UMLS:C0018801 - FACTA Search

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Query: UMLS:C0018801 (heart failure)
72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Differential diagnosis of patients who present with chest pain remains problematical. It has been shown that 11.8-7% of patients with acute myocardial infarction (AMI) are sent home from the emergency department (ED). Audit of our own ED has shown the incidence of missed prognostically significant myocardial damage to be 6.7%. Diagnostic criteria for AMI have classically been based on the triad of history, ECG and measurement of cardiac enzymes. The choice of 'cardiac enzymes' has been dictated by the evolution of laboratory techniques, commencing with measurement of aspartate transaminase and progressing to measurement of creatine kinase (CK) and its MB isoenzyme (CK-MB). Measurement of CK-MB has been shown by both clinical studies and rigorous statistical analysis to represent the best test for the diagnosis of AMI. The advent of real time immunoassay together with advances in therapeutic options for management of acute coronary syndromes (ACS) has resulted in a paradigm shift in the approach to laboratory testing. Immunoassay for CK-MB (CK-MB mass measurement) is diagnostically superior to CK-MB activity measurement and is the test of choice for 'classical' AMI. Development of immunoassays for the cardiac troponins, i.e. cardiac troponin T (cTnT) and cardiac troponin I (cTnI), has enhanced diagnostic specificity. These measurements are completely specific for cardiac damage, allow quantitation of the extent of infarction and are diagnostically superior to CK-MB measurement. Applications of this specificity have included the differential diagnosis of CK elevation in arduous physical training, detection of myocardial damage after DC cardioversion and prediction of ejection fraction. Of more interest is the utility of these markers in management of patients presenting without clear electrocardiographic changes. Diagnosis and management of patients presenting with ST segment elevation has been clarified by large clinical trials of thrombolytic agents. In such patients, thrombolysis is the treatment of choice. Patients presenting with ST segment elevation represents the minority of patients with probable ACS 9.6% of all patients presenting to our hospital. The majority require risk stratification into high- and low-risk groups. It is here that cardiac troponins have a major role. The measurement of cTnT has been shown in a large number of studies to enable risk stratification of patients with unstable angina. The combination of cTnT, admission ECG and stress ECG can be used for a comprehensive risk stratification of patients with unstable angina. The combination of cTnT, admission ECG and stress ECG can be used for a comprehensive risk stratification which can be completed by 24 h from admission, as well as allowing a safe discharge policy from the ED. Measurements of cardiac troponins can also be used to predict prognosis in patients with other diagnostic categories. Patients with cardiac failure can be risk stratified according to cTnT status. cTnT status on admission allows subdivision into high- and low-risk groups in patients presenting with ST segment elevation. Certainly, cTnT measurement can be incorporated into a clinical decision-making strategy to assign patients to investigation and management pathways. There is evidence that cTnT may be useful to guide therapeutic options. The major issue is one of cost. In the U.K. model of managed care with undemanding diagnostic standards, the role of cTnT will be to enhance clinical decision-making strategies, to provide accurate diagnosis and to reduce lengths of stay. This can be shown to have potential for major improvements in cost efficiency. Improvements in diagnostic accuracy can reduce inappropriate long-term drug therapy. In systems with a more aggressive laboratory investigation strategy, rationalization of test numbers will provide an immediate cost reduction while improving quality. Finally, use of point-of-care testing (POCT) means that biochemical testing can be pe
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PMID:Troponin T or troponin I or CK-MB (or none?). 985 34

The present authors recently suggested, on the basis of studies using polymerase chain reaction (PCR), that hepatitis C virus (HCV) infection is involved in the etiology or pathogenesis of cardiomyopathic disorders. They have also reported that the serum concentration of cardiac troponin T is an indicator of ongoing myocyte degeneration in patients with dilated cardiomyopathy (DCM) and hypothesized that its serial measurement may be a marker of therapeutic efficacy. This is the first case report of DCM and striated myopathy, associated with HCV infection, treated with interferon therapy guided by monitoring of serial serum concentrations of cardiac troponin T. Positive-plus strands of HCV RNA were found in the patient's myocardium, as well as plus and minus strands in the quadriceps muscle specimens. Serum levels of creatine kinase (CK), CK-MB and cardiac troponin T fell as serum HCV titers decreased during treatment with interferon, whereas conventional treatment of heart failure had no effect. Monitoring of serial serum concentrations of cardiac troponin T may allow the earlier diagnosis and treatment of patients with HCV-associated cardiomyopathy and improve their clinical course.
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PMID:Interferon treatment for dilated cardiomyopathy and striated myopathy associated with hepatitis C virus infection based on serial measurements of serum concentrations of cardiac troponin T. 1078 58

