Moderatio Rebus Omnibus

Moderation in All Things

Corresponding Author

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• arrhythmia
• arrhythmogenic right ventricular cardiomyopathy
• athlete’s heart
• exercise duration
• exercise intensity
• myocardial function
• ventricular arrhythmia

Sudden cardiac death (SCD) is always a tragic event, regardless of age, sex, race, or comorbidities. However, SCD in the young athletic population is especially alarming, as these individuals comprise a particularly healthy cohort with long life expectancies. The incidence of SCD in athletes has varied from as low as 0.4 per 100,000 person-years (2) to as high as 2.6 per 100,000 person-years (3) depending upon the time-period and region. In the United States, hypertrophic cardiomyopathy has been attributed as the most common cause of SCD in athletes, accounting for as many as 36% of cases (4). Although arrhythmogenic right ventricular cardiomyopathy (ARVC) has been implicated in 4% of SCD cases in the United States (4), the condition accounts for a significant portion of SCD of athletes in Europe—anywhere from 14% (5) in the United Kingdom to as a high as 24% (6) in the Veneto region of Italy. Given this burden of disease, strategies to mitigate SCD in this patient cohort are warranted.

Several studies have shown the role of exercise in the phenotypic development of ARVC in susceptible individuals, along with increasing arrhythmic risk in this cohort. First described in a mice model of ARVC, endurance training with swimming led to worsening right ventricular dysfunction and development of arrhythmias (7). These observations have been consistent in human studies. In a retrospective study of 87 patients who were carriers for ARVC-associated mutations, endurance athletes were noted to have higher rates of clinical disease progression to meet the diagnosis of ARVC, develop heart failure symptoms earlier in life, and have higher rates of ventricular arrhythmias (VAs) (8). In a larger study of 108 patients who met affected or borderline diagnosis of ARVC per the 2010 task force criteria, those who participated in competitive sports had a higher risk of ventricular arrhythmias and death compared with those who were inactive or participated in recreational sports only (9). Interestingly, there was no difference in these outcomes between the recreational sports cohort and those who were inactive, implying that there might be a threshold and dose-response relationship between exercise and risk. Given these findings, the current American Heart Association (AHA) and American College of Cardiology (ACC) guidelines recommend patients with a possible, borderline, or definite diagnosis of ARVC to not participate in competitive sports, with the possible exception of low-intensity Class 1A sports (10).

Physical activity and exercise have been shown to have a multitude of health benefits, including, but not limited to, a reduction of cardiovascular disease, diabetes, cancer, stroke, obesity, and depression. Currently, the AHA and the American College of Sports Medicine recommend moderate-intensity aerobic physical activity for at least 30 min for 5 days/week, or vigorous-intensity aerobic physical activity for at least 20 min 3 days/week (11). For the ARVC patient, the deprivation of the benefits of physical activity and exercise can create a challenging clinical dilemma, as these patients often tend to be young and active at the time of diagnosis.

In this issue of JACC: Clinical Electrophysiology, Lie et al. (12) have published a study that may offer clinicians practical guidance on the management of this patient cohort. In this retrospective observational cohort study, the authors interviewed ARVC patients at the time of diagnosis and categorized their past 3-year exercise habits by intensity and duration as either: 1) low intensity and short duration; 2) low intensity and long duration; 3) high intensity and short duration; or 4) high intensity and long duration. High intensity was defined as >6 metabolic equivalents (METs) (e.g., running, bicycling, aerobics, fast swimming, or competitive sports), and low intensity was defined as 3 to 6 METs (e.g., walking, dancing, or weight lifting). Exercise duration was classified as long or short using the median time as a pre-defined cut-off, with long duration ultimately being defined as exercising >2.5 h/week, and short duration as exercising ≤2.5 h/week. The authors then correlated the pattern of exercise to rates of VA, defined as aborted cardiac arrest, sustained ventricular tachycardia on monitoring, or appropriate implantable cardioverter-defibrillator therapy. Secondary outcomes of cardiac function and dimensions as assessed by echocardiography and cardiac magnetic resonance imaging were also included.

The authors found that in 173 patients with ARVC, 83 patients experienced the primary outcome of VA. For this VA endpoint, the data was reasonably consistent. On multivariate analysis, high-intensity exercise was associated with higher rates of VA, and longer duration of exercise in the high-intensity exercise was associated with increased arrhythmic risk. Low-intensity exercise had reduced rates of ventricular arrhythmias whether or not it was long duration.

The association between exercise intensity and duration with progression of structural abnormalities was less clear. The highest rates of LV dysfunction, RV dysfunction, and RV dilation were seen in the high-intensity and long-duration cohort. However, more RV dilation was observed in the low-intensity, long-duration than high-intensity, short-duration group. But, for RV dilatation, long duration appeared to be as important as intensity. On multivariate analysis comparing duration alone, the association between longer duration and increased RV dilation reached borderline statistical significance (p = 0.07).

There are limitations of this study, including that exercise activity was self-reported at the time of diagnosis, and only included the 3 years prior to diagnosis. Exercise habits may change over time, especially after a diagnosis of ARVC is made. So, heterogeneity may exist in the exposure variable of this study. Another limitation is the retrospective and observational design of the study. Although such studies have clear limitations, we should acknowledge that a prospective, randomized clinical trial examining various doses of exercise and arrhythmic risk in ARVC patients is not an ethical, feasible, or practical study design.

Despite these limitations, we applaud Lie et al. (12) for their findings. The results provide valuable information in the management of ARVC patients. High-intensity exercise, especially in long duration, may be associated with arrhythmic risk and progression of structural abnormalities compared with low-intensity exercise. Duration of exercise appears to be most important only in those with high-intensity exercise. In this cohort, high intensity was defined as 6 METs, achieved by sports such as running 13-min miles, bicycling at 9 miles/h or faster, and casual soccer (13). Low-intensity exercise is not associated with arrhythmic risk, but may not prevent the progression of structural abnormalities. Given that the benefits of physical activity are seen with as little as 2.6 to 5 METs (e.g., light jogging or leisure bicycling) (11), we can provide some practical guidance to our patients with ARVC. Although the data for competitive and strenuous exercise is becoming more compelling, we must acknowledge that we do not yet know where the exercise threshold for harm occurs for patients with ARVC.

• 2018 American College of Cardiology Foundation