Background
Elevated cardiac troponin (cTn) levels are relatively common in acute heart failure (AHF).
Aims
To evaluate the prevalence and prognostic significance of elevated cTnI and cTnT in AHF.
Methods
FINN-AKVA is a prospective, multicenter study in AHF. In this analysis, 364 non-ACS patients with measurements of cTnI and cTnT taken on admission and 48 h thereafter were analyzed.
Results
Of the 364 AHF patients, 51.1% had cTnI and 29.7% cTnT levels above the cut-off value. Six-month all-cause mortality was 18.7%. Both cTnI (OR 2.0, 95% CI 1.2–3.5, p = 0.01) and cTnT (OR 2.6, 95% CI 1.5–4.4, p = 0.0006) were associated with adverse outcome. The mortality risk was proportional to the magnitude of cTn release. On multivariable analysis, Cystatin C (OR 6.3, 95% CI 3.2–13, p < 0.0001), logNT-proBNP (OR 1.4, 95% CI 1.0–1.8, p = 0.03) and systolic blood pressure on admission (/10 mm Hg increase, OR 0.9, 95% CI 0.8–0.9, p = 0.0004) were independent risk markers, whereas the troponins were not significantly associated with increased mortality.
Conclusions
cTn elevations are frequent in AHF patients without ACS. cTnI is more often elevated than cTnT. Both cTnI and cTnT elevations are associated with increased mortality proportional to the degree elevation but they do not act as independent risk markers.
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Tuesday
Cardiac dysfunction after burns
Objectives
Using transoesophageal echocardiography (TEE) we investigated the occurrence, and the association of possible abnormalities of motion of the regional wall of the heart (WMA) or diastolic dysfunction with raised troponin concentrations, or both during fluid resuscitation in patients with severe burns.
Patients and methods
Ten consecutive adults (aged 36–89 years, two women) with burns exceeding 20% total burned body surface area who needed mechanical ventilation were studied. Their mean Baux index was 92.7, and they were resuscitated according to the Parkland formula. Thirty series of TEE examinations and simultaneous laboratory tests for myocyte damage were done 12, 24, and 36 h after the burn.
Results
Half (n = 5) the patients had varying grades of leakage of the marker that correlated with changeable WMA at 12, 24 and 36 h after the burn (p ≤ 0.001, 0.044 and 0.02, respectively). No patient had WMA and normal concentrations of biomarkers or vice versa. The mitral deceleration time was short, but left ventricular filling velocity increased together with stroke volume.
Conclusion
Acute myocardial damage recorded by both echocardiography and leakage of troponin was common, and there was a close correlation between them. This is true also when global systolic function is not deteriorated. The mitral flow Doppler pattern suggested restrictive left ventricular diastolic function.
ARTICLE
Using transoesophageal echocardiography (TEE) we investigated the occurrence, and the association of possible abnormalities of motion of the regional wall of the heart (WMA) or diastolic dysfunction with raised troponin concentrations, or both during fluid resuscitation in patients with severe burns.
Patients and methods
Ten consecutive adults (aged 36–89 years, two women) with burns exceeding 20% total burned body surface area who needed mechanical ventilation were studied. Their mean Baux index was 92.7, and they were resuscitated according to the Parkland formula. Thirty series of TEE examinations and simultaneous laboratory tests for myocyte damage were done 12, 24, and 36 h after the burn.
Results
Half (n = 5) the patients had varying grades of leakage of the marker that correlated with changeable WMA at 12, 24 and 36 h after the burn (p ≤ 0.001, 0.044 and 0.02, respectively). No patient had WMA and normal concentrations of biomarkers or vice versa. The mitral deceleration time was short, but left ventricular filling velocity increased together with stroke volume.
Conclusion
Acute myocardial damage recorded by both echocardiography and leakage of troponin was common, and there was a close correlation between them. This is true also when global systolic function is not deteriorated. The mitral flow Doppler pattern suggested restrictive left ventricular diastolic function.
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Monday
C-reactive protein, obesity, atopy and asthma symptoms in middle-aged British adults
Recent research suggested an association between circulating C-reactive protein (CRP) and adult asthma, confined to those without evidence of allergic predisposition. We investigated the role of smoking and obesity as explanations for this relationship.
At age 44–45, members of the British 1958 birth cohort participated in a biomedical survey involving the measurement of C-reactive protein (CRP), specific IgE to grass, cat and dust mite, standing height and weight. Information on asthma and related symptoms was collected by computer aided interview at age 42. Complete data were available for 6490 subjects.
