Thresholds of Kidney Function Decline and Congestion Status and Their Relation with Outcomes Among Discharged Heart Failure Patients

Background: While both volume overload and reduced level of kidney function are associated with higher mortality in heart failure (HF), decongestion can lead to kidney function decline. The optimal balance between sustaining decongestion and preserving kidney function remains uncertain among outpatients with HF. We compared associations of post-discharge changes in kidney function and congestion status with mortality in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial. Methods: This post-hoc analysis of a randomized controlled trial included 3,404 participants discharged from an HF hospitalization. Compared to estimated glomerular filtration rate (eGFR) and clinical congestion score at discharge, eight time-varying exposure groups were defined: improved or worsened congestion, with varying degrees of eGFR decline (no decline, 1–20%, 21–40%, and 41% or greater). The association of these groups with all-cause mortality was assessed using marginal structural models to account for time-dependent confounding. Results: The mean (SD) age and eGFR at discharge were 66 (12) years and 59.6 (22.3) mL/min/1.73 m 2 , respectively. Over a median (IQR) follow-up of 44 (25–71) weeks, 740 patients died. Both higher degrees of eGFR decline and worsened congestion were associated with higher mortality risk. Compared to patients with worsened congestion and no eGFR decline, those with improved congestion had lower mortality risk (HR, 0.51 [95% CI, 0.35–0.74] for no eGFR decline; HR, 0.56 [95% CI, 0.38–0.85] for 1–20% eGFR decline; and HR, 0.80 [95% CI, 0.46–1.39] for 21–40% eGFR decline), while those with improved congestion and 41% or greater eGFR decline had higher risk (HR, 2.23; 95% CI, 1.06–4.66). Conclusions: Compared to worsened congestion and no GFR decline, improved congestion is generally associated with lower mortality risk but higher risk when eGFR decline exceeds 40%, suggesting the importance of sustaining decongestion over preserving kidney function if eGFR decline is modest.