or at the end of atrial fibrillation during acute myocardial infarction. Subclinical hyperthyroidism is an increasingly recognized entity that is defined as a normal serum free thyroxine and free triiodothyronine levels with a thyroid-stimulating hormone level suppressed below the normal range and usually undetectable. It has been reported that subclinical hyperthyroidism is not associated with coronary heart disease or mortality from cardiovascular causes but it is sufficient to induce arrhythmias including atrial fibrillation and atrial flutter. It has also been reported that increased factor X activity in patients with subclinical hyperthyroidism represents a potential hypercoagulable state. Serum troponin-I is a sensitive indicator of myocardial damage but abnormal troponin-I levels have been also reported without acute coronary syndrome and without cardiac damage. Abnormal troponin-I levels after supraventricular tachycardia have been also reported. We present a case of changing axis deviation in a 49-year-old Italian man with atrial fibrillation, exogenous subclinical hyperthyroidism and troponin-I positive without acute coronary syndrome. Also this case focuses attention on changing axis deviation, on subclinical hyperthyroidism and on the importance of a correct evaluation of abnormal troponin-I levels.

  18. High Sensitivity Troponin T as a Marker of Silent Myocardial Injury in Diabetics

    Directory of Open Access Journals (Sweden)

    Priyanka Datta

    2014-04-01

    Full Text Available Introduction: The new high sensitivity (hs troponin T is speci c biomarkers of myocardial necrosis. It has signi cant bene ts for early recognition of acute myocardial infarction. CK-MB in serum is an important marker in diagnosis of myocardial ischemia. Aim and objective: We aimed to analyse and compare the relationship between glycated haemoglobin levels and hs troponin T, CK-MB in chronic hyperglycaemic patients as a marker of silent micro infarcts. Method and materials: hs Troponin T and CK-MB levels were measured using ECLIA and glycated haemoglobin by using HPLC method by variant turbo II. We grouped 119 chronic diabetic aged 30 - 70yrs in three categories according to HbA1c level Group A 8 %. Diabetic patients with cardiovascular disorder, renal failure, sepsis, skeletal muscle disorder and acute cholecystitis were excluded. Results: There was a 4 fold increase in values of hsTrop T in group II while 9.4 fold for group III in comparison to group I. CK-MB was elevated by 2.7 fold in group II and 3.11 in group III in comparison to group I. Conclusion: The prevalence of detectable hs-cTnT was increased in diabetic population and found speci c than CK-MB to diagnose minimal myocardial cell injury. Troponin T levels can be used to detect early and minimal myocardial cell injury even in the presence of normal CK-MB. These data raise the possibility that hs Troponin T can be used as a predictor of minimal cardiac injury and micro infract in diabetic patients before symptoms manifest.

  19. Malondialdeído e troponina I cardíaca em equinos da raça Puro Sangue Árabe submetidos ao exercício e à suplementação com vitamina E Malondialdehyde and cardiac troponin I in Arabian horses subjected to exercise and vitamin E supplementation

    Directory of Open Access Journals (Sweden)

    Letícia Andreza Yonezawa

    2010-06-01

    Full Text Available Para avaliar o efeito do exercício físico, do treinamento e da suplementação com vitamina E sobre o malondialdeído (MDA e a troponina I cardíaca (cTnI séricos, foram utilizados 16 equinos da raça Puro Sangue Árabe, sem treinamento, divididos em dois grupos de oito: controle e suplementado com vitamina E. Ambos os grupos foram submetidos a provas de exercício progressivo em esteira de alta velocidade inclinada a +7%, antes (P1 e após (P2 o período de treinamento de 20 dias. Foram determinadas as concentrações séricas de MDA, vitamina E e cTnI e realizou-se o eletrocardiograma de repouso antes e após as provas P1 e P2. Os resultados sugerem a ocorrência do estresse oxidativo ocasionado pelo exercício, determinado por meio do aumento de MDA sérico. Em alguns animais, houve um discreto aumento de cTnI associado à detecção de complexos ventriculares prematuros, mas que não representou lesão cardíaca expressiva. Não houve efeito do treinamento sobre o estresse oxidativo. Portanto, é possível concluir que o exercício físico progressivo promoveu a lipoperoxidação nessas condições, que não foi prevenida pela suplementação com vitamina E nem pelo treinamento, mas não foi suficiente para causar uma lesão cardíaca significativa.To evaluate the effect of exercise, training and vitamin E supplementation on serum malondialdehyde (MDA and cardiac troponin I (cTnI, sixteen adult untrained Arabian horses were divided into 2 groups of 8 animals each, control and supplemented with vitamin E. Both groups had incremental exercise tests performed on a high-speed treadmill at a +7% slope, before (P1 and after (P2 a training period of 20 days. Serum concentrations of MDA, vitamin E and cTnI, and resting electrocardiogram were performed before and after P1 and P2. Results suggested that oxidative stress was induced by exercise as measured by serum MDA increase. In some animals, there was a subtle increase in cTnI concentration

  20. Determination and clinical significance of serum hypersensitivity C-reactive protein and hypersensitivity cardiac troponin in patients with coronary heart disease%冠心病患者血清超敏C-反应蛋白、超敏肌钙蛋白T检测及意义

    Institute of Scientific and Technical Information of China (English)

    戴仁森; 李伟林

    2013-01-01

    Objective To research the determination of hypersensitivity C-reactive protein(Hs-CRP) and cardiac troponin T(Hs-cTnT) in patients with coronary heart disease,and to analyze the correlation with cardiac function.Methods The function of left ventricle and the serum levels of Hs-CRP and Hs-cTnT in 100 patients with coronary heart disease and 50 healthy subjects were detected.Results The function of left ventricle and the serum levels of Hs-CRP and Hs-cTnT were significantly different in patients with coronary heart disease and healthy subjects(P <0.01).The function of left ventricle and the serum levels of Hs-CRP and Hs-cTnT were significantly different in coronary heart disease patients with different New York Heart Association class(P < 0.01).The serum levels of Hs-CRP and Hs-cTnT were positively correlated with class of New York Heart Association,left ventricular end diastolic diameter,and negatively correlated with left ventricular ejection fraction and fraction shortening (Absolute value of r:0.536 ~ 0.849,P < 0.05).Conclusion The serum levels of Hs-CRP and Hs-cTnT significantly increase in patients with coronary heart disease,which is correlated to function of left ventricle,and it can be used as the indicators of cardiac function in patients with coronary heart disease.%目的 研究冠心病患者血清超敏C-反应蛋白(Hs-CRP)、超敏肌钙蛋白T(Hs-cTnT)的测定及分析两者与左心室功能的关系.方法 100例冠心病患者(观察组)和50例(对照组)年龄相当的健康受试者纳入该研究,分别测定左心室功能以及血清Hs-CRP和Hs-cTnT水平.结果 与对照组相比,观察组Hs-CRF和Hs-cTnT水平明显升高(t=11.745、7.803,均P<0.01),观察组左室舒张末内径(LVEDD)水平显著升高(t =4.984,P<0.01),而左室射血分数(LVEF)和左室短轴缩短率(FS)均显著降低(t=5.021、4.672,均P<0.01).观察组不同YNHA分级,其Hs-CRF、Hs-cTnT水平、LVEF、LVEDD及FS等差异均有统计学意义(F=89

  1. The influence of sevoflurane inhalation on serum troponin Ⅰ and MB isoenzyme of creatine kinase in non-cyanosis congenital heart disease infants undergoing cardiac surgery%吸入七氟烷麻醉对非发绀型先天性心脏病患儿心脏手术围术期心肌损伤的影响

    Institute of Scientific and Technical Information of China (English)

    吴琼; 董秀华; 卿恩明; 卢家凯

    2012-01-01

    目的:观察吸入七氟烷麻醉对非发绀型先天性心脏病(先心病)患儿心脏手术围术期血浆心肌坏死标记物肌钙蛋白Ⅰ(TnⅠ)及肌酸激酶同工酶(CKMB)的影响.方法:择期行心脏手术的非发绀型先心病患儿60例,随机分为七氟烷组(S组)及氯胺酮组(K组),分别在术中实施七氟烷-芬太尼或氯胺酮-芬太尼麻醉,观察术中的血流动力学及围术期TnⅠ、CKMB、血糖(Glu)及乳酸(Lac)水平变化.结果:S组与K组比较,S组平均动脉压(MAP)在诱导后、切皮及术毕均比K组高(P<0.05),S组HR在术毕比K组低(P<0.05),S组在术后4h及24 hTnⅠ水平显著低于K组(P<0.05),CKMB在术后24h显著低于K组水平(P<0.05),2组Glu及Lac浓度在各时点差异无统计学意义(P>0.05).结论:吸入七氟烷麻醉在非发绀型先心病患儿心脏手术围术期,可以降低血浆TnⅠ及CKMB水平,对患儿心肌可能起到保护作用.%Objective:To observe the effect of sevoflurane inhalation anesthesia on myocardial injury bi-omarker Troponin I (Tnl) and MB isoenzyme of creatine kinase (CKMB) in non-cyanosis congenital heart disease infants undergoing cardiac surgery. Methods: Sixty non-cyanosis congenital heart disease infants undergoing selective cardiac surgery were recruited for present study. Patients were randomly assigned to sevoflurane group (Group S) and ketamine group (Group K) and received sevoflurane inhalation or ketamine injection for anesthetic induction and maintenance respectively. Intraoperative hemodynamics were recorded and perioperative serum level of Tnl, CKMB, blood glucose and lactate were measured. Results; Mean artery pressure increased significantly in Group S compared with Group K at post-induction, skin incision and at the end of the surgery(P < 0. 05 ) , Heart rate in Group S was significantly lower than that of in Group K (P < 0.05 ). The serum Tnl level in group S was significantly lower than that of Group K at postoperative 4h and 24 h

  2. Minor myocardial damage is a prevalent condition in patients with acute heart failure syndromes and preserved systolic function with long-term prognostic implications: a report from the CIAST-HF (Collaborative Italo-Argentinean Study on cardiac Troponin T in Heart Failure) study.

