Shetty Naman S, Pampana Akhil, Gaonkar Mokshad, Patel Nirav, Vekariya Nehal, Smith J Gustav, Kalra Rajat, Chahal C Anwar A, Semsarian Christopher, Li Peng, Arora Garima, Arora Pankaj
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston (N.S.S.).
Harvard Medical School, Boston, MA (N.S.S.).
Circ Genom Precis Med. 2025 Jun;18(3):e005113. doi: 10.1161/CIRCGEN.124.005113. Epub 2025 May 28.
This study aimed to evaluate the prevalence of pathogenic/likely pathogenic cardiomyopathy variant carriers in a multiancestry US population and examine the risk of adverse clinical outcomes.
This retrospective cohort study included multiancestry US adults aged ≥18 years with sequencing data from the All of Us Research Program. Pathogenic/likely pathogenic variants in cardiomyopathy genes were identified using the ClinVar database. The primary outcome was heart failure. Secondary outcomes included cardiomyopathy and arrhythmia. Outcomes were identified from electronic health records. Interval-censored Cox models, taking age on the timescale, were used to assess the risk of outcomes in pathogenic/likely pathogenic variant carriers with noncarriers as the reference group.
Among 167 435 individuals (median age, 55.2 [39.5-66.3] years; 61.7% female; 40.7% non-European ancestry) included, the prevalence of pathogenic/likely pathogenic cardiomyopathy variant carriers was 0.7% in the overall population and 0.8%, 0.8%, 0.5%, and 1.2% among European, African, East Asian, and South Asian ancestry individuals, respectively. Over their lifetime, there were 12 867 heart failure events (205 in carriers and 12 662 in noncarriers), with an incidence rate of 3.05 (95% CI, 2.66-3.49) per 1000 person-years in carriers and 1.37 (95% CI, 1.35-1.40) in noncarriers (adjusted hazard ratio, 2.30 [95% CI, 2.04-2.60]). Cardiomyopathy occurred in 5164 (161 in carriers and 5003 in noncarriers), with an incidence rate of 2.38 (95% CI, 2.04-2.78) per 1000 person-years among carriers and 0.54 (95% CI, 0.53-0.56) in noncarriers (adjusted hazard ratio, 4.31 [95% CI, 3.73-4.97]). There were 19 405 arrhythmia events (263 in carriers and 19 142 in noncarriers), with an incidence rate of 3.93 (95% CI, 3.48-4.44) per 1000 person-years among carriers and 2.09 (95% CI, 2.06-2.12) in noncarriers (adjusted hazard ratio, 2.12 [95% CI, 1.78-2.53]).
Pathogenic/likely pathogenic cardiomyopathy variant carriers have an increased risk of heart failure, cardiomyopathy, and arrhythmias. Despite the modest overall prevalence, the associated risks suggest potential benefits of targeted genetic screening for early detection and management.
本研究旨在评估美国多血统人群中致病性/可能致病性心肌病变异携带者的患病率，并研究不良临床结局的风险。
这项回顾性队列研究纳入了年龄≥18岁、有来自“我们所有人研究计划”测序数据的美国多血统成年人。使用ClinVar数据库鉴定心肌病基因中的致病性/可能致病性变异。主要结局是心力衰竭。次要结局包括心肌病和心律失常。结局通过电子健康记录确定。采用以年龄为时间尺度的区间删失Cox模型，以非携带者为参照组，评估致病性/可能致病性变异携带者发生结局的风险。
在纳入的167435名个体中（中位年龄55.2[39.5 - 66.3]岁；61.7%为女性；40.7%为非欧洲血统），总体人群中致病性/可能致病性心肌病变异携带者的患病率为0.7%，欧洲、非洲、东亚和南亚血统个体中的患病率分别为0.8%、0.8%、0.5%和1.2%。在其一生中，发生了12867例心力衰竭事件（携带者205例，非携带者12662例），携带者每1000人年的发病率为3.05（95%CI，2.66 - 3.49），非携带者为1.37（95%CI，1.35 - 1.40）（校正风险比，2.30[95%CI，2.04 - 2.60]）。心肌病发生5164例（携带者161例，非携带者5003例），携带者每1000人年的发病率为2.38（95%CI，2.04 - 2.78），非携带者为0.54（95%CI，0.53 - 0.56）（校正风险比，4.31[95%CI，3.73 - 4.97]）。发生了19405例心律失常事件（携带者263例，非携带者19142例），携带者每1000人年的发病率为3.93（95%CI，3.48 - 4.44），非携带者为2.09（95%CI，2.06 - 2.12）（校正风险比，2.12[95%CI，1.78 - 2.53]）。
致病性/可能致病性心肌病变异携带者发生心力衰竭、心肌病和心律失常的风险增加。尽管总体患病率不高，但相关风险提示了进行靶向基因筛查以早期检测和管理的潜在益处。
