Direct Bilirubin, but not Indirect Bilirubin, is Associated with Short-term Adverse Events in HFpEF

Area of Science:

• Cardiology
• Hepatology
• Clinical Medicine

Background:

• Abnormal liver function tests are linked to poor outcomes in heart failure patients.
• Previous studies have not differentiated the prognostic value of direct bilirubin (DBIL) and indirect bilirubin (IBIL).
• Heart failure with preserved ejection fraction (HFpEF) prognosis requires better predictive markers.

Purpose of the Study:

• To investigate the independent association of DBIL and IBIL with short-term prognosis in HFpEF patients.
• To determine whether DBIL or IBIL is a superior predictor of adverse outcomes in HFpEF.
• To evaluate the impact of bilirubin levels on in-hospital mortality and re-admission rates in HFpEF.

Main Methods:

• Retrospective analysis of 19,837 HFpEF patients hospitalized between January 2012 and January 2022.
• Primary endpoint: in-hospital all-cause mortality. Secondary endpoints: in-hospital cardiovascular mortality and 30-day heart failure re-admission.
• Multivariable regression models and C-statistic analysis were used to assess independent risk factors and predictive capacity.

Main Results:

• Elevated DBIL and IBIL were associated with increased mortality and re-admission risk in univariable analysis.
• In multivariable models, ln-transformed DBIL and total bilirubin (TBIL), but not IBIL, were independent predictors of in-hospital all-cause and cardiovascular mortality.
• DBIL was the only bilirubin fraction independently associated with 30-day heart failure re-admission, and it improved model discrimination.

Conclusions:

• Direct bilirubin (DBIL), unlike indirect bilirubin (IBIL), is significantly associated with short-term adverse prognosis in HFpEF.
• DBIL emerges as a potentially superior and independent predictor for short-term outcomes in patients with HFpEF.
• These findings highlight the clinical utility of monitoring DBIL levels for risk stratification in HFpEF management.