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

Composite safety endpoint of clinical and arrhythmic events.

Safety of the 12-week supervised moderate-intensity exercise program will be evaluated as a composite endpoint defined by the absence of a clinically relevant increase in ventricular arrhythmias or major adverse cardiovascular events. Arrhythmic safety includes ventricular arrhythmia burden (sustained and non-sustained ventricular tachycardia) detected via prolonged ambulatory Holter monitoring and ICD (Implantable Cardioverter-Defibrillator) interrogation logs. Clinical safety events track the incidence of major complications during the study period, including sudden cardiac death, appropriate or inappropriate ICD therapies (shocks or antitachycardia pacing), and arrhythmic syncope, comparing the intervention cohort against the standard physical restriction control group.

Change from baseline in peak oxygen consumption (VO2 peak)

Change in peak oxygen consumption (VO2 peak). Breath-by-breath gas exchange measurements (oxygen uptake in mL/min and carbon dioxide production in mL/min) and total body weight in kilograms (Kg) will be combined to report VO2 peak in mL/kg/min. This value represents the highest 30-second average of oxygen consumption attained during the maximal effort stage of a cardiopulmonary exercise test (CPET).

Change from baseline in metabolic equivalents (METs)

Preliminary clinical efficacy on functional capacity will be evaluated using objective cardiopulmonary metrics. Change in metabolic equivalents (METs). Peak oxygen uptake (mL/kg/min) and the resting metabolic constant (3.5 mL/kg/min) will be combined to report the peak METs achieved during maximal cardiopulmonary exercise testing (CPET). This value is calculated as the ratio of peak oxygen consumption to the resting metabolic rate.

Change from baseline in 6-minute walk distance

Change in total distance walked during the 6-Minute Walk Test (6MWT). Walking speed (m/s) and the duration of the test (6 minutes) will be combined to report the total distance covered in meters. The distance is measured from start to finish based on the participant's total displacement during the 6-minute period.

Change from baseline in Hospital Anxiety and Depression Scale (HADS) score

The psychological impact of the rehabilitation program will be assessed using validated psychometric scales. Change in anxiety and depression levels. Individual item scores (responses to 14 questions) will be combined to report the total HADS score. This scale aggregates responses to assess anxiety and depression symptoms; higher scores indicate greater symptom severity (a worse outcome). Unit of Measure: Scale (on a scale of 0 to 42)