How do patients with heart failure with preserved ejection fraction die?

Understanding how patients with heart failure with preserved ejection fraction (HFPEF) die provides insight into the natural history and pathophysiology of this complex syndrome, thereby allowing better prediction of response to therapy in designing clinical trials. This review summarizes the current state of knowledge surrounding mortality rates, modes of death, and prognostic factors in HFPEF. Despite the lack of uniform reporting, the following conclusions may be drawn from previous studies. The mortality burden of HFPEF is substantial, ranging from 10% to 30% annually, and higher in epidemiological studies than in clinical trials. Mortality rates compared with heart failure with reduced ejection fraction (HFREF) appear to be strongly influenced by the type of study, but are clearly elevated compared with age- and co-morbidity-matched controls without heart failure. The majority of deaths in HFPEF are cardiovascular deaths, comprising 51-60% of deaths in epidemiological studies and ∼70% in clinical trials. Among cardiovascular deaths, sudden death and heart failure death are the leading cardiac modes of death in HFPEF clinical trials. Compared with HFREF, the proportions of cardiovascular deaths, sudden death, and heart failure deaths are lower in HFPEF. Conversely, non-cardiovascular deaths constitute a higher proportion of deaths in HFPEF than in HFREF, particularly in epidemiological studies, where this difference may be related to fewer coronary heart deaths in HFPEF. Key mortality risk factors, including age, gender, body mass index, burden of co-morbidities, and coronary artery disease, offer some explanation for the differences in mortality rates observed across studies.