CRP levels were positively correlated with body mass index (BMI), higher among women than men and among heavy smokers (>=20 cigarettes·day-1) than never smokers. Adjusted for sex and region, odds ratios comparing asthma prevalence in subjects above the fourth CRP quartile with subjects below the first were 1.85 (95% confidence interval 1.15 to 2.99) for non-atopics and 0.94 (0.62 to 1.41) for atopics changing to 1.36 (0.80 to 2.32) and 1.07 (0.67 to 1.69) respectively when additionally adjusted for smoking and BMI.
Any association between C-reactive protein (CRP) and asthma prevalence confined to non-atopics may be due to confounding or may reflect a more general association of CRP with smoking-related obstructive airways disease.
At age 44–45, members of the British 1958 birth cohort participated in a biomedical survey involving the measurement of C-reactive protein (CRP), specific IgE to grass, cat and dust mite, standing height and weight. Information on asthma and related symptoms was collected by computer aided interview at age 42. Complete data were available for 6490 subjects.
CRP levels were positively correlated with body mass index (BMI), higher among women than men and among heavy smokers (>=20 cigarettes·day-1) than never smokers. Adjusted for sex and region, odds ratios comparing asthma prevalence in subjects above the fourth CRP quartile with subjects below the first were 1.85 (95% confidence interval 1.15 to 2.99) for non-atopics and 0.94 (0.62 to 1.41) for atopics changing to 1.36 (0.80 to 2.32) and 1.07 (0.67 to 1.69) respectively when additionally adjusted for smoking and BMI.
Any association between C-reactive protein (CRP) and asthma prevalence confined to non-atopics may be due to confounding or may reflect a more general association of CRP with smoking-related obstructive airways disease.
The familial hypertrophic cardiomyopathy related cardiac troponin C mutation L29Q affects Ca2+ binding and myofilament contractility
The cardiac troponin C (cTnC) mutation, L29Q, has been associated with familial hypertrophic cardiomyopathy. We observed that L29, together with neighboring residues, Asp2, Val28, and Gly30, plays an important role in determining the Ca2+ affinity of site II, the regulatory site of mammalian cTnC (McTnC). Here we report on the Ca2+ binding characteristics of L29Q McTnC and D2N/V28I/L29Q/G30D McTnC (NIQD) utilizing a F27W substitution, allowing one to monitor Ca2+ binding and release. We also studied the effect of these mutants on the Ca2+ activation of force generation in single mouse cardiac myocytes using cardiac troponin C (cTnC) replacement, together with the sarcomere length (SL) dependence. The Ca2+-binding affinity of site II of L29Q McTnCF27W and NIQD McTnCF27W were ~1.3- and ~1.9-fold higher, respectively, than that of McTnCF27W. The Ca2+-disassociation rate from site II of L29Q McTnCF27W and NIQD McTnCF27W were not significantly different than that of control (McTnCF27W). However, the rate of Ca2+ binding to site II was higher in L29Q McTnCF27W and NIQD McTnCF27W relative to control (~1.5-fold and ~2.0-fold respectively). The Ca2+ sensitivity of force generation was significantly higher in myocytes reconstituted with L29Q McTnC (~1.4-fold) and NIQD McTnC (~2-fold). Interestingly, the change in Ca2+ sensitivity of force generation in response to SL change (1.9, 2.1 and 2.3 µm) was significantly reduced in myocytes containing either L29Q McTnC or NIQD McTnC. Together, these results demonstrate that the L29Q mutation enhances the Ca2+-binding characteristics of cardiac troponin C (cTnC), and that when incorporated into cardiac myocytes, this mutant alters myocyte contractility.
Ca2+ exchange with troponin C and cardiac muscle dynamics
Controversy abounds in the cardiac muscle literature over the rate-limiting steps of cardiac muscle contraction and relaxation. However, the idea of a single biochemical mechanism being the all-inclusive rate-limiting step for cardiac muscle contraction and relaxation may be oversimplified. There is ample evidence that Ca2+ concentration and dynamics, intrinsic cross-bridge properties, and even troponin C (TnC) Ca2+ binding and dissociation can all modulate the mechanical events of cardiac muscle contraction and relaxation. However, TnC has generally been thought to play no role in influencing cardiac muscle dynamics due to the idea that Ca2+ exchange with TnC is very rapid. This definitely is the case for isolated troponin C (TnC), but not for the more sophisticated biochemical systems of reconstituted thin filaments and myofibrils. This review will discuss the biochemical influences on Ca2+ exchange with TnC and their physiological implications.