    Science.gov (United States)

    Perna, Eduardo R; Aspromonte, Nadia; Cimbaro Canella, Juan P; Di Tano, Giuseppe; Macin, Stella M; Feola, Mauro; Coronel, María L; Milani, Loredano; Parras, Jorge I; Milli, Massimo; García, Edgar H; Valle, Roberto

    2012-11-01

    Half of patients with acute heart failure syndromes (AHFS) have preserved left ventricular ejection fraction (PLVEF). In this setting, the role of minor myocardial damage (MMD), as identified by cardiac troponin T (cTnT), remains to be established. To evaluate the prevalence and long-term prognostic significance of cTnT elevations in patients with AHFS and PLVEF. This retrospective, multicenter, collaborative study included 500 patients hospitalized for AHFS with PLVEF (ejection fraction ≥40%) between October 2000 and December 2006. Blood samples were collected within 12 hours after admission and were assayed for cTnT. MMD was defined as a cTnT value of ≥0.020 ng/mL. Mean age was 73 ± 12 years, 47% were female, 38% had an ischemic etiology, and New York Heart Association (NYHA) class was 2.2 ± 0.7. Mean cTnT value was 0.149 ± 0.484 ng/mL, and cTnT was directly correlated with serum creatinine (Spearman's Rho = 0.35, P < .001) and NYHA class (0.25, P < .001). MMD was diagnosed in 220 patients (44%). Patients with MMD showed lower left ventricular ejection fraction (P < .05), higher serum creatinine (P < .001), higher prevalence of ischemic etiology and diabetes mellitus, a worse NYHA class (P < .001), and higher natriuretic peptide levels (P < .001) as compared with patients without MMD. At 6-month follow-up, overall event-free survival was 55% and 75% in patients with and without MMD (P < .001), respectively. On multivariate Cox regression analysis, only NYHA class (HR = 1.50; P = .002) and MMD (HR = 1.81; P = .001) were identified as predictors of events. Increased cTnT levels were detected in approximately 50% of patients with AHFS with preserved systolic function, and were found to correlate with clinical measures of disease severity. The presence of MMD was associated with a worse long-term outcome, lending support to cTnT-based risk stratification in the setting of AHFS. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Association between high-sensitive troponin I and coronary artery calcification in a Danish general population

    DEFF Research Database (Denmark)

    Olson, Fredrik; Engborg, Jonathan; Grønhøj, Mette H.;

    2016-01-01

    BACKGROUND: High-sensitive troponin I (hs-TnI) is an individual predictor of future cardiovascular disease (CVD). However, the relationship between hs-TnI and coronary artery calcification (CAC) as determined by computed tomography (CT) has not previously been investigated in a general population....... METHODS: 1173 randomized, middle-aged subjects without known CVD underwent a non-contrast cardiac-CT scan for CAC determination. Hs-TnI was detected using ARCHITECT STAT High Sensitive Troponin-I immunoassay. Total 10-year cardiovascular mortality risk was estimated using HeartScore. The relationship...... between hs-TnI and CAC was assessed using logistic regression analyses and receiver operating characteristic curves (ROC). RESULTS: Concentrations of hs-TnI above the limit of detection were measured in 89.3% of all subjects. Presence of CAC (Agatston score >0) was detected in 29% in the lowest hs...

  4. Thin filament activation probed by fluorescence of N-((2-(iodoacetoxy)ethyl)-N-methyl)amino-7-nitrobenz-2-oxa-1,3-diazole-labeled troponin I incorporated into skinned fibers of rabbit psoas muscle.

    Science.gov (United States)

    Brenner, B; Kraft, T; Yu, L C; Chalovich, J M

    1999-11-01

    A method is described for the exchange of native troponin of single rabbit psoas muscle fibers for externally applied troponin complexes without detectable impairment of functional properties of the skinned fibers. This approach is used to exchange native troponin for rabbit skeletal troponin with a fluorescent label (N-((2-(iodoacetoxy)ethyl)-N-methyl)amino-7-nitrobenz-2-oxa-1, 3-diazole, IANBD) on Cys(133) of the troponin I subunit. IANBD-labeled troponin I has previously been used in solution studies as an indicator for the state of activation of reconstituted actin filaments (. Proc. Natl. Acad. Sci. USA. 77:7209-7213). In the skinned fibers, the fluorescence of this probe is unaffected when cross-bridges in their weak binding states attach to actin filaments but decreases either upon the addition of Ca(2+) or when cross-bridges in their strong binding states attach to actin. Maximum reduction is observed when Ca(2+) is raised to saturating concentrations. Additional attachment of cross-bridges in strong binding states gives no further reduction of fluorescence. Attachment of cross-bridges in strong binding states alone (low Ca(2+) concentration) gives only about half of the maximum reduction seen with the addition of calcium. This illustrates that fluorescence of IANBD-labeled troponin I can be used to evaluate thin filament activation, as previously introduced for solution studies. In addition, at nonsaturating Ca(2+) concentrations IANBD fluorescence can be used for straightforward classification of states of the myosin head as weak binding (nonactivating) and strong binding (activating), irrespective of ionic strength or other experimental conditions. Furthermore, the approach presented here not only can be used as a means of exchanging native skeletal troponin and its subunits for a variety of fluorescently labeled or mutant troponin subunits, but also allows the exchange of native skeletal troponin for cardiac troponin.

  5. Cardiac biomarkers in neonatal hypoxic ischaemia.

    LENUS (Irish Health Repository)

    Sweetman, D

    2012-04-01

    Following a perinatal hypoxic-ischaemic insult, term infants commonly develop cardiovascular dysfunction. Troponin-T, troponin-I and brain natriuretic peptide are sensitive indicators of myocardial compromise. The long-term effects of cardiovascular dysfunction on neurodevelopmental outcome following perinatal hypoxic ischaemia remain controversial. Follow-up studies are warranted to ensure optimal cardiac function in adulthood. CONCLUSION: Cardiac biomarkers may improve the diagnosis of myocardial injury, help guide management, estimate mortality risk and may also aid in longterm neurodevelopmental outcome prediction following neonatal hypoxic-ischaemia.

  6. Can we monitor heart attack in the troponin era: evidence from a population-based cohort study

    Directory of Open Access Journals (Sweden)

    Rankin Jamie M

    2011-06-01

    Full Text Available Abstract Background Troponins (highly sensitive biomarkers of myocardial damage increase counts of myocardial infarction (MI in clinical practice, but their impact on trends in admission rates for MI in National statistics is uncertain. Methods Cases coded as MI or other cardiac diagnoses in the Hospital Morbidity Data Collection (MI-HMDC in Western Australia in 1998 and 2003 were classified using revised criteria for MI developed by an International panel convened by the American Heart Association (AHA criteria using information on symptoms, ECGs and cardiac biomarkers abstracted from samples of medical notes. Age-sex standardized rates of MI-HMDC were compared with rates of MI based on AHA criteria including troponins (MI-AHA or traditional biomarkers only (MI-AHAck. Results Between 1998 and 2003, rates of MI-HMDC decreased by 3.5% whereas rates of MI-AHA increased by 17%, a difference largely due to increased false-negative cases in the HMDC associated with marked increased use of troponin tests in cardiac admissions generally, and progressively lower test thresholds. In contrast, rates of MI-AHAck declined by 18%. Conclusions Increasing misclassification of MI-AHA by the HMDC may be due to reluctance by clinicians to diagnose MI based on relatively small increases in troponin levels. These influences are likely to continue. Monitoring MI using AHA criteria will require calibration of commercially available troponin tests and agreement on lower diagnostic thresholds for epidemiological studies. Declining rates of MI-AHAck are consistent with long-standing trends in MI in Western Australia, suggesting that neither MI-HMDC nor MI-AHA reflect the true underlying population trends in MI.

  7. Association between Angiotensin-Converting Enzyme Inhibitors and Troponin in Acute Coronary Syndrome

    Directory of Open Access Journals (Sweden)

    Luiz Minuzzo

    2014-12-01

    Full Text Available Background: Cardiovascular disease is the leading cause of mortality in the western world and its treatment should be optimized to decrease severe adverse events. Objective: To determine the effect of previous use of angiotensin-converting enzyme inhibitors on cardiac troponin I measurement in patients with acute coronary syndrome without ST-segment elevation and evaluate clinical outcomes at 180 days. Methods: Prospective, observational study, carried out in a tertiary center, in patients with acute coronary syndrome without ST-segment elevation. Clinical, electrocardiographic and laboratory variables were analyzed, with emphasis on previous use of angiotensin-converting enzyme inhibitors and cardiac troponin I. The Pearson chi-square tests (Pereira or Fisher's exact test (Armitage were used, as well as the non-parametric Mann-Whitney's test. Variables with significance levels of 0.5 ng / mL were high blood glucose at admission (p = 0.0034 and ST-segment depression ≥ 0.5 mm in one or more leads (p = 0.0016. The use of angiotensin-converting inhibitors prior to hospitalization was associated with troponin ≤ 0.5 ng / mL (p = 0.0482. The C-statistics for this model was 0.77. Conclusion: This study showed a correlation between prior use of angiotensin-converting enzyme inhibitors and reduction in the myocardial necrosis marker troponin I in patients admitted for acute coronary syndrome without ST-segment elevation. However, there are no data available yet to state that this reduction could lead to fewer severe clinical events such as death and re-infarction at 180 days.

  8. Sensitive troponins--which suits better for hemodialysis patients? Associated factors and prediction of mortality.

    Directory of Open Access Journals (Sweden)

    Ferruh Artunc

    Full Text Available BACKGROUND: In hemodialysis patients, elevated plasma troponin concentrations are a common finding that has even increased with the advent of newly developed sensitive assays. However, the interpretation and relevance of this is still under debate. METHODS: In this cross-sectional study, we analyzed plasma concentrations of sensitive troponin I (TnI and troponin T (TnT in stable ambulatory hemodialysis patients (n = 239 and investigated their associations with clinical factors and mortality. RESULTS: In all of the enrolled patients, plasma TnI or TnT was detectable at a median concentration of 14 pg/ml (interquartile range: 7-29 using the Siemens TnI ultra assay and 49 pg/ml (31-74 using the Roche Elecsys high sensitive TnT assay. Markedly more patients exceeded the 99th percentile for TnT than for TnI (95% vs. 14%, p<0.0001. In a multivariate linear regression model, TnT was independently associated with age, gender, systolic dysfunction, time on dialysis, residual diuresis and systolic blood pressure, whereas TnI was independently associated with age, systolic dysfunction, pulse pressure, time on dialysis and duration of a HD session. During a follow-up period of nearly two years, TnT concentration above 38 pg/mL was associated with a 5-fold risk of death, whereas elevation of TnI had a gradual association to mortality. CONCLUSION: In hemodialysis patients, elevations of plasma troponin concentrations are explained by cardiac function and dialysis-related parameters, which contribute to cardiac strain. Both are highly predictive of increased risk of death.

