Prevalence and clinical implications of liver dysfunction in chronic heart failure

Abstract

Introduction: The aim of this study was to assess the prevalence of liver function test (LFT) abnormalities and their impact on hospital admissions among patients with chronic heart failure (HF). Methods: We prospectively investigated 195 ambulatory chronic HF patients (median age 68.8 [IQR 61.7-74.8] years; 21.5% female, New York Heart Association class 2.3±0.6) with left ventricular ejection fraction [LVEF] ≤40% (70.3%) and LVEF >40% (29.7%). All patients were enrolled between February 2010 and December 2012 at the Charité Medical School Berlin as part of the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF). We measured serum LFTs and creatinine at baseline. Patients were followed-up for 180 days and hospital admissions for cardiovascular (CV) reasons were recorded. Associations between LFTs and hospital admissions were determined using Cox proportional hazard analysis. Results: Overall, 39.0% of patients had at least one abnormal LFT. The most frequent LFT abnormalities were low albumin (below lower limit of normal in 24.6%), elevated gamma-glutamyl transferase (GGT, above upper limit of normal in 27.7%) and elevated direct bilirubin (above upper limit of normal in 13.8%). Patients with advanced HF (NYHA III/IV) had significantly higher prevalence of abnormal GGT, alkaline phosphatase (AP), direct and total bilirubin compared to patients in NYHA I/II (all p ≤0.01), suggesting even more pronounced cholestatic liver dysfunction. A total of 53 (27.2%) subjects were hospitalized for CV reasons during follow-up. Single predictor Cox analysis showed that the following LFTs were predictive of CV hospitalizations: direct bilirubin (hazard ratio [HR] 12.0, 95% confidence interval [CI] 3.3–43.6, p<0.001), total bilirubin (HR 2.3, 95% CI 1.3–3.9), AP as well as aspartate aminotransferase (ASAT). In adjusted multivariable Cox analysis, only direct bilirubin (HR 8.6, 95% CI 1.6–45.9) and ASAT (HR 1.02, 95% CI 1.0003–1.04) carried predictive value (both p≤0.01) independently of age, LVEF and creatinine. Conclusion: Liver dysfunction is relatively frequent in patients with HF with predominance of cholestatic LFT abnormalities. Assessment of LFTs, especially direct bilirubin may help to identify patient with high risk of hospitalization for cardiovascular reasons.