Troponin T is an independent predictor of mortality in renal transplant recipients
Background
Numerous reports have demonstrated an association between elevated Troponin T levels and adverse cardiovascular outcomes in patients with chronic kidney disease. However, whether raised Troponin T levels are an independent predictor of mortality in renal transplant recipients has not yet been established. The aim of this study was, therefore, to assess the use of Troponin T as a prognostic marker in a population of renal transplant recipients.
Methods
Three hundred and seventy-two asymptomatic renal transplant recipients were recruited between June 2000 and December 2002. Troponin T was measured at baseline and prospective follow-up data were collected at a median of 1739 days.
Results
In Kaplan-Meier analysis a Troponin T level 0.03 µg/l was a significant predictor of mortality (P < 0.001). In Cox Regression analysis, an elevated Troponin T level remained a significant predictor of mortality following adjustment for traditional cardiovascular risk factors (P < 0.001) and following adjustment for estimated glomerular filtration rate and high sensitivity C reactive protein (P < 0.001).
Conclusions
Elevated Troponin T level is a strong independent predictor of all cause mortality in patients with a renal transplant. Troponin T, therefore, represents a promising biochemical marker that identifies those renal transplant recipients who are most likely to benefit from aggressive cardiovascular risk factor modification.
Numerous reports have demonstrated an association between elevated Troponin T levels and adverse cardiovascular outcomes in patients with chronic kidney disease. However, whether raised Troponin T levels are an independent predictor of mortality in renal transplant recipients has not yet been established. The aim of this study was, therefore, to assess the use of Troponin T as a prognostic marker in a population of renal transplant recipients.
Methods
Three hundred and seventy-two asymptomatic renal transplant recipients were recruited between June 2000 and December 2002. Troponin T was measured at baseline and prospective follow-up data were collected at a median of 1739 days.
Results
In Kaplan-Meier analysis a Troponin T level 0.03 µg/l was a significant predictor of mortality (P < 0.001). In Cox Regression analysis, an elevated Troponin T level remained a significant predictor of mortality following adjustment for traditional cardiovascular risk factors (P < 0.001) and following adjustment for estimated glomerular filtration rate and high sensitivity C reactive protein (P < 0.001).
Conclusions
Elevated Troponin T level is a strong independent predictor of all cause mortality in patients with a renal transplant. Troponin T, therefore, represents a promising biochemical marker that identifies those renal transplant recipients who are most likely to benefit from aggressive cardiovascular risk factor modification.
Cardiac Troponin T and C-Reactive Protein for Predicting Prognosis, Coronary Atherosclerosis, and Cardiomyopathy in Patients Undergoing Long-term Hemo
Context
Cardiac troponin T (cTnT) and C-reactive protein (CRP) are prognostic markers in acute coronary syndromes. However, for patients with end-stage renal disease (ESRD) the ability of combinations of these markers to predict outcomes, and their association with cardiac pathology, are unclear.
Objective
To investigate the association between levels of cardiac troponin T (cTnT) and C-reactive protein (CRP) and long-term risk of cardiac pathology and death in patients with ESRD.
Design, Setting, and Participants
A prospective cohort study initiated February through June 1998 and enrolling 224 patients with ESRD from 5 hemodialysis centers in the Houston-Galveston region of Texas. Levels of cardiac troponin T (cTnT) and C-reactive protein (CRP) were analyzed at study entry in patients without ischemic symptoms.
Main Outcome Measures
All-cause mortality during a mean follow-up of 827 (range, 29-1327) days. Secondary outcomes in predefined substudies were coronary artery disease (CAD), decreased (40%) left ventricular ejection fraction (LVEF), and presence of left ventricular hypertrophy (LVH).
Results
One hundred seventeen (52%) patients died during follow-up. For levels of cardiac troponin T (cTnT) and C-reactive protein (CRP), progressively higher levels predicted increased risk of death compared with the lowest quartile (for cTnT quartile 2: unadjusted hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.2-4.1; quartile 3: HR, 2.7; 95% CI, 1.5-4.9; quartile 4: HR, 3.0; 95% CI, 1.6-5.3. For CRP quartile 2: HR, 0.9; 95% CI, 0.5-1.6; quartile 3: HR, 1.8; 95% CI, 1.1-3.1; quartile 4: HR, 1.8; 95% CI, 1.1-3.2). Both cTnT and CRP remained independent predictors of death after adjusting for a number of potential confounders. The combination of cTnT and CRP results provided prognostic information when patients were divided into groups at or above and below the biomarker medians (high cTnT/high CRP levels vs low cTnT/low CRP levels for risk of death: HR, 2.5; 95% CI, 1.5-4.0). Elevated levels of cTnT, but not CRP, were strongly associated with diffuse CAD (n = 67; 0%, 25%, 50%, and 62% prevalence of multivessel CAD across progressive cTnT quartiles, P<.001). An LVEF of 40% or less was identified in 4 (9%), 3 (8%), 10 (27%), and 7 (19%) of patients across cTnT quartiles (P = .07). No trend for cTnT levels was found among patients with LVH (P = .45); similarly, no trend for CRP was found among patients with LVH (P = .65) or an LVEF of 40% or less (P = .75).
