Kawano Kyoko, Kondo Hidekazu, Takahashi Masaki, Shinohara Tetsuji, Ohno Seiko, Horie Minoru, Takahashi Naohiko
Department of Cardiology and Clinical Examination, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Yufu-city 879-5593, Japan.
Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center, Osaka, Japan.
Eur Heart J Case Rep. 2022 Sep 23;6(10):ytac397. doi: 10.1093/ehjcr/ytac397. eCollection 2022 Oct.
Arrhythmogenic right-ventricular cardiomyopathy (ARVC) is a hereditary cardiomyopathy characterized by fibro-fat replacement of the right-ventricular myocardium. There are many factors associated with poor prognosis in patients with ARVC. Among these factors, intensive physical exertion is considered an important risk factor for sudden cardiac death.
Herein, we report a case series of siblings with ARVC and an early manifestation of ventricular tachyarrhythmia. Plakophilin-2 (PKP2) genetic variant, which is one of the causative genetic variants of ARVC, was detected by genetic testing in all three siblings. They were young athletes with lethal/symptomatic ventricular tachycardias. The eldest sibling was implanted with a transvenous implantable cardioverter defibrillator (ICD) due to resuscitated cardiopulmonary arrest at 18 years of age; the next oldest patient was treated with successful catheter ablation at 17 years; the youngest patient was treated with catheter ablation and subcutaneous ICD implantation at 17 years.
A recent experimental model revealed that physical exertion in PKP2 knockout mice diminished cardiac muscle mass and increased cardiac myocyte apoptosis, despite enhanced arrhythmogenicity such as increased fractional shortening and calcium transient amplitude. The three siblings were heterozygous for the previously reported pathologic splice site variant c.2489 + 1G > A in Intron 12 of the PKP2. The variant might play an important role in facilitating the vulnerability to arrhythmia under intensive endurance training. Most ARVC patients with PKP2 variant, especially pathologic splice site variant c.2489 + 1G > A in Intron 12 of the PKP2, might have to be managed strictly regarding daily exercise.
致心律失常性右室心肌病（ARVC）是一种遗传性心肌病，其特征是右室心肌被纤维脂肪组织替代。ARVC患者中有许多因素与预后不良相关。在这些因素中，剧烈体力活动被认为是心源性猝死的重要危险因素。
在此，我们报告一组患有ARVC且有室性快速心律失常早期表现的兄弟姐妹病例。通过基因检测在所有三名兄弟姐妹中均检测到了作为ARVC致病基因变异之一的盘状球蛋白2（PKP2）基因变异。他们是患有致命性/症状性室性心动过速的年轻运动员。最大的兄弟姐妹在18岁时因心肺复苏后心脏骤停而植入了经静脉植入式心律转复除颤器（ICD）；第二大的患者在17岁时接受了成功的导管消融治疗；最小的患者在17岁时接受了导管消融和皮下ICD植入治疗。
最近的一个实验模型显示，尽管PKP2基因敲除小鼠的致心律失常性增强，如缩短分数增加和钙瞬变幅度增加，但剧烈体力活动会减少心肌质量并增加心肌细胞凋亡。这三名兄弟姐妹对于先前报道的PKP2第12内含子中的病理性剪接位点变异c.2489 +1G>A是杂合子。该变异可能在强化耐力训练下促进心律失常易感性方面发挥重要作用。大多数携带PKP2变异的ARVC患者，尤其是PKP2第12内含子中的病理性剪接位点变异c.2489 +1G>A，可能在日常运动方面必须受到严格管理。
