Hypertrophic cardiomyopathy and exercise restrictions: time to let the shackles off?

Abstract

The health benefits of physical activity are well documented. Patients with hypertrophic cardiomyopathy (HCM) are often discouraged from participating in physical activity due to a perceived increase in the risk of sudden cardiac death (SCD). As a result, only 45% of patients with HCM meet the minimum guidelines for physical activity, and many report an intentional reduction in exercise following diagnosis. Despite most SCD being unrelated to HCM, guidelines traditionally focused on the avoidance of potential risk through restriction of exercise, without clear recommendations on how to negate the negative health impact of inactivity. Retrospective reviews have demonstrated that the majority of cardiac arrests in patients with HCM occurred at rest or on mild exertion and that the overall incidence of HCM-related SCD is significantly lower than previously reported. We will discuss current international guidelines and recommendations and consider the outcomes of various studies that have investigated the effects of exercise of different intensities on patients with HCM. In light of the growing evidence suggesting that carefully guided exercise can be both beneficial and safe in patients with HCM, we ask whether it is time to let the shackles off exercise restriction in HCM.

Introduction

Hypertrophic cardiomyopathy (HCM) predominantly results from genetic variants that affect cardiac sarcomeres. The result is a heterogeneous condition characterised by ventricular hypertrophy that cannot be explained by increased afterload (i.e. arterial hypertension, aortic stenosis). Various hypothesised mechanisms were potentially responsible for a perceived increased risk of arrhythmia during exercise in patients with HCM: dynamic left ventricular outflow tract obstruction (LVOTO) increasing left ventricular pressure and strain; sympathetic vagal imbalance; microvascular ischaemia and metabolic acidosis.¹ Subsequent international guidelines have discouraged participation in moderate-to-high-intensity competitive sports and made ambiguous statements about tailoring advice on recreational activities based on symptoms and risk of disease-related complications.¹ As a result, only 45% of patients with HCM meet minimum guidelines for physical activity,² and many report an intentional reduction in exercise following diagnosis.³

The benefits of physical activity in the general population are well documented, with incremental benefit from higher degrees of fitness. In contrast, inactivity is related to poor health outcomes and is the fourth leading cause of death worldwide.⁴ As a result of contemporary management, HCM associated mortality is low (about 0.5% per year) and only 25% of patients die from the disease.⁵ This highlights the importance of being able to safely avoid excess risk incurred due to inactivity.

Risk and recommendations for patients with HCM

Guidelines traditionally focused on the avoidance of potential risk through restriction of exercise, without clear recommendations on how to negate the negative health impact of inactivity. Obesity is a major public health issue and is estimated to have cost the National Health Service (NHS) £6.1 billion in 2014/15.⁶ Patients with HCM engage less with physical activity, have higher body mass index (BMI),⁷ and, as a result, obesity has a prevalence of up to 55% in this group.³ In patients with HCM, increasing BMI is associated with a reduction in mean maximal oxygen consumption (VO₂ max) and treadmill time, as well as abnormalities in heart rate response.⁸ Sorajja et al. found that, among minimally symptomatic patients, those with a low metabolic exercise capacity (VO₂ max <18 ml/kg/min) were at an increased risk of death or development of severe symptoms compared with their fitter counterparts.⁹ Additionally, 10% of patients with HCM suffer from psychiatric comorbidities, such as anxiety and depression, alcohol and substance abuse.¹⁰ Increasing recognition of the negative impact that restriction of physical activity has on patients with HCM has resulted in the investigation of the safety of less restrictive exercise regimens, with growing evidence suggesting that programmed moderate intensity exercise improves exercise capacity and state of mind, without additional risk of SCD in the short term.¹¹

Evidence that SCD risk in patients with HCM is reduced by avoiding exercise is lacking. Maron et al. investigated the deaths of 78 patients with HCM. Cardiac arrest only occurred during moderate-to-severe exertion in 39%.¹² Finocchiaro et al. found that only 19% of their 185 HCM patient cohort died during exertion.¹³ A large meta-analysis of 4,605 SCDs below the age of 35 years attributed the cause of death to HCM in only 10% of cases.¹⁴ Most recently, Weissler-Snir et al. reported on 53 deaths (44 definite, three probable, six possibly) related to HCM with an estimated annual incidence rate of 0.39 deaths per 1,000 HCM person-years, the majority of which occurred at rest (64.8%) or on light activity (18.5%).¹⁵

A Norwegian study investigated the relationship between exercise and risk of ventricular arrhythmia (VA) in 187 subjects with HCM and concluded that vigorous exercise did not increase the risk of VA.¹⁶ Klempfner et al. assessed the impact of a graded exercise programme on 20 patients with symptomatic HCM and observed a significant improvement in functional capacity and New York Heart Association (NYHA) class without any reported adverse events or ventricular arrhythmia.¹⁷

