Cardiac troponin I as prognostic marker in heart failure patients discharged from emergency department

Despite evidence that cardiac troponin I (cTnI) identifies patients with advanced heart failure (HF) at risk of death, data on heterogeneous HF populations are scarce. Our purpose was to verify and analyze the prognostic role of cTnI in acute HF patients admitted to the emergency department. This was an observational longitudinal prospective study carried out in an urban hospital. We studied 99 patients discharged from the department between March and December 2002 with a HF diagnosis and samples of cTnI. Patients with acute coronary syndromes, myocarditis or renal failure were excluded. The main outcome was death from any cause. The detection level of the cTnI assay was 0.05 ng/ml. cTnI was detected in 45.5% of HF patients. These patients had a higher NYHA class (P < 0.001) at initial presentation and longer hospitalization (P = 0.004) than cTnI-negative patients. Nineteen deaths occurred during the study: 17 for HF and 2 for acute coronary syndrome. Finally, detectable cTnI was associated with increased mortality risk (RR 4.7; 95% CI 1.3–17.1; P = 0.021) also after adjustment for other adverse prognosis factors (age, NYHA class and presence of relapses). Our HF cTnI-positive patients had a worse clinical presentation and longer hospitalization. cTnI is a significant independent predictor of death and of longer hospitalization. It could be used for the early identification of HF patients at an increased risk of death in the long term, and of longer hospitalization. Thus, cTnI can aid decision-making and clinical management in the emergency department. A short abstract of the paper was presented at the A.C.E.P. Scientific Assembly-Research Forum in Boston U.S.A. October 2003.     

Cardiac troponin I: a potential marker of exercise intolerance in patients with moderate heart failure

Background In severe heart failure, increased values of cardiac troponins have been detected during decompensation. In this study, we investigated whether an increase of cardiac troponin I can be observed after symptom-limited exercise and after an exercise training session in patients with moderate heart failure. Methods Twenty-seven patients with moderate heart failure (New York Heart Association II-III, ejection fraction 31% ± 8%) were compared with 9 patients with mild heart failure and 10 subjects without heart failure. They underwent a symptom-limited exercise test and a bicycle exercise training session at >80% of maximal heart rate over 20 to 30 minutes. Plasma cTnI levels were measured at baseline, after symptom-limited exercise (hourly for 5 hours), and after training (4 and 10 hours). Results Patients with moderate heart failure showed an increase of cTnI from 37 ± 49 pg/mL to 73 ± 59 pg/mL (P < .001) after symptom-limited exercise. Four patients with moderate and 1 with mild heart failure and normal cTnI values at rest showed an increase of cTnI above 100 pg/mL after acute exercise but not after training. Subjects without heart failure had lower cTnI levels at rest and significantly lower values after symptom-limited exercise and training (P < .05 for each). Conclusion Patients with symptomatic heart failure reveal an increase of cTnI after symptom-limited exercise at levels that indicate minor myocardial damage. The prognostic impact of this finding should, therefore, be further investigated. (Am Heart J 2002;144:351-8)     

Cardiac troponin T vs other biochemical markers in patients with congestive heart failure.

