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)

Recent reports have demonstrated the presence of two isoforms of troponin I in the human fetal heart, namely, cardiac troponin I and slow skeletal muscle troponin I. Structural and physiological considerations indicate that these isoforms would confer differing contractile properties on the myocardium, particularly on the phosphorylation-mediated regulation of contractility by adrenergic agonists. We have investigated the developmental expression of these isoforms in the human heart from 9 weeks of gestation to 9 months of postnatal life, using Western blots revealed with troponin I antibodies to detect troponin protein isoforms and Northern blots to detect the corresponding mRNAs. The results show the following: 1) Slow skeletal muscle troponin I is the predominant isoform throughout fetal life. 2) After birth, the slow skeletal isoform is lost, with cardiac troponin I being the only isoform detectable by 9 months of postnatal development. 3) The protein isoforms and their corresponding mRNAs follow the same pattern of accumulation, suggesting that the transition in troponin expression is regulated at the level of gene transcription. The developmental transition in troponin I isoform content has implications for contractility of the fetal and postnatal myocardium. We further analyzed right and left ventricular muscle samples from 17 hearts in end-stage heart failure resulting from pulmonary hypertension, ischemic heart disease, or dilated cardiomyopathy. Cardiac troponin I mRNA remained abundant in each case, and slow skeletal muscle troponin I mRNA was not detectable in any of sample. We conclude that alterations in troponin I isoform content do not therefore contribute to the altered contractile characteristics of the adult failing ventricle.
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PMID:Troponin I gene expression during human cardiac development and in end-stage heart failure. 847 26

Our objective was to evaluate the safety of coronary anastomosis on the beating heart by measuring the release of cardiac troponin I during minimally invasive coronary artery bypass grafting (MICABG). Cardiac troponin I (cTnI) is a reliable marker of cardiac ischemia during heart operations under cardiopulmonary bypass (CPB). Ten patients (8 males and 2 females, aged 41-63) underwent MICABG with single vessel bypass grafting for left anterior descending coronary artery (LAD) stenosis (n = 7) or occlusion (n = 3). Video-assisted surgery with left anterior minithoracotomy was performed in all patients. Serial venous blood samples were collected for measurement of cTnI before LAD occlusion (T0), during anastomosis (T1) and 10 min (T2), 6 h (T3), 24 h (T4), 48 h (T5), and 72 h (T6) after coronary reperfusion. The assay method used a specific enzyme-linked immunosorbent Stratus autoanalyzer. Control coronary angiography was performed in all patients. There were no operative complications or reoperations for bleeding. The cTnI concentrations were expressed in ng/ml +/- SD. The mean cTnI level was less than 3.05 +/- 0.2 ng/ml (range 0-32.8). Values were T0 = 0, T1 = 0.4 +/- 0.03, T2 = 1.15 +/- 0.2, T3 = 2.16 +/- 0.6, T4 = 1.5 +/- 0.3, T5 = 0.6 +/- 0.02, and T6 = 0.4 +/- 0.01. Angiography showed patent grafts in 9 patients. In one case, early internal thoracic artery (ITA) graft occlusion in a patient with 2 vessel disease was correlated with a higher cTnI concentration (17.8 ng/ml). Percutaneous angioplasty was performed on the right coronary artery, complicated with dissection and cardiac failure. This patient died 3 months after the MICABG despite support from a ventricular assist device. In conclusion, collateral circulation developed in the setting of chronic coronary occlusion may be efficient for myocardial preservation during short periods such as coronary anastomosis. cTnI immunoassay confirmed the safety of coronary anastomosis on the beating heart during minimally invasive coronary operations.
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PMID:Safety of beating heart anastomosis during video-assisted coronary surgery attested by cardiac troponin I. 965 Jun 74

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 progression of cardiac failure is related to the loss of functional myocytes. The aim of these studies was to describe the structural degradation of the myocardium by the use of cardiac troponins as specific and sensitive markers of cardiac cell necrosis. The cardiac isoforms of troponin I and troponin T were measured in patients with NYHA class III-IV heart failure using second generation immunoassays without cross-reactivity with the skeletal isoforms of the two proteins. The results showed that the cardiac troponin I (72.1 +/- 15.8 vs 20.4 +/- 3.2 pg/mL; p < 0.01) and troponin T (0.21 +/- 0.6 vs 0.0005 +/- 0.002 ng/mL; p < 0.001) concentrations were significantly higher in patients with cardiac failure compared to a control population of healthy volunteers. These results suggest that troponin I and troponin T may have valuable clinical applications in the biological monitoring of cardiac failure and the appreciation of its progression.
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PMID:[The troponin complex: a new biochemical approach to cardiac insufficiency]. 989 19

