Centre de Référence Pour les Maladies Cardiaques Héréditaires, APHP, Hôpital de la Pitié Salpêtrière, Paris, France.
Sorbonne Universités, UPMC Université Paris 6, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, ICAN, Département de Cardiologie, Paris, France.
Eur J Heart Fail. 2019 Jun;21(6):792-800. doi: 10.1002/ejhf.1423. Epub 2019 Feb 21.
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.
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).
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.
先前的研究表明，遗传状态会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。本研究旨在比较桥粒芯糖蛋白-2（DSG2）突变携带者和最常见的 ARVC/D 相关基因桥粒斑蛋白-2（PKP2）突变携带者的结局。
从国家 ARVC/D 注册处中选择携带 PKP2 或 DSG2 致病性突变的连续 ARVC/D 患者。评估随访期间持续性室性心律失常和心脏移植/心力衰竭（HF）相关死亡的累积无事件率，并比较 PKP2 和 DSG2 之间的差异，确定预测室性心律失常和 HF 事件的因素。总体而言，纳入了 78 个家系的 118 名患者：27 名（23%）携带 DSG2 突变，91 名（77%）携带 PKP2 突变。DSG2 和 PKP2 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。DSG2 患者更常出现 ε波（37%比 17%，P=0.048）和诊断时左心室功能障碍（54%比 10%，P<0.001）。在中位数为 5.6 年（2.5-16 年）的随访期间，DSG2 和 PKP2 突变携带者持续性室性心律失常的风险相似（对数秩 P=0.20），但 DSG2 突变携带者心脏移植/HF 相关死亡的风险更高（对数秩 P<0.001）。在单因素 Cox 分析中，与 PKP2 突变相比，存在 DSG2 突变是心脏移植/HF 相关死亡的预测因素（P=0.0005）。
在本多中心队列中，与 PKP2 突变携带者相比，DSG2 突变携带者发生终末期 HF 的风险更高，这支持对这些患者进行仔细的血液动力学监测。需要评估 DSG2 携带者早期 HF 治疗的获益。
