Cardiac defects, morbidity and mortality in patients affected by RASopathies. CARNET study results
Cardiac defects, morbidity and mortality in patients affected by RASopathies. CARNET study results
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DOI：
10.1016/j.ijcard.2017.07.068
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发表时间：
2017-10-15
影响因子：
3.5
通讯作者：
Marino, Bruno
中科院分区：
文献类型：
--
作者：
Calcagni, Giulio;Limongelli, Giuseppe;Marino, Bruno
背景：RASopathies是由编码RAS-MAPK级联信号转导子的基因突变引起的发育性疾病。本研究的目的是提供一个全面的描述发病率和死亡率的患者与分子证实RASopathy.Methods：一个多中心，观察性，回顾性研究进行了7个欧洲心脏中心参加CARDIAC Rasopathy网络（CARNET）。回顾了371例经分子诊断确诊的RAS病患者的临床记录。死亡率描述为粗死亡率、累积生存率和限制估计平均生存率。采用多变量回归分析评估突变基因对干预次数和总体预后的影响。结果：80.3%的病例发生心脏缺陷，其中近一半至少接受了一次干预。总体而言，粗死亡率为0.29/100患者-年。1年、5年、10年和20年的累积生存率分别为98.8%、98.2%、97.7%和94.3%。20年随访时的限制性估计平均生存期为19.6年。10例患者死亡（整个队列的2.7%;心脏缺陷患者的3.4%）。肥厚型心肌病（HCM）患者和年龄< 2岁或年轻人，以及受试者与双心室梗阻和PTPN 11突变有较高的心源性death.Conclusions：风险干预是较高的努南综合征和肺动脉狭窄携带PTPN 11突变。总体而言，死亡率相对较低，尽管HCM、双心室流出道梗阻和PTPN 11突变之间的特定关联似乎与早期死亡率相关，包括术后即刻事件和猝死。(C)2017爱思唯尔B. V.保留所有权利。
Background: RASopathies are developmental disease caused by mutations in genes encoding for signal transducers of the RAS-MAPK cascade. The aim of the present study was to provide a comprehensive description of morbidity and mortality in patients with molecularly confirmed RASopathy.Methods: A multicentric, observational, retrospective study was conducted in seven European cardiac centres participating to the CArdiac Rasopathy NETwork (CARNET). Clinical records of 371 patients with confirmed molecular diagnosis of RASopathy were reviewed. Mortality was described as crude mortality, cumulative survival and restricted estimated mean survival. Multivariable regression analysis was used to assess the impact of mutated genes on number of interventions and overall prognosis.Results: Cardiac defects occurred in 80.3% of cases, almost half of them underwent at least one intervention. Overall, crude mortality was 0.29/100 patients-year. Cumulative survival was 98.8%, 98.2%, 97.7%, 94.3%, at 1, 5, 10, and 20 years, respectively. Restricted estimated mean survival at 20 years follow-up was 19.6 years. Ten patients died (2.7% of the entire cohort; 3.4% of patients with cardiac defect). Patients with hypertrophic cardiomyopathy (HCM) and age < 2 years or young adults, as well as subjects with biventricular obstruction and PTPN11 mutations had a higher risk of cardiac death.Conclusions: The risk of intervention was higher in individuals with Noonan syndrome and pulmonary stenosis carrying PTPN11 mutations. Overall, mortality was relatively low, even though the specific association between HCM, biventricular outflow tract obstructions and PTPN11 mutations appeared to be associated with early mortality, including immediate post-operative events and sudden death. (C) 2017 Elsevier B.V. All rights reserved.