Exercise in hypertrophic cardiomyopathy: towards a personalised approach

More than 20 years ago, a study from the United States (US) alerted the medical community. ¹ In a case series of competitive athletes who died suddenly, 85% had an underlying cardiovascular disease, and the most common cause was hypertrophic cardiomyopathy (HCM; 36%). Ninety per cent of sudden cardiac deaths (SCDs) occurred during or immediately after a training session. ¹ A subsequent analysis confirmed the prevalence of HCM in a large registry on SCD in competitive athletes. ²

From that moment, the association of exercise as a trigger for life-threatening arrhythmias in HCM was deeply anchored in the brain of physicians. The observation made in competitive athletes created substantial uncertainty about the risk-to-benefit ratio of exercise and leisure-time sports in non-athletes with HCM. Patients with inherited cardiomyopathies are not immune to cardiometabolic diseases, and inactivity is common in patients with HCM, probably in part due to fear of exercise-induced adverse events. While the European Society of Cardiology (ESC) HCM guidelines clearly advise to abstain from competitive sports and intense physical activity, they remain vague towards leisure-time sports and exercise for maintaining or improving cardiovascular health. ³ A recent position statement of the Sport Cardiology Section of the European Association of Preventive Cardiology has addressed recommendations on competitive and leisure-time sports in athletes with cardiomyopathies. ⁴ However, the vast majority of adults with HCM are non-athletes who seek advice about recreational activities.

Against this background, the paper of Cavigli and colleagues is a timely initiative. ⁵ It adds to existing viewpoints on exercise training in HCM^6–8 by focusing on tailored exercise prescription and titration for the prevention of comorbidities.

The personalised approach is justified. Since the early studies on SCDs in athletes our knowledge on exercise with HCM has grown. We have learned that the initial registry data may have overestimated the prevalence of HCM among athletic SCD individuals. Local registries, by their nature, are at risk of ascertainment bias. In addition, autopsy diagnoses do not always correlate with adjudicated diagnoses by experts. When cases of SCD in US college athletes were reviewed by a multidisciplinary panel, HCM was only infrequently seen, and unexplained death with a structurally normal heart was the most common finding. ⁹ Other regions of the world have reported a substantially lower prevalence of HCM in athletic SCD individuals, compared to the initial US data.^10–13

Moreover, we may have overestimated the risk of exercise-related SCD in HCM. In a prospective registry on athletes with implantable cardioverter defibrillators (ICDs), exercise-related shocks were uncommon in athletes with HCM. ¹⁴ In US college athletes with HCM who died suddenly, half of the cases occurred at rest. ¹⁵ In a prospective study on SCD among children and young adults from Australia and New Zealand including molecular autopsy, most cases occurred during sleep, rest and light activities, and HCM was a rare cause. ¹⁶

Last but not least, we may have overestimated the malignancy of HCM in general. In a population-based registry of patients with inherited cardiac conditions, 18% were cardiac arrest survivors. Only 8% of the HCM patients were affected, compared to 53% of patients with catecholaminergic polymorphic ventricular tachycardia, 25% of patients with arrhythmogenic cardiomyopathy and 20% of patients with long QT-syndrome. ¹⁷ Contemporary diagnostic and treatment options have reduced the mortality directly attributable to HCM, providing many patients with an opportunity to experience longevity with a good quality of life. ¹⁸

Individualised risk stratification is key for clinical decision-making in HCM. The ESC HCM risk-SCD score calculates the 5-year risk of SCD to guide the indication for or against ICD implantation. ³ Variables of this score such as a family history of SCD, unexplained syncope, left ventricular outflow tract (LVOT) gradient, and non-sustained ventricular tachycardia (nsVT) may also guide tailored exercise training recommendations. ⁴ Advanced imaging techniques and genetic analyses may contribute to the definition of HCM subtypes in the future.

As suggested by Cavigli and colleagues, ⁵ cardiopulmonary exercise testing may be considered for assessing the haemodynamic response to exercise and choosing exercise intensity zones based on ventilatory thresholds. However, the authors did not propose an algorithm, how exercise intensity should be tailored in HCM patients with different risk features. Sex-related differences in exercise performance and outcome should be considered. Observational data suggest that female patients with HCM have a significant age-related impairment in functional capacity compared with men, and are at greater risk of HCM-related complications and death. ¹⁹ Furthermore, the authors did not address whether low-risk patients should be allowed to perform high-intensity exercise. A word of caution needs to be added about their key recommendation for resistance training of moderate intensity. The rationale is not discussed in the text, and data on safety, in particular in patients with high-risk features such as LVOT obstruction, severe left ventricular hypertrophy or nsVT, are lacking. As for competitive and leisure-time sports, a risk-based approach would be desirable. ⁴ The potential value of supervised exercise training for selected HCM patients is noteworthy. In a large HCM cohort, lack of cardiac rehabilitation enrolment and cardiovascular risk factors were predictive of non-improvement of exercise capacity following septal myectomy surgery. ²⁰

While it seems reasonable to believe that moderate and high-intensity aerobic exercise is safe and efficacious for carefully selected HCM subtypes, so far only one randomised and one non-randomised clinical trial have investigated moderate-intensity aerobic exercise in HCM patients, and a pilot study on high-intensity exercise is on its way.^6,7 All studies are small and focus on cardiorespiratory fitness and cardiac morphology and function. Hence, data on safety are still lacking. It remains to be seen whether an adequately powered trial will ever be conducted.

Until then, a level of uncertainty regarding the long-term safety of exercise at higher intensities in HCM will remain. However, viewpoints such as the one of Cavigli and colleagues ⁵ and others^6–8 may convince the medical community that exercise recommendation can be less restrictive in low-risk HCM patients than two decades ago. The ESC guideline on sports cardiology and exercise will be published this year and probably supports this view. As in other areas of medicine, recommendations on exercise in HCM should be subject to a shared and informed decision-making model that supports patient autonomy. ⁷