Conclusions
Among stable patients with ESRD, increasing levels of cardiac troponin T (cTnT) and C-reactive protein (CRP) are associated with increased risk of death. Furthermore, higher levels of cTnT may identify patients with severe angiographic coronary disease.
Cardiac troponin T (cTnT) and C-reactive protein (CRP) are prognostic markers in acute coronary syndromes. However, for patients with end-stage renal disease (ESRD) the ability of combinations of these markers to predict outcomes, and their association with cardiac pathology, are unclear.
Objective
To investigate the association between levels of cardiac troponin T (cTnT) and C-reactive protein (CRP) and long-term risk of cardiac pathology and death in patients with ESRD.
Design, Setting, and Participants
A prospective cohort study initiated February through June 1998 and enrolling 224 patients with ESRD from 5 hemodialysis centers in the Houston-Galveston region of Texas. Levels of cardiac troponin T (cTnT) and C-reactive protein (CRP) were analyzed at study entry in patients without ischemic symptoms.
Main Outcome Measures
All-cause mortality during a mean follow-up of 827 (range, 29-1327) days. Secondary outcomes in predefined substudies were coronary artery disease (CAD), decreased (40%) left ventricular ejection fraction (LVEF), and presence of left ventricular hypertrophy (LVH).
Results
One hundred seventeen (52%) patients died during follow-up. For levels of cardiac troponin T (cTnT) and C-reactive protein (CRP), progressively higher levels predicted increased risk of death compared with the lowest quartile (for cTnT quartile 2: unadjusted hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.2-4.1; quartile 3: HR, 2.7; 95% CI, 1.5-4.9; quartile 4: HR, 3.0; 95% CI, 1.6-5.3. For CRP quartile 2: HR, 0.9; 95% CI, 0.5-1.6; quartile 3: HR, 1.8; 95% CI, 1.1-3.1; quartile 4: HR, 1.8; 95% CI, 1.1-3.2). Both cTnT and CRP remained independent predictors of death after adjusting for a number of potential confounders. The combination of cTnT and CRP results provided prognostic information when patients were divided into groups at or above and below the biomarker medians (high cTnT/high CRP levels vs low cTnT/low CRP levels for risk of death: HR, 2.5; 95% CI, 1.5-4.0). Elevated levels of cTnT, but not CRP, were strongly associated with diffuse CAD (n = 67; 0%, 25%, 50%, and 62% prevalence of multivessel CAD across progressive cTnT quartiles, P<.001). An LVEF of 40% or less was identified in 4 (9%), 3 (8%), 10 (27%), and 7 (19%) of patients across cTnT quartiles (P = .07). No trend for cTnT levels was found among patients with LVH (P = .45); similarly, no trend for CRP was found among patients with LVH (P = .65) or an LVEF of 40% or less (P = .75).
Conclusions
Among stable patients with ESRD, increasing levels of cardiac troponin T (cTnT) and C-reactive protein (CRP) are associated with increased risk of death. Furthermore, higher levels of cTnT may identify patients with severe angiographic coronary disease.
Cardiac-Specific Troponin I Levels and Risk of Coronary Artery Disease and Graft Failure Following Heart Transplantation
Context
Previous studies have yielded conflicting data regarding whether a relationship exists between elevated cardiac troponin levels and acute allograft rejection in patients who have received heart transplants.
Objective
To determine whether cardiac troponin I levels after heart transplantation were associated with a procoagulant microvasculature and long-term allograft outcome.
Design
Prospective cohort study with a mean (SE) follow-up of 45.1 (2.5) months. Serum troponin I levels were measured 9.9 (0.2) times per patient during the first 12 months after heart transplantation.
Setting
Heart transplant center in the United States.
Patients
A total of 110 consecutive patients who received a heart transplant between 1989 and 1997 and survived at least 1 year after transplantation.
