Predictors of Long-Term Outcome in Heart Failure with Preserved Ejection Fraction: A Follow-Up from the KaRen Study

AIMS: Heart failure (HF) with preserved ejection fraction (HFpEF) has poor long-term prognosis. We assessed rates and predictors of outcome 10 years after an acute episode of HF. METHODS AND RESULTS: The Karolinska-Rennes (KaRen) study enrolled HFpEF patients with acute HF, ejection fraction ≥ 45%, and N-terminal pro-brain natriuretic peptide > 300 ng/L in 2007-11. Clinical data were collected at enrolment and after 4-8 weeks including detailed echocardiography. Follow-up data were collected 10 years after study initiation, starting from 6 months after enrolment until 2018 assessed by telephone. Independent predictors of primary (all-cause mortality or HF hospitalization) and secondary (all-cause mortality) outcomes were assessed by multivariable Cox regression. Of 539 patients, long-term follow-up data were available for 397 patients 52% female; median (interquartile range) age 79 (73, 84) years. Over a follow-up of 5.44 (2.06-7.89) years, 1, 3, 5, and 10 year mortality rates were 15%, 31%, 47%, and 74%, respectively, with an incidence rate of 130/1000 patient-years. The primary outcome was met in 84% of the population, with an incidence rate of 227/1000 patient-years. The independent predictors of the primary outcome were tricuspid regurgitation peak velocity (m/s) hazard ratio 1.87 (1.34-2.62), diabetes mellitus 1.75 (1.11-2.74), and cancer 1.75 (1.01-3.03) while female sex was associated with reduced risk 0.64 (0.41-0.98). CONCLUSIONS: In HFpEF, 1, 3, 5, and 10 year mortality was 15%, 31%, 47%, and 74% and mortality or first HF hospitalization was 35%, 54%, 67%, and 84%, respectively. Independent predictors of mortality or HF hospitalization were tricuspid regurgitation peak velocity, diabetes mellitus, cancer, and male sex. In clinical management of HFpEF, attention should be paid to both cardiac and non-cardiac conditions.