Background:The impact of sex on phenotypic expression in hypertrophic cardiomyopathy (HCM) has not been well characterized in genotyped cohorts.Methods:Retrospective cohort study from an international registry of patients receiving care at experienced HCM centers. Sex-based differences in baseline characteristics and clinical outcomes were assessed.Results:Of 5873 patients (3788 genotyped), 2226 (37.9%) were women. At baseline, women were older (49.0±19.9 versus 42.9±18.4 years, P<0.001) and more likely to have pathogenic/likely pathogenic sarcomeric variants (HCM patients with a sarcomere mutation; 51% versus 43%, P<0.001) despite equivalent utilization of genetic testing. Age at diagnosis varied by sex and genotype despite similar distribution of causal genes. Women were 3.6 to 7.1 years older at diagnosis (P<0.02) except for patients with MYH7 variants where age at diagnosis was comparable for women and men (n=492; 34.8±19.2 versus 33.3±16.8 years, P=0.39). Over 7.7 median years of follow-up, New York Heart Association III-IV heart failure was more common in women (hazard ratio, 1.87 [CI, 1.48–2.36], P<0.001), after controlling for their higher burden of symptoms and outflow tract obstruction at baseline, reduced ejection fraction, HCM patients with a sarcomere mutation, age, and hypertension. All-cause mortality was increased in women (hazard ratio, 1.50 [CI, 1.13–1.99], P<0.01) but neither implantable cardioverter-defibrillator utilization nor ventricular arrhythmia varied by sex.Conclusions:In HCM, women are older at diagnosis, partly modified by genetic substrate. Regardless of genotype, women were at higher risk of mortality and developing severe heart failure symptoms. This points to a sex-effect on long-term myocardial performance in HCM, which should be investigated further.

中文翻译：

---

肥厚型心肌病中女性、肌节变异和临床结果之间的关联

背景：性别对肥厚型心肌病 (HCM) 表型表达的影响尚未在基因分型队列中得到很好的表征。方法：来自在经验丰富的 HCM 中心接受治疗的患者的国际登记处的回顾性队列研究。评估了基线特征和临床结果的性别差异。结果：在 5873 名患者（3788 名基因分型）中，2226 名（37.9%）为女性。在基线时，女性年龄较大（49.0±19.9 岁与 42.9±18.4 岁，P <0.001）并且更有可能具有致病性/可能致病性肌节变异（具有肌节突变的 HCM 患者；51% 与 43%，P<0.001) 尽管基因检测的利用相当。尽管致病基因的分布相似，但诊断时的年龄因性别和基因型而异。女性诊断时年龄大 3.6 至 7.1 岁（P <0.02），但MYH7变异患者的诊断年龄与男性和女性相当（n = 492；34.8±19.2 与 33.3±16.8 岁，P = 0.39）。超过 7.7 年的中位随访时间，纽约心脏协会 III-IV 期心力衰竭在女性中更为常见（风险比，1.87 [CI，1.48-2.36]，P<0.001)，在控制了基线时较高的症状负担和流出道阻塞、射血分数降低、肌节突变、年龄和高血压的 HCM 患者后。女性的全因死亡率增加（风险比，1.50 [CI，1.13-1.99]，P <0.01）但植入式心律转复除颤器的使用和室性心律失常均因性别而异。结论：在 HCM 中，女性在诊断时年龄较大，部分被遗传底物修饰。无论基因型如何，女性死亡和出现严重心力衰竭症状的风险都更高。这表明性别对 HCM 长期心肌功能的影响，应进一步研究。