Worsening renal function (WRF) may be associated with left ventricular ejection fraction (LVEF) in patients with acute heart failure (AHF), according to a study published in the European Journal of Heart Failure.

In this study, the data of 6112 patients with AHF enrolled across 546 centers in 35 countries in the multicenter, randomized, double-blind, placebo-controlled phase 3 Serelaxin in Acute Heart Failure (RELAX-AHF-2; ClinicalTrials.gov Identifier: NCT01870778) trial were examined. Participants were randomly assigned to receive serelaxin (48-hour infusion, 30 mg/kg/day) or placebo and followed for 180 days to determine clinical outcomes (ie, cardiovascular death, heart failure, renal failure, and rehospitalization).

Patients were stratified based on LVEF quartile (Q1-Q4). The incidence of a set of baseline characteristics increased with each LVEF quartile: age, female gender, White ethnicity, systolic blood pressure, body mass index, and history of hypertension, atrial fibrillation, heart failure, chronic kidney disease, and depression (P <.001 for all).

Total doses of intravenous and loop diuretics decreased with increased LVEF during hospitalization. Response to diuretic therapy and weight loss were inversely related to LVEF.


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Creatinine and blood nitrogen urea increased and estimated glomerular filtration rate decreased in a stepwise pattern with increasing LVEF. Patients with the highest LVEF had increased rates of residual congestion. Patients with the lowest LVEF had the greatest reduction in systolic blood pressure.

WRF increased progressively with increasing LVEF quartiles (Q1, 23.1%; Q2, 27.1%; Q3, 29.4%; Q4, 34.4%; P <.001). After correcting for possible cofounders, patients in the highest vs lowest LVEF quartile were found to be at increased risk for WRF at hospitalization day 5 (hazard ratio [HR], 1.2; 95% CI, 1-1.43; P =.050).

After hospital discharge, patients with vs without WRF were at increased risk until day 180 for: cardiovascular mortality or rehospitalization (HR, 1.18; 95% CI, 1.05-1.31; P =.004), cardiovascular mortality alone (HR, 1.25; 95% CI, 1.04-1.50; P =.018), and all-cause mortality (HR, 1.29; 95% CI, 1.10-1.51, P =.002).

Study limitations include its exclusion criteria (ie, systolic blood pressure <125 mmHg and inotrope treatment), which may have led to fewer patients with WRF in the lower LVEF quartiles.

“[T]he increased susceptibility of these patients for developing WRF appears to be related to their more advanced age and worse baseline kidney function,” noted the study authors. “While WRF in-hospital was not associated with post-discharge outcomes in patients in the lowest LVEF quartile, it did portend a less favorable course in patients in the upper quartiles.”

Reference

Feng S, Janwanishstaporn S, Teerlink J, et al. Association of left ventricular ejection fraction with worsening renal function in patients with acute heart failure: Insights from the RELAX-AHF-2 study. [published online September 22, 2020] Eur J Heart Fail. doi:10.1002/ejhf.2012