Troponin I is a subunit of the thin filament-associated troponin-tropomyosin complex involved in calcium regulation of skeletal and cardiac muscle contraction. We deleted the cardiac isoform of troponin I by using gene targeting in murine embryonic stem cells to determine the developmental and physiological effects of the absence of this regulatory protein. Mice lacking cardiac troponin I were born healthy, with normal heart and body weight, because a fetal troponin I isoform (identical to slow skeletal troponin I) compensated for the absence of cardiac troponin I. Compensation was only temporary, however, as 15 days after birth slow skeletal troponin I expression began a steady decline, giving rise to a troponin I deficiency. Mice died of acute heart failure on day 18, demonstrating that some form of troponin I is required for normal cardiac function and survival. Ventricular myocytes isolated from these troponin I-depleted hearts displayed shortened sarcomeres and elevated resting tension measured under relaxing conditions and had a reduced myofilament Ca sensitivity under activating conditions. The results show that (1) developmental downregulation of slow skeletal troponin I occurs even in the absence of cardiac troponin I and (2) the resultant troponin I depletion alters specific mechanical properties of myocardium and can lead to a lethal form of acute heart failure.
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PMID:Cardiac troponin I gene knockout: a mouse model of myocardial troponin I deficiency. 991 81

The objective of this study was to determine if perioperative elevation of cardiac troponin I (cTnI) predicts mortality in infants and children after surgical correction of congenital heart defects. One hundred infants and children having open heart surgery were studied. Blood samples for cTnI analysis were collected before cardiopulmonary bypass (CPB) and at 4, 8, 12, and 24 h after initiation of CPB. Demographic information, cardiac defect, repair performed, duration of CPB, complications, and outcome were recorded. Cardiac defects were categorized as atrial septal defect (ASD), ventricular septal defect (VSD), hypoplastic left heart syndrome (HLHS), complex, and "other." Baseline cTnI was significantly lower in survivors (mean 0.42 ng/ml, median 0.35 ng/ml) than in nonsurvivors (mean 1.89, median 1.30), p = 0.0001. Baseline cTnI was significantly higher in the HLHS group (mean 1.47, median 1.10) than in all other subgroups (mean 0.62, median 0.35), p </= 0.009. There were no significant differences between survivors and nonsurvivors at the remaining sampling times. Children who died from cardiac failure (n = 2) were more likely to have 4 h cTnI >125 ng/ml compared to survivors (2 of 90). Within cardiac defect subgroups, 4 h cTnI was significantly higher in the complex group (mean = 53.51, median = 32.30) than in the ASD (mean = 23.84, median = 19.85) and other (mean = 21.59, median 21.50) subgroups. Perioperative measurement of cTnI identifies children within specific cardiac defect subgroups at risk of mortality after cardiac surgery. We speculate that detection of myocardial injury may decrease mortality and morbidity in children with complicated congenital cardiac lesions by leading to improvements in perioperative management.
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PMID:Prognostic value of pre- and postoperative cardiac troponin I measurement in children having cardiac surgery. 1059 32

The cardiac troponin I gene has been described to be associated with hypertrophic cardiomyopathy. Until now, mutations in this gene have been found only in the Japanese population. We now present the first non-Japanese family, from northern Sweden, with a mutation in the cardiac troponin I gene. Clinical diagnose was based on echocardiography, with a maximum left ventricular wall thickness of >13 mm, or major electrocardiographic abnormalities, excluding subjects with other known causes of cardiac hypertrophy. Mutation screening was performed with a single-strand conformation polymorphism analysis and identification of mutation by direct DNA sequencing. We have identified a 33-bp deletion in exon 8 encompassing the stop codon. Nine individuals in three generations were tested, and four were carriers of this deletion. The mother was genetically affected and died of heart failure aged 90. Echocardiography at 71 years of age revealed no hypertrophy, but the electrocardiogram showed signs of left ventricular hypertrophy. Her two sons, also genetically affected, had left ventricular hypertrophy, with maximum wall thickness of 15 and 16 mm, respectively. One daughter and four grandchildren were clinically unaffected, but one of them, a 27-year-old woman with maximum wall thickness of 8 mm and normal electrocardiogram, was found to be genetically affected. In conclusion, we describe a non-Japanese family in which hypertrophic cardiomyopathy is due to a genetic defect in the cardiac troponin I gene. This mutation is a deletion of 33 bp in the last exon, whereas the previously described mutations in this gene are single nucleotide changes and a single codon deletion. The deletion of the C-terminal part of the cardiac troponin I protein, seems in this particular family to be associated with a mild phenotypic expression of familial hypertrophic cardiomyopathy.
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PMID:Deletion in the cardiac troponin I gene in a family from northern Sweden with hypertrophic cardiomyopathy. 1073 50

