Li Qin, Gruner Christiane, Chan Raymond H, Care Melanie, Siminovitch Katherine, Williams Lynne, Woo Anna, Rakowski Harry
From the Division of Cardiology, Peter Munk Cardiac Center, Toronto General Hospital, Toronto, Ontario, Canada (Q.L., L.W., A.W., H.R.); Division of Cardiology, University Hospital of Zurich, Zurich, Switzerland (C.G.); Department of Medicine (Cardiovascular Division) and Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (R.H.C.); Fred A. Litwin and Family Center in Genetic Medicine, Mount Sinai Hospital, University Health Network, Toronto, Ontario, Canada (M.C., K.S.); and Department of Medicine, University of Toronto and Samuel Lunenfeld and Toronto General Research Institutes, Toronto, Ontario, Canada (K.S.).
Circ Cardiovasc Genet. 2014 Aug;7(4):416-22. doi: 10.1161/CIRCGENETICS.113.000331. Epub 2014 Jun 8.
The aim of the study was to clarify the relationship between genotype status and major cardiovascular outcomes in a large cohort of patients with hypertrophic cardiomyopathy.
Genetic testing was performed in 558 consecutive proband patients with hypertrophic cardiomyopathy. Baseline and follow-up (mean follow-up 6.3 years) clinical and echocardiographic data were obtained. Pathogenic mutations were identified in 198 (35.4%) patients. Genotype-positive patients were more likely to be women (44% versus 30%; P=0.001), younger (39 versus 48 years; P<0.001), and have a family history of hypertrophic cardiomyopathy (53% versus 20%; P<0.001), as well as family history of sudden cardiac death (17% versus 7%; P=0.002). There were no significant differences in the rates of atrial fibrillation, stroke, or septal reduction procedures. Multivariable analysis demonstrated that genotype-positive status was an independent risk factor for the development of combined heart failure end points (decline in left ventricular ejection fraction to <50%, New York Heart Association III or IV in the absence of obstruction, heart failure-related hospital admission, transplantation, and heart failure-related death; hazards ratio, 4.51; confidence interval, 2.09-9.31; P<0.001). No difference was seen in heart failure events between the myosin heavy chain and myosin-binding protein C genotype-positive patients.
The presence of a pathogenic sarcomere mutation in patients with hypertrophic cardiomyopathy was associated with an increase in heart failure events, with no differences in event rates seen between myosin heavy chain and myosin-binding protein C genotype-positive patients. The presence of a disease-causing mutation seems more clinically relevant than the specific mutation itself.
本研究的目的是阐明在一大群肥厚型心肌病患者中基因型状态与主要心血管结局之间的关系。
对558例连续性肥厚型心肌病先证者进行了基因检测。获取了基线和随访（平均随访6.3年）的临床和超声心动图数据。在198例（35.4%）患者中鉴定出致病性突变。基因型阳性患者更可能为女性（44%对30%；P=0.001）、更年轻（39岁对48岁；P<0.001），并且有肥厚型心肌病家族史（53%对20%；P<0.001），以及心源性猝死家族史（17%对7%；P=0.002）。房颤、中风或室间隔减容手术的发生率无显著差异。多变量分析表明，基因型阳性状态是发生合并心力衰竭终点事件（左心室射血分数降至<50%、在无梗阻情况下纽约心脏协会III或IV级、因心力衰竭住院、移植以及心力衰竭相关死亡；风险比，4.51；置信区间，2.09 - 9.31；P<0.001）的独立危险因素。肌球蛋白重链和肌球蛋白结合蛋白C基因型阳性患者之间的心力衰竭事件无差异。
肥厚型心肌病患者中致病性肌节突变的存在与心力衰竭事件增加相关，肌球蛋白重链和肌球蛋白结合蛋白C基因型阳性患者之间的事件发生率无差异。致病突变的存在似乎比特定突变本身在临床上更具相关性。
