Delpire Boris, Ghekiere Olivier, Dilling-Boer Dagmara, Koopman Pieter, Claessen Guido
Jessa Hospital, Department of Cardiology, Hartcentrum, Stadsomvaart 11, 3500 Hasselt, Belgium.
UHasselt, Faculty of Medicine and Life Sciences/LCRC, Agoralaan, 3590 Diepenbeek, Belgium.
Eur Heart J Case Rep. 2025 Sep 6;9(9):ytaf442. doi: 10.1093/ehjcr/ytaf442. eCollection 2025 Sep.
Arrhythmogenic cardiomyopathy (ACM) is characterized by fibrofatty replacement of myocardium, predisposing to ventricular arrhythmias and sudden cardiac death. Arrhythmogenic cardiomyopathy is often linked to desmosomal gene mutations, particularly PKP2, which encodes plakophilin-2, a key structural protein in cardiac intercalated discs. In individuals with PKP2 mutations, exercise has been shown to accelerate disease progression.
A 22-year-old male semi-professional rower presented with palpitations, pre-syncope, and a history of presumed myocarditis with subepicardial fibrosis on cardiac magnetic resonance (CMR). Workup revealed anterior T-wave inversions on resting ECG and sustained monomorphic right ventricular (RV) outflow tract tachycardia, induced during exercise testing. Repeat CMR showed RV dysfunction and non-ischaemic RV and LV fibrosis with fibrofatty replacement. The patient met diagnostic criteria for biventricular ACM and underwent catheter ablation targeting the arrhythmic substrate. A multidisciplinary team carefully considered ICD therapy. However, due to the limited extent of the arrhythmic substrate, the exercise-induced nature of the ventricular tachycardia, and the successful ablation, ICD implantation was deferred at this stage. An ILR was implanted for continuous rhythm monitoring, with a low threshold for future ICD placement. High-intensity sports restriction, pharmacological therapy, and genetic counselling were initiated. Genetic testing identified a pathogenic PKP2 mutation.
This case highlights the complex interplay of genetic predisposition, myocardial inflammation, and exercise in ACM expression. The presumed myocarditis likely represented a 'hot phase' of ACM, accelerating structural cardiac changes. High-intensity exercise then acted as a 'second hit,' triggering phenotypic expression. Multidisciplinary evaluation combining rhythm monitoring, imaging, and genetic testing was key to diagnosis and management.
致心律失常性心肌病（ACM）的特征是心肌被纤维脂肪组织替代，易发生室性心律失常和心源性猝死。致心律失常性心肌病常与桥粒基因突变有关，尤其是PKP2基因，该基因编码桥粒斑蛋白-2，这是心脏闰盘中的一种关键结构蛋白。在携带PKP2基因突变的个体中，运动已被证明会加速疾病进展。
一名22岁的男性半职业赛艇运动员出现心悸、先兆晕厥，心脏磁共振成像（CMR）显示曾患心肌炎并伴有心外膜下纤维化。检查发现静息心电图有前壁T波倒置，运动试验诱发持续性单形性右心室（RV）流出道心动过速。重复CMR显示右心室功能障碍以及非缺血性右心室和左心室纤维化伴纤维脂肪组织替代。该患者符合双心室ACM的诊断标准，并接受了针对心律失常基质的导管消融术。多学科团队仔细考虑了植入式心律转复除颤器（ICD）治疗。然而，由于心律失常基质范围有限、室性心动过速由运动诱发且消融成功，现阶段推迟了ICD植入。植入了一个植入式循环记录仪（ILR）用于持续心律监测，设定了较低的未来植入ICD阈值。开始实施高强度运动限制、药物治疗和遗传咨询。基因检测发现了一个致病性PKP2突变。
该病例突出了遗传易感性、心肌炎症和运动在ACM表现中的复杂相互作用。推测的心肌炎可能代表了ACM的“活跃期”，加速了心脏结构变化。然后高强度运动起到了“二次打击”的作用，触发了表型表达。结合心律监测、影像学和基因检测的多学科评估是诊断和管理的关键。
