Exercise prescription in cardiomyopathies: rationale, benefits and exercise modalities

Keywords

cardiomyopathies, cardiopulmonary exercise testing, exercise prescription, hypertrophic cardiomyopathies

Take-home messages

• Exercise is possible in individuals with cardiomyopathies when prescribed in a tailored manner.
• Exercise prescription in cardiomyopathies is safe and effective in improving functional capacity.
• Cardiopulmonary exercise testing is essential to define an appropriate intensity of aerobic exercise, taking into account the characteristics of each patient.

Introduction

While exercise is a crucial component of a healthy lifestyle and can benefit many individuals, it requires careful consideration and a tailored prescription for those with cardiomyopathies. Exercise prescription in cardiomyopathies primarily aims to improve or maintain cardiovascular fitness, enhance overall well-being, and manage symptoms while minimising the risk of adverse events [1]. Exercise prescriptions for cardiomyopathies should be individualised based on the assessment results and the specific type of cardiomyopathy, with a specific prescription of exercise mode, intensity, frequency and duration. The monitoring of training activities and a re-evaluation in the months following the initial evaluation are essential. Establishing an appropriate progression (i.e., a gradual increase in exercise intensity and duration based on individual progress and tolerance, avoiding sudden, significant increases in workload) is important, particularly for sedentary patients who start a training program [2]. Patient education is part of the exercise program, notably, from the outset, providing education on the importance of hydration (particularly in patients with hypertrophic cardiomyopathy [HCM]), recognising signs of overexertion, and knowing when to seek medical attention.

This article provides an overview of exercise prescription for individuals with cardiomyopathies, examines various types of cardiomyopathies and the importance of a tailored prescription according to each diagnosis while taking into consideration each patient's specific needs.

Beneficial effects of exercise prescription in cardiomyopathies

Hypertrophic cardiomyopathy

Despite the striking body of evidence in favour of physical activity, patients suffering from HCM are often physically inactive, as physical activity (PA) is not encouraged (on the contrary, often discouraged) by health professionals, and a personalised prescription is an exception rather than rule [3]. Patients with HCM are known to be less active and spend significantly less time either at work or in recreational PA than the general population [4] and most HCM patients admit an intentional reduction in PA following the diagnosis of HCM despite a negative impact on their emotional well-being and mental health. As a result, HCM patients are often overweight, with a prevalence of obesity as high as 40% [5]. Beyond the well-known negative effects of obesity on health, in patients with HCM, obesity is independently associated with adverse cardiac remodelling, increased left ventricular (LV) mass and a higher likelihood of dynamic obstruction and congestive symptoms [5,6].

Unfortunately, despite the international scientific and clinical community agreeing on the importance of an exercise prescription in HCM, there have been few trials on exercise training in HCM patients to help guide clinical practice. Notably, The Randomised Exploratory Study of Exercise Training in Hypertrophic Cardiomyopathy (RESET-HCM) was a clinical trial that investigated the effects of individualised moderate-intensity aerobic exercise training versus usual activity in 136 patients with HCM [7]. The authors demonstrated that, after 16 weeks, peak VO2 increased slightly but significantly in the exercise training group but not in the usual activity group (p=0.02). There were no occurrences of sustained ventricular arrhythmia, sudden cardiac death or appropriate defibrillator shock in either subset. Another prospective, non-randomised interventional study on exercise training programs in HCM patients demonstrated an improvement in functional capacity by 46% (p=0.01) in NYHA Functional Class by 1 grade in 10 patients (50%), and the majority of patients reported subjective improvement in their clinical condition [8]. This study supports the view that symptomatic HCM patients benefit from supervised exercise programmes and can exercise safely.

Collectively, the scant evidence currently available are proof that the issue of physical activity in HCM has been neglected but that exercise programmes for HCM patients are safe. The evidence of favourable outcomes and benefits in terms of exercise capacity and quality of life suggests that it is high time such evidence should be translated into clinical practice. However, given the lack of large-scale studies with long-term follow-up, monitoring the long-term effects of exercise programmes in HCM patients is necessary. An international registry should be developed for systematic data collection in the field.

