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

Key Points The optimal balance between decongestion and kidney function preservation remains uncertain in outpatients with heart failure. Improved congestion is generally associated with lower mortality risk with eGFR declines and only higher risk when eGFR exceeds 40%. Background Although both volume overload and reduced level of kidney function are associated with higher mortality in heart failure, decongestion can lead to kidney function decline. The optimal balance between sustaining decongestion and preserving kidney function remains uncertain among outpatients with heart failure. We compared associations of postdischarge changes in kidney function and congestion status with mortality in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan trial. Methods This post hoc analysis of a randomized controlled trial included 3404 participants discharged from a heart failure hospitalization. Compared with 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 per 1.73 m 2 , respectively. Over a median (interquartile range) 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 with patients with worsened congestion and no eGFR decline, those with improved congestion had lower mortality risk (hazard ratio [HR], 0.51 [95% confidence interval (CI), 0.35 to 0.74] for no eGFR decline; HR, 0.56 [95% CI, 0.38 to 0.85] for 1%–20% eGFR decline; and HR, 0.80 [95% CI, 0.46 to 1.39] for 21%–40% eGFR decline), whereas those with improved congestion and 41% or greater eGFR decline had higher risk (HR, 2.23; 95% CI, 1.06 to 4.66). Conclusions Compared with worsened congestion and no eGFR decline, improved congestion is generally associated with lower mortality with eGFR declines, unless eGFR decline exceeds 40%. Clinical Trial registry name and registration number: NCT00071331.