Haemodynamics and Ventricular Arrhythmias During Exercise in Patients With Arrhythmogenic Cardiomyopathy

Overview

Patients with definitive and borderline arrhythmogenic cardiomyopathy (ACM) are usually recommended to refrain from high intensity exercise due to an increased risk of malignant arrhythmias. However, little is known about the effects of prolonged, low-to moderate endurance or resistance exercise on the burden of arrhythmias or central haemodynamics. This pilot interventional study assesses the impact of these modes of exercise on the electrophysiological substrate of the right ventricle (RV), measured by mapping of the RV, and central haemodynamics assessed by right heart catheterization. Patients older than 18 years of age with diagnosed borderline and definitive ACM are included with or without implantable cardioverter-defibrillator (ICD).

This is a one-armed, monocentric, unblinded pilot interventional study. Upon fulfilment of the inclusion criteria (age \>18 years of age, diagnosis of definitive or borderline ACM with or without implantable cardioverter defibrillator, ICD) and informed consent, patients will have two visits within one week. The baseline exam (V1), consists of a clinical history, a questionnaire on the quality of life (Kansas City Cardiomyopathy Questionnaire, KCCQ), laboratory examination, echocardiography, 24h-Holter monitoring, and exertional cardiopulmonary exercise testing (CPET). Morphological (echocardiography) and functional (CPET) capacity of the participants will be assessed. With the aid of CPET, exercise intensity for continuous low to moderate-intensity endurance exercise during exercise right heart catheterization (exRHC) will be assessed (power at first ventilatory threshold). During V1 the one repetition maximum (1RPM) of isometric handgrip strength will be assessed as well as during dynamic flexion of the upper arm (biceps curl) with the contralateral arm of the planned venous puncture during the invasive testing. Invasive Testing (V2): V2 will follow 48 hours after V1. Patients will first undergo supine resting right heart catheterization (RHC) followed by an electrophysiological study with mapping of the right ventricle (RV mapping) (condition 1, rest). Access for both procedures will be gained via the right internal jugular or brachial vein. After a 5-minute break isometric handgrip testing will assess haemodynamic changes (condition 2, isometric resistance test at 70% of the 1RPM for one minute). After another 5-minute break dynamic resistance testing will assess haemodynamic alterations (condition 3, dynamic resistance test, biceps curl at 70% of 1RPM for one minute with the contralateral arm of venous puncture). Following another 5-minute break, patients will perform supine bicycle exercise testing and haemodynamic measurements will be obtained at the end of 20 minutes of continuous, low to moderate-intensity endurance exercise (power at the first ventilatory threshold, condition 4, 20 minutes of moderate-intensity endurance test). Following haemodynamic testing, a prolonged low to moderate-intensity endurance exercise test will follow for another 20 minutes (power at the first ventilatory threshold), leading to a total time of 40 minutes, which is double the recommended duration from sports cardiology guidelines. Assessment of haemodynamics and RV mapping will be done at the end of this test (condition 5, 40-minutes low to moderate-intensity endurance test). In addition, cardiac biomarkers will be assessed before and after exercise. Following invasive testing, patients without an ICD will receive an implantable loop recorder (ILR). The aim of this interventional study is to assess changes of voltage maps during each of the exercise modes (20 minutes endurance test vs. 40 minutes endurance test vs. isometric handgrip vs. dynamic resistance exercise) as well as the change of pulmonary pressures. As patients with an ICD represent a high risk category, electrical and haemodynamic properties are compared between groups (ICD yes vs. no) in an exploratory approach. In this interventional study, which consists of assessments which are not part of routine medical care, the haemodynamic and electrophysiological effects of different exercise interventions (endurance and resistance tests) are evaluated.