Association of 48-h net fluid status with change in renal function and dyspnea among patients with decompensated heart failure: A pooled cohort analysis of three acute heart failure trials.

Abstract

Acute heart failure (AHF) exacerbations are a leading cause of hospitalization in the United States. Despite the frequency of AHF hospitalizations, there are inadequate data or practice guidelines on how quickly diuresis should be achieved. To study the association of 48-h net fluid change and (A) 72-h change in creatinine and (B) 72-h change in dyspnea among patients with acute heart failure. This is a retrospective, pooled cohort analysis of patients from the DOSE, ROSE, and ATHENA-HF trials. The primary exposure was 48-h net fluid status. The co-primary outcomes were 72-h change in creatinine and 72-h change in dyspnea. The secondary outcome was risk of 60-day mortality or rehospitalization. Eight hundred and seven patients were included. The mean 48-h net fluid status was -2.9 L. A nonlinear association was observed with net fluid status and creatinine change, such that creatinine improved with each liter net negative up to 3.5 L (-0.03 mg/dL per liter negative [95% confidence interval [CI]: -0.06 to -0.01) and remained stable beyond 3.5 L (-0.01 [95% CI: -0.02 to 0.001], p = .17). Net fluid loss was associated with a monotonic improvement of dyspnea (1.4-point improvement per liter negative [95% CI: 0.7-2.2], p = .0002). Each liter net negative by 48 h was also associated with 12% decreased odds of 60-day rehospitalization or death (odds ratio: 0.88; 95% CI: 0.82-0.95; p = .002). Aggressive net fluid targets within the first 48 h are associated with effective relief of patient self-reported dyspnea and improved long-term outcomes without adversely affecting renal function.