  9. High sensitive troponin T in individuals with chest pain of presumed ischemic origin.

    Science.gov (United States)

    Cuda, Giovanni; Lentini, Margherita; Gallo, Luigia; Lucia, Fortunata G; Giacinto Carinci, Lorenzina; Mancuso, Serafina; Biondi, Rosa A; Sinopoli, Raffaella; Casadonte, Rita; Guzzi, Pietro H; Cannataro, Mario; Mongiardo, Annalisa; Iaconetti, Claudio; Bochicchio, Angela; Curcio, Antonio; Torella, Daniele; Ricci, Pietroantonio; Indolfi, Ciro; Costanzo, Francesco

    2012-06-01

    This study was aimed at assessing the bias of high sensitive cardiac troponin T vs. the standard cardiac troponin T in a selected population with chest pain of presumed cardiac origin. Serum cTnT was determined in 132 patients and in 106 apparently healthy controls by both assays. The hs-cTnT outperformed the standard generation assay by: i) allowing a larger and earlier diagnosis of AMI (74.2 percent vs. 64.3 percent patients resulted positive at the final diagnosis of AMI when tested with the hs-cTnT or the std-cTnT assay, respectively); ii) showing a better time-dependent dynamics in patients with AMI due to a higher precision at low concentrations; iii) identifying, within the controls, 6 subjects in whom a further examination revealed the presence of chronic asymptomatic cardiac ischemia. The results underscore the excellent performance of the hs-cTnT assay in our population. The use of this test can thus be strongly recommended in subjects presenting to the emergency unit with chest pain of presumed ischemic origin in order to increase the probability of earlier diagnosis of AMI, especially in non-STEMI.

  10. Absence of mutation at the 5'-upstream promoter region of the TPM4 gene from cardiac mutant axolotl (Ambystoma mexicanum).

    Science.gov (United States)

    Denz, Christopher R; Zhang, Chi; Jia, Pingping; Du, Jianfeng; Huang, Xupei; Dube, Syamalima; Thomas, Anish; Poiesz, Bernard J; Dube, Dipak K

    2011-09-01

    Tropomyosins are a family of actin-binding proteins that show cell-specific diversity by a combination of multiple genes and alternative RNA splicing. Of the 4 different tropomyosin genes, TPM4 plays a pivotal role in myofibrillogenesis as well as cardiac contractility in amphibians. In this study, we amplified and sequenced the upstream regulatory region of the TPM4 gene from both normal and mutant axolotl hearts. To identify the cis-elements that are essential for the expression of the TPM4, we created various deletion mutants of the TPM4 promoter DNA, inserted the deleted segments into PGL3 vector, and performed promoter-reporter assay using luciferase as the reporter gene. Comparison of sequences of the promoter region of the TPM4 gene from normal and mutant axolotl revealed no mutations in the promoter sequence of the mutant TPM4 gene. CArG box elements that are generally involved in controlling the expression of several other muscle-specific gene promoters were not found in the upstream regulatory region of the TPM4 gene. In deletion experiments, loss of activity of the reporter gene was noted upon deletion which was then restored upon further deletion suggesting the presence of both positive and negative cis-elements in the upstream regulatory region of the TPM4 gene. We believe that this is the first axolotl promoter that has ever been cloned and studied with clear evidence that it functions in mammalian cell lines. Although striated muscle-specific cis-acting elements are absent from the promoter region of TPM4 gene, our results suggest the presence of positive and negative cis-elements in the promoter region, which in conjunction with positive and negative trans-elements may be involved in regulating the expression of TPM4 gene in a tissue-specific manner.

  11. RELEASE OF SERUM TROPONIN I AND ITS RELATIONSHIP TO MULTIFACTORS FOLLOWING OPEN HEART SURGERY IN CHILDREN

    Institute of Scientific and Technical Information of China (English)

    CAI Ji-ming; SHI Zhen-ying; ZHOU Yan-ping; CHEN Lin; SU Zhao-kang; YANG Yan-min

    2005-01-01

    Objective To be released specifically after myocardial damage. The goal of this study was to measure serum cardiac troponin I levels after open heart surgery in children, and to evaluate relevance between TnTi and perioperative multi-factors. Methods Fifty-seven consecutive pediatric patients undergoing elective correction of congenital heart diseases were divided into group A (TOF, n=31) and group B (VSD, n=26). Blood samples were drawn preoperatively, 5min(T0), 6h(T6), 12h(T12), 24h(T24), 48h(T48), 72h(T72) after removal of aortic cross clamping. Myocardial protection consisted of moderate systemic hypothermia (30℃~ 32℃), cold crystalloid cardioplegia and topical cooling. Demographic information, cardiac defect, repair procedure, duration of bypass (CPBT), cross-clamping time (CCT), clinical score for cardiac function, electrocardiographic changes and outcomes were recorded. Results Compared with the baseline value, serum concentration of troponin I peaked at T0 (P0.05). Peak CTnI was 118 and 55 times higher than the baseline value, respectively in group A and group B.There was a positive correlation between peak CTnI and CPBT, CCT (r=0.51; P<0.01), myocardial operative injury after ventriculotomy and muscle resection (r=0.35, P<0.01). Also the peak CTnI value was correlated to the clinical score for cardiac function (r=-0.52; P<0.01). 2.3μg/L was a cutoff value which was highly predictive for postoperative recovery and inotropic support.Conclusion Postoperative serum troponin I is a highly specific and sensitive marker for myocardial ischemia and injury; therefore, its measurement may contribute to the assessment of recovery and outcome after open heart surgery.

  12. Troponina cardíaca T para estratificação de risco na insuficiência cardíaca crônica descompensada Troponina cardiaca T para estratificación de riesgo en la insuficiencia cardiaca crónica descompensada Cardiac troponin T for risk stratification in decompensated chronic heart failure

    Directory of Open Access Journals (Sweden)

    Carlos Henrique Del Carlo

    2009-05-01

    durante un año. RESULTADOS: Durante el seguimiento, ocurrieron 44 muertes, 36 rehospitalizaciones por IC y 56 desenlaces compuestos. En el análisis multivariado, los predictores de eventos clínicos fueron: cTnT (cTnT > 0,100 ng/ml; hazard ratio (HR 3,95 intervalo de confianza (IC 95%: 1,64-9,49, p = 0,002, diámetro diastólico final del ventrículo izquierdo (DDVI >70 mm; HR 1,92, IC95%: 1,06-3,47, p = 0,031 y sodio sérico (Na 0,020 y 0,100 ng/ml, n = 12. Las probabilidades de sobrevida y sobrevida libre de eventos fueron: 54,2%, 31,5%, 16,7% (p = 0,020, y 36,4%, 11,5%, 8,3% (p = 0,005, respectivamente. CONCLUSÃO: La elevación de la cTnT está asociada con mal pronóstico en la IC descompensada, y el grado de esa elevación puede facilitar la estratificación de riesgo.BACKGROUND: The cardiac troponins are highly sensitive and specific markers of myocardial injury. They have been detected in heart failure (HF and are associated with a bad prognosis. OBJECTIVE: To evaluate the association of cardiac troponin T (cTnT and its ranges with prognosis in decompensated HF. METHODS: A total of 70 patients with chronic HF worsening that needed hospitalization were studied. Cox model was used to evaluate the variables at admission capable of predicting the combined outcome that consisted of death or re-hospitalization due to HF worsening during a 1-year follow-up. RESULTS: During the follow-up, there were 44 deaths, 36 re-hospitalizations due to HF and 56 combined outcomes. At the multivariate analysis, the predictors of clinical events were the cTnT (cTnT >0.100 ng/mL; hazard ratio [HR] 3.95 95% confidence interval [CI]: 1.64-9.49, p = 0.002, left ventricular end diastolic diameter (LVDD >70 mm; HR 1.92, 95%CI: 1.06-3.47, p = 0.031 and serum sodium (Na 0.020 and 0.100 ng/ml, n = 12.The probabilities of survival and event-free survival were 54.2%, 31.5%, 16.7% (p = 0.020 and 36.4%, 11.5%, 8.3% (p = 0.005, respectively. CONCLUSION: The increase in cTnT is associated with a bad

  13. Troponin elevation in acute ischemic stroke (TRELAS)--protocol of a prospective observational trial.

    Science.gov (United States)

    Scheitz, Jan F; Mochmann, Hans-Christian; Nolte, Christian H; Haeusler, Karl G; Audebert, Heinrich J; Heuschmann, Peter U; Laufs, Ulrich; Witzenbichler, Bernhard; Schultheiss, Heinz-Peter; Endres, Matthias

    2011-08-08

    Levels of the cardiac muscle regulatory protein troponin T (cTnT) are frequently elevated in patients with acute ischemic stroke and elevated cTnT predicts poor outcome and mortality. The pathomechanism of troponin release may relate to co-morbid coronary artery disease and myocardial ischemia or, alternatively, to neurogenic cardiac damage due to autonomic activation after acute ischemic stroke. Therefore, there is uncertainty about how acute ischemic stroke patients with increased cTnT levels should be managed regarding diagnostic and therapeutic workup. The primary objective of the prospective observational trial TRELAS (TRoponin ELevation in Acute ischemic Stroke) is to investigate the frequency and underlying pathomechanism of cTnT elevation in acute ischemic stroke patients in order to give guidance for clinical practice. All consecutive patients with acute ischemic stroke admitted within 72 hours after symptom onset to the Department of Neurology at the Campus Benjamin Franklin of the University Hospital Charité will be screened for cTnT elevations (i.e. ≥ 0.05 μg/l) on admission and again on the following day. Patients with increased cTnT will undergo coronary angiography within 72 hours. Diagnostic findings of coronary angiograms will be compared with age- and gender-matched patients presenting with Non-ST-Elevation myocardial infarction to the Department of Cardiology. The primary endpoint of the study will be the occurrence of culprit lesions in the coronary angiogram indicating underlying co-morbid obstructive coronary artery disease. Secondary endpoints will be the localization of stroke in the cerebral imaging and left ventriculographic findings of wall motion abnormalities suggestive of stroke-induced global cardiac dysfunction. TRELAS will prospectively determine the frequency and possible etiology of troponin elevation in a large cohort of ischemic stroke patients. The findings are expected to contribute to clarify pathophysiologic concepts of

  14. Cardiac involvement in canine babesiosis : review article

    Directory of Open Access Journals (Sweden)

    R.G. Lobetti

    2005-06-01

    Full Text Available Cardiac dysfunction in canine babesiosis has traditionally been regarded as a rare complication, with the majority of lesions reported as incidental findings at post-mortem examination. Recent studies have, however, demonstrated cardiac lesions in canine babesiosis. Cardiac troponins, especially troponin I, are sensitive markers of myocardial injury in canine babesiosis, and the magnitude of elevation of plasma troponin I concentrations appears to be proportional to the severity of the disease. ECG changes in babesiosis are similar to the pattern described for myocarditis and myocardial ischaemia and together with histopathological findings indicate that the heart suffers from the same pathological processes described in other organs in canine babesiosis, namely inflammation and hypoxia. The clinical application of the ECG appears to be limited and thus cardiovascular assessment should be based on functional monitoring rather than an ECG tracing. On cardiac histopathology from dogs that succumbed to babesiosis, haemorrhage, necrosis, inflammation and fibrin microthrombi in the myocardium were documented, all of which would have resulted in ECG changes and elevations in cardiac troponin. Myocardial damage causes left ventricular failure, which will result in hypotension and an expansion of the plasma volume due to homeostatic mechanisms.

