非家族性肥厚型心肌病：患病率、自然史及临床意义
Nonfamilial Hypertrophic Cardiomyopathy: Prevalence, Natural History, and Clinical Implications.
作者信息
Ingles Jodie, Burns Charlotte, Bagnall Richard D, Lam Lien, Yeates Laura, Sarina Tanya, Puranik Rajesh, Briffa Tom, Atherton John J, Driscoll Tim, Semsarian Christopher
机构信息
From the Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Sydney, New South Wales, Australia (J.I., C.B., R.D.B., L.L., L.Y., T.S., C.S.); Central Clinical School (J.I., C.B., R.D.B., R.P., C.S.), and School of Public Health (T.D.), Sydney Medical School, University of Sydney, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia (J.I., C.B., L.Y., R.P., C.S.); School of Population Health, Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia, Perth (T.B.); Department of Cardiology, Royal Brisbane & Women's Hospital, Australia (J.J.A.); and School of Medicine, University of Queensland, Brisbane, Australia (J.J.A.).
出版信息
Circ Cardiovasc Genet. 2017 Apr;10(2). doi: 10.1161/CIRCGENETICS.116.001620.
BACKGROUND
Yield of causative variants in hypertrophic cardiomyopathy (HCM) is increased in some probands, suggesting different clinical subgroups of disease occur. We hypothesized that a negative family history and no sarcomere mutations represent a nonfamilial subgroup of HCM. We sought to determine the prevalence, natural history, and potential clinical implications of this nonfamilial subgroup of HCM.
METHODS AND RESULTS
Four hundred and thirteen unrelated probands with HCM seen in a specialized HCM center between 2002 and 2015 and genetic testing performed were included in this retrospective cohort study. There were 251 (61%) probands with no reported family history of HCM, including 166 (40% of total) probands with no sarcomere mutation, that is, nonfamilial HCM. Quantified family pedigree data revealed no difference in mean number of first-degree relatives screened between nonfamilial and sarcomere-positive groups. Adjusted predictors of nonfamilial status were older age (odds ratio, 1.04; 95% confidence interval, 1.02-1.06; =0.0001), male sex (odds ratio, 1.96; 95% confidence interval, 1.11-3.45; =0.02), hypertension (odds ratio, 2.80; 95% confidence interval, 1.57-5.00; =0.0005), and nonasymmetric septal morphology (odds ratio, 3.41; 95% confidence interval, 1.64-7.08; =0.001). They had a less severe clinical course with greater event-free survival from major cardiac events (=0.04) compared with sarcomere-positive HCM probands. Genotype prediction scores showed good performance in identifying genotype-positive patients (area under the curve, 0.71-0.75) and, in combination with pedigree characteristics, were further improved.
CONCLUSIONS
Approximately 40% of HCM probands have a nonfamilial subtype, with later onset and less severe clinical course. We propose a revised clinical pathway for management, highlighting the role of genetic testing, a detailed pedigree, and refined clinical surveillance recommendations for family members.
背景
肥厚型心肌病（HCM）中一些先证者致病变异的检出率有所增加，提示该病存在不同的临床亚组。我们推测，无家族病史且无肌节突变代表HCM的一个非家族性亚组。我们试图确定这个HCM非家族性亚组的患病率、自然病史及潜在临床意义。
方法与结果
本回顾性队列研究纳入了2002年至2015年间在一家专业HCM中心就诊且进行了基因检测的413例无亲缘关系的HCM先证者。有251例（61%）先证者无HCM家族病史报告，其中166例（占总数的40%）无肌节突变，即非家族性HCM。量化的家族谱系数据显示，非家族性组和肌节阳性组筛查的一级亲属平均数量无差异。非家族性状态的校正预测因素包括年龄较大（比值比，1.04；95%置信区间，1.02 - 1.06；P = 0.0001）、男性（比值比，1.96；95%置信区间，1.11 - 3.45；P = 0.02）、高血压（比值比，2.80；95%置信区间，1.57 - 5.00；P = 0.0005）和非对称性室间隔形态（比值比，3.41；95%置信区间，1.64 - 7.08；P = 0.001）。与肌节阳性的HCM先证者相比，他们的临床病程较轻，主要心脏事件的无事件生存期更长（P = 0.04）。基因型预测评分在识别基因型阳性患者方面表现良好（曲线下面积，0.71 - 0.75），并且结合谱系特征后进一步得到改善。
结论
约40%的HCM先证者有非家族性亚型，起病较晚，临床病程较轻。我们提出了一种修订的临床管理路径，强调了基因检测、详细谱系以及针对家庭成员的精细临床监测建议的作用。
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