Dilated cardiomyopathy is one of the leading causes of heart failure and a primary cause for heart transplantation in patients below the age of 40 years. Despite major advances in diagnostic procedures such as examination of myocardial biopsies, the etiology remains unknown in many patients. Chronic inflammation or myocarditis and chronic alcohol abuse are considered two main etiologic factors in dilated cardiomyopathy. A third causal factor, namely genetic transmission of the disease, is at least as common as myocardial inflammation or toxic damage. Several prospective studies of relatives of patients with dilated cardiomyopathy proved that about 25-30% of all cases are of familial etiology. The most common mode of inheritance is autosomal dominant. Less frequently is the disease inherited as an X-chromosomal trait. Autosomal recessive and mitochondrial transmission is rare. The penetrance is highly variable and age dependent. Many relatives of patients with DCM show only minor cardiac abnormalities and it is unknown whether they progress to full cardiomyopathy in later life. Examination of families has identified so far eight disease genes, namely the dystrophin, tafazzin, cardiac actin, desmin, lamin A/C, delta- sarcoglycan, cardiac beta-myosin heavy chain, and cardiac troponin T gene. Certain mutations in lamin A/C cause conduction system disease and dilated cardiomyopathy, whereas other mutations cause in addition skeletal muscle myopathy. Dystrophin mutations are the cause of the rare X-linked dilated cardiomyopathy without skeletal muscle involvement and a progressive course in young men. Other mutations in the dystrophin gene, mainly deletions, are the cause of the muscular dystrophy Becker and Duchenne which also present with dilated cardiomyopathy. Mutations of the desmin, delta-sarcoglycan, the cardiac actin and beta-myosin heavy chain as well as the troponin T gene are known to cause autosomal dominant-dilated cardiomyopathy without other abnormalities. The infantile X-linked DCM is caused by mutations of the tafazzin gene. The onset of the disease is typically within the first year of life and death occurs usually in childhood. Most patients may in addition be characterized by skeletal myopathy, short stature, neutropenia and abnormal mitochondria, also referred to as Barth syndrome. Knowledge of the DCM disease genes led to the new hypothesis that dilated cardiomyopathy is a disease of the myocardial force generation or force transmission. Many more disease loci are known but the responsible disease genes are not yet identified. Better understanding of the expression and function of disease genes may eventually result in new diagnostic and therapeutic tools in order to improve the prognosis of this severe disorder.
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PMID:[Genetics of dilated cardiomyopathy]. 1151 75

Troponin T is a central component of the thin filament-associated troponin-tropomyosin system and plays an essential role in the Ca(2+) regulation of striated muscle contraction. The importance of the structure and function of troponin T is evident in the regulated isoform expression during development and the point mutations resulting in familial hypertrophic and dilated cardiomyopathies. We report here that turkeys with inherited dilated cardiomyopathy and heart failure express an unusual low molecular weight cardiac troponin T missing 11 amino acids due to the splice out of the normally conserved exon 8-encoded segment. The deletion of a 9-bp segment from intron 7 of the turkey cardiac troponin T gene may be responsible for the weakened splicing of the downstream exon 8 during mRNA processing. The exclusion of the exon 8-encoded segment results in conformational changes in cardiac troponin T, an altered binding affinity for troponin I and tropomyosin, and an increased calcium sensitivity of the actomyosin ATPase. Expression of the exon 8-deleted cardiac troponin T prior to the development of cardiomyopathy in turkeys indicates a novel RNA splicing disease and provides evidence for the role of troponin T structure-function variation in myocardial pathogenesis and heart failure.
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PMID:Exon skipping in cardiac troponin T of turkeys with inherited dilated cardiomyopathy. 1188 65

