Why do People with Heart Failure Die? Rationale and Design of the RHYTHM-HF Study

AIMS: The aim of RHYTHM-HF is to provide novel insights into the causes and mechanisms of death in near-consecutive patients discharged following a heart failure hospitalization using data from insertable cardiac monitors (ICMs) and autopsy examinations. METHODS: RHYTHM-HF enrolled an unselected, prospective, near-consecutive, observational cohort of 257 patients admitted to hospital with a primary diagnosis of decompensated heart failure over a 2-year period. Potential participants were screened using N-terminal pro-B-type natriuretic peptide and echocardiography. All enrolled participants received a subcutaneously implanted ICM (which provides long-term cardiac rhythm recordings) before hospital discharge. An optional sub-study invited participants to consent prospectively to autopsy in the event of death. Following hospital discharge, there was no physical follow-up, with longitudinal ICM data obtained by remote upload. Participants were followed for up to 4 years. Data permitting determination of the cause, mode and mechanism of death were collected, including ICM-derived terminal cardiac rhythm and pathological findings at autopsy. Rigorous stepwise clinical adjudication processes were employed in the study (step 1 using clinical data alone, step 2 using additional post-mortem data, and step 3 using additional terminal rhythm data). CONCLUSIONS: The RHYTHM-HF study is a contemporary natural history study which investigated causes and mechanisms of death in patients with heart failure. It is the largest study to report terminal rhythm data in patients with heart failure, the largest contemporary prospective autopsy study in heart failure, and the only study to describe the interaction between terminal rhythm and pathological cause of death using modern adjudication standards. We anticipate new mechanistic insights into the cause and mode of death in heart failure. These findings will generate hypotheses for future clinical research into reducing death in heart failure.