Pre-discharge and early post-discharge troponin elevation among patients hospitalized for heart failure with reduced ejection fraction: findings from the ASTRONAUT trial

Abstract

Aims: Troponin levels are commonly elevated among patients hospitalized for heart failure (HF), but the prevalence and prognostic significance of early post-discharge troponin elevation are unclear. This study sought to describe the frequency and prognostic value of pre-discharge and post-discharge troponin elevation, including persistent troponin elevation from the inpatient to outpatient settings.

Methods and results: The ASTRONAUT trial (NCT00894387; http://www.clinicaltrials.gov) enrolled hospitalized HF patients with ejection fraction ≤40% and measured troponin I prior to discharge (i.e. study baseline) and at 1-month follow-up in a core laboratory (elevation defined as >0.04 ng/mL). This analysis included 1469 (91.0%) patients with pre-discharge troponin data. Overall, 41.5% and 29.9% of patients had elevated pre-discharge [median: 0.09 ng/mL; interquartile range (IQR): 0.06-0.19 ng/mL] and 1-month (median: 0.09 ng/mL; IQR: 0.06-0.15 ng/mL) troponin levels, respectively. Among patients with pre-discharge troponin elevation, 60.4% had persistent elevation at 1 month. After adjustment, pre-discharge troponin elevation was not associated with 12-month clinical outcomes. In contrast, 1-month troponin elevation was independently predictive of increased all-cause mortality [hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.18-2.13] and cardiovascular mortality or HF hospitalization (HR 1.28, 95% CI 1.03-1.58) at 12 months. Associations between 1-month troponin elevation and outcomes were similar among patients with newly elevated (i.e. normal pre-discharge) and persistently elevated levels (interaction P ≥ 0.16). The prognostic value of 1-month troponin elevation for 12-month mortality was driven by a pronounced association among patients with coronary artery disease (interaction P = 0.009).

Conclusions: In this hospitalized HF population, troponin I elevation was common during index hospitalization and at 1-month follow-up. Elevated troponin I level at 1 month, but not pre-discharge, was independently predictive of increased clinical events at 12 months. Early post-discharge troponin I measurement may offer a practical means of risk stratification and should be investigated as a therapeutic target.

Keywords: Heart failure; Hospitalization; Outcomes; Post-discharge; Troponin.

Conflict of interest statement

Conflict of interest: S.J.G. is supported by the National Heart, Lung and Blood Institute (NHLBI) T32 post-doctoral training grant (5T32HL069749–14). J.B. reports research support from the National Institutes of Health, European Union and the Patient-Centered Outcomes Research Institute, and has served a consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Meyers Squib, Cardiocell, Janssen, Novartis, Relypsa, ZS Pharma, Medtronic, Merck and CVRx. G.C.F. reports significant consulting for Novartis, and modest consulting for Amgen, Bayer, Medtronic and Janssen, holds the Eliot Corday Chair of Cardiovascular Medicine at the University of California Los Angeles and is also supported by the Ahmanson Foundation (Los Angeles, CA, USA). M.V. is supported by the NHLBI T32 postdoctoral training grant (T32HL007604). S.D.S. has received grant funding, consultant fees and travel support from Novartis. A.P.M. has served on committees of clinical studies sponsored by Amgen, Bayer, Abbott Vascular, Cardiorentis, Johnson & Johnson and Novartis Pharma. M.B. has served as a consultant for AstraZeneca, Bayer, Boehringer-Ingelheim, Daiichi-Sankyo, AWD Dresden, Berlin-Chemie, MSD, Novartis, Pfizer, Sanofi-Aventis and Servier. F.Z. has received grant funding from Novartis, BG Medicine and Roche Diagnostics, served on a board for Boston Scientific and as a consultant for Novartis, Takeda, AstraZeneca, Boehringer-Ingelheim, GE Healthcare, Relypsa, Servier, Boston Scientific, Bayer, Johnson & Johnson and ResMed. M.G. has served as a consultant for Abbott Laboratories, Astellas, AstraZeneca, Bayer HealthCare, CorThera, Cytokinetics, DebioPharm, Errekappa Terapeutici, GlaxoSmithKline, Ikaria, Johnson & Johnson, Medtronic, Merck, Novartis Pharma, Otsuka Pharmaceuticals, Palatin Technologies, Pericor Therapeutics, Protein Design Laboratories, Sanofi-Aventis, Sigma Tau, Solvay Pharmaceuticals, Takeda Pharmaceutical and Trevena Therapeutics. All other authors have no conflicts to declare.

© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Figures

Figure 1

Selection of the analytic cohort and breakdown of troponin testing at pre-discharge (baseline) through 1-month follow-up. BNP, B-type natriuretic peptide; eGFR, estimated glomerular filtration rate; LVEF, left ventricular ejection fraction

Figure 2

All-cause mortality at 12 months by (A) pre-discharge and (B) 1-month post-discharge troponin I level

Figure 3

Kaplan–Meier curves for (A) all-cause mortality and (B) cardiovascular mortality or hospitalization for heart failure at 12 months follow-up by pre-discharge troponin I status, and (C) all-cause mortality and (D) cardiovascular mortality or hospitalization for heart failure at 12 months follow-up by 1-month post-discharge troponin I status. Times to events were compared using log-rank tests