Main Outcome Measures
Histological and immunohistochemical biopsy findings, development of coronary artery disease (CAD), and graft failure in patients with vs without elevated serum cardiac troponin I levels.
Results
All recipients had elevated troponin I levels during the first month after transplantation. Troponin I levels remained persistently elevated during the first 12months in 56 patients (51%) and became undetectable in 54 patients (49%). Persistently elevated troponin I levels were associated with increasing fibrin deposits in microvasculature and cardiomyocytes (P<.001). Patients with persistently elevated levels of troponin I had significantly increased risk for subsequent development of CAD (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.8-10.1; P<.001) and graft failure (OR, 3.4; 95% CI, 1.2-9.7; P = .02), and also developed more severe CAD (OR, 4.2; 95% CI, 1.9-9.3; P<.001) and showed more disease progression (OR, 3.7; 95% CI, 1.3-10.4; P = .009).
Conclusion
In this study, elevated cardiac troponin I levels, which are considered to be a noninvasive surrogate marker of a procoagulant microvasculature, identified a subgroup of patients with high risk for developing CAD and graft failure after cardiac transplantation.
Previous studies have yielded conflicting data regarding whether a relationship exists between elevated cardiac troponin levels and acute allograft rejection in patients who have received heart transplants.
Objective
To determine whether cardiac troponin I levels after heart transplantation were associated with a procoagulant microvasculature and long-term allograft outcome.
Design
Prospective cohort study with a mean (SE) follow-up of 45.1 (2.5) months. Serum troponin I levels were measured 9.9 (0.2) times per patient during the first 12 months after heart transplantation.
Setting
Heart transplant center in the United States.
Patients
A total of 110 consecutive patients who received a heart transplant between 1989 and 1997 and survived at least 1 year after transplantation.
Main Outcome Measures
Histological and immunohistochemical biopsy findings, development of coronary artery disease (CAD), and graft failure in patients with vs without elevated serum cardiac troponin I levels.
Results
All recipients had elevated troponin I levels during the first month after transplantation. Troponin I levels remained persistently elevated during the first 12months in 56 patients (51%) and became undetectable in 54 patients (49%). Persistently elevated troponin I levels were associated with increasing fibrin deposits in microvasculature and cardiomyocytes (P<.001). Patients with persistently elevated levels of troponin I had significantly increased risk for subsequent development of CAD (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.8-10.1; P<.001) and graft failure (OR, 3.4; 95% CI, 1.2-9.7; P = .02), and also developed more severe CAD (OR, 4.2; 95% CI, 1.9-9.3; P<.001) and showed more disease progression (OR, 3.7; 95% CI, 1.3-10.4; P = .009).
Conclusion
In this study, elevated cardiac troponin I levels, which are considered to be a noninvasive surrogate marker of a procoagulant microvasculature, identified a subgroup of patients with high risk for developing CAD and graft failure after cardiac transplantation.
Prognostic Implications of Normal (<0.10 ng/ml) and Borderline (0.10 to 1.49 ng/ml) Troponin Elevation Levels in Critically Ill Patients Without ...
Borderline increase of troponin I (cTnI) is associated with higher rates of cardiovascular events compared with normal levels in the setting of acute coronary syndrome (ACS), but the significance of borderline cTnI levels in patients without chest pain may differ. The aim of this study was to determine the prognostic implications of intermediate serum troponin I (cTnI) levels in patients without ACS in the intensive care unit (ICU). This was a 12-month retrospective study of 240 patients without ACS in the ICU with normal (<0.1 ng/ml) or intermediate (0.1 to 1.49 ng/ml) cTnI levels. End points included in-hospital mortality, lengths of ICU and hospital stays, and rates of postdischarge readmission and mortality. Overall in-hospital mortality was 13%, with 5% in the normal cTnI group and 28% in the intermediate cTnI group. By multivariate analysis, intermediate cTnI was independently associated with in-hospital mortality (p = 0.004) and length of ICU stay (p = 0.028). The only other independent risk factor for inpatient mortality was a standardized ICU prognostic measurement (Simplified Acute Physiology Score II score). Intermediate troponin I (cTnI) had no prognostic implications regarding length of hospital stay, readmission rate, or postdischarge mortality at 6 months. In conclusion, an intermediate level of cTnI in patients without ACS in the ICU is an independent prognostic marker predicting in-hospital mortality and length of ICU stay. Patients with intermediate cTnI levels who survive to discharge have equivalent out-of-hospital courses for up to 6 months compared with patients with normal cTnI levels.
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