BACKGROUND: Several pathologic processes can cause myocardial injury, which is followed by cardiac remodeling and congestive heart failure (CHF). Cardiac troponin T (cTnT), a specific and sensitive marker of myocardial injury, has been related to long-term outcome in patients with CHF, so the relationship between cTnT and other biochemical markers associated with the pathophysiology of CHF was investigated in the present study. METHODS AND RESULTS: Between February 2004 and December 2005, 145 consecutive hospitalized patients (mean left ventricular ejection fraction (LVEF) 31.6+/-0.9%) with CHF were divided into low (<0.01 ng/ml) and high (> or =0.01 ng/ml) serum cTnT groups. Correlations with other prognostic biochemical markers, including brain natriuretic peptide (BNP), type I collagen C-terminal telopeptide (ICTP), procollagen type III peptide (PIIIP), renin, norepinephrine (NOREPI), C-reactive protein (CRP), cholesterol, hemoglobin (Hb), uric acid and HbA1c were examined. cTnT was high in 46 (32%) and low in 99 (68%) patients at baseline. Patients with high cTnT had abnormally high blood concentrations of BNP (p<0.0001), ICTP (p<0.0001), PIIIP (p=0.0006), NOREPI (p=0.0119), CRP (p=0.0003), uric acid (p=0.0026) and HbA1c (p=0.0361). In contrast, concentrations of cholesterol and Hb were significantly lower in patients with high cTnT (p=0.0319 and 0.0005, respectively). Death from or rehospitalization for CHF occurred in 41% in the high vs 9% in the low cTnT group (p=0.0002). Univariate analysis showed that high cTnT (p=0.0005), BNP (p=0.0001), renin (p=0.0158), NOREPI (p=0.0094), old age (p=0.0390), low LVEF (p=0.0231) and high New York Heart Association (NYHA) class (p=0.0006) were predictors of death from or rehospitalization for CHF. By multivariate analysis including BNP, NOREPI, age, LVEF and NYHA class, high cTnT and renin remained as significant predictors. CONCLUSIONS: Patients with ongoing myocardial injury and high cTnT had associated findings consistent with activation of the sympathetic system, synthesis of cardiac fibrosis, inflammation and metabolic abnormalities. By multivariate analysis, high cTnT and renin remained significant predictors of death or rehospitalization.     

儿茶酚抑制素是心力衰竭患者预后新标志物

儿茶酚抑制素(Catestatin,CST)是一个具有21个氨基酸残基的内源性多肽,其前体嗜铬细胞颗粒蛋白A (chromogranin A,CHGA)是在肾上腺嗜铬细胞和肾上腺能神经元胞浆颗粒中与儿茶酚胺共同储备及释放的一种主要蛋白[1].CHGA的酶切产物CST有较强的抑制烟碱型乙酰胆碱能受体(nAChR)的作用,CST具有刺激释放儿茶酚胺、扩张血管、降低血压、调节心脏、降低心肌收缩力和促进血管新生的活性[2].     

Cardiac troponin levels in heart failure

Congestive heart failure (CHF) is a major cardiovascular disorder that is increasing in incidence, prevalence, and lethality. The prognostic significance of cardiac troponin levels among symptomatic and asymptomatic CHF has attracted recent interest. We sought to assess the significance of cardiac troponins in heart failure. These cardiac markers are associated with decreased left ventricular ejection fraction and poor prognosis in patients with CHF and are related to the severity of heart failure. The mechanism for the release of these markers seems to be from ventricular remodeling, ongoing myocyte degeneration, the presence of coronary artery disease, and reduced coronary reserve. In addition to B-type (brain) natriuretic peptide (BNP), cardiac troponin levels measured in patients admitted to the hospital could help risk-stratify patients and manage them effectively. BNP and cardiac troponins are easy to measure and can be repeated many times to follow patients, without interobserver variability. Theoretically, BNP is a marker of heart failure status and cardiac troponin is a marker of myocyte injury. The first therapeutic goal could be relief of circulatory congestion and lowering of BNP. The second goal could be attenuation of myocyte injury and lowering of cardiac troponins. Measuring and monitoring the levels of both could be highly effective means to reliably stratify the patients into low-, intermediate-, and high-risk groups for cardiac events and progression of heart failure. Furthermore, large-scale trials are necessary to establish them as noninvasive monitoring markers of heart failure and effectiveness of treatment.     

Persistent atrial fibrillation as a prognostic factor of outcome in patients with advanced heart failure

