MYH7 相关心肌病的外显率和预后：一项荷兰多中心队列研究的结果。
Penetrance and Prognosis of MYH7 Variant-Associated Cardiomyopathies: Results From a Dutch Multicenter Cohort Study.
机构信息
Department of Genetics, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands; Department of Cardiology, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands; Netherlands Heart Institute, Utrecht, the Netherlands; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart).
Netherlands Heart Institute, Utrecht, the Netherlands; Department of Cardiology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.
出版信息
JACC Heart Fail. 2024 Jan;12(1):134-147. doi: 10.1016/j.jchf.2023.07.007. Epub 2023 Aug 9.
BACKGROUND
MYH7 variants cause hypertrophic cardiomyopathy (HCM), noncompaction cardiomyopathy (NCCM), and dilated cardiomyopathy (DCM). Screening of relatives of patients with genetic cardiomyopathy is recommended from 10 to 12 years of age onward, irrespective of the affected gene.
OBJECTIVES
This study sought to study the penetrance and prognosis of MYH7 variant-associated cardiomyopathies.
METHODS
In this multicenter cohort study, penetrance and major cardiomyopathy-related events (MCEs) were assessed in carriers of (likely) pathogenic MYH7 variants by using Kaplan-Meier curves and log-rank tests. Prognostic factors were evaluated using Cox regression with time-dependent coefficients.
RESULTS
In total, 581 subjects (30.1% index patients, 48.4% male, median age 37.0 years [IQR: 19.5-50.2 years]) were included. HCM was diagnosed in 226 subjects, NCCM in 70, and DCM in 55. Early penetrance and MCEs (age <12 years) were common among NCCM-associated variant carriers (21.2% and 12.0%, respectively) and DCM-associated variant carriers (15.3% and 10.0%, respectively), compared with HCM-associated variant carriers (2.9% and 2.1%, respectively). Penetrance was significantly increased in carriers of converter region variants (adjusted HR: 1.87; 95% CI: 1.15-3.04; P = 0.012) and at age ≤1 year in NCCM-associated or DCM-associated variant carriers (adjusted HR: 21.17; 95% CI: 4.81-93.20; P < 0.001) and subjects with a family history of early MCEs (adjusted HR: 2.45; 95% CI: 1.09-5.50; P = 0.030). The risk of MCE was increased in subjects with a family history of early MCEs (adjusted HR: 1.82; 95% CI: 1.15-2.87; P = 0.010) and at age ≤5 years in NCCM-associated or DCM-associated variant carriers (adjusted HR: 38.82; 95% CI: 5.16-291.88; P < 0.001).
CONCLUSIONS
MYH7 variants can cause cardiomyopathies and MCEs at a young age. Screening at younger ages may be warranted, particularly in carriers of NCCM- or DCM-associated variants and/or with a family history of MCEs at <12 years.
背景
MYH7 变异可导致肥厚型心肌病（HCM）、非致密性心肌病（NCCM）和扩张型心肌病（DCM）。建议对遗传性心肌病患者的亲属从 10 至 12 岁起进行筛查，无论受影响的基因如何。
目的
本研究旨在研究 MYH7 变异相关心肌病的外显率和预后。
方法
在这项多中心队列研究中，通过 Kaplan-Meier 曲线和对数秩检验评估携带（可能）致病性 MYH7 变异的携带者的外显率和主要心肌病相关事件（MCEs）。使用具有时变系数的 Cox 回归评估预后因素。
结果
共纳入 581 名受试者（30.1%为索引患者，48.4%为男性，中位年龄 37.0 岁[IQR：19.5-50.2 岁]）。226 名受试者被诊断为 HCM，70 名为 NCCM，55 名为 DCM。与 HCM 相关变异携带者相比，NCCM 相关变异携带者（分别为 21.2%和 12.0%）和 DCM 相关变异携带者（分别为 15.3%和 10.0%）更常见早期外显和 MCEs（年龄<12 岁）。携带转换区变异的携带者的外显率明显增加（校正 HR：1.87；95%CI：1.15-3.04；P=0.012），在 NCCM 或 DCM 相关变异携带者年龄≤1 岁（校正 HR：21.17；95%CI：4.81-93.20；P<0.001）和有早期 MCEs 家族史的受试者中（校正 HR：2.45；95%CI：1.09-5.50；P=0.030）。有早期 MCEs 家族史的受试者（校正 HR：1.82；95%CI：1.15-2.87；P=0.010）和 NCCM 或 DCM 相关变异携带者年龄≤5 岁的受试者（校正 HR：38.82；95%CI：5.16-291.88；P<0.001）的 MCE 风险增加。
结论
MYH7 变异可导致年轻患者发生心肌病和 MCE。可能需要进行更年轻的筛查，特别是在 NCCM 或 DCM 相关变异携带者和/或有 12 岁以下 MCEs 家族史的患者中。
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