Department of Cardiology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark; Department of Cardiology, Lillebaelt Hospital, Vejle, Denmark.
Department of Cardiology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
J Am Coll Cardiol. 2023 Oct 31;82(18):1751-1761. doi: 10.1016/j.jacc.2023.08.041.
Current guidelines recommend that relatives of index patients with hypertrophic cardiomyopathy (HCM) are offered clinical investigations to identify individuals at risk of adverse disease complications and sudden cardiac death. However, the value of family screening in relatives of index patients with a normal genetic investigation of recognized HCM genes is largely unknown.
The purpose of this study was to perform family screening among relatives of HCM index patients with a normal genetic investigation to establish the frequency of familial disease and the clinical characteristics of affected individuals.
Clinical and genetic investigations were performed in consecutive and unrelated HCM index patients. Relatives of index patients who did not carry pathogenic/likely pathogenic variants in recognized HCM genes were invited for clinical investigations.
In total, 60% (270 of 453) of HCM index patients had a normal genetic investigation. A total of 80% of their relatives (751 of 938, median age 44 years) participated in the study. Of these, 5% (34 of 751) were diagnosed with HCM at baseline, whereas 0.3% (2 of 717 [751-34]) developed the condition during 5 years of follow-up. Their median age at diagnosis was 57 years (IQR: 51-70 years). Two-thirds (22 of 36) were diagnosed following family screening, whereas one-third (14 of 36) had been diagnosed previously because of cardiac symptoms, a murmur, or an abnormal electrocardiogram. None of the affected relatives experienced adverse disease complications. The risk of SCD was low.
Systematic family screening of index patients with HCM and normal genetic investigations was associated with a low frequency of affected relatives who appeared to have a favorable prognosis.
目前的指南建议肥厚型心肌病（HCM）患者的亲属进行临床检查，以确定有不良疾病并发症和心源性猝死风险的个体。然而，在 HCM 基因遗传检查正常的索引患者亲属中进行家族筛查的价值在很大程度上尚不清楚。
本研究旨在对 HCM 索引患者进行正常遗传检查的亲属进行家族筛查，以确定家族疾病的发生率和受影响个体的临床特征。
对连续和无关联的 HCM 索引患者进行临床和遗传检查。未携带公认的 HCM 基因中致病/可能致病变异的索引患者亲属受邀进行临床检查。
共有 60%（453 例中的 270 例）的 HCM 索引患者遗传检查正常。他们的亲属中有 80%（938 例中的 751 例，中位年龄 44 岁）参加了这项研究。其中，5%（751 例中的 34 例）在基线时被诊断为 HCM，而在 5 年的随访中有 0.3%（717 例中的 2 例[751-34]）发展为该疾病。他们的中位诊断年龄为 57 岁（IQR：51-70 岁）。三分之二（36 例中的 22 例）是通过家族筛查诊断的，而三分之一（36 例中的 14 例）以前因为心脏症状、杂音或心电图异常而被诊断。受影响的亲属均未出现不良疾病并发症。SCD 风险较低。
对 HCM 基因遗传检查正常的索引患者进行系统的家族筛查与亲属发病率低有关，这些亲属的预后似乎较好。