INTRODUCTION: Chronic heart failure (CHF) is associated with high morbidity and mortality and is diagnosed more and more frequently. Fifteen to 30% of patients with systolic CHF develop atrial fibrillation (AF). AIM: To establish whether persistent AF was an independent predictor of mortality, and had a predictive value with respect to late clinical outcomes in patients with systolic CHF. METHODS: Analysis comprised 120 men with systolic CHF. In 35 (58%) patients CHF was the result of ischaemic heart disease and in 25 (42%)--idiopathic dilated cardiomyopathy (DCM). Presence or absence of AF was a criterion of patients' subsequent division into two subgroups. Sixty patients with AF were assigned to the AF group. The control group involved 60 individuals with CHF and sinus rhythm (SR) on enrollment. Mean follow-up time was 36 months. RESULTS: Overall 59 (49%) patients died during 3-year follow-up, including 33 (56%) in the AF group. Deaths were noted more often in CHF patients with underlying ischaemic heart disease than DCM (66% vs 34%). This difference reached statistical significance in the AF group (72% vs 28%, p<0.001). Moreover, patients with AF more often complained of palpitations (p<0.01), had worse exercise capacity (p<0.01) as well as more frequently presented complex ventricular arrhythmia (p<0.01). The rate of hospital readmission was also higher (p<0.02). In univariate as well as multivariate analysis, AF was not found to be an independent predictor of mortality. Factors with a potential impact on adverse prognosis were concomitant complex ventricular arrhythmias (p=0.01), diabetes (0.04) and reduced exercise capacity (p<0.01). CONCLUSIONS: Persistent AF is not an independent risk factor of death in patients with advanced systolic CHF. However, it has an unfavourable impact on functional status. Concomitant complex ventricular arrhythmias and reduced exercise capacity worsen prognosis in this group of patients.     

Evaluation of heart-rate turbulence as a new prognostic marker in patients with chronic heart failure.

The significance of heart-rate turbulence (HRT) in patients with chronic heart failure (CHF) was evaluated to examine whether it is sensitive to the risk of ventricular tachycardia (VT). HRT is reported to predict the prognosis after myocardial infarction (MI), but its prognostic value in patients with CHF remains unknown. HRT was measured in 50 CHF patients (left ventricular ejection fraction <50% and/or left ventricular end-diastolic diameter >55 mm, 34 cardiomyopathy, 16 post-MI) and 21 patients without obvious heart diseases (control). HRT slope and HRT onset were measured by the original definitions using digitized Holter ECG recordings. Cardiac pump function was assessed by echocardiography. The value of the HRT slope was significantly lower in CHF than in control (3.7 +/- 1.7 vs 16.4 +/- 5.3, mean +/- SD, p < 0.01). The value of the HRT onset in patients with CHF was significantly higher than that in control patients (-1.1 +/- 1.9 vs -3.6 +/- 1.7, mean +/- SD, p < 0.05). The HRT slope and onset in CHF patients with VT were nearly identical to those without VT. The HRT slope appears to be a powerful prognostic marker that shows significant differences between CHF subgroups when divided by clinical events; that is, CHF death and CHF hospitalization. However, it has limited value for predicting fatal ventricular arrhythmias.     

Admission troponin T as a prognostic marker and it relationship to streptokinase treatment patients with acute myocardial infarction

The relationship between the admission troponinT (TnT) level and the response to streptokinase (SK) was examined in 76 patients with acute myocardial infarction (AMI). Of 27 TnT positive patients, 10 (37%) showed a response to SK as suggested by a non-invasive criterion for reperfusion, while 24 (49%) were 'responders' among 49 TnT negative patients. There appeared to be a trend towards a better response to SK in the TnT negative group but the difference lacked statistical power due to the small sample size. The mean time-interval between the onset of symptoms and thrombolytic treatment among TnT positive 'non-responders' was significantly (P < 0.005) higher than the TnT negative 'non-responders' (5.23 + 3.42 h versus 2.38 +/- 1.37 h). An 18 month follow up on 61 patients revealed a higher mortality (33%) among TnT positive patients than TnT negative patients (10%). Mortality among TnT positive 'non-responders' was significantly higher (P = 0.0494) than mortality among TnT-negative 'non-responders' (43% versus 9%), indicating that TnT positive patients, non-responsive to SK were at a greater risk of cardiac death. The data suggest that the admission TnT level can be of value in risk stratification of patients with AMI.     