We prospectively evaluated whether the combination of admission measurements of a marker for myocardial cell injury and a marker for left ventricular overload would effectively risk stratify patients with acutely decompensated heart failure. We measured serum concentrations of cardiac troponin T (cTnT) using a second-generation assay, as well as serum cardiac troponin I (cTnI) and plasma atrial and brain natriuretic peptide (BNP) concentrations on admission in 98 consecutive patients hospitalized for worsening chronic heart failure (mean age 69 years; 5 patients were in New York Heart Association functional class II, 35 were in class III, and 58 patients were in class IV). During a mean follow-up period of 451 days, there were 37 cardiac events, including 21 cardiac deaths (14 in-hospital deaths) and 16 readmissions for worsening heart failure. In a stepwise Cox regression analysis, including these biochemical markers, age, sex, functional class, and left ventricular ejection fraction, cTnT, and BNP were found to be significantly independent predictors of both cardiac death (p <0.05) and cardiac events (p <0.01). A cTnT >0.033 microg/L and/or a BNP >440 pg/ml on admission was correlated with an incremental increase in in-hospital cardiac mortality, overall cardiac mortality, and cardiac event rate. Kaplan-Meier analysis revealed that this combination could reliably stratify the patients into low-, intermediate-, and high-risk groups for cardiac events. Measuring the combination of admission concentrations of cTnT and BNP may be a highly effective means of risk stratification of patients hospitalized for worsening chronic heart failure.
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PMID:Risk stratification using a combination of cardiac troponin T and brain natriuretic peptide in patients hospitalized for worsening chronic heart failure. 1189 11

Mutations of the gene (TNNT2) encoding the thin-filament contractile protein cardiac troponin T are responsible for 15% of all cases of familial hypertrophic cardiomyopathy, the leading cause of sudden death in young athletes. Mutant proteins are thought to act through a dominant-negative mode that impairs function of heart muscle. TNNT2 mutations can also lead to dilated cardiomyopathy, a leading cause of heart failure. Despite the importance of cardiac troponin T in human disease, its loss-of-function phenotype has not been described. We show that the zebrafish silent heart (sih) mutation affects the gene tnnt2. We characterize two mutated alleles of sih that severely reduce tnnt2 expression: one affects mRNA splicing, and the other affects gene transcription. Tnnt2, together with alpha-tropomyosin (Tpma) and cardiac troponins C and I (Tnni3), forms a calcium-sensitive regulatory complex within sarcomeres. Unexpectedly, in addition to loss of Tnnt2 expression in sih mutant hearts, we observed a significant reduction in Tpma and Tnni3, and consequently, severe sarcomere defects. This interdependence of thin-filament protein expression led us to postulate that some mutations in tnnt2 may trigger misregulation of thin-filament protein expression, resulting in sarcomere loss and myocyte disarray, the life-threatening hallmarks of TNNT2 mutations in mice and humans.
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PMID:Cardiac troponin T is essential in sarcomere assembly and cardiac contractility. 1196 35

Protein kinase C (PKC)-mediated phosphorylation of cardiac myofilament (MF) proteins has been shown to depress the actomyosin interaction and may be important during heart failure. Biochemical studies indicate that phosphorylation of Ser(43) and Ser(45) of cardiac troponin I (cTnI) plays a substantial role in the PKC-mediated depression. We studied intact and detergent-extracted papillary muscles from nontransgenic (NTG) and transgenic (TG) mouse hearts that express a mutant cTnI (Ser43Ala, Ser45Ala) that lacks specific PKC-dependent phosphorylation sites. Treatment of NTG papillary muscles with phenylephrine (PE) resulted in a transient increase and a subsequent 62% reduction in peak twitch force. TG muscles showed no transient increase and only a 45% reduction in force. There was a similar difference in maximum tension between NTG and TG fiber bundles that had been treated with a phorbol ester and had received subsequent detergent extraction. Although levels of cTnI phosphorylation correlated with these differences, the TG fibers also demonstrated a decrease in phosphorylation of cardiac troponin T. The PKC-specific inhibitor chelerythrine inhibited these responses. Our data provide evidence that specific PKC-mediated phosphorylation of Ser(43) and Ser(45) of cTnI plays an important role in regulating force development in the intact myocardium.
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PMID:alpha-Adrenergic response and myofilament activity in mouse hearts lacking PKC phosphorylation sites on cardiac TnI. 1200 51

