Risk factors and outcomes associated with heart failure with preserved and reduced ejection fraction in persons with chronic kidney disease

ABSTRACT Background Heart failure (HF) is associated with poor outcomes in persons with chronic kidney disease (CKD), yet there are limited data on whether outcomes differ by HF subtype. This study aimed to examine associations of incident preserved (HFpEF) versus reduced (HFrEF) ejection fraction (EF) with risk of progression to end-stage-kidney-disease (ESKD) and mortality. Methods We studied individuals with mild to severe CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study who were free of HF at cohort entry. Incident HF hospitalizations were adjudicated during study follow-up and classified into HFpEF (EF > 50%) or HFrEF (EF<50%) based on echocardiograms performed during the hospitalization or at a research study visit within one year of the hospitalization. ESKD was defined as need for chronic dialysis or kidney transplant during follow-up. Cox proportional hazards were used to evaluate the association of time-updated HF subtype with risk of ESKD and mortality, adjusting for demographics, comorbidities and medication use. Results Among the 3,557 study participants without HF at cohort entry, mean age was 57 years and mean eGFR 45 ml/min/1.73 m 2 at baseline. Incidence rates for HFpEF and HFrEF were 0.9 (95% CI 0.8, 1.0) and 0.7 (95% CI 0.6, 0.8) per 100 person-years, respectively. Adjusted associations of incident HF with progression to ESKD were similar for HFpEF (HR 1.59, 95% CI: 1.24, 2.02) and HFrEF (HR 1.26, 95% CI: 0.93, 1.70) (test for difference p-value=0.35). The adjusted associations of HFpEF and HFrEF HF with mortality were stronger for HFrEF (HR 1.68, 95% CI: 1.34, 2.11) compared with HFpEF (HR 1.24, 95% CI: 1.00, 1.54) (test for difference p-value = 0.02). Conclusions In a large U.S. CKD population, the rates of HFpEF hospitalizations were greater than that of HFrEF. Both types of HF had similar associations with risk of ESKD; however, there was a stronger association of HFrEF with mortality. Prevention and treatment of both HFpEF and HFrEF should be central priorities to improve clinical outcomes in patients with CKD.