Associations between changes in kidney function and volume status with heart failure outcomes
Patients with a history of hospitalisation for heart failure face a substantially greater risk of mortality compared with those who have never been hospitalised. Both volume overload and reduced kidney function are associated with higher mortality in heart failure. Decongestion, however, can lead to kidney function decline.
In the treatment of outpatients with heart failure, this poses a dilemma over whether to prioritise further decongestion or preserve kidney function at the expense of worsening congestion. Using data from the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan) trial, Oka and colleagues examined how changes in kidney function and congestion status over time were associated with heart failure outcomes following discharge.
EVEREST was a randomised controlled trial that investigated the efficacy and safety of tolvaptan in patients hospitalised for acute decompensated heart failure. Participants were randomised to either 30 mg/day of tolvaptan or placebo in addition to standard care. The post hoc analysis included 3404 patients who were followed-up from discharge to the date of death or end of trial period or until they were lost to follow-up.
Kidney function exposure, defined as changes in eGFR after discharge, was categorised into four groups: no decline, 1%–20% decline, 21%–40% decline and ≥40% decline. Volume status exposure was categorised into two groups: congestion improved (clinical congestion score [CCS] decreased) and congestion worsened (CCS increased).
This led to eight time-varying exposure groups being defined: congestion improved with no eGFR decline, with 1%–20% decline, 21%–40% decline and with ≥40% decline; and congestion worsened with no eGFR decline, with 1%–20% decline, 21%–40% decline and with ≥40% decline.
At discharge, the mean (SD) age and eGFR were 66 (12) years and 59.6 (22.3) mL/min/1.73 m2, respectively. There were 740 deaths over a median follow-up of 44.0 weeks.
After fully adjusting for confounders, eGFR decline was associated with a higher risk of all-cause mortality, with the highest risk in the ≥41% decline group. The congestion worsened group was associated with a 116% higher risk compared with the congestion improved group.
Compared with the worsened congestion and no eGFR decline reference group, the risks of all-cause mortality were significantly lower in the congestion improved with no eGFR decline group (HR, 0.51 [95% CI, 0.35 to 0.74] and the congestion improved with 1%–20% decline group (HR, 0.56 [0.38 to 0.85]), and lower (but not significantly) in the congestion improved with 21%–40% decline group (HR, 0.80 [0.46 to 1.39]). However, for those with improved congestion and ≥41% eGFR decline, the risk was higher (HR, 2.23 [1.06 to 4.66]).
The findings suggest that prioritising sustained decongestion over preserving kidney function is preferable up to an eGFR decline of 20% and may extend to approximately 40% among recently discharged patients with heart failure. The authors caution that, because of the observational nature of the study, these findings cannot be directly applied to clinical practice.
The full article can be read here.