Adult cardiac muscle normally expresses a single cardiac troponin T (cTnT). As a potential pathogenic mechanism for turkey dilated cardiomyopathy, the splice-out of a normally constitutive exon generates an additional low molecular weight cTnT with altered conformation and function. We further found that aberrant splicing of cTnT also occurs in several mammals correlating to dilated cardiomyopathy. Skipping of the same exon as that in the turkey was found in the canine cTnT. Splice-out of the adjacent exon 6 occurred in the guinea pig cTnT. Retention of the embryonic exon 5 was found in the cTnT of cat, dog, and guinea pig. These aberrant splicing variants significantly altered the structure of cTnT to sustain functional effects as that in the myopathic turkey cTnT. The genomic sequence of canine cTnT gene shows no specific alterations. However, the alternative splicing patterns of canine cTnT are different in developing cardiac and skeletal muscles, suggesting abnormality of trans-regulatory factors. Transgenic expression of the aberrant cTnT variants resulted in contractile changes in mouse cardiomyocytes. The findings support the hypothesis that thin filament heterogeneity due to the co-expression of alternatively spliced cTnT variants may desynchronize myocardial contraction and contribute to the pathogenesis and pathophysiology of cardiomyopathy and heart failure.
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PMID:Cardiac troponin T variants produced by aberrant splicing of multiple exons in animals with high instances of dilated cardiomyopathy. 1237 84

Cardiac troponin(cTn) is a sensitive marker for acute myocardial infarction(AMI). However, some cases of renal failure have been reported to show false positive results for cardiac troponin T(cTnT). Recently, it has been reported that heart-type fatty acid-binding protein(H-FABP) is a sensitive marker for AMI in the early phase. We evaluated the usefulness of cardiac troponin I(cTNI) using serum samples from patients(age 57-96) confirmed to have AMI with chest pain(n = 48), unstable angina pectoris(n = 11), cardiac failure(n = 5), others with high creatine phosphokinase(CK) activity(n = 81) and renal failure(n = 28), by comparing among cTnT(qualitative and quantitative), H-FABP, CK and creatine phosphokinase isoenzyme MB(CK-MB) activity. The diagnostic validity of cTn was assessed by receiver operating characteristic(ROC) curve analysis. The cut off value for AMI of cTnI was 0.8 ng/ml, cTnT was 0.16 ng/ml and H-FABP was 19.0 ng/ml. The overall diagnostic sensitivity of cTnI was 83.1%, and 84.8% for cTnT (quantitative), 72.3% for cTnT(qualitative), 64.8% for H-FABP, 81.8% for CK and 59.3% for CK-MB. The overall diagnostic specificity of cTnI was 90.9%, and 81.3% for cTnT(quantitative), 60.5% for cTnT (qualitative), 53.2% for H-FABP, 52.9% for CK and 87.7% for CK-MB. The overall diagnostic efficiency of cTnI was 86.5%, and 82.7% for cTnT(quantitative), 63.6% for cTnT(qualitative), 59.8% for H-FABP, 69.0% for CK and 71.9% for CK-MB. False positive results for cTnI were found in a few cases with renal failure. cTnT(qualitative) showed false positive results in 22/28 with serum creatinine over 2.1 mg/dl due to renal failure. In conclusion, cTnI detection is considered a useful and sufficiently sensitive marker for AMI.
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PMID:[Usefulness of cardiac troponin I in patients with acute myocardial infarction]. 1245 79

There is increasing support for the idea that excessive production of proinflammatory mediators such as tumor necrosis factor (TNF) and reactive oxygen species (ROS) contribute to the pathogenesis of cardiac dysfunction. However, the mechanisms by which cytokine/ROS production mediates cardiac dysfunction have not been established. Given that apoptosis signal-regulating kinase 1 (ASK1) is highly expressed in cardiac muscle and that ASK1 is an important mediator in the signaling pathways induced by tumor necrosis factor, interleukin-1, and ROS, we used the yeast two-hybrid system with ASK1 as bait to identify ASK1 substrates from a human heart cDNA library. The cDNA encoding the cardiac troponin T (cTnT) was isolated. ASK1 specifically interacted with cTnT, but not cTnI, in vitro and in vivo via the C-terminal ASK1 domain. ASK1 specifically phosphorylated cTnT in vitro and in vivo. Mutations in cTnT (T194/S198) at an ASK1-phosphorylation consensus sequence significantly reduced phosphorylation by ASK1. ROS-induced ASK1 activation, cTnT phosphorylation, and contractile dysfunction in cardiomyocytes showed similar kinetics. Moreover, overexpression of constitutively active ASK1 induces cTnT phosphorylation and inhibits shortening and calcium transient in adult cardiomyocytes. We conclude that ASK1 plays an important role in regulation of cardiac contractile function by phosphorylating cTnT and may participate in cytokine/ROS-induced pathogenesis of cardiomyopathy and heart failure.
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PMID:ASK1 associates with troponin T and induces troponin T phosphorylation and contractile dysfunction in cardiomyocytes. 1281 28

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