Francia Pietro, Adduci Carmen, Ricotta Agnese, Stanzione Rosita, Sensini Isabella, Uccellini Arianna, Frattari Alessandra, Balla Cristina, Cotugno Maria, Cappato Riccardo, Rubattu Speranza, Volpe Massimo
Division of Cardiology, Department of Clinical and Molecular Medicine, Sapienza University of Rome Sant'Andrea Hospital, Via di Grottarossa, 00189, Rome, Italy,
J Interv Card Electrophysiol. 2013 Dec;38(3):169-77. doi: 10.1007/s10840-013-9827-1. Epub 2013 Sep 19.
Defective Ca²⁺ handling in failing cardiomyocites predisposes patients with heart failure (HF) to ventricular arrhythmia. We investigated whether gene variants of Ca²⁺ handling proteins are associated with the occurrence of ventricular tachycardia/fibrillation (VT/VF) in HF patients implanted with a primary prevention implantable cardioverter-defibrillator (ICD).
One hundred thirty-six patients with HF were followed from ICD implantation to the time of first appropriate ICD intervention for VT > 170 bpm. The following polymorphisms were genotyped: ATP2A2 rs1860561 and rs56243033; RYR2 rs4142933; CASQ2 rs4074536; SLC8A1 g.-23449C > A; PLN rs12198461; FKBP1B rs7568163. Hazard ratios (HR) were derived from Cox proportional-hazards regression analysis.
After a mean follow-up of 879 days (IQ range, 327 to 1,459), 34 patients (25%) had appropriate ICD intervention. Non-sustained VT (HR, 2.12; 95%CI, 0.87-5.19; p = 0.09) and atrial fibrillation (AF) at ICD implantation (HR, 2.33; 95%CI, 0.89-6.10; p = 0.08) predicted appropriate ICD interventions with borderline statistical significance. Prevalence of ATP2A2 rs1860561 variant was 17% in patients without VT/VF and 4% in those with ventricular arrhythmia (p = 0.009). After adjustment for AF and NSVT, the rs1860561 A mutant allele independently predicted lower incidence of VT/VF (HR, 0.29; 95%CI, 0.09-0.98; p = 0.04).
The observation that ATP2A2 rs1860561 gene variant associated with lower risk of life-threatening arrhythmia in HF patients suggests that selected calcium gene variants may modify the risk of SD even within the complex and polygenic pathological condition of HF. Combining traditional risk factors and genetic profiling could reveal helpful to identify HF patients who will benefit most from ICD implantation.
衰竭心肌细胞中钙处理功能缺陷使心力衰竭（HF）患者易发生室性心律失常。我们研究了钙处理蛋白的基因变异是否与植入一级预防植入式心脏复律除颤器（ICD）的HF患者发生室性心动过速/心室颤动（VT/VF）有关。
对136例HF患者从ICD植入开始随访，直至首次因VT>170次/分进行适当的ICD干预。对以下多态性进行基因分型：ATP2A2 rs1860561和rs56243033；RYR2 rs4142933；CASQ2 rs4074536；SLC8A1 g.-23449C>A；PLN rs12198461；FKBP1B rs7568163。风险比（HR）来自Cox比例风险回归分析。
平均随访879天（四分位间距，327至1459天）后，34例患者（25%）进行了适当的ICD干预。非持续性VT（HR，2.12；95%CI，0.87 - 5.19；p = 0.09）和ICD植入时的心房颤动（AF）（HR，2.33；95%CI，0.89 - 6.10；p = 0.08）预测适当的ICD干预，具有临界统计学意义。ATP2A2 rs1860561变异在无VT/VF患者中的患病率为17%，在有心律失常患者中为4%（p = 0.009）。在调整AF和非持续性VT后，rs1860561 A突变等位基因独立预测VT/VF的发生率较低（HR，0.29；95%CI，0.09 - 0.98；p = 0.04）。
ATP2A2 rs1860561基因变异与HF患者危及生命的心律失常风险较低相关这一观察结果表明，即使在HF复杂的多基因病理状态下，特定的钙基因变异也可能改变心脏性猝死的风险。结合传统风险因素和基因谱分析可能有助于识别将从ICD植入中获益最大的HF患者。
