Prognostic comparison of different sensitivity cardiac troponin assays in stable heart failure

Abstract

Background: Cardiac troponin (cTn) levels offer prognostic information for patients with heart failure. Highly sensitive assays detect levels of cTn much lower than the 99th percentile of standard cTn assays. We hypothesize that cardiac troponin levels measured by a high-sensitivity assay provide better prognostic value compared with cTn levels measured by a standard assay in patients with chronic heart failure.

Methods: We measured high-sensitivity cTnT (hs-cTnT) and standard cardiac troponin I (cTnI) levels, as well as amino-terminal pro B-type natriuretic peptide (NT-proBNP) in 504 sequential stable patients with a history of heart failure who underwent elective coronary angiography, without acute coronary syndrome, and with 5-year follow-up of all-cause mortality.

Results: The median hs-cTnT level was 21.2 (interquartile range 12.3-40.9) ng/L and 170 subjects died over 5 years. In a head-to-head overall comparison, hs-cTnT provided increased prognostic utility compared with cTnI (area under the curve [AUC] 66.1% and AUC 69.4%, respectively, P = .03; 9.0% integrated discrimination improvement, P < .001; and 13.6% event-specific reclassification, P < .001), and was independent of NT-proBNP and renal function. Even within the subset of patients where cTn levels by both assays were above the limit of quantification, higher hs-cTnT is associated with a 2-fold increase in 5-year mortality risk after adjusting for traditional risk factors (tertile 1 vs 3: hazard ratio [95% confidence interval] 2.0 [1.3-3.2]; P = .0002).

Conclusion: Cardiac troponin can be detected by the high-sensitivity assay in more patients with chronic heart failure than the standard assay, and may yield independent and better prognostic accuracy for mortality prediction than standard assay.

Keywords: Cardiac troponin; Heart failure; High-sensitivity cardiac troponin; Prognosis.

Figure 1. Distribution of High Sensitivity Cardiac Troponin T Levels

All values are ≥ the limit of detection for the high sensitivity cardiac troponin T assay, 3 ng/L and 302 (59.9%) subjects had detectable cTnI.

Figure 2. Cardiac Troponin Levels Stratified by Left Ventricular Ejection Fraction

p-value calculated by Wilcoxon Test. Left Ventricular Ejection Fraction: left ventricular ejection fraction; cTnI: cardiac troponin I; hs-cTnT: high sensitivity cardiac troponin T.

Figure 3a. Kaplan-Meier Estimates of 5-Year Survival Rates According to cTnI Levels Above or Below the Limit of Detection (n=504)

cTnI = cardiac troponin I. P-value calculated by the log-rank test.

Figure 3b. Kaplan-Meier Estimates of 5-Year Survival Rates According to hs-cTnT Levels (n=504)

hs-cTnT = high sensitivity cardiac troponin T. P-value calculated by the log-rank test.

Figure 4. Cox Proportional Hazards Models and Forest Plot for Risk of 5-Year Mortality

Tertiles 1 vs 3. For the detectable cTnI subgroup, hs-cTnT tertiles 1-3 were < 23.6, 23.6-52.1, and >52.1 ng/L. For the undetectable cTnI subgroup, hs-cTnT tertiles 1-3 were < 9.7, 9.7-12.4, and >12.4 ng/L. *adjustment for age, sex, systolic blood pressure, diabetes, smoking history, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. †LOD: limit of detection; for cTnI = 0.01.