Association between Beta1-Adrenergic Receptor Polymorphism and Risk of ICD Shock in Heart Failure Patients

Background: Sympathetic activation in heart failure patients favors the development of ventricular arrhythmias, thus leading to an increased risk of sudden cardiac death. β1- and β2-adrenergic receptor polymorphisms have been linked to the risk of sudden death. Implantable cardioverter-defibrillators (ICD) are implanted in a large percentage of heart failure patients, and beyond preventing sudden cardiac death they provide a continuous monitoring of major ventricular arrhythmias and of their own interventions. We investigated whether functionally relevant β1- and β2-adrenergic receptor polymorphisms are associated with risk of ICD shocks, as evidenced in ICD memory. Methods: 311 patients with systolic heart failure were enrolled, and number and timing of shocks in ICD memory were recorded. Four selected polymorphisms were determined: β1-adrenergic receptor polymorphisms Ser49Gly and Arg389Gly and β2-adrenergic receptor polymorphisms Arg16Gly and Gln27Glu. Results: Only Ser49Gly was significantly correlated with time free from ICD shocks, both considering time to the first event in a Cox model (hazard ratio 2.117), and modeling repeated events with the Andersen-Gill method (hazard ratio 2.088). Gly allele carriers had a higher probability of ICD shock. The relationship remained significant even after adjusting for ejection fraction and beta-blocker dosage (hazard ratio 1.910). Conclusions: Data from our study suggest that the β adrenoreceptor Gly 49 allele of the β1-adrenergic receptor Ser49Gly polymorphisms may increase the risk of ICD shock in patients with heart failure, independent of beta-blocker dosage.