Time to Brain Natriuretic Peptide Decrease and Outcomes in Acute Heart Failure

Introduction In acute heart failure (AHF), prompt treatment may mitigate adverse effects of congestion and myocardial damage in the early phase of hospitalization, which may improve outcomes. Hypothesis Early intervention with diuretic therapy is associated with early decrease in BNP, favorable biomarker changes and improved prognosis. Methods: The Acute Kidney Injury NGAL Evaluation of Symptomatic heart faIlure Study (AKINESIS) was a prospective, international, multicenter study of AHF patients. We investigated the relationship between time to first intravenous loop diuretic, time to BNP decrease, changes in biomarkers, and one-year mortality. BNP and high sensitivity cardiac troponin I (hscTnI) were measured at admission, 4-hour, day 1, 2, 3 and discharge. Time to BNP decrease was defined as the time when BNP decrease by ≥ 30% compared to admission in patients and the last BNP value was also ≥ 30% lower than admission. Results Among 814 patients investigated, median time to diuretics was 2.95 (1.75 - 5.78) hours. BNP decrease at day 1, day 2, day 3 and discharge were observed with 20%, 18%, 7%, and 6%, respectively, while 48% had no BNP decrease at discharge. Time to diuretics was not significantly correlated with time to BNP decrease (day 1, 2.8 hours; day 2, 2.9 hours; day 3, 3.4 hours; discharge 4.9 hours; no BNP decrease, 2.9 hours, p = 0.107). Earlier BNP decrease but not diuretic therapy was associated with favorable biomarker changes including earlier hscTnI decrease ( Figure 1 and 2 ). Stepwise increase in one-year mortality was observed with later time to BNP decrease and no BNP decrease at discharge but not with later time to diuretics ( Figure 3 ). After adjustment for confounders, only no BNP decrease at discharge was significantly associated with increased risk compared to decrease at day 1 (adjusted HR 2.38, 95% CI 1.29-4.38, p = 0.006). Conclusions Earlier time to decongestion but not time to diuretics was associated with better biomarker trajectories. However, residual congestion at discharge but not time to decongestion was an independent predictor of poor prognosis.