Prognostic use of cardiac troponin T and troponin I in patients with heart failure

BACKGROUND: Troponin T (cTnT) and troponin I (cTnI) are present in the sera of some heart failure (HF) patients and have potential importance as prognostic markers. OBJECTIVE: To prospectively evaluate the prognostic value of cTnT and cTnI in well-characterized HF patients and clarify their relationship to other clinical markers of HF severity. METHODS: cTnT and cTnI were measured in 78 HF patients (45 inpatients, 33 outpatients) who were followed up prospectively for 12 months. RESULTS: Plasma cTnT (> or =0.02 ng/mL) and cTnI (> or =0.3 ng/mL) were detected in 51% and 46% of patients, respectively. These patients were more likely to be inpatients (70% versus 45% for cTnT, 75% versus 43% for cTnI, P<0.05 for both), have a higher plasma creatinine (153 versus 119 micromol/L for cTnT; 157 versus 118 micromol/L for cTnI, P<0.05) and lower plasma sodium (134 versus 138 mmol/L for both, P<0.05). At 12 months, they were more likely to have died or undergone cardiac transplantation (41% versus 14%, P=0.01 for cTnT; 43% versus 15%, P=0.004 for cTnI). After adjustment for New York Heart Association class, plasma sodium and inpatient status, a significant association with events was still evident for both troponins. CONCLUSIONS: Both cTnT and cTnI are strongly associated with other clinical indicators of HF severity and remain independent predictors of prognosis after adjustment for these factors. These results indicate a potential role for cTnT and cTnI in the clinical management of HF patients.     

Global longitudinal strain as a potential prognostic marker in patients with chronic heart failure and systolic dysfunction

Introduction and objectiveThe prognostic value of myocardium deformation measurements in chronic heart failure (CHF) is still poorly addressed. The purpose of this study was to evaluate the correlation of left ventricular (LV) global longitudinal strain (GLS) with clinical and prognostic indicators in patients with CHF and systolic dysfunction.MethodsAmbulatory patients with CHF and LV ejection fraction (LVEF) <45% were studied by two-dimensional and Doppler transthoracic echocardiogram with assessment of GLS. An indication of prognostic status was obtained by the Seattle Heart Failure Model (SHFM) prognostic estimates for life expectancy.ResultsWe included 54 CHF patients (mean age 55 ± 12 years; 80% male). GLS was significantly correlated with NYHA functional class (r=0.41, p=0.002), BNP levels (r=0.47, p=0.001), LVEF (r=−0.69, p<0.001) and LV end-diastolic pressure, assessed by E/e’ ratio (r=0.35, p<0.014) and left atrial maximal volume index (r=0.57, p<0.001). A significant correlation was found between GLS and SHFM prognostic estimates for life expectancy (r=−0.41, p=0.002). The multivariate logistic regression analysis showed that GLS independently predicted an estimated life expectancy <10 years (OR 2.614 [95% CI 1.010–6.763]). The corresponding area under the ROC curve was 0.802 (0.653–0.951) and the best obtained threshold was −9.5 (80% sensitivity, 65% specificity, p=0.003).ConclusionsGLS was strongly associated with a higher disease severity status and predicted a lower prognostic estimate for life expectancy.     

Usefulness of the percentage of plasma lymphocytes as a prognostic marker in patients with congestive heart failure

This prospective study was designed to evaluate the prognostic value of the percentage of plasma lymphocytes in patients with diastolic dysfunction as well as systolic dysfunction of the left ventricle. The subjects were 70 consecutive patients who were hospitalized in our institution from April 2001 to August 2002. Following the improvement of congestive heart failure, leukocyte differentiation and neurohumoral factors (plasma levels of atrial and brain natriuretic peptide, norepinephrine, epinephrine, and dopamine) were measured. During the follow-up period (17 +/- 9 months), 18 patients experienced a cardiac event. In the univariate analysis, the percentage of plasma lymphocytes in the cardiac event group was significantly less than that in the noncardiac event group (24.7 +/- 8.40 vs 33.3 +/- 7.64%, P = 0.0006), and brain natriuretic peptide was significantly larger in the cardiac event group (402 +/- 168 vs 153 +/- 51 pg/mL, P = 0.04). However, in patients with preserved systolic function, there was a significant difference in the percentage of plasma lymphocytes between the cardiac and noncardiac event groups (21.7 +/- 9.42 vs 34.2 +/- 8.21%, P = 0.037), although no difference was observed in brain natriuretic peptide (133 +/- 43 vs 125 +/- 50 pg/mL, P = 0.87). Multivariate analysis showed the percentage of plasma lymphocytes was an independent predictor of a cardiac event. The percentage of plasma lymphocytes may be useful for predicting the course of patients with congestive heart failure based on diastolic dysfunction as well as systolic dysfunction.     

