Relationship of ejection fraction and natriuretic peptide trajectories in heart failure with baseline reduced and mid-range ejection fraction

Abstract

BackgroundThe prognostic importance of trajectories of neurohormones relative to left ventricular function over time in heart failure with reduced and mid-range EF (HFrEF and HFmrEF) is poorly defined. ObjectiveTo evaluate left ventricular ejection fraction (LVEF) and B-type natriuretic peptide (BNP) trajectories in HFrEF and HFmrEF. MethodsAnalyses of LVEF and BNP trajectories after incident HF admissions presenting with abnormal LV systolic function were performed using 3 methods: a Cox proportional hazards model with time-varying covariates, a dual longitudinal-survival model with shared random effects, and an unsupervised analysis to capture 3 discrete trajectories for each parameter. ResultsAmong 1,158 patients (68.9 ± 13.0 years, 53.3% female), both time-varying LVEF measurements (P=.001) and log-transformed BNP measurements (p-values=2 × 10−16) were independently associated with survival during 6 years after covariate adjustment. In the dual longitudinal/survival model, both LVEF and BNP trajectories again were independently associated with survival (P<.0001 in each model); however, LVEF was more dynamic than BNP (P <.0001 for time covariate in LVEF longitudinal model versus P=.88 for the time covariate in BNP longitudinal model). In the unsupervised analysis, 3 discrete LVEF trajectories (dividing the cohort into approximately thirds) and 3 discrete BNP trajectories were identified. Discrete LVEF and BNP trajectories had independent prognostic value in Kaplan-Meier analyses (P<.0001), and substantial membership variability across BNP and LVEF trajectories was noted. ConclusionAlthough LVEF trajectories have greater temporal variation, BNP trajectories provide additive prognostication and an even stronger association with survival times in heart failure patients with abnormal LV systolic function.