Heart Rhythm:房颤风险等位基因预测消融术后房颤复发

　　来自美国田纳西州范德比尔特大学医学中心的一项研究表明，染色体4q25的风险等位基因位点，可预测典型房颤为主的患者人群对房颤消融治疗的临床反应受损。这一研究结果表明，rs2200733多态性可能作为一种有希望的AF患者客观检测特征，并作为选择房颤消融患者的一个临床工具。研究在2012年11月26日在线发表于《心脏节律》（Heart Rhythm）杂志。

　　在染色体4q25常见的单核苷酸多态性（SNP）位点（rs2200733，rs10033464）与孤立性和典型的AF相关联。近期研究表明，染色体4q25的风险等位基因可预测孤立性房颤消融为主的人群的房颤复发，但孤立性房颤只占房颤病例的5％至30％。该研究旨在评价4q25 AF风险等位基因能否在大多数AF病例中，预测的房颤消融术的反应。

　　研究在2004年至2011年共纳入378例接受了导管消融术为基础治疗的房颤患者（平均年龄60岁，71％为男性，89％为典型AF），患者来源于范德比尔特AF注册研究。主要终点是任何非窦性心动过速[房性心动过速，心房扑动，或AF；（AT/AF）]的复发时间。

　　结果表明，200例患者发生AT / AF复发（53％）。多变量分析显示，与野生型基因相比，rs2200733风险等位基因可预测的24％更短的无复发时间[存活时间比为0.76 ，95％可信区间（CI）为0.6-0.95，P=0.016]。杂合子单倍型表现出21％更短的无复发时间（存活时间比为0.79，95％CI为0.62-0.99）。纯合子风险等位基因携带者表现出39％更短的无复发时间（存活时间比=0.61，95％CI 0.37-1.0）（P=0.037）。

Common Atrial Fibrillation Risk Alleles at 4q25 Predict Recurrence after Catheter-based Atrial Fibrillation Ablation

Background

Common single nucleotide polymorphisms (SNPs) at chromosome 4q25 (rs2200733, rs10033464) are associated with both lone and typical AF. Risk alleles at 4q25 have recently been shown to predict recurrence of AF after ablation in a population of predominately lone AF, but lone AF represents only 5-30% of AF cases.

Objective

To test the hypothesis that 4q25 AF risk alleles can predict response to AF ablation in the majority of AF cases.

Methods

Patients enrolled in the Vanderbilt AF Registry underwent 378 catheter-based AF ablations (median age 60 years, 71% male, 89% typical AF) between 2004 and 2011. The primary endpoint was time to recurrence of any non-sinus atrial tachyarrhythmia (atrial tachycardia, atrial flutter, or AF; [AT/AF]).

Results

Two-hundred AT/AF recurrences (53%) were observed. In multivariable analysis, the rs2200733 risk allele predicted a 24% shorter recurrence-free time (survival time ratio 0.76 95% confidence interval [CI] 0.6-0.95, P=0.016) compared with wild-type. The heterozygous haplotype demonstrated a 21% shorter recurrence-free time (survival time ratio = 0.79, 95% CI 0.62-0.99) and the homozygous risk allele carriers a 39% shorter recurrence-free time (survival time ratio = 0.61, 95% CI 0.37-1.0) (P=0.037).

Conclusion

Risk alleles at the 4q25 loci predict impaired clinical response to AF ablation in a population of predominately typical AF patients. Our findings suggest the rs2200733 polymorphism may hold promise as an as an objectively measured patient characteristic that can used as a clinical tool for selection of patients for AF ablation.