Abstract 12208: Mode of Death in Heart Failure With Preserved Ejection Fraction: A Systematic Review

Introduction: Despite its tremendous clinical and economic impact, remarkably little is known about the specific modes of death (MOD) in patients with heart failure with preserved ejection fraction (HFpEF). Methods: We conducted a systematic review of published HFpEF clinical trials and epidemiological studies from January 1 st , 1985 to December 31 st , 2015 using the PubMed and EMBASE databases. Two independent investigators manually screened 1,608 articles in duplicate, selected studies, and extracted relevant data. The systematic search yielded 8 major randomized controlled trials and 24 epidemiological studies that reported MOD data. Results: Definitions of cardiovascular (CV), sudden, heart failure (HF), and non-CV deaths in HFpEF trials were similar to those used in contemporary trials of HF with reduced ejection fraction (HFrEF). CV causes accounted for ~60-70% of total deaths in HFpEF clinical trials (Figure), while this proportion was more variable (14-83%) in epidemiological studies. Only 4 (50%) trials and 5 (20.8%) epidemiological studies reported data on sudden death (SD). SD accounted for ~40% of the CV deaths in clinical trials, but only 20-28% in epidemiological studies. Proportions of HF deaths were consistent across clinical trials (20-30% of CV deaths) but varied in epidemiological studies (17-60%). Cancer was the most frequently reported non-CV MOD (~30-40% of non-CV deaths), followed by infection/sepsis, which accounted for a quarter of non-CV deaths. Conclusions: Cause-specific mortality is infrequently reported, informed by <1,000 events (in trials) and <500 events (in epidemiological studies), and when it is, event definitions are directly applied from HFrEF studies. The definition of SD is non-specific and suboptimal in the majority of studies; therefore, it is unclear whether these truly represent arrhythmic deaths. Reporting and definitions of MOD must be standardized and tailored to the HFpEF population.