Exercise Increases Age-Related Penetrance and Arrhythmic Risk in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy–Associated Desmosomal Mutation Carriers

Abstract

Objectives To determine how exercise influences penetrance of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) among patients with desmosomal mutations. Background While animal models and anecdotal evidence suggest exercise is a risk factor for ARVD/C, there have been no systematic human studies. Methods Eighty-seven carriers (46 male, mean age 44±18) were interviewed about regular physical activity from age ten. The relationship of exercise with; 1) sustained ventricular arrhythmia (VT/VF), 2) stage C heart failure (HF), and 3) meeting diagnostic criteria for ARVD/C (TFC) was studied. Results Endurance athletes (n=56) developed symptoms at a younger age (30.1±13.0 vs. 40.6±21.1 years, p=0.05), were more likely to meet TFC at last follow-up (82% vs. 35%, p<0.001), and had a lower lifetime survival free from VT/VF (p=0.013) and HF (p=0.004). Compared to those who did the least (lowest quartile) exercise per year prior to presentation, those in the second (OR=6.64, p=0.013), third (OR=16.7, p=0.001), and top (OR=25.3, p<0.0001) quartiles were increasingly likely to meet TFC. Among 61 who did not present with VT/VF, the 13 subjects experiencing a first VT/VF event over a mean 8.4±6.7 year follow-up were all endurance athletes (p=0.002). Survival from first VT/VF was lowest among those who exercised most (top quartile) both prior to (p=0.036) and after (p=0.005) clinical presentation. Among individuals in the top quartile, a reduction in exercise decreased VT/VF risk (p=0.04). Conclusions Endurance exercise and frequent exercise increase risk of VT/VF, HF, and ARVD/C in desmosomal mutation carriers. These findings support exercise restriction for these patients.

Right ventricular dysplasia: management and treatment in light of current evidence

“…Other treatment strategies including medications such as beta blocker (BB) and antiarrhythmics, radiofrequency ablation (RFA), cardiac transplantation, and lifestyle changes all may help in ARVC manifestations, but none of them have proven mortality benefits [29–35]. …”

“…Strenuous exercise can induce ventricular tachyarrhythmias, manifesting at an earlier age and promoting the disease progression due to right ventricular dilation with increased risk for VT [35–37]. The risk of SCD is significantly higher among competitive athletes compared with either recreational athletes or inactive patients [37].…”

“…The risk of SCD is significantly higher among competitive athletes compared with either recreational athletes or inactive patients [37]. It is thought that exercise leads to disruption of cellular junctions by increasing myocardial stress thus accelerating disease progression [35]. Both endurance and frequent exercise increase the risk of VA in patients with ARVC [35].…”

“…It is thought that exercise leads to disruption of cellular junctions by increasing myocardial stress thus accelerating disease progression [35]. Both endurance and frequent exercise increase the risk of VA in patients with ARVC [35]. Therefore, physical exercise should be minimized with an exception of low-intensity recreational sports (class IIa) [38].…”

“…Increasing physical activity leads to increased heart rate, myocardial stress, and oxygen demand, predisposing patients to recurrent arrhythmias [16,35,39–41]. BBs blunt these effects; however, no current clinical trial showed definitive mortality benefit for BB in patients with ARVC.…”