Dilated cardiomyopathy

Exercise prescription is one of the most important intervention options to improve cardiopulmonary function, NYHA Class and quality of life; for this reason, it is recommended by the ESC guidelines for heart failure. Several studies have demonstrated its efficacy and safety in patients with dilated cardiomyopathy (DCM). The main beneficial effect of exercise intervention is improving functional capacity, with a VO_2peak improvement ranging from 8% to 27%, depending on studies [9]. Furthermore, several studies have found an improvement in left ventricular ejection fraction (LVEF). An improved exercise capacity not only translates into a better quality of life and independence in everyday activity but is also a strong predictor of all-cause mortality. Even a minor improvement in peak VO₂ is related to a better outcome [10] and an increase in 1 metabolic equivalent  (MET) is associated with a 13% to 15% reduction in all-cause mortality. Furthermore, including strength training has further beneficial effects on exercise capacity and quality of life, counteracting the effects of wasting syndrome.

Arrhythmogenic cardiomyopathy

Arrhythmogenic cardiomyopathy (ACM) is characterised by a progressive myocardial atrophy with fibro-fatty replacement of the myocardium. This cardiomyopathy phenotype is associated with an alteration of the intercalated disc, resulting in a disruption of normal cell adhesion and mechanical stability. The haemodynamic overload associated with high-intensity training results in wall stress on the right ventricle, accelerating the disease progression [11]. For this reason, patients are usually advised to abstain from intensive exercise. On the one hand, intensive exercise training seems to have a negative effect on disease progression; on the other hand, inactivity leads to increased mobility and mortality. For this reason, it has been hypothesised that low-moderate intensity exercise training may have beneficial effects by reducing cardiovascular risk without accelerating the disease progression.

Current evidence

Dilated cardiomyopathy

Although DCM is probably the cardiomyopathy with the highest evidence, most of it is postulated from studies on heart failure with reduced ejection fraction (HFrEF) patients and, therefore, is not specific to this condition. Disease-specific evidence is rare and does not include a vast study population. A systemic review of the literature [9] in 2019 included 4 prospective studies on the effect of exercise intervention on DCM, all of which showed an increase in functional capacity (ranging from 8% to 24%) and quality of life. In one study, the intervention consisted of 7 weeks of home-based aerobic exercise; functional capacity was assessed with a 6-minute walking test and included 15 patients with no control group [12]. In the other two studies, a centre-based, supervised exercise intervention was prescribed and a control group was included; they enrolled 24 [13] (no dropouts) and 20 [14] (4 patients dropped out) patients with 10 (2 supervised and 8 unsupervised) and 3 months of aerobic exercise, respectively. The study by Stolen et al also included resistance training. Functional capacity was assessed by cardiopulmonary exercise test (CPET). The most recent and larger study is from Mehani et al [15]. It was a randomised controlled trial that included 40 patients. The dropout rate was 25%, and only 30 patients completed the study (15 exercise group, 15 control group). The patients were evaluated at baseline and the end of the study with CPET, echocardiography and the Kansas City Cardiomyopathy Questionnaire (KCCQ). The exercise group underwent a 7 month training period of supervised aerobic exercise starting at 55% of the heart rate and increasing up to 80% by the end of the training period. A significant increase in peak VO2 (from 16.1±3.65 to 21.08±5.47) was observed only in the training group; furthermore, the training group experienced a decrease in resting heart rate (HR), better diastolic filling, and better quality of life assessed by KCCQ.

Hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy response to exercise has also gained interest in recent years; a retrospective study on athletes with low-risk HCM showed that subjects who continued to exercise did not show an increase in disease progression or arrhythmic risk. Moving to the benefit of exercise prescription, two prospective studies exist to date on the prescription of moderate-intensity exercise. Klempfner et al [8] conducted a prospective non-randomised trial that enrolled 20 patients with symptomatic HCM who completed a supervised cardiac rehabilitation programme of 60 minutes of aerobic exercise 2 days a week at an HR that progressed from 50% to 85%. Patients exercised for an average of 41±8h. There were no adverse events and functional capacity, assessed by a graded exercise test, improved by 2.5 METs. The second study, from Saberi et al [7] was a randomised control trial that enrolled 136 patients with HCM; all patients were evaluated with a 12-lead electrocardiogram (ECG), echocardiogram, CPET, genetic testing and biomarker analysis. The exercise group participated in a 16-week unsupervised exercise program; both groups were monitored during this period using an HR monitor and pedometers. The exercise prescription was designed to start with 3 sessions per week of 20 minutes of aerobic exercise at an HR corresponding to 60% of the HR reserve. The participant would then increase the duration by 5 to 10 minutes per week up to a maximum of 60 minutes per session and 4 sessions weekly, gradually increasing the target HR at 70% of the HR reserve. 17 patients were lost at follow-up (10 in the usual activity group and 7 in the exercise group). All the patients were revaluated at the end of the exercise programme. The study found a significant but modest increase in peak VO₂ (+1.35 ml/Kg/min). There was no occurrence of major cardiac events in either group.

