Impact of Exercise Restriction on Arrhythmic Risk Among Patients With Arrhythmogenic Right Ventricular Cardiomyopathy

Abstract

BackgroundPrior studies have shown a close link between exercise and development of arrhythmogenic right ventricular cardiomyopathy. How much exercise restriction reduces ventricular arrhythmia (VA), how genotype modifies its benefit, and whether it reduces risk sufficiently to defer implantable cardioverter‐defibrillator (ICD) placement in arrhythmogenic right ventricular cardiomyopathy are unknown.Methods and ResultsWe interviewed 129 arrhythmogenic right ventricular cardiomyopathy patients (age: 34.0±14.8 years; male: 60%) with ICDs (36% primary prevention) about exercise participation. Exercise change was defined as annual exercise duration and dose in the 3 years before clinical presentation minus that after presentation. The primary outcome was appropriate ICD therapy for VA. During the 5.1 years (interquartile range: 2.7–10.8 years) after presentation, 74% (95/129) patients reduced exercise dose and 85 (66%) patients experienced the primary outcome. In multivariate analyses, top tertile reduction in exercise duration and dose were both associated with less VA (duration: hazard ratio: 0.23 [95% confidence interval, 0.07–0.81]; dose: hazard ratio: 0.14 [95% confidence interval, 0.04–0.44]). Greater reduction in exercise dose conferred greater reduction in VA (P=0.01 for trend). Patients without desmosomal mutations and those with primary‐prevention ICDs benefited more from exercise reduction (P=0.16 and P=0.06 for interaction); however, 58% (18/31) of athletes who reduced exercise dose by >80% still experienced VA.ConclusionsExercise restriction should be recommended to all arrhythmogenic right ventricular cardiomyopathy patients with ICDs. Patients who are “gene‐elusive” and those with primary‐prevention devices may particularly benefit. Exercise reduction is unlikely to reduce arrhythmia sufficiently in high‐risk patients to alter decision‐making regarding ICD implantation.

Fibrosis in Arrhythmogenic Cardiomyopathy: The Phantom Thread in the Fibro-Adipose Tissue

“…In ACM patients, due to (Wang et al, 2018) the genetically determined fragility of desmosomes, the mechanical stretch of CM during endurance exercise may favor cell injury and accentuate the development of the disease. Moreover, a mechanotransduction mechanism (the Hippo pathway), translating mechanical stimuli into activation of fibro-adipogenic signals, is known to participate in ACM pathogenesis (Dupont et al, 2011;Chen et al, 2014).…”

“…Cardiac overload reduction therapies have been proposed based on ACM animal model findings (Fabritz et al, 2011). Detraining has only a limited effect on arrhythmias reduction (Wang et al, 2018).…”

Exercise: A Risky Subject in Arrhythmogenic Cardiomyopathy

“…Countries that implemented preparticipation screening had shown dramatic reduction of ACM‐related deaths in athletes 12. The current study of Wang and colleagues10 offers data suggesting that the electrophysiologic changes that strenuous exercise determine could be at least partially reversed by removing the “stressor” (ie, intense physical activity).…”

“…A follow‐up study from the same group6 then demonstrated how exercise has an even more severe contribution to disease progression in “gene‐elusive” patients, diagnosed by Task Force criteria in the absence of a positive genetic hit. In the current issue of this journal, Wang and colleagues10 moved a step further in unraveling the relations between sport and ACM and focused their analysis on the impact of lifestyle changes and exercise reduction in patients with ACM with an implantable cardioverter defibrillator (ICD) implanted in primary or secondary prevention. The 129 patients studied reflect somehow a higher‐risk group, who has already shown clinical features of the disease to the point of having an indication to an ICD.…”

“…The 129 patients studied reflect somehow a higher‐risk group, who has already shown clinical features of the disease to the point of having an indication to an ICD. In this issue of the Journal of the American Heart Association ( JAHA ), Wang et al10 addressed the important question of whether exercise reduction could alter the incidence of appropriate shocks in this specific group and whether there was a quantitative relation between the extent of exercise reduction and the probability of having ventricular arrhythmias. Their results add to the body of data supporting restriction from endurance and strenuous exercise in the context of ACM, by showing that those patients who followed the advice of limiting physical activity had a significantly better survival from appropriate ICD therapy.…”