  15. High-efficiency multiplex capillary electrophoresis single strand conformation polymorphism (multi-CE-SSCP) mutation screening of SCN5A: a rapid genetic approach to cardiac arrhythmia.

    Science.gov (United States)

    Hofman-Bang, J; Behr, E R; Hedley, P; Tfelt-Hansen, J; Kanters, J K; Haunsøe, S; McKenna, W J; Christiansen, M

    2006-06-01

    Mutations in the SCN5A gene coding for the alpha-subunit of the cardiac Na(+) ion channel cause long QT syndrome, Brugada syndrome, idiopathic ventricular fibrillation, sick sinus node syndrome, progressive conduction disease, dilated cardiomyopathy and atrial standstill. These diseases exhibit variable expressivity, and identification of gene carriers is clinically important, particularly in sudden infant and adult death syndromes. The SCN5A gene comprises 28 exons distributed over 100 kbp of genomic sequence at chromosome 3p21. Disease-causing mutations are private and scattered over the DNA sequence, making it difficult to screen for specific mutations. We developed a multiplex capillary-electrophoresis single-strand conformation polymorphism (Multi-CE-SSCP) mutation screening protocol on the ABI 3100 platform and applied it to 10 previously slab-gel SSCP identified mutations and SNPs and used it to identify one novel deletion. The method is highly efficient, with a turnover of 23 patients per 24 h and a false positive rate of 0.5% of the analyzed amplicons. Each variant has a particular elution pattern, and all 20 carriers of the H558R polymorphism out of 57 persons were correctly identified. We suggest that the method could become part of routine work-up of patients with suspicious syncope and of members of families with sudden unexplained death.

  16. Fatal infantile cardiac glycogenosis with phosphorylase kinase deficiency and a mutation in the gamma2-subunit of AMP-activated protein kinase.

    Science.gov (United States)

    Akman, Hasan O; Sampayo, James N; Ross, Fiona A; Scott, John W; Wilson, Gregory; Benson, Lee; Bruno, Claudio; Shanske, Sara; Hardie, D Grahame; Dimauro, Salvatore

    2007-10-01

    A 10-wk-old infant girl with severe hypertrophy of the septal and atrial walls by cardiac ultrasound, developed progressive ventricular wall thickening and died of aspiration pneumonia at 5 mo of age. Postmortem examination revealed ventricular hypertrophy and massive atrial wall thickening due to glycogen accumulation. A skeletal muscle biopsy showed increased free glycogen and decreased activity of phosphorylase b kinase (PHK). The report of a pathogenic mutation (R531Q) in the gene (PRKAG2) encoding the gamma2 subunit of AMP-activated protein kinase (AMPK) in three infants with congenital hypertrophic cardiomyopathy, glycogen storage, and "pseudo PHK deficiency" prompted us to screen this gene in our patient. We found a novel (R384T) heterozygous mutation in PRKAG2, affecting an arginine residue in the N-terminal AMP-binding domain. Like R531Q, this mutation reduces the binding of AMP and ATP to the isolated nucleotide-binding domains, and prevents activation of the heterotrimer by metabolic stress in intact cells. The mutation was not found in DNA from the patient's father, the only available parent, and is likely to have arisen de novo. Our studies confirm that mutations in PRKAG2 can cause fatal infantile cardiomyopathy, often associated with apparent PHK deficiency.

  17. Cystatin C for enhancement of risk stratification in non-ST elevation acute coronary syndrome patients with an increased troponin T.

    NARCIS (Netherlands)

    Windhausen, F.; Hirsch, A.; Fischer, J.; Zee, P.M. van der; Sanders, G.T.; Straalen, J.P. van; Cornel, J.H.; Tijssen, J.G.P.; Verheugt, F.W.A.; Winter, R.J. de

    2009-01-01

    BACKGROUND: We assessed the value of cystatin C for improvement of risk stratification in patients with non-ST elevation acute coronary syndrome (nSTE-ACS) and increased cardiac troponin T (cTnT), and we compared the long-term effects of an early invasive treatment strategy (EIS) with a selective

  18. Cystatin C for enhancement of risk stratification in non-ST elevation acute coronary syndrome patients with an increased troponin T.

    NARCIS (Netherlands)

    Windhausen, F.; Hirsch, A.; Fischer, J.; Zee, P.M. van der; Sanders, G.T.; Straalen, J.P. van; Cornel, J.H.; Tijssen, J.G.P.; Verheugt, F.W.A.; Winter, R.J. de

    2009-01-01

    BACKGROUND: We assessed the value of cystatin C for improvement of risk stratification in patients with non-ST elevation acute coronary syndrome (nSTE-ACS) and increased cardiac troponin T (cTnT), and we compared the long-term effects of an early invasive treatment strategy (EIS) with a selective in

  19. Cystatin C for Enhancement of Risk Stratification in Non-ST Elevation Acute Coronary Syndrome Patients with an Increased Troponin T

    NARCIS (Netherlands)

    F. Windhausen; A. Hirsch; J. Fischer; P.M. van der Zee; G.T. Sanders; J.P. van Straalen; J.H. Cornel; J.G.P. Tijssen; F.W.A. Verheugt; R.J. de Winter

    2009-01-01

    BACKGROUND: We assessed the value of cystatin C for improvement of risk stratification in patients with non-ST elevation acute coronary syndrome (nSTE-ACS) and increased cardiac troponin T (cTnT), and we compared the long-term effects of an early invasive treatment strategy (EIS) with a selective in

  20. Effect of levosimendan on the contractility of muscle fibers from nemaline myopathy patients with mutations in the nebulin gene.

    Science.gov (United States)

    de Winter, Josine M; Joureau, Barbara; Sequeira, Vasco; Clarke, Nigel F; van der Velden, Jolanda; Stienen, Ger Jm; Granzier, Henk; Beggs, Alan H; Ottenheijm, Coen Ac

    2015-01-01

    Nemaline myopathy (NM), the most common non-dystrophic congenital myopathy, is characterized by generalized skeletal muscle weakness, often from birth. To date, no therapy exists that enhances the contractile strength of muscles of NM patients. Mutations in NEB, encoding the giant protein nebulin, are the most common cause of NM. The pathophysiology of muscle weakness in NM patients with NEB mutations (NEB-NM) includes a lower calcium-sensitivity of force generation. We propose that the lower calcium-sensitivity of force generation in NEB-NM offers a therapeutic target. Levosimendan is a calcium sensitizer that is approved for use in humans and has been developed to target cardiac muscle fibers. It exerts its effect through binding to slow skeletal/cardiac troponin C. As slow skeletal/cardiac troponin C is also the dominant troponin C isoform in slow-twitch skeletal muscle fibers, we hypothesized that levosimendan improves slow-twitch muscle fiber strength at submaximal levels of activation in patients with NEB-NM. To test whether levosimendan affects force production, permeabilized slow-twitch muscle fibers isolated from biopsies of NEB-NM patients and controls were exposed to levosimendan and the force response was measured. No effect of levosimendan on muscle fiber force in NEB-NM and control skeletal muscle fibers was found, both at a submaximal calcium level using incremental levosimendan concentrations, and at incremental calcium concentrations in the presence of levosimendan. In contrast, levosimendan did significantly increase the calcium-sensitivity of force in human single cardiomyocytes. Protein analysis confirmed that the slow skeletal/cardiac troponin C isoform was present in the skeletal muscle fibers tested. These findings indicate that levosimendan does not improve the contractility in human skeletal muscle fibers, and do not provide rationale for using levosimendan as a therapeutic to restore muscle weakness in NEB-NM patients. We stress the

  1. Altered RyR2 regulation by the calmodulin F90L mutation associated with idiopathic ventricular fibrillation and early sudden cardiac death.

    Science.gov (United States)

    Nomikos, Michail; Thanassoulas, Angelos; Beck, Konrad; Vassilakopoulou, Vyronia; Hu, Handan; Calver, Brian L; Theodoridou, Maria; Kashir, Junaid; Blayney, Lynda; Livaniou, Evangelia; Rizkallah, Pierre; Nounesis, George; Lai, F Anthony

    2014-08-25

    Calmodulin (CaM) association with the cardiac muscle ryanodine receptor (RyR2) regulates excitation-contraction coupling. Defective CaM-RyR2 interaction is associated with heart failure. A novel CaM mutation (CaM(F90L)) was recently identified in a family with idiopathic ventricular fibrillation (IVF) and early onset sudden cardiac death. We report the first biochemical characterization of CaM(F90L). F90L confers a deleterious effect on protein stability. Ca(2+)-binding studies reveal reduced Ca(2+)-binding affinity and a loss of co-operativity. Moreover, CaM(F90L) displays reduced RyR2 interaction and defective modulation of [(3)H]ryanodine binding. Hence, dysregulation of RyR2-mediated Ca(2+) release via aberrant CaM(F90L)-RyR2 interaction is a potential mechanism that underlies familial IVF.

