Abstract 12884: Arginine Vasopressin Levels Predict Post-Discharge Morbidity and Mortality in Patients Admitted for Worsening Heart Failure With Reduced Ejection Fraction: Insights From the EVEREST Trial
Introduction: Arginine vasopressin (AVP) levels are elevated in proportion to the severity of HF and associated with higher cardiovascular mortality (CVM) in ambulatory patients.
Hypothesis: In patients hospitalized for worsening HF with reduced ejection fraction (EF), elevated AVP levels are predictive of post-discharge morbidity and mortality.
Methods: A post-hoc analysis of The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST), which randomized 4133 patients hospitalized for worsening HF and EF ≤40% to tolvaptan (TVP) or placebo, in addition to standard therapy, for a median follow-up of 9.9 months. Co-primary endpoints included all-cause mortality (ACM) and CVM and HF hospitalization (CVM/H). This analysis included all 3196 patients with baseline, off-treatment AVP levels, as there was no interaction between TVP therapy, AVP levels, and outcomes. Patients were subdivided into quartiles (Q1-Q4) of AVP. Q1 and Q2 were combined (Q1) since 59% of patients had AVP levels below the lower limit of detection (5.6 pg/mL). Times to events were compared with log-rank tests and Cox regression models adjusted for baseline risk factors.
Results: Increasing AVP was associated with higher natriuretic peptide measurements (median BNP Q1 617, Q3 917, and Q4 928 pg/mL) as well as shorter times to ACM (Figure) and CVM/H (all p-value <0.01). After adjusting for covariates, the highest AVP quartile was still associated with increased risk for ACM (Q4 HR 1.34, 95% CI 1.13 -1.58) and CVM/H (Q4 HR 1.19, 95% CI 1.04 -1.36).
Conclusions: Elevated baseline, off-treatment AVP levels are an independent predictor of post-discharge morbidity and mortality in patients hospitalized for worsening HF with reduced EF. Most patients had undetectable levels, possibly due to rapid degradation. Improved AVP assays or measurement of surrogates, such as copeptin, may be critical to defining the specific HF phenotype responsive to vasopressin antagonism.
- © 2011 by American Heart Association, Inc.