AIMS: Elevation of cardiac troponin (cTn) is a strong predictor of mortality in acute heart failure (AHF), but the mechanisms underlying cTn release are not fully understood. Beyond acute myocardial ischaemia, ventricular stretch, systemic inflammation and renal dysfunction may contribute. We evaluated the prognostic association between high-sensitivity cardiac troponin I (hs-cTnI) and 180-day mortality in AHF, considering congestion, inflammation and renal function as potential mediators. METHODS: We enrolled patients hospitalized for AHF without acute coronary syndrome. At admission, congestion, inflammation and renal function were assessed using brain natriuretic peptide (BNP, pg/mL), high-sensitivity C-reactive protein (hs-CRP, mg/L) and estimated glomerular filtration rate (GFR, mL/min), respectively. After confirming associations of these variables with hs-cTnI and mortality, we performed parallel mediation analysis to quantify mediation effects. RESULTS: Among 431 patients (79±10 years; 51% men), 180-day mortality was 36%. Admission hs-cTnI levels did not differ between patients with and without chronic coronary artery disease and correlated with BNP (r=0.38), hs-CRP (r=0.21) and GFR (r=−0.23). In multiple regression, hs-CRP, BNP and GFR explained 18% of hs-cTnI variability. In univariable Cox models, hs-cTnI, hs-CRP, BNP and GFR predicted all-cause death. The hs-cTnI–mortality association was partially mediated by inflammation, congestion and renal function, accounting for 23%, 16% and 23% of the total effect, respectively; together these mediators explained 62% of the association. In multivariable Cox models, ln(hs-CRP) (HR 1.21, 95% CI 1.08–1.37), ln(BNP) (HR 1.37, 95% CI 1.09–1.74) and GFR (HR 0.99, 95% CI 0.98–1.00) remained independently associated with mortality, whereas ln(hs-cTnI) did not (HR 1.07, 95% CI 0.97–1.17). CONCLUSIONS: In AHF, circulating troponin is associated with mortality, but this relationship is largely explained by systemic inflammation, congestion and renal impairment. Troponin appears to reflect disease severity rather than provide independent prognostic information.