For individuals diagnosed with cardiovascular disease such as hypertrophic cardiomyopathy (HCM), whether and how much exercise or sports participation is safe is a question that may have significant impact on quality of life. HCM is the most common genetic cardiomyopathy, with epidemiological studies from several parts of the world reporting a similar prevalence of about 0.2% (i.e., 1:500) in the general population, which is equivalent to at least 600,000 people affected in the United States.¹ Current guidelines recommend restricting competitive sports participation for individuals with HCM to low-static/low-dynamic sports such as golf or bowling,^1-3 and vigorous recreational exercise has also been recommended against.⁴ However, as noted in these statements themselves, there are few data and these recommendations are based predominantly on expert opinion.

Sudden Death, HCM, and Exercise in Healthy (Undiagnosed) Athletes

In recent population-based studies, the incidence of sudden death in young people under 35 ranges from 1.3 to 2.8 per 100,000 person-years.^5-7 Some studies suggest athletes have a higher rate of sudden cardiac death (SCD) than non-athletes. In one prospective study of over 2000 high schools, the incidence of sudden death overall was 0.63 per 100,000 while the incidence of SCD in student athletes (excluding commotion cordis) was 0.95 per 100,000,⁸ with a relative risk of SCD in student athletes versus student non-athletes of 3.65. However, in a post-mortem-based study by Harmon et al. of SCD in National Collegiate Athletic Association (NCAA) athletes,⁹ the overall incidence of SCD in NCAA athletes was 2.3 per 100,000 athlete-years, similar to that in population studies.

One early series of athlete sudden deaths, the US National Registry of Sudden Death in Athletes, found over one-third to be due to HCM.¹⁰ Other series,^9,11 however, have found that the largest proportion of sudden death in athletes, as well as young people in general,^5-7 is autopsy-negative (normal heart), with HCM accounting for under 10%. Differences in ascertainment as well as potential reporting biases in voluntary registries may explain some of these differences.

If or to what extent vigorous exertion increases risk of sudden death in HCM is unknown. In the US National Registry of Sudden Death in Athletes, most of the reported deaths occurred during exertion,¹² but there may have been reporting bias. When an athlete dies in his sleep, it may be less likely to appear in the media or be reported to a registry of sudden death in athletes. Among young people in general, most sudden deaths do not occur during exertion.^5,7 Among SCDs in young people found to be due to HCM, most also do not occur during exertion with studies showing 30% during or post exercise.⁶ In a UK study of athlete sudden death, almost 40% died outside the context of exercise. Of the 23 athletes with HCM who suffered SCD in this study; 43% died at rest. In the NCAA athlete study,⁹ 56% of the sudden deaths occurred with exertion although the breakdown for those with HCM is not reported.

Arrhythmic Risk in the Diagnosed, Risk-Assessed, and Treated Athlete with HCM

While these studies demonstrate that HCM is an important contributor to SCD in young athletes, it is critical to note that in all of these series, the young athletes dying suddenly had not been previously diagnosed with the cardiovascular disease which resulted in their deaths. For an athlete diagnosed with heart disease who undergoes appropriate risk assessment and treatment, the risk of sudden death if he/she continues to play is not known. After the diagnosis of HCM, clinical features can identify those at risk of sudden death in whom consideration for ICD is warranted. An individualized risk prediction model is now available that incorporates traditional risk factors as well as age, left atrial size, and left ventricular outflow tract gradient, and weights them according to their relative influence on risk.^1,13 Newer markers, such as fibrosis (late gadolinium enhancement) seen on magnetic resonance imaging, may also contribute to risk.¹⁴

Once an ICD is implanted, there is evidence that risk of sports participation is very low. In the ICD Sports Safety Registry, 372 athletes with ICDs who were continuing to participate in sports, of whom 77 had HCM, were followed prospectively for over two years. There were no incidences of physical injury or failure to terminate the arrhythmia despite the occurrence of both inappropriate and appropriate shocks.¹⁵ Patients with HCM received shocks during both rest and physical exertion, and there were no electrical storms related to exertion in this group. Subanalysis of this group is pending.

What about the athlete who is diagnosed with HCM and found by clinical risk assessment to be at low enough risk for sudden death that an ICD is not indicated? Whether exercise increases SCD risk in an HCM patient independently from traditional risk factors is unknown. The updated European Guidelines for HCM recommend exclusion from competitive sports as a Class I indication for prevention of SCD,³ but there are no prospective data to support this. While some sudden deaths in HCM occur during exercise, the "paradox of exercise" as has been described for other populations may also apply to those with HCM.¹⁷ Acutely, exercise can act as a trigger of sudden death, increasing the immediate risk of SCD even in well-trained athletes.^18,19 Overall, habitual exercise reduces the risk of sudden death. This is likely due to the role of the autonomic nervous system. Sympathetic activity is arrhythmogenic in most disorders, suggesting the risk of SCD will be highest at the time of maximum sympathetic drive. For a runner, this will be while running; for a non-athlete, this may be running for a bus or with other daily activities.

