Arrhythmogenic Activity During Exercise in ARVC Patients

Characterization of Arrhythmogenic Activity During and After Physical Exercise in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

Current guidelines advocate that ARVC patients, typically young and active individuals with a significant history of competitive endurance sports, cease endurance training in favour of activities with low cardiac burden such as bowling and golf. Empirically, it is often suggested that heart rate during exercise should not exceed 100-120 bpm in these patients, but these guidelines are arbitrary and not scientifically based. In practice, it is estimated that up to 50% of patients do not comply with these recommendations .

Adequate quantification of the arrhythmogenic burden, defined as premature ventricular beats in proportion to all heart beats in each period of time, and cardiac load (defined as stroke volume for volume load and systolic blood pressure for pressure load) experienced by ARVC patients when performing different types of physical exercise would be a first step towards designing a safe and effective intervention so that these patients can profit from an active life style.

This study therefore aims to quantify and describe the arrhythmogenic burden and cardiac load experienced by patients with ARVC while performing different physical exercise over a range of intensities - all strictly within the range currently recommended by different cardiological societies.

Study Overview

• Status: Recruiting
• Conditions: Arrhythmogenic Right Ventricular Cardiomyopathy
• Intervention / Treatment: Other: Exercise

Detailed Description

In this study, ARVC patients with different genotypes will perform a series of different physical activities, including treadmill walking, cycling at different intensities, biceps curls and loaded squats while undergoing extensive cardiovascular monitoring.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fernando G Beltrami, PhD; Phone Number: +41446330472; Email: fernando.beltrami@hest.ethz.ch
• Study Contact Backup: Name: Christina M Spengler, PhD, MD; Phone Number: +41446325007; Email: spengler@ethz.ch

Study Locations

• Switzerland
  • Canton of Zurich
    • Zurich, Canton of Zurich, Switzerland, 8092
      • Recruiting
      • Exercise Physiology Lab, Institute of Human Movement Sciences and Sport, ETH Zurich
      • Contact: Fernando G Beltrami, PhD; Email: fernando.beltrami@hest.ethz.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Definitive ARVC diagnosis according to the modified 2010 ARVC Task Force Criteria
• Pathogenic / likely pathogenic variant in one of the following desmosomal genes: plakophilin-2 (PKP-2), desmoglein-2 (DSG-2) or desmoplakin (DSP) or gene-elusive definite ARVC (i.e., genetic test performed but no pathogenic / likely pathogenic variant found)
• Control group: diagnosed ischemic heart disease with ejection fraction above 35%
• Agreement with responsible primary cardiologist that study participation is not considered beyond acceptable levels of physical activity for this particular patient
• No history of exercise-induced syncope in the 6 months prior to study participation
• No history of sudden cardiac arrest in the 6 months prior to study participation
• In patients who suffered from sudden cardiac arrest/arrhythmic syncope, only those having an implantable cardioverter-defibrillator (ICD) and being under beta-blockers/antiarrhythmic drugs are eligible for study inclusion
• Informed Consent as documented by signature (Appendix Informed Consent Form)
• Age: > 14 years
• Body-Mass-Index (BMI): 18.5 - 39.9 kg･m-2

• Willing to adhere to the following study rules:

  • No intense exercise 48h prior to testing
  • No exercise 24h prior to testing
  • Sleep at least 7h the two nights before testing On test day
  • No caffeinated food or drink before testing on test day
  • No alcohol before testing on test day
  • Fully compliant with normal medication regimen including beta-blockers and antiarrhythmic medication

Exclusion Criteria:

• No genetic test history for ARVC variants
• Heart failure with severely reduced left ventricular ejection fraction (LVEF <35%)
• For women: Pregnancy, breastfeeding, or intention to become pregnant during the study.
• Known or suspected non-compliance, drug, or alcohol abuse
• Inability to follow the procedures of the study, e.g., due to language problems, psychological disorders, dementia, etc. of the participant
• Previous enrolment into the current study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients Group; All patients will perform all exercises. Arrhythmogenic activity will compared with that assessed during treadmill walking.	Other: Exercise; Participants will perform 3 min of the different activities, followed by a 10-min recovery window.; Other Names: cycling, squats, biceps curls, walking

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
count of premature ventricular beats during and after the activities	count of premature ventricular beats during and after the activities	measured during the 3 min of activity and the 10 min of recovery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cardiac load during different activities, as rate-pressure product	product of heart rate and systolic blood pressure	measured during the 3 min of activity
cardiac load during different activities, as cardiac output	product of heart rate and stroke volume, in L/min	measured during the 3 min of activity
cardiac load during different activities, as peak blood pressure	systolic blood pressure, in mmHg	measured during the 3 min of activity

Collaborators and Investigators

• Sponsor: Swiss Federal Institute of Technology
• Collaborators: University of Zurich
• Investigators: Principal Investigator: Christina M Spengler, PhD, MD, ETH Zurich, Exercise Physiology Lab, Institute of Human Movement Sciences and Sport

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: September 8, 2023
• First Submitted That Met QC Criteria: September 8, 2023
• First Posted (Actual): September 15, 2023

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: physical activity; exercise; cycling
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Cardiomyopathies; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Behavior; Arrhythmogenic Right Ventricular Dysplasia; Motor Activity; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Locomotion; Exercise; Walking
• Other Study ID Numbers: EAP_2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No