Brigham and Women's Hospital (N.K.L., A.L.C., C.E.S., C.Y.H.), Harvard Medical School, MA.
Department of Internal Medicine, University of Pennsylvania, Philadelphia (S.M.D.).
Circ Genom Precis Med. 2021 Feb;14(1):e003062. doi: 10.1161/CIRCGEN.120.003062. Epub 2020 Dec 7.
The impact of sex on phenotypic expression in hypertrophic cardiomyopathy (HCM) has not been well characterized in genotyped cohorts.
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.
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, <0.001) and more likely to have pathogenic/likely pathogenic sarcomeric variants (HCM patients with a sarcomere mutation; 51% versus 43%, <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 (<0.02) except for patients with variants where age at diagnosis was comparable for women and men (n=492; 34.8±19.2 versus 33.3±16.8 years, =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], <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], <0.01) but neither implantable cardioverter-defibrillator utilization nor ventricular arrhythmia varied by sex.
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.
性别的影响在肥厚型心肌病（HCM）的表型表达中尚未在基因分型队列中得到很好的描述。
这是一项来自接受经验丰富的 HCM 中心治疗的患者国际登记处的回顾性队列研究。评估了基线特征和临床结局的性别差异。
在 5873 名患者（3788 名基因分型）中，2226 名（37.9%）为女性。基线时，女性年龄较大（49.0±19.9 岁比 42.9±18.4 岁，<0.001），更有可能携带致病性/可能致病性的肌节变异（HCM 患者的肌节突变；51%比 43%，<0.001），尽管基因检测的利用率相同。尽管病因基因的分布相似，但诊断时的年龄因性别而异且与基因型有关。除了女性和男性的诊断年龄相当的 变异患者（n=492；34.8±19.2 岁比 33.3±16.8 岁，=0.39）外，女性的诊断年龄要大 3.6 到 7.1 岁（<0.02）。在 7.7 年的中位随访期间，纽约心脏协会心功能 III-IV 级心力衰竭在女性中更为常见（风险比，1.87 [CI，1.48-2.36]，<0.001），在控制了基线时的症状负担和流出道梗阻、射血分数降低、肌节突变、年龄和高血压等因素后。女性的全因死亡率更高（风险比，1.50 [CI，1.13-1.99]，<0.01），但性别不影响植入式心脏复律除颤器的使用或室性心律失常。
在 HCM 中，女性的诊断年龄较大，部分受遗传底物的影响。无论基因型如何，女性的死亡率和出现严重心力衰竭症状的风险都更高。这表明 HCM 中存在与性别相关的长期心肌功能影响，需要进一步研究。