  2. A coarse-grained model to study calcium activation of the cardiac thin filament

    Science.gov (United States)

    Zhang, Jing; Schwartz, Steven

    2015-03-01

    Familial hypertrophic cardiomyopathy (FHC) is one of the most common heart disease caused by genetic mutations. Cardiac muscle contraction and relaxation involve regulation of crossbridge binding to the cardiac thin filament, which regulates actomyosin interactions through calcium-dependent alterations in the dynamics of cardiac troponin (cTn) and tropomyosin (Tm). An atomistic model of cTn complex interacting with Tm has been studied by our group. A more realistic model requires the inclusion of the dynamics of actin filament, which is almost 6 times larger than cTn and Tm in terms of atom numbers, and extensive sampling of the model becomes very resource-demanding. By using physics-based protein united-residue force field, we introduce a coarse-grained model to study the calcium activation of the thin filament resulting from cTn's allosteric regulation of Tm dynamics on actin. The time scale is much longer than that of all-atom molecular dynamics simulation because of the reduction of the degrees of freedom. The coarse-grained model is a good template for studying cardiac thin filament mutations that cause FHC, and reduces the cost of computational resources.

  3. 真彩色图像体视学分析系统对心脏功能受损的评估%Evaluation of impaired cardiac function by true color image and sterotic analysis system

    Institute of Scientific and Technical Information of China (English)

    陈文笔; 田瑞霞; 严家春; 马勇; 徐长江

    2001-01-01

    @@Background:Some studies showed the significance of troponin-T in the diagnosis of acute myocardial ischemia.A number of studies evaluated level of troponin-T in blood,no expression of troponin-T has been reported. Objective:To investigate significance of troponin-T in abnormal cardiac function. Design:Descending anterior branch of left coronary artery in pigs was ligated to establish ischemic acute cardiac infarction model.Myocardial necrosis and expression of troponin-T in cardiac tissue were showed by histochemical techniques and immunohistochemical techniques respectively.Quantitative analysis of expression of troponin-T was performed with true color image and sterostatic analysis system.

  4. Review article: elevated troponin: diagnostic gold or fool's gold?

    Science.gov (United States)

    Rahman, Atifur; Broadley, Simon A

    2014-04-01

    Troponin is a highly sensitive biomarker of myocardial injury and has been used extensively in everyday clinical practice in the community as well as in hospitals for the diagnosis of acute myocardial infarction (AMI) and for risk stratification of patients with acute coronary symptoms. Dynamic elevations in biomarkers (troponin) are considered fundamental to the diagnosis of AMI. Unfortunately, many clinical conditions can cause troponin elevation in the absence of myocardial ischaemia, and elevated levels sometimes pose a diagnostic dilemma. In some cases, inappropriate diagnosis of 'AMI' based primarily on a raised troponin can have a deleterious impact on an individual, including on driving, insurance and other medicolegal matters. An incorrect diagnosis of myocardial infarction can also lead to the oversight of serious life-threatening alternative causes of troponin elevation (e.g. pulmonary embolism). This article discusses the role of troponin in our everyday clinical practice in the ED.

  5. 肌钙蛋白Ⅰ对老年不稳定型心绞痛患者危险分层的判断价值%The value of cardiac troponin Ⅰ in risk stratification of elderly patients with unstable angina pectoris

    Institute of Scientific and Technical Information of China (English)

    党彦平; 耿秀双

    2009-01-01

    Objective To study the value of serum troponin I(cTnI)in risk stratification of elderly patients with unstable angina pectoris(UAP).Methods Serum cTnI levels were measured in 22 healthy subjects(control group),27 stable angina peetoris(SAP)and 72 UAP elderly patients,respectively.Cardiac events(non fatal myocardial infarction,cardiac sudden death)were observed within 1 month of hospitalization.Serum cTnI≥1.5 μg/L was considered as the cutoff level for myocardial damage.Results Serum cTnI levels in the UAP group were higher than those in the SAP and control group [(1.96±0.61)μg/L,(0.68±0.19)μg/L and(0.46±0.10)μg/L,respectively](P<0.01).In the UAP group,serum cTnI levels increased with increase of Braunwald classification class[(1.25±0.38)μg/L,(2.12±0.34)μg/L and(3.06±0.72)μg/L,respectively](P<0.05).In Braunwald class Ⅲ patients,the rate of cardiac events in patients with serum cTnI≥1.5 μg/L was much higher than that in those with cTnI<1.5μg/L(16.7%vs 6.3%,P<0.05),risk ratio 2.05(95%confidence limit 1.02-9.78).The positive predictive value of serum cTnI≥1.5μg/L for cardiac events was 44.3%and the negative predictive value was 84.8%.Conclusions Detection of serum cTnI has clinical value in risk stratification of elderly atients with UAP.%目的 探讨心脏肌钙蛋白Ⅰ(cTnI)对老年不稳定型心绞痛(UAP)患者危险分层的价值.方法 对72例老年UAP患者、27例稳定型心绞痛(SAP)患者及22例健康对照者分别进行血清cTnI测定,并观察住院1个月内心脏事件发生情况.结果 UAP组血清cTnI值为(1.96±0.61)μg/L,明显高于SAP组的(0.68±0.19)μg/L及对照组的(0.46±0.10)μg/L(P均<0.01).UAP组内,随着Braunwald临床分级增高,Ⅰ~Ⅲ级血清cTnI值相应增高[分别为(1.25±0.38)μg/L、(2.12±0.34)μg/L及(3.06±0.72)μg/L](P<0.05).对照组、SAP组及Braunwald Ⅰ级UAP患者无一例发生心脏事件;18例Ⅱ级患者中,1例(其血清cTnI≥1.5μg/L)发

  6. Fluorescence Based Characterization of Calcium Sensitizer Action on the Troponin Complex

    Energy Technology Data Exchange (ETDEWEB)

    Schlecht, William; Li, King-Lun; Hu, Dehong; Dong, Wen-Ji

    2016-02-01

    By examining the behavior of each Ca2+ -sensitizer on cTnC at different levels of reconstitution (cTnI-cTnC, full troponin, or full troponin in thin filament) the importance of these proteins on sensitizer efficacy was evaluated, lending insight into the mechanism of action behind each drug. A fluorescence based approach was used to monitor the opening and closing of cardiac troponin C's hydrophobic pocket in the presence and absence of four common Ca2+ -sensitizers: EMD 57033, levosimendan, bepridil and pimobendan. Ca2+ -titration experiments were employed to determine the effect on Ca2+- sensitivity and cooperativity of cTnC opening, while stopped flow experiments were used to investigate the impact on cTnC relaxation kinetics. This study shows EMD 57033 is unable to sensitize cTnC to Ca2+, and likely requires the presence of myosin to illicit a response. Levosimendan, bepridil, and pimobendan were all able to increase the sensitivity of cTnC for Ca2+ to varying degrees; levosimendan and pimobendan reduced the rate of cTnC closing, while bepridil increased this rate. Additionally the same experiments were run on thin filament samples containing cTnT (T204E), a known Ca2+- blunting phosphorylation mimic. Levosimendan, bepridil, and pimobendan were found to elevate the Ca2+-sensitivity of cTnT(T204E) containing thin filaments to within range of the wild type thin filaments.

  7. Troponin elevation after noncardiac surgery: Significance and management.

    Science.gov (United States)

    Horr, Samuel; Reed, Grant; Menon, Venu

    2015-09-01

    How to interpret and manage troponin elevations after noncardiac surgery is a common clinical question for cardiologists and internists. An estimated 5% to 25% of patients who undergo noncardiac surgery have an elevated postoperative troponin level. Patients with troponin elevation are at higher short-term and long-term risk of morbidity and mortality. Current guidelines provide few recommendations on how to manage these patients. The authors review the evidence and guidelines and propose treatment strategies.

  8. The regulation of troponins I, C and ANP by GATA4 and Nkx2-5 in heart of hibernating thirteen-lined ground squirrels, Ictidomys tridecemlineatus.

    Directory of Open Access Journals (Sweden)

    Bryan E Luu

    Full Text Available Hibernation is an adaptive strategy used by various mammals to survive the winter under situations of low ambient temperatures and limited or no food availability. The heart of hibernating thirteen-lined ground squirrels (Ictidomys tridecemlineatus has the remarkable ability to descend to low, near 0°C temperatures without falling into cardiac arrest. We hypothesized that the transcription factors GATA4 and Nkx2-5 may play a role in cardioprotection by facilitating the expression of key downstream targets such as troponin I, troponin C, and ANP (atrial natriuretic peptide. This study measured relative changes in transcript levels, protein levels, protein post-translational modifications, and transcription factor binding over six stages: euthermic control (EC, entrance into torpor (EN, early torpor (ET, late torpor (LT, early arousal (EA, and interbout arousal (IA. We found differential regulation of GATA4 whereby transcript/protein expression, post-translational modification (phosphorylation of serine 261, and DNA binding were enhanced during the transitory phases (entrance and arousal of hibernation. Activation of GATA4 was paired with increases in cardiac troponin I, troponin C and ANP protein levels during entrance, while increases in p-GATA4 DNA binding during early arousal was paired with decreases in troponin I and no changes in troponin C and ANP protein levels. Unlike its binding partner, the relative mRNA/protein expression and DNA binding of Nkx2-5 did not change during hibernation. This suggests that either Nkx2-5 does not play a substantial role or other regulatory mechanisms not presently studied (e.g. posttranslational modifications are important during hibernation. The data suggest a significant role for GATA4-mediated gene transcription in the differential regulation of genes which aid cardiac-specific challenges associated with torpor-arousal.

