Abstract 16940: Serum Amine-based Metabolites and Their Association With Outcomes in Primary Prevention Implantable Cardioverter Defibrillator Patients
Background: Heart failure patients are at increased risk of ventricular arrhythmias and all-cause mortality. However, existing clinical and serum markers only modestly predict these adverse events.
Objective: We sought to use metabolic profiling to identify novel biomarkers in two independent prospective cohorts of patients with implantable cardioverter defibrillators (ICDs) for primary prevention of sudden cardiac death (SCD).
Methods and Results: Baseline serum was quantitatively profiled for 42 known biologically-relevant amine-based metabolites among 402 patients from the PROSE-ICD Study (derivation group) and 240 patients from the GRADE Study (validation group) for ventricular arrhythmia-induced ICD shocks and all-cause mortality. In multivariate Cox models adjusted for traditional cardiovascular risk factors, 3 amines (N-methyl-L-histidine, symmetric dimethylarginine [SDMA], and L-kynurenine) were associated with all-cause mortality in both derivation and validation cohorts (Figure 1). Additionally, L-histidine, SDMA, L-kynurenine, L-4-hydroxyproline, and L-glutamine were associated with ventricular arrhythmia-induced ICD shocks in one of the cohorts, suggesting their potential to be novel markers of ventricular arrhythmia (Figure 2).
Conclusions: Utilizing metabolic profiling, we identified several novel amine markers that were associated with appropriate shock and mortality in primary prevention ICD patients. These findings shed insight into the potential biologic pathways leading to adverse events in these patients, which will in turn aid the development of newer therapeutics for reducing SCD and mortality.
- sudden cardiac death
- implantable cardioverter defibrillator
- ventricular arrhythmia
Author Disclosures: Y. Zhang: None. E. Blasco-Colmenares: None. A. Harms: None. B. London: None. I. Halder: None. M. Singh: None. S. Dudley: None. R. Gutmann: None. E. Guallar: None. T. Hankemeier: None. G. Tomaselli: None. A. Cheng: Honoraria; Modest; Boston Scientific, Medtronic, St. Jude Medical.
- © 2015 by American Heart Association, Inc.