Abstract 16991: Multiple Peripheral Blood Protein Biomarkers Are Associated with Appropriate ICD Therapy in the DISCERN Study
Background: The decision to implant an ICD for primary prevention of ventricular arrhythmia is challenging and has relied on ventricular ejection fraction as a primary decision making factor, although improved risk stratification methodologies are clearly needed. Recent evidence suggests that inflammation plays a role in the generation of ventricular arrhythmias; we and others have demonstrated that increased C-reactive protein (CRP) levels are associated with appropriate ICD therapy. We have expanded these initial observations by interrogating a large set of circulating proteins in a population of patients with ICDs.
Methods: Levels of 103 proteins in plasma were assessed in a case:control cohort of 152 subjects (72 cases) enrolled in DISCERN (NCT00500708), a multi-center study designed to identify markers associated with ventricular arrhythmia. Assays were chosen from an existing set of proteins largely associated with inflammation. Patients had ejection fractions of <50%, 92% were male and 91% had ischemic HF. ICD firing data was captured for all subjects; cases had appropriate adjudicated ICD therapy in response to VT/VF, controls had no appropriate therapy within two years of ICD implant.
Results: In a logistic regression model adjusting for age, sex and WBC, the levels of 10 proteins (NTproBNP, CRP, SAA, MMP9, sMET, CCL2, Ang2, Resistin, TNFR1, E-Selectin) were significantly associated with appropriate ICD therapy (p < 0.05). In an exploratory analysis, grouping subjects by number of events (events = 0, 1, >1) resulted in even stronger associations, with an additional 11 proteins identified (p < 0.05). Multiple biological pathways were represented in the set of proteins, including inflammation, cell adhesion, and glucose regulation.
Conclusions: Multiple protein biomarkers were significantly associated with appropriate ICD therapy, showing stronger associations in patients with multiple events. The use of such markers may provide an approach to risk stratify heart failure patients for ICD implantation.
Author Disclosures: J. Wingrove: Employment; Significant; CardioDx,Inc. P. Beineke: Employment; Significant; CardioDx, Inc. K. Fitch: Employment; Significant; CardioDx, Inc.. D. Darbar: None. S. Rosenberg: Ownership Interest; Significant; CardioDx, Inc.. Consultant/Advisory Board; Significant; CardioDx, Inc..
- © 2014 by American Heart Association, Inc.