Cardiac Rehabilitation in Patients With High-Genetic-Risk Arrhythmogenic Cardiomyopathy: The HGEN-CARE-AC Trial

The goal of this clinical trial is to evaluate a structured and personalized cardiac rehabilitation program for patients diagnosed with arrhythmogenic cardiomyopathy (ACM) who carry high-risk genetic mutations. Historically, physical exercise has been strictly restricted in these patients due to the potential risk of triggering life-threatening arrhythmias and accelerating structural heart disease. However, complete inactivity leads to severe physical deconditioning and reduced quality of life. This study aims to address this clinical dilemma by investigating a safe way to prescribe exercise. The primary research question is: Is a supervised, moderate-intensity exercise program safe, and does it avoid increasing the risk of cardiac arrhythmias or worsening right ventricular function compared to standard physical restriction? Secondary objectives include the evaluation of the impact of this tailored physical intervention on the participants' functional capacity, specifically measuring changes in physical fitness and peak oxygen consumption through cardiovascular testing. Additionally, the trial assesses the psychological benefits of the program, analyzing its effects on health-related quality of life, anxiety, and depression levels. The experimental group undergoing cardiac rehabilitation will be compared to a control group receiving conventional physical restriction guidelines to determine if the program is both safe and comprehensive.

Inclusion Criteria: * Participant must be 18 years of age or older at the time of signing the informed consent. * Definite diagnosis of arrhythmogenic cardiomyopathy (ACM) according to the 2024 European Task Force criteria. * Documented left or right ventricular involvement confirmed via transthoracic echocardiography or cardiac magnetic resonance imaging (MRI), characterized by abnormalities in regional contractility, presence of aneurysms, reduced ejection fraction, and/or late gadolinium enhancement (LGE). * Confirmed presence of a pathogenic or likely pathogenic genetic variant in the LMNA, DSP, FLNC, TMEM43, PLN, or DES genes. * Clinical stability maintained for 3 months or longer prior to inclusion, defined as the absence of hospital admissions, sustained ventricular arrhythmic events, or implantable cardioverter-defibrillator (ICD) shocks. * Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form. Exclusion Criteria: * Inability or physical contraindication to perform physical exercise at the time of inclusion. * Presence of overlapping phenotypes associated with other non-arrhythmogenic cardiomyopathies. * Active pregnancy. * Current engagement in competitive or high-intensity sports or exercise programs at the time of inclusion.