Changes in Liver Function Tests, Congestion, and Prognosis After Acute Heart Failure: The STRONG-HF Trial

Abstract

Background: Elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (tBil) may reflect congestion and liver dysfunction in acute heart failure (AHF), while lower ALT also associates with sarcopenia. Objectives: The purpose of this study was to assess ALT, AST, and tBil levels in AHF patients during high-intensity care (HIC) vs usual care (UC) follow-up. Methods: ALT, AST, and tBil were measured 1 to 2 days predischarge in 1,062 AHF patients, and again after 90 days of either HIC or UC according to the STRONG-HF (Safety, Tolerability and efficacy of Rapid Optimization, helped by NT-proBNP testinG, of Heart Failure therapies) protocol. The primary endpoint was 180-day all-cause death or HF hospitalization. Results: Median (Q1-Q3) baseline ALT, AST, and tBil were 21 (15-32) U/L, 23 (17-32) U/L, and 14(10-21) umol/L, respectively. Patients with lower ALT had lower body mass index. Patients with lower ALT, but not tBil or AST, were more likely to have edema, elevated jugular venous pressure, and orthopnea, and use more diuretics prerandomization. A nonsignificant inverse association between ALT and the primary outcome (HR: 0.82 [95% CI: 0.66-1.01] per log-unit, P = 0.06) was observed. Greater reductions of ALT, AST, and tBil to 90 days were associated with greater improvement of edema, rales, NYHA functional class, and N-terminal pro-B-type natriuretic peptide. After 90 days, the HIC group had a greater reduction in AST and tBil than the UC group, while nonsignificant for ALT. The treatment effect of HIC over UC on the primary outcome was consistent across the baseline ALT, AST, and tBil range (all P interaction >0.10), but patients with lower ALT experienced greater health status improvement from HIC. Conclusions: Lower ALT was associated with lower body mass index and more congestion in AHF, supporting previous studies suggesting ALT as a sarcopenia marker. The beneficial effect of HIC on health status was greater in low baseline ALT patients.