RESET-HCM (Randomized Exploratory Study of Exercise Training in Hypertrophic Cardiomyopathy) was the first randomised-controlled trial (RCT) to investigate the effect of prescribed training in HCM. One hundred and thirty-six patients were randomised to normal activity or a 16-week programme of escalating moderate-intensity training (60–70% heart rate reserve). This included aerobic exercises such as running or cycling, however, as no strength or high-intensity interval training was prescribed, we should remain cautious when advocating such programmes. At 16 weeks, the primary outcome, a change of VO₂ max, was found to be +1.35 ml/kg/min in the exercise group and +0.08 ml/kg/min in the normal activity group, representing a 6% absolute difference. A previous study demonstrated that a 6% increase in VO₂ max is associated with an 8% lower risk of all-cause cardiovascular mortality and heart failure hospitalisations.¹⁸ Importantly, no major adverse events, including death, aborted sudden cardiac death, appropriate implantable cardioverter defibrillator (ICD) shocks, or sustained ventricular tachycardia were observed in either group.¹¹

As the evidence for safety of light-to-moderate intensity exercise in patients with HCM grows, the cardiomyopathy community are taking more interest in observing the impact exercise has on quality of life (QoL) and clinical outcomes. The multi-centre observational trial Lifestyle and Exercise in HCM (LIVE HCM) has completed recruiting HCM patients and is providing step counter FitBit devices to track activity. The aim is to determine how lifestyle and exercise impact the well-being of patients with HCM, collecting QoL questionnaires, FitBit data and clinical outcomes.

Risk and recommendations — for athletes with HCM

As a result of early associations between HCM and exercise-related SCD, various screening protocols were developed.¹⁹ Exercise was proposed as an independent risk factor for SCD as it may alter blood volume, electrolytes, metabolism, catecholamine levels and autonomic tone.²⁰ Sheikh et al. compared electrical, structural and functional parameters in >100 sedentary patients with HCM to a similar number of their athletic counterparts, and concluded that athletes with HCM exhibit less left ventricular (LV) hypertrophy, have larger LV cavities and more normal indices of diastolic function than sedentary patients.²¹

Pelliccia et al. followed up 35 athletes with HCM over a nine-year period.²² They were all advised to avoid competitive sport, however, 15 continued to train regularly (88% were low risk in accordance with the European Society of Cardiology [ESC] calculator²³ and none were offered ICD). There was no difference observed in the incidence of the development of symptoms or events between the two groups, and only one cardiac arrest occurred in an amateur tennis player while shopping. Maron et al. published a case series of 14 patients fortuitously diagnosed with HCM having completed many years (mean 15 years) of high-level training across a variety of disciplines without SCD. Mean LV wall thickness was 20 mm (18–28 mm), with most displaying a relatively localised septal pattern.²⁴ In August 2018, Malhotra et al. published their registry of >11,000 adolescent footballers who had been screened for known causes of SCD. Despite advice, two athletes with HCM continued to compete and subsequently died during intensive exercise.²⁵

Recently, the ESC has recognised that this growing body of evidence suggests that in certain low-risk athletes with HCM, continued participation in competitive sports may be reasonable. Recommendations published in January 2019 suggested that participation in intensive exercise programmes and competitive sport should be considered on an individual basis. Those of adult age with a mild clinical expression of HCM and a low ESC risk score may be allowed to participate in all competitive sport in the absence of any absolute contraindications:

1. History of aborted SCD/cardiac arrest (CA).

2. Symptoms, particularly unheralded syncope.

3. Exercise-induced ventricular tachycardia.

4. High ESC five-year risk score.

5. Significant increase in LV outflow gradient (>50 mmHg).

6. Abnormal blood pressure response to exercise.

As a result, those with: mild clinical expression of HCM; low ESC risk score; and of adult age may be allowed to selectively participate in all competitive sports.²⁶

Conclusion

A growing body of evidence suggests that guided exercise is safe in selected patients with HCM and that not all athletes need to curtail their careers. Aerobic cardiovascular exercise targeting 60% of heart rate reserve and sub-maximal weight training with low-weight and high reps (>10) may be reasonably suggested to patients with HCM, while the evidence is awaited to tailor more specific exercise prescriptions. There are wide-ranging, accepted benefits of exercise in terms of improvement of general physical health and psychological wellbeing, both facets of care that are often overlooked when managing HCM patients. Given the significant improvements in other aspects of care for these patients, and the lack of compelling data to suggest that participation in low-tomoderate intensity exercise is dangerous, it is perhaps time to reappraise our advice and encourage guided physical activity in patients with HCM

Key messages

• The perceived risk of sudden cardiac death (SCD) during mild-to-moderate exercise in patients with hypertrophic cardiomyopathy (HCM) is probably overestimated

• The safety and benefit of mild-to-moderate intensity exercise should be discussed with most patients with HCM; such advice, however, should carry the caveat that safety can never be guaranteed

• There are six high-risk features which can be used to identify patients who should avoid moderate-to-intensive exercise. These are:

  1. History of aborted SCD/cardiac arrest

  2. Symptoms, particularly unheralded syncope

  3. Exercise-induced ventricular tachycardia

  4. High European Society of Cardiology (ESC) five-year risk score

  5. Significant increase in left ventricular outflow gradient (>50 mmHg)

  6. Abnormal blood pressure response to exercise

Conflicts of interest

None declared.

Funding Statement

Funding None.