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.

BACKGROUND: 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. OBJECTIVE: 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. DESIGNS, SETTINGS, AND PARTICIPANTS: This is a retrospective, pooled cohort analysis of patients from the DOSE, ROSE, and ATHENA-HF trials. INTERVENTIONS: The primary exposure was 48-h net fluid status. MAIN OUTCOMES AND MEASURES: 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. RESULTS: 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). CONCLUSION: 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.