Incident Atrial Fibrillation Is Associated With MYH7 Sarcomeric Gene Variation in Hypertrophic Cardiomyopathy Results From the International Sarcomeric Human Cardiomyopathy Registry
Incident Atrial Fibrillation Is Associated With MYH7 Sarcomeric Gene Variation in Hypertrophic Cardiomyopathy Results From the International Sarcomeric Human Cardiomyopathy Registry
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DOI：
10.1161/circheartfailure.118.005191
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发表时间：
2018-09-01
影响因子：
9.7
通讯作者：
Perez, Marco V.
中科院分区：
文献类型：
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作者：
Lee, Seung-Pyo;Ashley, Euan A.;Perez, Marco V.
背景技术背景：虽然心房颤动（AF）在肥厚型心肌病（HCM）患者中很常见，但遗传变异与AF之间的关系一直不清楚。表征HCM的遗传亚型及其与AF的关联可能有助于改善个性化医疗护理。我们的目的是调查肌节基因变异和事件AF在HCM patients.METHODS和结果之间的联系：患者从多国肌节人类心肌病登记处事件AF。那些可能致病或致病的肌节基因变异被列入。通过审查每个研究中心的病历和心电图确定AF发生率。纳入了1040例成人HCM患者，无基线AF，MYH 7（n=296）、MYBPC 3（n=659）或细丝基因（n=85）可能存在致病性或致病性变异。与其他肌节基因变异的患者相比，MYH 7变异的患者在肌节人类心肌病登记处首次临床就诊时更年轻，并且比MYBPC 3变异更可能成为先证者。在平均7.2年的随访期间，发生了198起AF事件。在调整年龄、性别、先证者状态、左心房大小、最大室壁厚度和峰值压差后，MYH 7中可能存在致病性或致病性突变的患者AF发生率最高（风险比，1.7; 95% CI，1.1-2.6; P=0.009）。在平均7.2年的随访中，19%的肌节突变HCM患者新发AF。与其他肌节基因相比，MYH 7可能致病或致病变异的患者有更高的AF发病率，与临床和超声心动图因素无关。
BACKGROUND: Although atrial fibrillation (AF) is common in hypertrophic cardiomyopathy (HCM) patients, the relationship between genetic variation and AF has been poorly defined. Characterizing genetic subtypes of HCM and their associations with AF may help to improve personalized medical care. We aimed to investigate the link between sarcomeric gene variation and incident AF in HCM patients.METHODS AND RESULTS: Patients from the multinational Sarcomeric Human Cardiomyopathy Registry were followed for incident AF. Those with likely pathogenic or pathogenic variants in sarcomeric genes were included. The AF incidence was ascertained by review of medical records and electrocardiograms at each investigative site. One thousand forty adult HCM patients, without baseline AF and with likely pathogenic or pathogenic variation in either MYH7 (n=296), MYBPC3 (n=659), or thin filament genes (n=85), were included. Compared with patients with variation in other sarcomeric genes, those with MYH7 variants were younger on first clinical encounter at the Sarcomeric Human Cardiomyopathy Registry site and more likely to be probands than the MYBPC3 variants. During an average follow-up of 7.2 years, 198 incident AF events occurred. Patients with likely pathogenic or pathogenic mutations in MYH7 had the highest incidence of AF after adjusting for age, sex, proband status, left atrial size, maximal wall thickness, and peak pressure gradient (hazard ratio, 1.7; 95% CI, 1.1-2.6; P=0.009).CONCLUSIONS: During a mean follow-up of 7.2 years, new-onset AF developed in 19% of HCM patients with sarcomeric mutations. Compared with other sarcomeric genes, patients with likely pathogenic or pathogenic variation in MYH7 had a higher rate of incident AF independent of clinical and echocardiographic factors.