Congestion, Inflammation, and Renal Impairment Mediate the Association Between Cardiac Troponin and Mortality in Acute Heart Failure

INTRODUCTION: Cardiac troponin is recognized as a strong predictor of mortality in patients with acute heart failure (AHF). The aim of this study was to evaluate the prognostic impact of high-sensitivity cardiac troponin I (hs-cTnI) on mortality risk in patients with AHF in relation to inflammatory, congestion, and renal indices. METHODS: We enrolled 431 patients (79 ± 10 years, 51% male) with AHF. At admission, hemodynamic congestion, inflammatory status, and renal function were assessed by means of brain natriuretic peptide (BNP, ng/l), high-sensitivity C-reactive protein (hs-CRP, mg/l), and estimated glomerular filtration rate (eGFR, ml/min), respectively. Mediation analyses were performed to assess the presence and magnitude of these components. RESULTS: The cumulative incidence of mortality at 180-day follow-up was 36%. hs-cTnI significantly correlated with BNP (r = 0.28), hs-CRP (r = 0.31), and eGFR (r = - 0.23); these variables explained 18% of the overall variability in hs-cTnI. In univariate Cox regression analysis, hs-cTnI, hs-CRP, BNP, and eGFR were predictors of all-cause death. The association between hs-cTnI and mortality was largely mediated by inflammation, congestion, and renal function, which collectively explained 69% of the total effect. In multivariate analysis, only ln hs-CRP (HR: 1.21; 1.08-1.37), ln BNP (HR: 1.37; 1.09-1.74), and eGFR (HR: 0.99; 0.98-1.00) remained independent predictors of mortality. CONCLUSIONS: Elevated troponin levels in AHF might be influenced by the coexistence of systemic inflammation, hemodynamic congestion, and renal dysfunction. Therefore, circulating troponin in AHF may be considered an integrated biomarker reflecting multiple pathophysiological processes.