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

NCT07708311 | Not Yet Recruiting

• 1 other identifier: HGEN-CARE-AC STUDY
• Study Type: interventional
• Target: 70
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Arrhythmogenic Cardiomyopathy (AC, ARVD/C)

Outcome Measures

Primary Outcomes (1)

• 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.

  From baseline up to 6 months.

Secondary Outcomes (13)

• Change from baseline in peak oxygen consumption (VO2 peak)

  Baseline and 12 weeks

• Change from baseline in metabolic equivalents (METs)

  Baseline and 12 weeks

• Change from baseline in 6-minute walk distance

  Baseline and 12 weeks.

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

  Baseline and 6 months.

• Change from baseline in SF-36 health-related quality of life score

  Baseline and 6 months.

Study Arms (2)

Cardiac Rehabilitation Program

EXPERIMENTAL

Participants randomized to this experimental arm will engage in a structured, personalized, and supervised physical exercise program at the hospital's specialized Cardiac Rehabilitation Unit for a duration of 12 weeks. The intervention consists of customized, moderate-intensity training sessions designed and supervised by qualified clinical personnel. Training intensity is strictly individualized, bounded by safe target heart rate thresholds and workloads derived from each participant's baseline maximal cardiopulmonary exercise testing (CPET).

Behavioral: Cardiac Rehabilitation Programme

Standard Physical Restriction

NO INTERVENTION

Participants randomized to this active comparator control arm will maintain conventional clinical care as prescribed by current guidelines for high-genetic-risk arrhythmogenic cardiomyopathy. This involves strict adherence to physical restriction guidelines, including complete abstinence from competitive, high-intensity sports and strenuous physical exercise. Participants are encouraged to maintain basic activities of daily living and light leisure-time physical habits, serving as a direct control baseline to evaluate safety outcomes.

Interventions

Cardiac Rehabilitation Programme BEHAVIORAL

A structured, personalized, and supervised cardiac rehabilitation program based on moderate-intensity physical exercise, tailored specifically for high-risk genotype-positive arrhythmogenic cardiomyopathy (ACM) patients. The intervention follows the FITT (Frequency, Intensity, Time, Type) principles: Frequency: 2 to 3 supervised sessions per week for a total duration of 12 consecutive weeks. Intensity: Strictly restricted to a moderate-intensity zone. The target training heart rate is set individually, bounded between the first ventilatory threshold (VT1) and a safe ceiling well below the second ventilatory threshold (VT2) or any individual arrhythmic thresholds identified during baseline cardiopulmonary exercise testing (CPET). Time: Each session lasts between 90 minutes, including a 10-minute progressive warm-up and a 10-minute cool-down phase. Type: Continuous aerobic exercise primarily performed on a cycle ergometer o

Cardiac Rehabilitation Program

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

You may not qualify if:

• Presence of overlapping phenotypes associated with other non-arrhythmogenic cardiomyopathies.
• Active pregnancy.

Sponsors & Collaborators

• Juan Jiménez Jáimez: lead
• Fundación Pública Andaluza para la Investigación Biomédica Andalucía Oriental: collaborator

MeSH Terms

Conditions

Arrhythmogenic Right Ventricular Dysplasia

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Cardiomyopathies; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD, Head of the Arrhythmia and Familial Cardiopathies Unit in Virgen de las Nieves Hospital in Granada, Spain

Study Record Dates

• First Submitted: July 3, 2026
• First Posted: July 16, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2028
• Last Updated: July 20, 2026

Record last verified: 2026-07