  9. Comparison of Point-of-Care Versus Laboratory Troponin Testing in an Emergency Department Setting.

    Science.gov (United States)

    Juliano, Michael; Wason, Courtney

    2017-07-01

    There have been concerns regarding troponin results accuracy between point-of-care (POC) testing preformed in an emergency department (ED) setting and laboratory testing. The purpose of this study was to compare the results of cardiac troponin I testing as concerns POC testing and laboratory analysis as a way to show that these results are interchangeable. A retrospective chart review was performed from October 2012 through September 2013 to identify all patients who presented to the ED that received both a POC and laboratory troponin associated with the same blood draw. A total of 189 patients met inclusion criteria. Three laboratory samples were hemolyzed and not available for comparison. Of the remaining 186 samples, when a positive cutoff value of 0.034 ng/mL was used: 37 POC tests were positive and 149 POC tests were negative, sensitivity 0.85 (95% confidence interval [CI] = 0.69-0.94), specificity 0.98 (95% CI = 0.94-0.99), positive predictive value 91.9% (95% CI = 77-97.9%), and negative predictive value 96% (95% CI = 91.1-98.4%). When a POC troponin positive cutoff value of 0.12 ng/mL was used: 20 POC tests were positive and 164 were negative: sensitivity 1.0 (95% CI = 0.8-1.0), specificity 0.99 (95% CI = 0.95-1.0), positive predictive value 91% (95% CI = 69-98.4%), and negative predictive value 100% (95% CI = 97.1-100%). In an ED setting; POC testing is accurate and correlates well with laboratory testing. Considering that the POC analysis takes a fraction of time to yield results, the validity of its data is important. The results of this study show that the POC system is a suitable test for rapid evaluation of patients presenting to the ED. This correlation increased with a higher testing positive cutoff value (0.12 versus 0.034 ng/mL). These data can assist the emergency physician with rapid identification of evidence of cardiac injury and be assured that the results are accurate. POC lab testing should be considered whenever possible to provide the

  10. Neonatal multiorgan failure due to ACAD9 mutation and complex I deficiency with mitochondrial hyperplasia in liver, cardiac myocytes, skeletal muscle, and renal tubules.

    Science.gov (United States)

    Leslie, Nancy; Wang, Xinjian; Peng, Yanyan; Valencia, C Alexander; Khuchua, Zaza; Hata, Jessica; Witte, David; Huang, Taosheng; Bove, Kevin E

    2016-03-01

    Complex I deficiency causes Leigh syndrome, fatal infant lactic acidosis, and neonatal cardiomyopathy. Mutations in more than 100 nuclear DNA and mitochondrial DNA genes miscode for complex I subunits or assembly factors. ACAD9 is an acyl-CoA dehydrogenase with a novel function in assembly of complex I; biallelic mutations cause progressive encephalomyopathy, recurrent Reye syndrome, and fatal cardiomyopathy. We describe the first autopsy in fatal neonatal lethal lactic acidosis due to mutations in ACAD9 that reduced complex I activity. We identified mitochondrial hyperplasia in cardiac myocytes, diaphragm muscle, and liver and renal tubules in formalin-fixed, paraffin-embedded tissue using immunohistochemistry for mitochondrial antigens. Whole-exome sequencing revealed compound heterozygous variants in the ACAD9 gene: c.187G>T (p.E63*) and c.941T>C (p.L314P). The nonsense mutation causes late infantile lethality; the missense variant is novel. Autopsy-derived fibroblasts had reduced complex I activity (53% of control) with normal activity in complexes II to IV, similar to reported cases of ACAD9 deficiency.

  11. Prognostic Impact of Myocardial Injury Related to Various Cardiac and Noncardiac Conditions

    DEFF Research Database (Denmark)

    Sarkisian, Laura; Saaby, Lotte; Poulsen, Tina S;

    2016-01-01

    were classified into 5 categories of plausible related conditions: cardiac ischemic, cardiac nonischemic, noncardiac, multifactorial, or indeterminate. Follow-up was a minimum of 3 years, with all-cause mortality as the single end-point. RESULTS: A total of 3762 patients were considered, of whom 1089......BACKGROUND: Elevated cardiac troponins in clinical conditions other than myocardial infarction are well known. For such occurrences, the term "myocardial injury" has been proposed. The long-term outcome in patients with myocardial injury related to various cardiac and noncardiac clinical disorders...... is unknown. METHODS: During January 2010 to January 2011, we prospectively studied hospitalized patients who had cardiac troponin I measured on clinical indication. Patients with cardiac troponin I values >30 ng/L and no evidence of myocardial ischemia were diagnosed as having myocardial injury. Patients...

  12. Proteomic identification of putative biomarkers for early detection of sudden cardiac death in a family with a LMNA gene mutation causing dilated cardiomyopathy.

    Science.gov (United States)

    Izquierdo, Irene; Rosa, Isaac; Bravo, Susana Belén; Guitián, Esteban; Pérez-Serra, Alexandra; Campuzano, Oscar; Brugada, Ramon; Mangas, Alipio; García, Ángel; Toro, Rocio

    2016-10-04

    Dilated cardiomyopathy (DCM) is a severe heart disease characterized by progressive ventricular dilation and impaired systolic function of the left ventricle. We recently identified a novel pathogenic mutation in the LMNA gene in a family affected by DCM showing sudden death background. We now aimed to identify potential biomarkers of disease status, as well as sudden death predictors, in members of this family. We analysed plasma samples from 14 family members carrying the mutation, four of which (with relevant clinical symptoms) were chosen for the proteomic analysis. Plasma samples from these four patients and from four sex- and age-matched healthy controls were processed for their enrichment in low- and medium-abundance proteins (ProteoMiner™) prior to proteomic analysis by 2D-DIGE and MS. 111 spots were found to be differentially regulated between mutation carriers and control groups, 83 of which were successfully identified by MS, corresponding to 41 different ORFs. Some proteins of interest were validated either by turbidimetry or western blot in family members and healthy controls. Actin, alpha-1-antytripsin, clusterin, vitamin-D binding protein and antithrombin-III showed increased levels in plasma from the diseased group. We suggest following these proteins as putative biomarkers for the evaluation of DCM status in LMNA mutation carriers. We developed a proteomic analysis of plasma samples from a family showing history of dilated cardiomyopathy caused by a LMNA mutation, which may lead to premature death or cardiac transplant. We identified a number of proteins augmented in mutation carriers that could be followed as potential biomarkers for dilated cardiomyopathy on these patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. 高敏心肌肌钙蛋白在不稳定型心绞痛心肌早期损伤诊断的应用研究%Study of application of high-sensitivity cardiac troponin in diagnosis of early myocardial damage in unstable angina pectoris

    Institute of Scientific and Technical Information of China (English)

    陈波; 杨万勇; 周利龙; 郭乃芸; 程奎山; 曾庆贤

    2012-01-01

    Objective To investigate the value of serum high-sensitivity cardiac troponin T (hs-cTnT) determination in the early clinical diagnosis of minor myocardial damage of unstable angina pectoris (UAP). Methods For the 60 patients diagnosed with UAP, the venous blood was collected for hs-cTnT test at the 2nd, 6th, 8th, 12th and 24th hour of chest pain attack. The UAP group, the SAP group and the healthy control group were compared; the low, medium and high risk groups were compared. Results At the 2nd hour of chest pain attack, positive samples appeared in the patients of the UAP group. The serum positive rate was 53.3% in the UAP group, which was higher than the 13.3% in the SAP group and 1.7% in the control group, with significant differences (P < 0.05); among UAP patients, the positive rates of medium and high risk groups were 78.9% and 93.7%, which were significantly higher than the 5.3% of the low risk group (P < 0.05). Conclusion Serum hs-cTnT determination is a sensitive and specific indicator reflecting patients' early myocardial damage, and is of high clinical value in the early diagnosis of minor myocardial damage in patients with unstable angina pectoris.%目的 探讨血清高敏心肌肌钙蛋白T(hs-cTnT)测定在不稳定型心绞痛(UAP)患者心肌轻微损伤的早期临床诊断价值.方法 检测最终确诊的60例不稳定型心绞痛患者,分别于胸痛发作2、6、8、12、24 h采静脉血进行hs-cTnT检测,分别对UAP组与稳定型心胶痛(SAP)组及健康对照组低、中、高危险组间患者进行比较.结果 UAP患者胸痛2 h既有阳性标本出现,UAP组血清阳性率为53.3%,高于SAP组的13.3%和对照组的1.7%,差异有统计学意义(P < 0.05);UAP患者中、高危险组阳性率为78.9%和93.7%,明显高于低危险组的5.3%(P < 0.05).结论 血清hs-cTnT测定是反映患者心肌早期损伤的敏感性和特异性指标,对UAP患者轻微心肌损伤的早期诊断有较高临床价值.

  14. 慢性肾脏病心肌损害与心型脂肪酸结合蛋白及心肌钙蛋白的相关性分析%Correlation Analysis of Heart Type Fatty Acid Binding Protein and Cardiac Troponin with Myocardial Damage in Chronic Kidney Disease

    Institute of Scientific and Technical Information of China (English)

    谢瑜; 沈颖; 罗惠民; 周晓萍; 江勇

    2015-01-01

    分析心型脂肪酸结合蛋白(HFABP)及心肌钙蛋白(cTnI)对慢性肾脏病(CKD)患者缺血性心肌损害的评估应用价值.选取非透析的慢性肾脏病患者,进行腺苷负荷心肌灌注显像检查,同时检测 HFABP、cTnI,并与腺苷负荷试验结果进行对比分析,明确 HFABP 及 cTnI 对缺血性心肌损害的评估价值.结果发现 HFABP 与 eGFR 负相关,与 CREA、BUN 正相关,cTnI 与 IVST、LVPWT 正相关,有31.1%的患者腺苷负荷心肌灌注显像试验阳性,HFABP 在腺苷负荷试验阳性组及阴性组患者间的差异无统计学意义,cTnI 的差异有统计学意义,腺苷负荷试验阳性结果与HFABP 不相关(r =0.041,P =0.654),与 cTnI 正相关(r =0.649,P <0.01).结果表明:HFABP受肾小球滤过率的影响较大,不是反映慢性肾脏病患者缺血性心脏损害的理想指标,cTnI 不受年龄和肾功能的直接影响,是腺苷负荷心肌灌注缺损的独立危险因素,腺苷负荷核素心肌灌注显像是评估 CKD 患者冠状动脉疾病的有效手段.%The ischemic myocardial damage evaluation value of heart type fatty acid binding protein and cardiac troponin I in CKD patients is explored in this paper.Adenosine stress myocardial perfusion imaging is performed to all patients whose levels of HFABP and cTnI are also measured and compared with adenosine stress test results to assess the ischemic myocardial damage evaluation value of HFABP and cTnI.It is observed that HFABP is negatively correlated with eGFR,and positively correlated to CREA and BUN,and that cTnI is positive corre-lated with IVST and LVPWT.31.1% patients have positive results in adenosine stress test,the positive results being positively correlated with cTnI(r =0.649,P <0.01),and having no correlation with HFABP (r =0.041, P =0.654).The results show that HFABP is strongly influenced by glomerular filtration rate,and thus not an i-deal index of

