Abstract 4124: Polymorphisms can Predict Appropriate Therapies in Patients with Heart Failure and Implantable Cardioverter Defibrillators

Abstract

Introduction: The use of implantable cardioverter defibrillators (ICD) reduces mortality in patients with heart failure (HF). However, given its elevated cost, an adequate selection of individuals with higher risk is warranted. Yet, known predictors of risk of sudden cardiac death have shown limited value to select use of ICD. More recently, genetic polymorphisms have been considered as potentially interesting tools to guide therapeutic strategies. Objective: To study the role of three genetic polymorphisms (β1 Arg389Gly, GNB3 C825T and GP IIb/IIIa Pl A1 /Pl A2 ) as predictors of appropriate ICD therapies in patients with heart failure (HF) who received an ICD implant for primary or secondary prevention. Patients and Methods: Retrospective cohort study of patients with ICD use during at least 6 months for primary and secondary prevention, followed at our HF outpatient clinic. Clinical data were registered and ICD analyses were made by telemetry. ICD therapies were defined as appropriate or inappropriate by a cardiac electrophysiologist. Twenty mL of blood were collected for polymorphism analysis by the PCR-RFLP technique. For univariate analysis, Student’s t-test and the χ 2 (chi-square) test were used; logistic regression was used for multivariate analysis. Results: The sample included 73 patients (75% male, 89% white and 56% ischemic etiology). The mean ejection fraction was 34.9 ± 9.8%. Individually, the Arg389 allele of the β1 Arg389Gly polymorphism, the T825 allele of the GNB3 C825T polymorphism, and the Pl A2 allele of the GP IIb/IIIa Pl A1 /Pl A2 polymorphism were not associated with appropriate ICD therapy. Nevertheless, the combined presence of these alleles identified patients with higher risk for appropriate shocks (p=0.03). Survival rate free of appropriate shocks was significantly lower in patients with 2 or 3 risk genotypes when compared with others (p=0.03). Conclusions: When analyzed in combination, the presence of the β1 Arg389Gly, GNB3 C825T, and GP IIb/IIIa Pl A1 /Pl A2 polymorphisms possibly act as predictors of appropriate therapies in ICD recipients with HF. Further studies are needed to determine the clinical applicability of these genetic markers.