Rates and predictors of cardiovascular and non‐cardiovascular outcomes in heart failure with preserved ejection fraction

Aims The detailed sub‐categories of death and hospitalization, and the impact of comorbidities on cause‐specific outcomes, remain poorly understood in heart failure (HF) with preserved ejection fraction (HFpEF). We sought to evaluate rates and predictors of cardiovascular (CV) and non‐CV outcomes in HFpEF. Methods The Karolinska–Rennes study was a bi‐national prospective observational study designed to characterize HFpEF (ejection fraction ≥45%). Patients were followed for cause‐specific death and hospitalization. Baseline characteristics were pre‐selected based on clinical relevance and potential eligibility criteria for HFpEF trials. The associations between characteristics and cause‐specific outcomes were assessed with univariable and multivariable Cox regressions. Results Five hundred thirty‐nine patients [56% females; median (inter‐quartile range) age 79 (72–84) years; NT‐proBNP/BNP 2448 (1290–4790)/429 (229–805) ng/L] were included. Over 1196 patient‐years follow‐up [median (min, max) 744 days (13–1959)], there were 159 (29%) deaths (13 per 100 patient‐years: CV 5.1 per 100, dominated by HF 3.9 per 100; and non‐CV 5.8 per 100, dominated by cancer, 2.3 per 100). There were 723 hospitalizations in 338 patients (63%; 60 per 100 patient‐years: CV 33 per 100, dominated by HF 17 per 100; and non‐CV 27 per 100, dominated by lung disease 5 per 100). Higher age and natriuretic peptides, lower serum natraemia and NYHA class III–IV were independent predictors of CV death; lower serum natraemia, anaemia and stroke of non‐CV death; and anaemia and lower serum natraemia of non‐CV death or hospitalizations. There were no apparent predictors of CV death or hospitalization. Conclusions In a clinical cohort hospitalized and diagnosed with HFpEF, death and hospitalization rates were roughly similar for CV and non‐CV causes. CV deaths were predicted primarily by severity of HF; non‐CV deaths primarily by anaemia and prior stroke. Lower serum sodium predicted both. Hospitalizations were difficult to predict.