  15. Prognostic implications of myocardial creatine kinase and cardiac troponin in coronary artery bypass surgery Implicação prognóstica da creatino-quinase miocárdica e troponina na revascularização do miocárdio

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    Fábio P. Taniguchi

    2003-09-01

    Full Text Available OBJECTIVES: To evaluate the prognostic implications of myocardial creatine kinase and troponin I (cTn I in blood samples from the coronary sinus of patients submitted to coronary artery bypass surgery both with and without ischemic preconditioning. METHODS: From October 1998 to May 1999, 35 patients with coronary artery disease who were submitted to coronary artery bypass surgery were studied. Samples containing creatine kinase and cTn I were obtained from the great cardiac vein during surgery at the onset of cardiopulmonary bypass, at the end of the first anastomosis, and at the end of cardiopulmonary bypass. In May 2002, 29 patients were evaluated in regards to the angina functional class, congestive heart failure, number of hospitalizations, myocardial infarction and death. There were 15 patients in the Preconditioned group and 14 in the Control group. Each group was subdivided into patients with and without cardiovascular symptoms. RESULTS: The Control and Preconditioned groups were not significantly different in relation to frequency of cardiovascular symptoms. There were progressive increases of the creatine kinase and cTn I levels at different Interval s of the study. The cTn I in the Preconditioned group was 1.21 ± 0.64 ng/mL and 3.19 ± 3.21 ng/mL in the Control group (pOBJETIVO: Avaliar a implicação prognóstica da dosagem da creatino-quinase miocárdica (CKMB e Troponina I (cTn I em amostras no seio coronariano, na evolução de pacientes submetidos a revascularização do miocárdio (RM, com e sem o pré-condicionamento isquêmico. MÉTODO: Entre outubro de 1998 e maio de 1999, 35 pacientes com insuficiência coronariana foram submetidos a RM foram estudados. No intra-operatório foram coletadas amostras do seio coronariano para dosagem de CKMB e cTn I. Os momentos de coleta foram: momento 1-no início da circulação extracorpórea (CEC, momento 2- após a primeira anastomose e momento 3- no final da CEC. Em maio de 2002, 29

  16. The influence of hemolysis, turbidity and icterus on the measurements of CK-MB, troponin I and myoglobin.

    Science.gov (United States)

    Kwon, Hi J; Seo, Eun J; Min, Ki O

    2003-03-01

    To decide on the acceptability of a specimen for the measurement of serum CK-MB, troponin I and myoglobin, we investigated the influence of hemolysis, turbidity, and icterus on those tests by adding arbitrarily made interferents. A total of 16 cases each for CK-MB and troponin I, and 18 cases for myoglobin tests were studied to verify the effects of hemolysis, turbidity, and unconjugated hyperbilirubinemia. A total of 16 cases were studied to clarify the effects of the conjugated hyperbilirubinemia. We graded the severity of hemolysis, turbidity, and icterus as mild, moderate, and severe after adding hemolysate, Intralipos (20% soybean oil), and unconjugated or conjugated bilirubin to sera. ACS180SE automated chemiluminescence system was used to measure CK-MB, troponin I, and myoglobin. CK-MB and troponin I were affected by any degree of hemolysis, turbidity, unconjugated hyperbilirubinemia, and conjugated hyperbilirubinemia, while myoglobin was affected only by severe unconjugated hyperbilirubinemia and conjugated hyperbilirubinemia in the samples with concentration higher than reference range, resulting in concentration level lower than baseline. In conclusion, the results of cardiac markers should be carefully interpreted when the specimens are hemolyzed, turbid or icteric.

  17. 高敏C反应蛋白联合高敏心肌肌钙蛋白T对急性冠状动脉综合征患者预后的判断价值%The value of high-sensitivity C-reactive protein combined with high-sensitivity cardiac troponin T for prognosis of patients with acute coronary syndrome

    Institute of Scientific and Technical Information of China (English)

    李永勤; 范艳梅; 薛嘉红; 张春燕; 张岩; 栾春红

    2014-01-01

    Objective To investigate the value of high-sensitivity C-reactive protein (hs-CRP) combined with high-sensitivity cardiac troponin T (hs-cTnT) for prognosis of patients with acute coronary syndrome (ACS).Methods One hundred and eighteen patients with ACS were selected from July 2011 to December 2012.According to the clinical feature,they were divided into unstable angina pectoris (UAP) group (38 cases),non ST segment elevation myocardial infarction (NSTEMI) group (38 cases) and ST segment elevation myocardial infarction (STEMI) group(42 cases).They were followed up for 3 months,and the incidence of cardiovascular events and cardiac death was observed.Twenty healthy people were selected as control group.Results The serum level of hs-CRP on admission in UAP group,STEMI group,NSTEMI group was higher than that in control group,and NSTEMI group was highest.And there was significant difference between NSTEMI group and STEMI group,and also between NSTEMI group and control group (P < 0.05).The serum level of hs-cTnI was increased in STEMI group and NSTEMI group.The increased degree in STEMI group was higher than that in NSTEMI group,and there was significant difference (P <0.05).The incidence of cardiovascular events and cardiac death within 3 months after discharge in patients with the serum level of hs-CRP ≥ 3 mg/L on admission in UAP group and NSTEMI group,STEMI group was 6/11,40.0% (12/30),46.4% (13/28),which was higher than that in patients with the serum level of hs-CRP < 3 mg/L[11.1%(3/27),3/8,5/14],and there was significant difference(P< 0.05).The incidence of cardiovascular events and cardiac death within 3 months after discharge in patients with the serum level of hs-cTnT≥ 1.0 μ g/L on admission in NSTEMI group and STEMI group was 16.7%(5/30) and 18.4%(7/38),which was higher than that in patients with the serum level of hs-cTnT < 1.0 μ g/L (1/8,1/4),and there was significant difference (P < 0.05).Conclusion Significantly increased hs

  18. Electrocardiographic Findings and Serum Troponin I in Carbon Monoxide Poisoned Patients

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    Scott Reza Jafarian Kerman

    2012-03-01

    Full Text Available Carbon monoxide (CO poisoning, though with different sources, is one of the most deadly emergencies in all countries. CO can threaten men's life by several paths especially cardiac complications, which can mimic other cardiac problems such as myocardial infarction. The objective of this study was to determine ECG findings and serum troponin I levels in CO poisoned patients. In this analytical cross-sectional study, 63 CO poisoning patients were consecutively included from hospital's emergency departments. CO content was measured by a CO-oximeter and an electrocardiography was taken first thing on admission. Arterial blood gas (ABG, troponin I and other data was collected afterwards. Data were divided by age groups (adults and children and gender. CO content was significantly higher only in subjects with normal T wave compared to patients with inverted T wave in their initial ECG (P=0.016. No other significant difference was noticed. None of the ABG findings correlated significantly with CO content. Also no significant correlation was found with CO content after stratification by gender and age groups, but pH in children (r=-0.484, P=0.026. CO content was significantly higher in adults (P=0.023, but other ABG data were not significantly different. Only 3 patients had elevated troponin I. Receiver operating characteristic (ROC analysis showed no significant cutoff points in CO content for ECG changes. No significant specific change in electrocardiograms (ECG could contribute carboxyhemoglobin content in carbon monoxide poisoned patients. In addition, no specific difference was found between adults and pediatric subjects' ECGs. All other findings seemed to be accidental.

  19. Fundamental concepts of effective troponin use: important principles for internists.

    Science.gov (United States)

    Sara, Jaskanwal D S; Holmes, David R; Jaffe, Allan S

    2015-02-01

    Troponin testing is an essential component of our diagnostic approach to patients in acute medical care settings. With the advent of high-sensitivity troponin assays, its importance will extend to patients in chronic disease settings. Although elevated troponin levels provide diagnostic information, inform treatment decisions, and influence patient prognosis, proper interpretation of the values is essential. This requires an understanding of the operating characteristics of troponin testing; the likelihood ratios associated with a positive/negative test result and the pre- and post-test probabilities related to individual clinical settings. These principles will become more important as high-sensitivity assays become introduced over the coming years in the United States. This article reviews the important principles of troponin testing focusing in particular on acute settings and is aimed at internal medicine and hospital specialists.

  20. Relationship of cardiac troponin I peak and short-term prognosis of acute myocardial infarction patients%肌钙蛋白峰值与急性心肌梗死患者早期预后的关系探讨

    Institute of Scientific and Technical Information of China (English)

    周一薇; 黄飞翔

    2011-01-01

    Objective To observe the influence of cardiac troponin I (cTnI) peak on the patients with acute myocardial infarction(AMI) on the short-term prognosis and to investigate the relationship between different peak levels and prognosis.Methods According to cTnI peak level,162 cases of patients with AMI divided into 3 groups:Group A (cTnI <6 μg/L),Group B (cTnI 6 ~60 μg/L) and Group C (cTnI >60 μg/L).The relationship between different cTnI peak levels and left ventricular ejection fraction (LVEF),heart failure,heart source shock,rate of cardiac death were compared.Results Group A had no deaths,the rates of heart source shock and newly heart failure were the lowest.Mortality of group B was 4.16%,the rates of heart source shock and newly heart failure were respectively 7.29% and 18.87%.In group C mortality was 27.77%,and the rate of heart source shock was 38.89%.The new heart failure rate was 55.56%,higher than group A and B.Conclusions The cTnI peak level is closely related to the short-term prognosis of AMI.The higher the cTnI peak level is,the worse the short-term prognosis is.Furthermore the lower the LVEF is,the higher incidence of heart failure,heart source shock and death there is.%目的 探讨急性心肌梗死( AMI)患者肌钙蛋白I(cTnI)峰值与早期预后的相关性.方法 收集2008年1月至2010年12月本院住院AMI患者162例的临床资料进行回顾性分析.根据cTnI峰值水平将患者分为A(cTnI <6 μg/L)、B( cTnI 6~60μg/L)、C(cTnI> 60 μg/L)3组,分别为48、96、18例.分析不同cTnI峰值水平与左心室射血分数(LVEF)、心源性休克发生率、新发心力衰竭发生率和院内死亡率之间的相关性.结果 A、B、C组cTnI峰值及LVEF分别为(2.4±1.6) μg/L、(55.5±4.3)%,(22.8士14.2)μg/L、(52.8±4.7)%,( 157.4±115.9) μg/L、(45.2±5.2)%.A组cTnI峰值最低,而LVEF值最高;C组cTnI峰值最高,而LVEF值则最低.A组与B组LVEF差异无统计学意义(P>0.05),而C组与A

  1. Titin and troponin: central players in the frank-starling mechanism of the heart.

    Science.gov (United States)

    Fukuda, Norio; Terui, Takako; Ohtsuki, Iwao; Ishiwata, Shin'ichi; Kurihara, Satoshi

    2009-05-01

    The basis of the Frank-Starling mechanism of the heart is the intrinsic ability of cardiac muscle to produce greater active force in response to stretch, a phenomenon known as length-dependent activation. A feedback mechanism transmitted from cross-bridge formation to troponin C to enhance Ca(2+) binding has long been proposed to account for length-dependent activation. However, recent advances in muscle physiology research technologies have enabled the identification of other factors involved in length-dependent activation. The striated muscle sarcomere contains a third filament system composed of the giant elastic protein titin, which is responsible for most passive stiffness in the physiological sarcomere length range. Recent studies have revealed a significant coupling of active and passive forces in cardiac muscle, where titin-based passive force promotes cross-bridge recruitment, resulting in greater active force production in response to stretch. More currently, the focus has been placed on the troponin-based "on-off" switching of the thin filament state in the regulation of length-dependent activation. In this review, we discuss how myocardial length-dependent activation is coordinately regulated by sarcomere proteins.

