Exercising caution: is there a role for exercise testing in the hypertrophic cardiomyopathy population?

It is well established that engaging in regular physical activity effectively reduces all-cause mortality. Notwithstanding, high intensity physical activity has been associated with sudden cardiac death (SCD) due to malignant cardiac arrhythmias, particularly in individuals with hypertrophic cardiomyopathy (HCM). Although most cases of SCD typically occur outside of the physical activity setting, individuals with HCM often purposefully limit their exercise participation, which can lead to secondary health complications arising from a sedentary lifestyle. Presently, there is no existing data that describe an ‘optimal’ dose of exercise that mitigates risk of arrhythmia for HCM patients. Therefore, investigation into the exercise intensities appropriate for this population is particularly important. In a recent issue of The Journal of Physiology, Shah et al. (2019) explored the relationship between exercise intensity and catecholamine levels, known pro-arrhythmic factors, in men (29 ± 8 years) diagnosed with mild non-obstructive HCM (n = 9) and age-matched healthy controls (n = 5). It was hypothesized that levels of adrenaline (epinephrine) and noradrenaline (norepinephrine) would remain stable at lowto-moderate exercise intensities, followed by an exponential rise at intensities progressing above the blood lactate threshold (LT) and ventilatory threshold (VT). Participants attended two visits in which the first comprised a resting echocardiograph to assess cardiac function, and a maximal effort cardiopulmonary exercise test on a cycle ergometer to determine the VT. During the second visit, participants completed a submaximal incremental exercise test that consisted of eight successive 3-min stages with intensities increasing by 20 W. Exercise intensities were individualized to each participant, which was an important addition in the methodology. This ensured participants would reach their VT by stage six. Capillary earlobe lactate and venous blood sampling from an intravenous catheter were acquired from each participant after every 3-min stage. Shah et al. (2019) demonstrated that exercise parameters, including maximal rate of oxygen consumption (V̇O2,max), VT and LT, were similar between patients with non-obstructive HCM and healthy controls. Plasma concentrations of adrenaline and noradrenaline did not differ between groups at rest or at any intensity during submaximal exercise. Both groups had similar catecholamine concentrations, in which levels remained stable up to low-to-moderate intensities, upon which concentrations rapidly increased at exercise intensities above the LT and VT. Importantly, the authors demonstrate that the catecholamine threshold occurs at an intensity that is higher than both the VT and LT. Based on their findings, the authors recommend personalized exercise prescriptions, safely developed through identification of each patient’s VT or LT. The current study provides an important contribution to the limited body of literature surrounding the relationship between exercise intensity, catecholamine kinetics, and the risk of arrhythmia in HCM patients. The authors were cognizant of the small sample size and of the possibility that catecholamine kinetics may also vary based upon the frequency or duration of exercise, which was not assessed. The authors should be commended for their work, as their results provide a foundational framework for future studies. However, the following factors should be considered when interpreting the findings: (i) the characteristics of the HCM population that was evaluated, (ii) the limited inclusion of post-exercise assessments, and (iii) the lack of female participants. The authors report no differences in the catecholamine response to exercise between HCM patients and healthy controls. In addition to being matched for age, HCM participants and healthy controls did not differ in most physiological measures including heart rate, VT, LT and cardiorespiratory fitness. While this may be a strength in the study design, this may also be perceived as a limitation that prevented any meaningful distinctions from being found between cohorts. Participants were recruited on the basis of having mild non-obstructive HCM, and were excluded if they presented with an obstructive form of HCM, an ejection fraction < 50%, a history of ventricular tachycardia, or any use of medications that interfered with the sympathetic nervous system. The authors report that patients with HCM were accumulating less than 5 h of aerobic exercise weekly, which is still a significant amount of activity, without participating in any form of competitive exercise in the past 12 months. Interestingly, the maximal cardiorespiratory fitness (V̇O2,max) of some HCM participants was well above the 80th percentile for their age (Wang et al. 2010), suggesting the HCM cohort was quite active. Perhaps the inclusion of patients with moderate-to-severe forms of HCM would have allowed for a more distinguishing comparison. Furthermore, patients with complicated forms of HCM may have benefitted to a greater extent from this type of investigation due to the likelihood that they are less active. The confirmation of safe exercise intensities may have helped encourage this population to increase their activity levels. The authors also suggest that future exercise prescriptions should be dealt with case-by-case. However, a larger and more heterogeneous sample size that includes patients across the spectrum of HCM may have produced observations with a broader relevance to a larger proportion of the HCM population and thus eliminate the need for time-consuming individualized tests. Participation in the present study involved two separate sessions that occurred within 1–2 weeks following the first visit. This design element minimized potential confounds of health status or exertional tolerance discrepancies between data collection sessions. The inclusion of a resting echocardiograph was another strong design element that provided a thorough characterization of cardiac function. Catecholamine kinetics was characterized throughout the eight stages of exercise; however, there was no assessment of catecholamines or cardiac function post exercise. As Shah et al. (2019)