Department of Cardiology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Department of Cardiology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
J Am Coll Cardiol. 2024 Nov 5;84(19):1854-1865. doi: 10.1016/j.jacc.2024.08.011. Epub 2024 Oct 2.
Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disease, and clinical and genetic family screening is recommended by guidelines.
This study sought to investigate the diagnostic yield of screening relatives of HCM patients and identify predictive factors for HCM development during long-term follow-up in relatives from gene-elusive families.
This was a retrospective cohort study of families screened at clinics for inherited cardiomyopathies in Eastern Denmark, from 2006 to 2023.
We included 1,230 relatives (55% female; age: 42 ± 17 years) from 531 families. The combined clinical and genetic yield at baseline was 26% (n = 321). After 7 years (mean) of follow-up (6,762 person-years), 43 (4%) additional relatives developed HCM. The strongest predictors of developing HCM were carrying a likely pathogenic/pathogenic variant (HR: 4.58; 95% CI: 2.50-8.40; P < 0.001) and larger left ventricular maximum wall thickness (MWT) (HR: 2.21 per mm; 95% CI: 1.76-2.77 per mm; P < 0.001). In gene-elusive families, we found that an MWT of ≥10 mm represented the optimal classification threshold for developing HCM (area under the curve: 0.80), with only 2 (0.4%) relatives from gene-elusive families with an MWT of <10 mm developing HCM during follow-up.
In HCM, the diagnostic yield of a single screening visit was 1 in 4, and the additional yield during 7 years of follow-up was 4%. Gene carriers and relatives from gene-elusive families with a baseline MWT of ≥10 mm were at the highest risk of developing HCM during follow-up. These findings may inform future recommendations on the management of relatives of HCM patients.
肥厚型心肌病（HCM）是一种常见的遗传性心脏病，指南建议对其进行临床和遗传家族筛查。
本研究旨在探讨对 HCM 患者亲属进行筛查的诊断效果，并确定在来自基因缺失家族的亲属中进行长期随访时发生 HCM 的预测因素。
这是一项回顾性队列研究，对象为 2006 年至 2023 年在丹麦东部遗传性心肌病诊所接受筛查的家族。
共纳入 531 个家族的 1230 名亲属（55%为女性；年龄：42±17 岁）。基线时，临床和遗传联合检出率为 26%（n=321）。在 7 年（平均）的随访（6762 人年）期间，又有 43 名（4%）亲属发生了 HCM。发生 HCM 的最强预测因素为携带可能致病/致病性变异（HR：4.58；95%CI：2.50-8.40；P<0.001）和更大的左心室最大壁厚度（MWT）（HR：每增加 1mm 为 2.21；95%CI：每增加 1mm 为 1.76-2.77；P<0.001）。在基因缺失家族中，我们发现 MWT≥10mm 是发生 HCM 的最佳分类阈值（曲线下面积：0.80），随访期间，只有 2 名（0.4%）基因缺失家族 MWT<10mm 的亲属发生了 HCM。
在 HCM 中，单次筛查的检出率为 1/4，随访 7 年的检出率为 4%。基因携带者和基线 MWT≥10mm 的基因缺失家族亲属在随访期间发生 HCM 的风险最高。这些发现可能为 HCM 患者亲属的管理提供未来的建议。
