High risk of heart failure associated with desmoglein-2 mutations compared to plakophilin-2 mutations in arrhythmogenic right ventricular cardiomyopathy/dysplasia
High risk of heart failure associated with desmoglein-2 mutations compared to plakophilin-2 mutations in arrhythmogenic right ventricular cardiomyopathy/dysplasia
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DOI：
10.1002/ejhf.1423
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发表时间：
2019-06-01
影响因子：
18.2
通讯作者：
Gandjbakhch, Estelle
中科院分区：
文献类型：
--
作者：
Hermida, Alexis;Fressart, Veronique;Gandjbakhch, Estelle
背景：以往的研究表明，遗传状态影响致心律失常性右心室心肌病/发育不良（ARVC/D）患者的临床病程。本研究的目的是比较桥粒芯糖蛋白-2（DSG 2）突变携带者与携带斑嗜蛋白-2（PKP 2）突变（最常见的ARVC/D相关基因）的患者的结局。方法和结果从国家ARVC/D登记处选择携带PKP 2或DSG 2致病突变的连续ARVC/D患者。评估了随访期间持续性室性心律失常和心脏移植/心力衰竭（HF）死亡的累积无率，比较了PKP 2和DSG 2，并确定了室性心律失常和HF事件的预测因子。总体而言，纳入了来自78个家族的118例患者：27例（23%）携带DSG 2突变，91例（77%）携带PKP 2突变。DSG 2和PKP 2突变携带者在性别、先证者状态、诊断时年龄、T波倒置或基线时右心室功能障碍方面无显著差异。DSG 2组患者在诊断时出现更频繁的右室收缩波（37% vs. 17%，P = 0.048）和左室功能不全（54% vs. 10%，P < 0.001）。在中位随访5.6年（2.5-16年）期间，DSG 2和PKP 2突变携带者显示出相似的持续性室性心律失常风险（对数秩P = 0.20），但DSG 2突变携带者的移植/HF相关死亡风险更高（对数秩P < 0.001）。在单变量考克斯分析中，DSG 2突变与PKP 2突变的存在是移植/HF相关死亡的预测因子（P = 0.0005）。结论：在这个多中心队列中，发现DSG 2突变携带者与PKP 2突变携带者相比，终末期HF的风险更高，支持对这些患者进行仔细的血液动力学监测。早期HF治疗的益处需要在DSG 2携带者中进行评估。
Background Previous studies suggested that genetic status affects the clinical course of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) patients. The aim of this study was to compare the outcome of desmoglein-2 (DSG2) mutation carriers to those who carry the plakophilin-2 (PKP2) mutation, the most common ARVC/D-associated gene. Methods and results Consecutive ARVC/D patients carrying a pathogenic mutation in PKP2 or DSG2 were selected from a national ARVC/D registry. The cumulative freedom from sustained ventricular arrhythmia and cardiac transplantation/death from heart failure (HF) during follow-up was assessed, compared between PKP2 and DSG2, and predictors for ventricular arrhythmia and HF events determined. Overall, 118 patients from 78 families were included: 27 (23%) carried a DSG2 mutation and 91 (77%) a PKP2 mutation. There were no significant differences between DSG2 and PKP2 mutation carriers concerning gender, proband status, age at diagnosis, T-wave inversion, or right ventricular dysfunction at baseline. DSG2 patients displayed more frequent epsilon wave (37% vs. 17%, P = 0.048) and left ventricular dysfunction at diagnosis (54% vs. 10%, P < 0.001). During a median follow-up of 5.6 years (2.5-16), DSG2 and PKP2 mutation carriers displayed a similar risk of sustained ventricular arrhythmia (log-rank P = 0.20), but DSG2 mutation carriers were at higher risk of transplantation/HF-related death (log-rank P < 0.001). The presence of a DSG2 mutation vs. PKP2 mutation was a predictor of transplantation/HF-related death in univariate Cox analysis (P = 0.0005). Conclusions In this multicentre cohort, DSG2 mutation carriers were found to be at high risk of end-stage HF compared to PKP2 mutation carriers, supporting careful haemodynamic monitoring of these patients. The benefit of early HF treatment needs to be assessed in DSG2 carriers.