An ongoing NIH-funded prospective observational study, Lifestyle and Exercise in HCM (LIVE-HCM) is comparing outcomes among individuals with HCM who are exercising moderately or vigorously compared to the sedentary. Patients can learn more and enroll directly through the central site, http://livehcm.org/.

Effect of Exercise on LV Function and Hypertrophy in Patients with HCM

How exercise may impact progression of disease in HCM is unknown. Isometric exercise induces physiological hypertrophy, which intuitively may seem deleterious in HCM. However, physiologic and pathological hypertrophy pathways are distinct from one another. For example, exercise does not influence pathways involved in the pathological hypertrophy of aortic stenosis.^20,21 Further, isotonic exercise induces cavity dilation which could be favorable in the HCM population with smaller LV cavities and tendency toward obstruction. In an animal study using a murine model of a myosin mutation, exercise prevented fibrosis, myocyte disarray, and induction of "hypertrophic" markers when initiated before established HCM pathology. If initiated in older HCM animals with documented disease, exercise reversed myocyte disarray and "hypertrophic" marker induction.²² Exercise-induced myocardial dysfunction in HCM seen on treadmill testing has been described, and is associated with worsened outcome. However, this is likely a marker of more significant myocardial disease, rather than an effect of exercise.²³

Potential Benefits of Exercise in HCM

While determining safe levels of athletic participation is an important question for a minority of HCM patients, for the majority, understanding how to increase activity in the sedentary may be a larger issue. A recent survey by Reinecke et al. compared HCM patients with NHANES participants (National Health and Nutrition Examination Survey), finding that the patients with HCM reported less time engaged in physical activity at work and for leisure, as well as higher body mass index.²⁴ An Australian study similarly found that a majority of HCM patients did not meet physical activity recommendations.²⁵ In that study, many participants reported that they had been advised not to exercise at all.

In a small pilot study, Klempfner et al. investigated the benefits and feasibility of increasing exercise in 20 symptomatic patients with HCM who were significantly limited in their everyday activity.²⁶ Patients exercised in a cardiac rehabilitation center twice a week, using treadmill, arm ergometer, and upright cycle exercise, with exercise prescription based on heart rate reserve determined from a symptom limited graded exercise stress test. Exercise intensity was gradually increased from 50% to 85% of the HRR over the training period. Functional capacity, assessed by a graded exercise test, improved significantly, and NYHA functional class improved from baseline by ≥1 grade in 10 patients (50%). During the study period and the following 12 months, none of the patients experienced clinical deterioration or significant adverse events.

This study suggests that moderate exercise may be not just safe but beneficial in decreasing symptom burden. There are several possible pathways through which exercise could improve symptoms—exercise improves diastolic function and improves endothelial function.²⁷

The larger, randomized RESET study, recently completed, is evaluating the safety of a home exercise program, with cardiopulmonary exercise test (CPET)-based individualized exercise-prescription, for patients with HCM. This study's hypotheses are that exercise parameters derived from a baseline cardiopulmonary exercise test will target an appropriately safe level of exercise intensity that will not cause significant arrhythmias or exacerbate symptoms and that exercise training for 4 months will result in significant improvements in peak oxygen consumption and quality of life, with neutral effects on the clinical characteristics.

What level of activity is safe for patients with HCM remains an active question. It is certain, however, that sitting on the couch is the wrong exercise prescription for patients with HCM.

References

1. Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA Guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2011;58:e212-60.
2. Maron BJ, Udelson JE, Bonow RO, et al. Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: task force 3: hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and other cardiomyopathies, and myocarditis: a scientific statement from the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015;66:2362-71.
3. Authors/Task Force members, Elliott PM, Anastasakis A, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J 2014;35:2733-79.
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Keywords: Arrhythmias, Cardiac, Athletes, Autonomic Nervous System, Body Mass Index, Cardiomyopathy, Hypertrophic, Death, Sudden, Dilatation, Epidemiologic Studies, Exercise, Exercise Test, Heart Rate, Hypertrophy, Magnetic Resonance Imaging, Oxygen Consumption, Physical Exertion, Registries, Risk Assessment, Risk Factors

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