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Associations Between Female Sex, Sarcomere Variants, and Clinical Outcomes in Hypertrophic Cardiomyopathy
Circulation: Genomic and Precision Medicine ( IF 6.0 ) Pub Date : 2020-12-07 , DOI: 10.1161/circgen.120.003062
Neal K Lakdawala 1 , Iacopo Olivotto 1 , Sharlene M Day 2 , Larry Han 3 , Euan A Ashley 4 , Michelle Michels 5 , Jodie Ingles 6 , Christopher Semsarian 6 , Daniel Jacoby 7 , John L Jefferies 8 , Steven D Colan 9 , Alexandre C Pereira 10 , Joseph W Rossano 11 , Sam Wittekind 12 , James S Ware 13 , Sara Saberi 14 , Adam S Helms 14 , Allison L Cirino 1 , Leslie A Leinwand 15 , Christine E Seidman 1, 16 , Carolyn Y Ho 1
Affiliation  

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。
更新日期:2020-12-07
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