  2. The content and distribution of troponin I, troponin T, myoglobin, and alpha-hydroxybutyric acid dehydrogenase in the human heart

    NARCIS (Netherlands)

    Swaanenburg, JCJM; Visser-VanBrummen, PJ; DeJongste, MJL; Tiebosch, ATHM

    2001-01-01

    We studied the content and distribution of heart-specific markers troponin I and troponin T in relation to conventional non-heart specific myoglobin and alpha-hydroxybutyric acid dehydrogenase (HBD) in the hearts of 34 patients who died of various causes. Tissue was obtained from the right and left

  3. Human SCN5A gene mutations alter cardiac sodium channel kinetics and are associated with the Brugada syndrome

    NARCIS (Netherlands)

    Rook, Martin B.; Alshinawi, CB; Groenewegen, WA; van Gelder, IC; van Ginneken, ACG; Jongsma, Habo J.; Mannens, MMAM; Wilde, AAM

    1999-01-01

    Background: Primary dysrhythmias other than those associated with the long QT syndrome, are increasingly recognized. One of these are represented by patients with a history of resuscitation from cardiac arrest but without any structural heart disease. These patients exhibit a distinct electrocardiog

  4. Can troponin T levels be useful in the diagnosis of rheumatic carditis?

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    Mehmet Halil Ertug

    2011-01-01

    Full Text Available Objective: Acute rheumatic fever (ARF is an endemic disease observed in children of developing countries. The purpose of this study was to test if it was possible to identify myocardial involvement in cases with rheumatic carditis by the measurement of serum cardiac TnT. Methods: 30 patients diagnosed as ARF underwent echocardiography and their cardiac troponin T (cTnT serum levels were measured. Patients were divided into group 1: Arthritis alone, group 2: carditis, and group 3 carditis with congestive heart failure (CHF. Results: cTnT serum levels were normal in all except one patient with in group 3. Two patients in carditis (group 2 and three patients in CHF (group 3 had dilation in left ventricular end diastolic diameter. Conclusions: Normal cTnT levels in our patient group suggests that inflammation rather than myocardial necrosis is predominant in ARF carditis.

  5. Ca2+ dependence of the distance between Cys-98 of troponin C and Cys-133 of troponin I in the ternary troponin complex. Resonance energy transfer measurements.

    Science.gov (United States)

    Tao, T; Gowell, E; Strasburg, G M; Gergely, J; Leavis, P C

    1989-07-11

    We have used resonance energy transfer to study the spatial relationship between Cys-98 of rabbit skeletal troponin C and Cys-133 of rabbit skeletal troponin I in the reconstituted ternary troponin complex. The donor was introduced by labeling either troponin C or troponin I with N-(iodoacetyl)-N'-(5-sulfo-1-naphthyl)ethylenediamine, while the acceptor was introduced by labeling either protein with N-[4-(dimethylamino)phenyl-4'-azophenyl]maleimide. The extent of energy transfer was determined by measuring the quenching of the donor fluorescence decay. The results indicate first that the distance between these two sites is not fixed, suggesting that the protein regions involved possess considerable segmental flexibility. Second, the mean distance between the two sites is dependent on the metal-binding state of troponin C, being 39.1 A when none of the metal-binding sites are occupied, 41.0 A when Mg2+ ions bind at the high-affinity sites, and 35.5 A when Ca2+ ions bind to the low-affinity sites. Neither the magnitude of the distances nor the trend of change with metal ions differs greatly when the locations of the probes are switched or when steady-state fluorometry was used to determine the transfer efficiency. Since the low-affinity sites have been implicated as the physiological triggering sites, our findings suggest that one of the key events in Ca2+ activation of skeletal muscle contraction is a approximately 5-A decrease in the distance between the Cys-98 region of troponin C and the Cys-133 region of troponin I.

  6. Solution conformation of the C-terminal domain of skeletal troponin C. Cation, trifluoperazine and troponin I binding effects.

    Science.gov (United States)

    Drabikowski, W; Dalgarno, D C; Levine, B A; Gergely, J; Grabarek, Z; Leavis, P C

    1985-08-15

    Proton magnetic resonance spectroscopy has been used to study the cation (Mg2+, Ca2+)-dependent conformational states of the C-terminal domain of rabbit skeletal troponin C under a variety of solution conditions. Nuclear Overhauser data and paramagnetic probe observations provide definition of the configuration of this region of troponin C. Comparative study of homologous proteins identify common features of the tertiary structure relevant to the cation binding reaction. Complex formation with troponin I and the drug trifluoperazine is observed to adjust the solution conformation of the C-terminal domain of troponin C. The interactive conformational response to cation coordination and the binding of the drug and troponin I are discussed.

  7. High sensitivity troponin and valvular heart disease.

    Science.gov (United States)

    McCarthy, Cian P; Donnellan, Eoin; Phelan, Dermot; Griffin, Brian P; Sarano, Maurice Enriquez-; McEvoy, John W

    2017-01-16

    Blood-based biomarkers have been extensively studied in a range of cardiovascular diseases and have established utility in routine clinical care, most notably in the diagnosis of acute coronary syndrome (e.g., troponin) and the management of heart failure (e.g., brain-natriuretic peptide). The role of biomarkers is less well established in the management of valvular heart disease (VHD), in which the optimal timing of surgical intervention is often challenging. One promising biomarker that has been the subject of a number of recent VHD research studies is high sensitivity troponin (hs-cTn). Novel high-sensitivity assays can detect subclinical myocardial damage in asymptomatic individuals. Thus, hs-cTn may have utility in the assessment of asymptomatic patients with severe VHD who do not have a clear traditional indication for surgical intervention. In this state-of-the-art review, we examine the current evidence for hs-cTn as a potential biomarker in the most commonly encountered VHD conditions, aortic stenosis and mitral regurgitation. This review provides a synopsis of early evidence indicating that hs-cTn has promise as a biomarker in VHD. However, the impact of its measurement on clinical practice and VHD outcomes needs to be further assessed in prospective studies before routine clinical use becomes a reality.

  8. Post-Pacing Abnormal Repolarization in Catecholaminergic Polymorphic Ventricular Tachycardia Associated with a Mutation in the Cardiac Ryanodine Receptor Gene (RyR2)

    Science.gov (United States)

    Nof, Eyal; Belhassen, Bernard; Arad, Michael; Bhuiyan, Zahurul A.; Antzelevitch, Charles; Rosso, Raphael; Fogelman, Rami; Luria, David; Eli-Ani, Dalia; Mannens, Marcel M.A.M.; Viskin, Sami; Eldar, Michael; Wilde, Arthur A.M.; Glikson, Michael

    2011-01-01

    Background Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease for which electrophysiological studies (EPS) have shown to be of limited value. Objective We present a CPVT family in which marked post-pacing repolarization abnormalities during EPS were the only consistent phenotypic manifestation of RyR2 mutation carriers. Methods The study was prompted by the observation of transient marked QT prolongation preceding initiation of ventricular fibrillation during atrial fibrillation in a boy with a family history of sudden cardiac death (SCD). Family members underwent exercise and pharmacologic ECG testing with epinephrine, adenosine and flecainide. Non-invasive clinical tests were normal in 10 patients evaluated, except for both epinephrine and exercise-induced ventricular arrhythmias in 1. EPS included bursts of ventricular pacing and programmed ventricular extrastimulation reproducing short-long sequences. Genetic screening involved direct sequencing of genes involved in LQTS as well as RyR2. Results Six patients demonstrated a marked increase in QT interval only in the first beat after cessation of ventricular pacing and/or extrastimulation. All 6 patients were found to have a heterozygous missense mutation (M4109R) in RyR2. Two of them, presenting with aborted SCD also had a second missense mutation (I406T- RyR2). Four family members without RyR2 mutations did not display prominent post-pacing QT changes. Conclusions M4109R- RyR2 is associated with a high incidence of SCD. The contribution of I406T to the clinical phenotype is unclear. In contrast to exercise testing, marked post-pacing repolarization changes in a single beat accurately predicted carriers of M4109R- RyR2 in this family. PMID:21699856

  9. Unusual towering elevation of troponin I after ST-elevation myocardial infarction and intensive monitoring with echocardiography post-percutaneous coronary intervention: a case report

    Directory of Open Access Journals (Sweden)

    Suryadevara Ramya

    2010-05-01

    Full Text Available Abstract Introduction The elevation of troponin levels directly corresponds to the extent of myocardial injury. Here we present a case of a robust rise in cardiac biomarkers that correspond to extensive damage to the myocardium but did not spell doom for our patient. It is important to note that, to the best of our knowledge, this is the highest level of troponin I ever reported in the literature after a myocardial injury in an acute setting. Case presentation A 53-year-old African American man with an unknown medical history presented to the emergency room of our hospital with chest pain associated with diaphoresis and altered mental status. He required emergency intubation due to acute respiratory failure and circulatory collapse within 10 minutes of his arrival. He was started on heparin and eptifibatide (Integrilin drips but he was taken immediately for c