Programmed myocyte cell death and activation of the immune system have been shown to occur in patients with congestive heart failure. Besides, unstable angina episodes are likely to be associated with immune activation. Our aim was to evaluate the role of changes in circulating levels of soluble Fas (sFas), suggestive of an enhanced inhibitory response to ongoing apoptosis, and soluble IL2 receptor (sIL2-R), indicative of T-lymphocyte activation, in chronic heart failure and unstable angina pectoris. Thirty patients affected by chronic heart failure (20 idiopathic and 10 ischemic cardiomyopathy) and 13 patients with unstable angina were evaluated. Twenty healthy individuals matched for age and gender were used as controls. A complete biochemical determination of indexes of myocardial damage including cardiac troponin I (cTnI) and creatine kinase (MB/CK) was performed. The results demonstrated that mean levels of sFas and sIL2-R were significantly increased in patients affected by chronic heart failure and unstable angina and were not associated with changes in renal function or with serum levels of cTnI. Highest values of sFas were found in NYHA class IV patients (IV NYHA class = 7.39 +/- 0.52 vs. controls = 1.34 +/- 0.12 ng/ml; P < 0.01) and more elevated in idiopathic than in ischemic cardiomyopathy (3.64 +/- 0.40 vs. 1.82 +/- 0.37 ng/ml; P < 0.01). Moreover, in chronic heart failure patients sFas and ejection fraction were negatively correlated (P = 0.01), whereas sFas and sIL2-R were positively correlated (P < 0.01). In unstable angina patients too, sFas and sIL2-R appeared to be correlated (P = 0.03); whereas sFas (angina group = 3.18 +/- 0.39 vs. controls = 1.34 +/- 0.12 ng/ml; P < 0.01) and sIL2-R (angina group = 0.46 +/- 0.11 vs. controls = 0.00 UI/ml; P < 0.01) were higher in angina group than in controls. In most of the cases, the increase of sFas was associated with comparable changes in sIL2-R serum levels, indicating that the activation of Fas system is strictly associated with autoimmune-inflammatory reactions. This phenomenon, both in chronic heart failure and in unstable angina, occurs in the absence of biochemical evidences of myocardial damage and seems to parallel the activation of T cell. Soluble Fas could have a role in sustaining inflammatory response and in prolonging the detrimental effects correlated with it in chronic heart failure and angina pectoris.
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PMID:Soluble antiapoptotic molecules and immune activation in chronic heart failure and unstable angina pectoris. 1082 61

Patients who have low-risk clinical features and negative cardiac troponin levels may be suitable for early discharge after a brief period of observation in the emergency department (ED). Little is known about the prevalence and severity of coronary artery disease in such patients, although this has implications for follow-up. Subjects included 570 patients who were at < or =7% risk of acute myocardial infarction (AMI), remained clinically stable (defined as the absence of new ischemic changes on their electrocardiograph, signs or symptoms of heart failure, the development of a cardiac arrhythmia or hypotension requiring either inotropes or volume repletion) and had cardiac troponin I (cTnI) levels <0.2 microgl(-1) during the initial 12 hours of hospitalization. Clinical features were documented and those undergoing stress tests and/or coronary angiograms had these graded by 2 independent observers. Overall, 190 (33.3%) of this population, who might be considered suitable for early discharge, had objective evidence of coronary artery disease. Patients with chest pain who are at low risk of AMI, remain clinically stable and have negative cTnI over the initial 12 hours of observation are a heterogeneous population, some of who have threatening coronary disease. This does not preclude early discharge from the ED but emphasizes the need for careful assessment and follow-up.
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PMID:Coronary artery disease in patients with chest pain who have low-risk clinical characteristics and negative cardiac troponin I. 1123 54

Ca(2+) binding to cardiac troponin C (cTnC) triggers contraction in heart muscle. In heart failure, myofilaments response to Ca(2+) are often altered and compounds that sensitize the myofilaments to Ca(2+) possess therapeutic value in this syndrome. One of the most potent and selective Ca(2+) sensitizers is the thiadiazinone derivative EMD 57033, which increases myocardial contractile function both in vivo and in vitro and interacts with cTnC in vitro. We have determined the NMR structure of the 1:1 complex between Ca(2+)-saturated C-domain of human cTnC (cCTnC) and EMD 57033. Favorable hydrophobic interactions between the drug and the protein position EMD 57033 in the hydrophobic cleft of the protein. The drug molecule is orientated such that the chiral group of EMD 57033 fits deep in the hydrophobic pocket and makes several key contacts with the protein. This stereospecific interaction explains why the (-)-enantiomer of EMD 57033 is inactive. Titrations of the cCTnC.EMD 57033 complex with two regions of cardiac troponin I (cTnI(34-71) and cTnI(128-147)) reveal that the drug does not share a common binding epitope with cTnI(128-147) but is completely displaced by cTnI(34-71). These results have important implications for elucidating the mechanism of the Ca(2+) sensitizing effect of EMD 57033 in cardiac muscle contraction.
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PMID:Structure of the C-domain of human cardiac troponin C in complex with the Ca2+ sensitizing drug EMD 57033. 1132 96

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