Cardiac troponin I levels in patients with left heart failure and cor pulmonale

Cardiac troponin levels are regarded as the most specific of currently available biochemical markers of myocardial damage. Elevated levels of troponin have been previously reported in patients with left heart failure, reflecting small areas of undetected myocardial cell death. The aim of this study was to compare the levels of the cardiac troponin I (cTnI) in patients with left- and right-sided heart failure. Cardiac troponin I levels were studied with immunochemical methods in patients with right heart failure (n = 17) resulting from chronic obstructive pulmonary disease, ischemic left heart failure (n = 23), and nonischemic left heart failure (n = 18) who were admitted to departments of cardiology and chest diseases. Also, cTnI levels were measured in 32 healthy subjects as control group. Protein markers of myocardial injury (cTnI and myoglobin) in patients with left and right heart failure were collected approximately 12 to 36 hours after onset of obvious symptoms. Serum creatine kinase MB band was determined on admission and thereafter twice a day during the first 3 days. Elevated levels of serum cTnI were found in patients with nonischemic (0.83 +/- 0.6 ng/mL, p<0.01) and ischemic left heart failure (0.9 +/- 0.5 ng/mL, p<0.01) when compared to healthy subjects, whereas serum cTnI levels in patients with right heart failure due to chronic obstructive pulmonary disease were not significantly different from those of control subjects (0.22 +/- 0.1 vs 0.16 +/- 0.1 ng/mL, p>0.05). In addition, creatine kinase MB band and myoglobin levels were not significantly different between patient and healthy groups. The mean of cTnI levels in ischemic and even nonischemic left heart failure were increased compared to the mean of values in healthy individuals but without significant creatine kinase MB band and myoglobin elevations. But cTnI levels were not increased in patients with right heart failure due to chronic obstructive pulmonary disease. These data indicate that the cTnI levels are abnormal in left heart failure but not in cor pulmonale.     

Natriuretic peptides as a prognostic marker and therapeutic target in heart failure

Natriuretic peptides may have an increasing role in assisting clinicians to target treatment in patients with chronic heart failure.     

Implications of elevated cardiac troponin T in ambulatory patients with heart failure: a prospective analysis

Background

Elevated concentrations of cardiac troponin T (TnT) have been reported in patients hospitalized for decompensated heart failure (HF). We assessed whether elevated TnT levels are associated with the severity, etiology, and prognosis of HF in stable, ambulatory patients.

Methods

From 1998-1999, we prospectively collected data from 136 ambulatory patients with HF, New York Heart Association functional class II to IV, ejection fraction ≤35%, and no recent unstable angina, myocardial infarction, surgery, or coronary revascularization. Blood was obtained and analyzed by immunoassay for TnT, and patients were followed for 14.0 ± 4.3 months for death or HF hospitalization (primary end point) and other adverse cardiovascular outcomes.

Results

Thirty-three patients (24%) had an elevated TnT level (≥0.02 ng/mL). Mean TnT concentration did not differ by etiology of HF (0.002 ± 0.03 ng/mL vs 0.02 ± 0.04 ng/mL for ischemic and nonischemic etiologies, P = .25). Compared with patients with normal (undetectable) levels of TnT, patients with elevated TnT were significantly older, had worse functional class, and had poorer renal function. Elevated TnT concentrations were associated with increased relative risks (RR) of death or HF hospitalization (RR 2.7, 95% CI 1.7-4.3, P = .001) and death alone (RR 4.2, 95% CI 1.8-9.5, P = .001) during follow-up. Elevated TnT and New York Heart Association class were significant, independent predictors of death or HF hospitalization. Increased age and serum creatinine concentrations were significant independent predictors of death alone.

Conclusions

Nearly one fourth of ambulatory patients with chronic HF have ongoing myocardial necrosis as shown by abnormal TnT values, which are associated with increased mortality and morbidity.     

