Hypertrophic cardiomyopathy and exercise: a need for more information

In this issue of The Journal of Physiology, Shah and colleagues report on what happens to patients with mild, generally asymptomatic, hypertrophic cardiomyopathy (HCM) during incremental exercise (Shah et al. 2019). The short answer is that these patients had remarkably normal responses to graded exercise to maximum. This included, importantly, a normal and not excessive catecholamine response. The haemodynamic and respiratory responses were also normal. Additionally, potentially worrisome ventricular arrhythmias were not provoked by heavy exercise. These observations suggest that vigorous aerobic exercise does not evoke inherently dangerous responses in patients with mild HCM (Alpert et al. 2015; Dias et al. 2018). This study was done in part because there is ongoing debate about exercise in HCM and guidelines from a number of professional organizations and experts support restrictions on vigorous/competitive exercise in patients with HCM (Maron et al. 2017). The rationale seems to be that HCM is associated with cardiac fibrosis and sudden death. The fibrotic tissue – the bioplausible reasoning goes – is a potential substrate for exercise-induced arrhythmias caused by high circulating catecholamines and increased cardiac sympathetic activity during vigorous exercise. In their introduction and discussion, the authors point out numerous holes in the chain of reasoning outlined above. They also note that many people with HCM have participated in vigorous forms of exercise for years without harm. Their questions about the guidelines are also consistent with recent reviews in clinical journals (Dias et al. 2018). As I read this paper I started to think about other clinical conditions where the recommendations suggested less exercise. Such recommendations fly in the face of one of the central public health messages of our time that getting more people to exercise more often and increase their general levels of physical activity is critical in the modern world (WHO, 2010). This message is backed by research ranging from molecular biology to population studies and recent evidence that vigorous exercise can be especially beneficial (Hawley et al. 2014; MacInnis & Gibala, 2017). However, this pro-exercise, pro-activity message comes with some caveats and there may be subgroups of ‘patients’ who should avoid exercise – especially vigorous exercise. There are also many examples of prohibitions against exercise that soften or are reversed when they are actually studied. For example, at this time for example, there is debate about the role of bed rest in improving outcomes in multiple pregnancies (da Silva Lopes et al. 2017). Perhaps the classic example of exercise and activity avoidance being overturned was the widespread implementation of bed rest and prolonged hospitalization protocols post-myocardial infarction that were in place until the 1970s, when they slowly receded (Hutter et al. 1973). Bedrest has since been progressively replaced by more activity and there has been evidence since at least the early 1980s that vigorous exercise can be beneficial in patients with coronary artery disease (Hagberg et al. 1983). It can also be done safely (Rognmo et al. 2012). Given the current state of the art on this topic, what was the rationale for extended bed rest and inactivity post-myocardial infarction in the first place? In talking with senior clinical investigators who saw practice changes over many decades (R. L. Frye, Mayo Clinic; personal communication). There were concerns about sympathetic activation triggering arrhythmias and also ideas about the need to ‘heal’ the fibrotic scar associated with the infarction. This latter point is important because there was evidence that an unhealed scar might be the substrate for either arrhythmia or less commonly catastrophic ventricular rupture, and that both might be triggered by exercise. The latter complication – acute ventricular rupture – is one of the more dramatic events that can be witnessed in clinical medicine. At some level the concerns about exercise in HCM echo the earlier ideas that dominated clinical guidelines concerning the role of physical activity in patients after myocardial infarction. The most obvious parallels are worries about sympathetic activation and its potential to evoke arrhythmias along with concerns about myocardial fibrosis and scar tissue. While acute exercise can clearly evoke arrhythmias under some circumstances, exercise training is protective for a variety of reasons including increases in vagal tone (Billman, 2009). Exercise is also protective or ameliorates many metabolic and other risk factors associated with a host of non-communicable diseases. In this context, it seems reasonable to ask what sort of evidence is needed in what subgroup of patients to confidently restrict exercise and/or moderate to high levels of physical activity? It also seems reasonable to assert that what is most needed on this general topic are high quality clinical trials informed by integrative physiology and monitoring. While it is easy (and probably a good idea) to be sceptical about the therapeutic and diagnostic utility of wearables and monitoring (Jakicic et al. 2016), it seems to me that it might be of high utility in conditions like exercise training in HCM. This could be part of structured training programmes or via observational studies in patients with mild HCM. These sorts of data would permit information to be accrued about the real risk of arrhythmias, when they occur, and what they are associated with in well-screened patients. This information could then be used to inform guidelines and advice to individual patients. The extent to which the guidelines relating to exercise and participation in competitive sports in patients with HCM might ultimately be revised remains to be seen. That this topic might be studied in a responsible and prospective way to better inform advice to patients and clinical decision making seems clear. None declared. Sole author. None declared. Discussions with Professor Robert L. Frye were very helpful in the generation of this commentary. His willingness to share his vast state-of-the-art knowledge and extensive historical perspective on the practice of physiologically informed cardiovascular medicine is one of the highlights of being a clinical investigator at Mayo Clinic.