In hospitalized patients with acute heart failure (HF) with reduced ejection fraction (rEF), the attainment of rapid decongestion is associated with a reduced risk for all-cause and cardiovascular (CV) mortality, as well as HF hospitalization. These findings were published in the American Journal of Medicine.

The multicenter, randomized, controlled Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST; Clinicaltrials.gov identifier: NCT00071331) trial evaluated use of the vasopressin V2 receptor blocker tolvaptan in patients with acute HF. The researchers sought to explore the link between the rate of decline in biomarkers of volume overload and rate of increase in biomarkers of hemoconcentration with mortality and CV outcomes. The primary outcomes of interest were all-cause mortality and a composite of CV mortality or first hospitalization for HF.

Eligibility criteria were reduced left ventricular EF of 40% or less, evidence of congestion based on 2 or more clinical signs or symptoms, and patients should have less than 48 hours into their hospitalization. Patients were randomly assigned to either tolvaptan 30 mg or placebo, in addition to their standard medical therapy. Volume overload was evaluated by biomarkers, including b-type natriuretic peptide (BNP) and N-terminal prohormone of BNP (NT-proBNP), as well as by clinical signs and symptoms.


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A total of 4133 patients were enrolled in the study. More rapid rates of in-hospital decongestion were associated with a decreased risk for mortality and the composite outcome over a median 10 months of follow-up. The quartile with the most rapid BNP and NT-proBNP decline had lower hazards of mortality (hazard ratio [HR], 0.43; 95% CI, 0.31-0.59; and HR, 0.27; 95% CI, 0.19-0.40; respectively) and lower hazards of the composite outcome (HR, 0.49; 95% CI, 0.39-0.60; and HR, 0.54; 95% CI, 0.42-0.71; respectively). The quartile with the fastest increase in hematocrit had lower hazards of mortality (HR, 0.77; 95% CI, 0.62-0.95) and the composite outcome (HR, 0.75; 95% CI, 0.64-0.88).

In continuous models, each weekly standard deviation more negative slope in BNP had a lower hazard for mortality (hazard ratio [HR], 0.71; 95% CI, 0.65-0.78). A graded relationship between rates of decline in BNP and all-cause mortality was observed, with a greater number of events reported in Quartile 1 (the quartile with the least rapid decongestion) and a fewer number of events among those with more rapid rates of BNP decline.

Additionally, each standard deviation more negative slope in BNP per week was associated with a lower hazard for the composite outcome (HR, 0.76; 95% CI, 0.71-0.82). A graded relationship between rate of decline in BNP and the composite outcome was reported, with a greater number of events observed among patients in Quartile 1  and a fewer number of events among those with more rapid rates of BNP decline.

Limitations of the study include the fact that rates of decongestion were not examined directly as an intervention; thus, with the observational nature of this study, the risk for residual and unmeasured confounding always exists.

“While it remains unknown whether faster decongestion is causally related to improved outcomes, it is not associated with cardiovascular harm and can serve as a proxy for less treatment-resistant heart failure and better prognosis,” the study authors wrote.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference  

McCallum W, Tighiouart H, Testani JM, et al. Rates of in-hospital decongestion and association with mortality and cardiovascular outcomes among patients admitted for acute heart failure. Am J Med. Published online April 23, 2022. doi:10.1016/j.amjmed.2022.04.003