Cardiac troponin T as a marker of myocardial damage caused by antineoplastic drugs in rabbits

Anthracycline derivatives are among the most effective antineoplastic drugs but their therapeutic use is limited by their adverse effects. The cardiac side-effects of antineoplastic drugs were investigated in rabbits in vivo from the viewpoint of release of cardiac troponin T (cTnT) measured by Elecsys Troponin T STAT immunoassay (Boehringer Mannheim, Germany). No increase in cTnT was found following administration of a single dose of daunorubicin (3 mg/kg i.v., n = 4). During development of daunorubicin-induced cardiomyopathy (daunorubicin 3 mg/kg i.v., once a week; maximum nine administrations, n = 7), the levels of cTnT were within the physiological range (i.e. cTnT < 0.1 μg/1) at the beginning of the experiment and before and after the 5th administration, but the pathological values of cTnT after the 8th administration in 43% animals (0.22 ± 0.08 μg/l) correlated with their premature death. In the control group, the levels of cTnT were always lower than 0.1 μg/l during the experiment. Following administration of a new antineoplastic drug – Oracin {6-[2-(2-hydroxyethyl) aminoethyl]-5,11-dioxo-5,6-dihydro-11H-indeno [1,2-c]-isoquinoline hydrochloride, 10 mg/kg i.v., once weekly, ten administrations, n = 7}, there was no increase in cTnT levels. These findings correlated with the PEP: LVET index, histological examination and no animal succumbing to premature death. It is possible to conclude that cTnT is a useful marker for the prediction of experimentally induced anthracycline cardiomyopathy and for the evaluation of cardiotoxic (and, possibly, cardioprotective) effects of new drugs in rabbits. Received: 1 October 1998 / Accepted: 23 November 1998     

High-sensitivity troponin T is a prognostic marker for patients with aortic stenosis after valve replacement surgery

BackgroundAortic stenosis (AS) is recognized as a cause of sudden cardiac death. Recently, the measurement of high-sensitivity troponin T (hs-TnT) has become possible. Several studies have clarified that hs-TnT is a marker to indicate mortality of cardiovascular diseases.ObjectivesTo examine whether hs-TnT can be used as a prognostic marker to predict the operative outcome of AS.MethodsWe enrolled 60 patients with AS (mean age = 68.7 ± 9.6 years, male/female = 30/30). Cardiac catheterization and echocardiography were performed to evaluate the severity of AS. Aortic valve replacement surgery was performed in all patients. We defined major adverse cardiac events (MACE) as composite events of heart failure, fatal arrhythmia, and all causes of death.ResultsWe followed up the patients for 922 ± 800 days. Mean left ventricular ejection fraction was 60.0 ± 1.8%. Mean aortic valve area was 0.61 ± 0.03 cm². MACE occurred in 11 patients (18%), including 5 sudden cardiac deaths. We divided the patients into three groups based on the percentile of the plasma levels of hs-TnT. Kaplan–Meier curve revealed a statistically significant difference in MACE rate among the groups (log-rank test, χ² = 13.0, p = 0.002). We conducted a Cox proportional hazard analysis with a model including age, sex, estimated glomerular filtration rate, and hs-TnT tertile as explanatory variables to predict MACE. We found that hs-TnT tertile to be a significant factor to predict MACE (hazard ratio: 3.71, p = 0.03).Conclusionshs-TnT can be a prognostic marker for patients with AS after valve replacement surgery.     

Cardiac troponin T in patients with kidney disease

Atherosclerosis is accelerated in dialysis patients and cardiovascular mortality is up to 20 times higher than in the general population. Cardiac troponin T (cTnT) is a sensitive marker of myocardial necrosis and studies have confirmed the superiority of this marker over traditional cardiac enzymes. Elevated cTnT has been observed in patients with various degrees of renal failure and treatment modalities in the absence of an acute coronary event. The possibility that increased troponins reflect decreased clearance or analytical interference from uremic serum is unlikely. It is accepted that cTnT detected in serum from patients with end-stage renal failure is derived from myocytes and this effect could be caused by subclinical myocardial ischemic release of troponin, myocardial remodeling, or from uremic pericarditis or myocarditis. The significance of cTnT in patients with different degrees of renal failure and different treatment modalities is presented in this review.