Efficacy of High Intensity Exercise (HIE) for Increasing Cardiorespiratory Fitness in Patients With Hypertrophic Cardiomyopathy (HCM)

Regular exercise reduces the risk of all-cause and cardiovascular mortality in the general population. Specifically, higher cardiorespiratory fitness is associated with a 10 - 20 % reduction in mortality risk for every 1 MET (metabolic equivalent tasks) improvement in fitness. A high degree of fitness is also protective against the development of heart failure and exercise training has become the standard of care for most patients with cardiovascular disease to improve functional capacity, and reduce morbidity and mortality. However, hypertrophic cardiomyopathy, the most common inherited cardiovascular disease, may be an exception. For more than 30 years, hypertrophic cardiomyopathy (HCM) has been identified as the most common cause of death in young athletes, and patients with HCM are excluded from participation in competitive sports. The fear of provocation of sudden cardiac death has often been extended to non-competitive athletic activities in such patients, though there is a distinct lack of evidence about the safety of exercise in this population. A recent multicenter clinical trial provided evidence that moderate intensity exercise (MIE) may be safe in this population, though the increase in fitness with this training paradigm was modest. Alternatively, an extensive series of reviews published over the last five years advocate for high intensity interval training (HIIT) as an efficacious stimulus for increasing cardiorespiratory fitness in clinical adult populations, including those with heart failure. While a pilot investigation and preliminary findings suggest that moderate to vigorous intensity exercise may be safe and efficacious in patients with HCM, and even protective in animal models, there is no Level A or B evidence comparing the efficacy or safety of MIE and high intensity exercise (HIE) training in this patient population to guide exercise prescription. Therefore, the primary purpose of this exercise trial is to compare the efficacy and safety of supervised MIE and HIE training in adults with HCM. Specific aims and hypotheses of the project are as follows:

Aim 1: Compare the efficacy of a high intensity and moderate intensity exercise intervention to improve cardiorespiratory fitness and functional diastolic reserve in patients with HCM.

• Primary hypothesis: HIE will result in greater increases in maximal oxygen uptake (V̇O2max) than MIE in patients with HCM.
• Secondary hypothesis: HIE will improve stroke volume reserve to a greater degree than MIE in patients with HCM.

Aim 2: To evaluate the safety of HIE training in patients with HCM.

• Hypothesis: Regular exercise training of a high or moderate intensity will be safe (no serious adverse events) in this patient population. Specifically, it is hypothesised that HIE will not increase arrhythmia burden in patients with HCM.