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.

Background Heart failure patients with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF) have different sensitivity to plasma volume change after decongestion, but the possible differential effects of loop diuretics dosage on worsening renal function (WRF) in heart failure (HF) categories remain unclear. Methods In 972 patients with HFpEF and 427 patients with HFrEF, we assessed the risk of WRF with the average daily furosemide equivalent dose, using multivariable logistic regression. WRF was defined as an increase in serum creatinine levels of more than 26.5 mmol/L during hospitalization. Results In patients with HFpEF and HFrEF, between-group differences in average daily furosemide equivalent dose (18.9 mg/d vs. 26.8 mg/d) and the prevalence of WRF (25.3% vs. 14.3%) were significant (p < 0.001). In multivariable-adjusted analyses, a doubling of the average furosemide equivalent dose was associated with higher risk of WRF in all patients, patients with HFpEF and HFrEF, with odds ratios amounting to 1.42, 1.41 and 1.60 (p ≤ 0.022), respectively. There was no interaction between heart failure categories and average furosemide equivalent dose (p = 0.37). The adjusted odds ratios of risk of WRF associated with intravenous furosemide were 1.26 (95% confidence interval [CI], 1.08–1.46; p = 0.002) in HFpEF but not significant in HFrEF(p = 0.099). Conclusions The risk of WRF was associated with higher furosemide dosage in both HF subtypes. Our observations highlight that close monitoring is required to prevent further renal impairment in all HF patients while using loop diuretics.