The influence of exercise modality and intensity on ventricular arrhythmia burden and perception of effort in patients with Arrhythmogenic Right Ventricular Cardiomyopathy with plakophilin-2 variants

Abstract

Introduction Intense endurance exercise is discouraged for patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), as it can increase the risk for adverse cardiac events as well as accelerate disease progression. While a sedentary lifestyle is also not advisable, there is currently no prospective data on the safety of physical activity for ARVC patients. To describe ARVC patients' average and peak ventricular arrhythmia burden – estimated from the prevalence of premature ventricular contractions (PVC) – measured during and after different exercise modalities and intensities, in context with cardiac and physiological load.

Methods Twenty ARVC patients (8 f/12 m, age 48 ± 15 years, BMI 24 ± 3 kg/m², resting PVC burden 4 ± 4%) with a heterozygous pathogenic/likely pathogenic plakophilin-2 (PKP-2) variant prospectively performed different exercises while monitored via 12-lead ECG. The order of modalities was randomized and participants were instructed to stop when surpassing perceived exertion of 15 (6-20 Borg scale). Resistance exercises included 2-min two-legged squats and single arm biceps curls (20 repetitions each) while endurance exercise included 5-min treadmill walking at comfortable speed and 3-min cycling bouts at a heart rate (HR) of 80, 100 and 120 bpm. Each activity was followed by a 10-min recovery period. Blood lactate concentration [La^-] was assessed at the end of each cycling bout, with 4 mmol/L defined as a threshold to describe high-intensity exercise.

Results No adverse events (including sustained ventricular tachyarrhythmia) nor premature terminations occurred. Average PVC burden during activities (including 5 min recovery) was lower for biceps curls compared with all other activities (p < 0.046), despite having the second highest level of perceived effort (13.8 ± 1.7 units). Biceps curls elicited ~20 mmHg (p < 0.001) lower peak systolic blood pressure and ~40 bpm peak lower HR (p < 0.001) compared with cycling at 120 bpm, despite similar perception of effort (12.9 ± 1.7, p = 0.818). Peak PVC burden during the different activities (highest PVC count in 1 min) ranged between 0–57% among participants and it was lower during the activities (5 ± 8%) than the subsequent 5-min recovery (8 ± 8%, p = 0.006). but no differences were detected between activities. Five patients (25%) presented [La^-] that exceeded 4.0 mmol/L when cycling at 120 bpm.

Discussion/Conclusion PVC burden, a marker for arrhythmogenicity, was generally higher during recovery than during exercise, with the smallest burden found during the exercise with a small muscle mass, despite high perceived exertion. Thus, such exercises might be better suited for training in ARVC patients. Generalized recommendations for a maximum HR of 120 bpm during exercise likely predispose a high number of ARVC patients to inadvertently perform high-intensity exercise, risking accelerating disease progression. Therefore, individualized exercise prescription should be recommended.