High-sensitivity cardiac troponin and the effect of finerenone in patients with heart failure and mildly reduced or preserved ejection fraction: a prespecified analysis of FINEARTS-HF

Background Although a higher high-sensitivity cardiac troponin T (hsTnT) level is associated with worse outcomes in patients with heart failure (HF) and reduced ejection fraction, little is known about the relationship between troponin, and serial changes in hsTnT, and subsequent outcomes in patients with HF and mildly reduced or preserved ejection fraction (HFmrEF/HFpEF). Additionally, the benefits of mineralocorticoid receptor antagonist (MRA) according to hsTnT levels and the effect of MRA on hsTnT levels have not been investigated in previous large-scale HF trials. Purpose To assess the prognostic value of hsTnT in HFmrEF/HFpEF, the effect of the non-steroidal MRA finerenone on outcomes according to baseline hsTnT levels, and the effect of finerenone on hsTnT levels. Methods FINEARTS-HF was a randomized, double-blind, multicentre, and event-driven trial in patients with HF and a left ventricular ejection fraction ≥40%, investigating the efficacy and safety of finerenone compared to placebo. Patients were divided into tertiles based on baseline hsTnT levels: <13.3 ng/L, 13.3-<23.9 ng/L, and ≥23.9 ng/L (a 99th percentile upper reference limit of the assay was 14.0 ng/L for women and 22.0 ng/L for men). The primary outcome of total HF events and cardiovascular deaths was compared across these three hsTnT groups. The effects of finerenone compared to placebo on outcomes and hsTnT levels were also examined. Results Overall, 5,812 patients who had a baseline hsTnT measurement were included in this study, with the following distribution: 1,934 (<13.3 ng/L), 1,940 (13.3-<23.9 ng/L), and 1,938 (≥23.9 ng/L). Patients with higher hsTnT were older, more often male, and had more impaired renal function at baseline. Higher hsTnT was associated with a greater adjusted risk of the primary outcome: the rate ratio (95% confidence interval [CI]) was 1.43 (1.16-1.78) for hsTnT >13.3-<23.9 ng/L, and 2.26 (1.80-2.84) for ≥23.9 ng/L, compared to <13.3 ng/L as the reference. The benefits of finerenone compared to placebo on the primary outcome were consistent across hsTnT categories (Pinteraction=0.75) and levels as a continuous variable (Pinteraction=0.33) (Figure 1). Finerenone did not reduce hsTnT from baseline to 1 year (P=0.66) (Figure 2). Conclusions Elevated hsTnT, possibly reflecting myocardial injury, was associated with worse cardiovascular outcomes in patients with HFmrEF/HFpEF. Despite its benefits on total HF events and cardiovascular death, finerenone did not reduce hsTnT compared to placebo. Reduction in chronic myocardial injury may not be the primary mechanism by which finerenone reduces cardiovascular events in HFmrEF/HFpEF.