Effect of Aggressive Diuresis in Acute Heart Failure with Reduced and Preserved Ejection Fraction

Abstract Background: HFrEF and HFpEF had distinct hemodynamic characteristics in the setting of acute heart failure (AHF). The objective of our study is to evaluate the differential response to aggressive diuresis in Heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Methods: Patients in DOSE trial with left ventricular ejection fraction (LVEF) measurement were included (n=300), and classified into HFrEF (n=193) and HFpEF (n=107). Effect of high-dose versus low-dose furosemide strategy was compared separately in HFrEF and HFpEF. Results: High-dose strategy significantly increased change in creatinine and cystatin C at 72 hours in HFpEF (treatment difference: 0.16; 95% confidence interval [CI]: 0.02-0.30 mg/dl; P=0.03 for creatinine, and treatment difference: 0.26; 95% CI: 0.09-0.43 mg/dl; P=0.003 for cystatin C) but not in HFrEF (treatment difference: -0.05, 95% CI: -0.14-0.03 mg/dl; P=0.24 for creatinine, and treatment difference: -0.06, 95% CI: -0.15-0.02 mg/dl; P=0.15 for cystatin C) (P for interaction<0.01 for both). There were significantly more net fluid loss, weight loss, and congestion-free patients at 72 hours in high-dose group in HFrEF, but not in HFpEF. Compared with low-dose group, high-dose group had a significantly lower risk of composite clinical outcome of death, total hospitalizations and unscheduled visits due to heart failure (hazard ratio [HR]: 0.50, 95% CI: 0.27-0.93; P=0.03) in HFrEF, but a comparable risk (HR: 0.99, 95% CI: 0.48-0.23; P=0.98) in HFpEF.Conclusions: AHF on the basis of HFrEF and HFpEF responded differently to aggressive diuresis. Future trials should be designed separately for HFrEF and HFpEF.