Association between Beta(1)-Adrenergic Receptor Polymorphism and Risk of ICD Shock in Heart Failure Patients

作者：Zanolla Luisa^*; Guarise Paola; Tomasi Luca; Vassanelli Corrado; Cicorella Nicola; Zanini Roberto; Guarrera Simonetta; Fiorito Giovanni; Matullo Giuseppe

来源：Pacing and Clinical Electrophysiology, 2016, 39(6): 557-564.

DOI：10.1111/pace.12860

• defibrillation-ICD
• congestive heart failure

Background: Sympathetic activation in heart failure patients favors the development of ventricular arrhythmias, thus leading to an increased risk of sudden cardiac death. beta(1)- and beta(2)-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 beta(1)- and beta(2)-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: beta(1)-adrenergic receptor polymorphisms Ser(49)Gly and Arg(389)Gly and beta(2)-adrenergic receptor polymorphisms Arg(16)Gly and Gln(27)Glu.
Results: Only Ser(49)Gly 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 beta adrenoreceptor Gly 49 allele of the beta(1)-adrenergic receptor Ser(49)Gly polymorphisms may increase the risk of ICD shock in patients with heart failure, independent of beta-blocker dosage.

• 出版日期2016-6