Short-term decongestion and clinical benefit in acute heart failure: a systematic review and trial-level meta-regression

Background Body weight, urine output, urinary sodium, and ultrasound findings are frequently used as early trial endpoints in acute heart failure (AHF). However, patient-level prognostic associations with residual congestion do not establish the fact that treatment-induced marker improvement predicts fewer deaths or heart failure events. Objectives The objectives of this work are to pair short-term decongestion and subsequent clinical treatment effects within the same randomized comparisons, explore the trial-level association for body weight, and qualitatively assess non-weight markers. Methods PubMed/MEDLINE, OpenAlex, and ClinicalTrials.gov databases were searched through 18 July 2026. Eligible randomized adult AHF trials reported an objective decongestion effect and ≥30-day mortality, heart failure events, or rehospitalization. The amended primary marker was weight change at 24–96 h (original window, 48–96 h); clinical effects were log hazard or risk ratios. An errors-in-variables meta-regression model used 10,000 trial cluster bootstrap fits and trial-level jackknife intervals. Results Twenty-four trials (27 reports) were accepted for qualitative synthesis; the primary analysis included 12 comparisons from only 10 independent trials. Endpoints, follow-up (30–302 days), effect measures, and mechanisms were heterogeneous. Each additional 1-kg between-group difference in weight loss corresponded to a clinical effect ratio of 0.74 (percentile 95% interval, 0.56–1.26; jackknife, 0.49–1.11). The pharmacological-only estimate was 1.04. Evidence for urine output, urinary sodium, and ultrasound was also inconsistent. Conclusions Short-term weight loss showed a directional but non-robust trial-level association with clinical benefit. The randomized trial-level evidence evaluated here is insufficient to validate short-term weight change as a surrogate for post-discharge clinical outcomes in AHF.