Serial measurement of cardiac troponin T using a highly sensitive assay in patients with chronic heart failure: data from 2 large randomized clinical trials.

BACKGROUND Cardiac troponins are emerging as important prognostic markers in chronic cardiovascular conditions like stable coronary artery disease or chronic heart failure (HF). Less is known about the relation between serial measurements of high-sensitivity cardiac troponin T (hs-cTnT) and future events in HF. We determined the association between changes over time in hs-cTnT and outcome in patients with chronic HF. METHODS AND RESULTS We analyzed 5284 patients with chronic HF from 2 independent randomized clinical trials, the Valsartan Heart Failure Trial (Val-HeFT) (n=4053) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca-Heart Failure (GISSI-HF) trial (n=1231). hs-cTnT was measured at randomization and after 3 months (GISSI-HF) or 4 months of follow-up (Val-HeFT). The association between changes over time of hs-cTnT and various outcomes was tested in multivariable models. In both studies, increases in hs-cTnT levels over time were associated with age, diabetes mellitus, worsening of renal function (reduction in estimated glomerular filtration rate), and baseline and increases in N-terminal pro-brain natriuretic peptide concentrations. Increases in hs-cTnT concentrations were associated with all-cause mortality (incidence rates, 8.19 [7.51-8.88] and 6.79 [5.98-7.61] per 100 person-years in Val-HeFT and GISSI-HF, respectively, with hazard ratios [95% confidence intervals] of 1.59 [1.39-1.82] and 1.88 [1.50-2.35]) after adjustment for conventional risk factors and baseline levels of hs-cTnT and N-terminal pro-brain natriuretic peptide. Changes in hs-cTnT concentration modestly improved prognostic discrimination beyond baseline values for fatal outcomes only. CONCLUSIONS Despite very low circulating concentrations, changes in hs-cTnT concentrations over time are robust predictors of future cardiovascular events in patients with chronic HF but add limited prognostic discrimination. CLINICAL TRIAL REGISTRATION http://www.clinicaltrials.gov. Unique identifier: NCT00336336.