Arrhythmogenic cardiomyopathy

To our knowledge, there are currently no trials on exercise prescription in ACM. All the knowledge we have comes from the arrhythmogenic right ventricular cardiomyopathy (ARVC) registry at Johns Hopkins (Baltimore, MD, USA) and from studies in Oslo, Norway, both demonstrating that high levels of exercise have a negative impact on disease progression and arrhythmic risk [16, 17]. Nevertheless, when patients reduced the intensity of exercise after the diagnosis, they had a better outcome. Furthermore, it was the intensity of the exercise rather than the duration that was correlated with the worst outcome [17]. One of the most interesting studies on this topic is probably the one by Sawant et al [18] from Johns Hopkins: they studied 10 extended families with plakophilin mutations. In this study, endurance athletes represented 67% of subjects meeting the Task Force Criteria, and, more importantly, of the 7 members of the families who exercised at a low-to-moderate intensity, only one met the Task Force Criteria, and none developed ventricular arrhythmias. From this data, we can suppose that low to moderate intensity aerobic training can be safe in this population.

Exercise prescription

Cardiomyopathies are characterised by different manifestations and functional capacities in each patient; therefore, it is imperative to abandon generalised advice on physical activity in favour of a personalised and specific exercise prescription. In doing so, one of the main challenges is how to determine exercise intensity properly. A recent position statement from the European Association of Preventive Cardiology concluded that the ventilatory thresholds (VT) derived from CPET should be used to identify exercise intensity (EI). The concept of VT is related to alteration in energy metabolism during exercise. Schematically, the VT₁ can be seen as the limit between mild and moderate EI, whereas the VT₂ can be seen as the limit between heavy and very heavy EI. If a CPET is unavailable, lactate testing can be used to assess the VT and give a personalised exercise prescription. Once we have obtained the information on EI from a CPET or lactate testing, this must be translated into a precise prescription. Exercise is medicine and should, therefore, be prescribed as such. The prescription should be based on the “FITT-VP” model, which takes into account the following:

• Frequency: the number of sessions per week
• Intensity: the amount of energy expenditure
• Time: the duration of the training sessions
• Type of exercise: aerobic, resistance training, balance and flexibility etc.,
• Volume: volume of training per week
• Progression: progression of training volume and, in selected cases, training intensity during the programme

The recommendation for patients with cardiomyopathies is to prescribe moderate-intensity (or low-intensity in selected cases) aerobic exercise. We should, therefore, give a range of target HR around the HR of that patient at VT₁. The range can be moved slightly based on the individual risk assessment conducted during the evaluation. For example, a patient with ACM should receive a more restrictive prescription with a max HR target matching the HR at first VT, while a low-risk HCM patient can receive a less restrictive prescription with an HR target range over the HR at first VT. The type of exercise should be decided after a discussion with the patient on what type of exercise they enjoy in order to assure maximum compliance.

Resistance and strength training can be included in the exercise programs of patients with cardiomyopathies. A specific prescription and definition of exercise intensity is essential to train safely and to benefit from the positive effects of exercise.

Conclusions and future directions

Exercise prescription for individuals with cardiomyopathies must be delicately balanced between improving cardiovascular fitness and managing symptoms while ensuring safety. It requires close collaboration between healthcare professionals, exercise specialists, and the patient. The goal is to enhance the overall quality of life, reduce the risk of complications, and empower individuals to lead active, fulfilling lives despite the challenges of cardiomyopathies. Each exercise plan should be personalised, regularly reviewed, and adjusted to accommodate changes in the individual's condition or goals. Patients should be encouraged to stay active within their limitations and under the guidance of their healthcare team. The evidence and clinical competence in this field should be encouraged to improve the appropriate management of HCM patients in terms of preventing comorbidities.