Introduction
Exercise has an undisputable benefit on health at a multiple organ level, including the cardiovascular system. On the contrary, the concern related to the association between exercise and cardiac arrest/sudden cardiac death (SCD) for those affected by cardiomyopathies has resulted in a prohibitive recommendation on competitive sports participation for decades.1,2 In an era with an increasing trend towards a sedentary lifestyle and obesity with associated cardiovascular diseases, the promotion of regular physical activity becomes crucial. This assumes fundamental importance in cardiomyopathies, wherein the disease is often diagnosed in the youngest. Over the past decades, data on the effect of regular exercise programmes in patients with cardiomyopathies accumulated and sparked the debate on the opportunity to have a less restrictive approach, at least in some specific groups. The latest version of the European Society of Cardiology on sport participation in patients with cardiovascular disease implemented guidelines tailoring recommendations based on disease and specific risk stratification.3 In addition to the individual risk profile, tailored exercise prescription should take into account the predominant component of sport disciplines and the intensity. An overall classification of sport disciplines related to the predominant component and intensity of exercise is provided by the current European guidelines on sports cardiology.3 The decision is driven by individual demand involving a shared decision-making. It is important to underline that results are limited to small cohorts and are not randomized (as reflected by the level of evidence in the guideline – Level C in most cases). This review focuses on studies exploring the effect of exercise on cardiomyopathies (hypertrophic, arrhythmogenic and dilated cardiomyopathy and left ventricle noncompaction) in terms of outcomes and disease progression.
Exercise and cardiomyopathies
Hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is among the leading causes of SCD in young athletes (≤35 years old).4 The circumstantial link between sport and SCD in patients with HCM has resulted in prohibitive exercise recommendations, leading to the exclusion of these individuals from any competitive or high-intensity physical activities and sports.1 In recent years, some studies reported that regular exercise improves left ventricular diastolic function,5,6 exercise tolerance and symptoms7 in patients with overt HCM and in genotype-positive phenotype-negative patients. The best dose of physical activity is still unknown, but some studies have been performed to solve this question. First, a single-centre study investigated the impact of supervised exercise sessions of 60 min twice a week at moderate intensity in 20 patients with symptomatic HCM and observed an improvement in functional capacity and New York Heart Association (NYHA) class from baseline at least 1 in 50% of patients.8 In the Randomised Exploratory Study of Exercise Training in HCM (RESET-HCM) study,9 136 patients with HCM were randomly assigned to 16 weeks of moderate-intensity exercise training (n = 67) or usual activity (n = 66). Patients underwent an unsupervised exercise programme individually prescribed based on heart rate reserve (HRR) derived from the baseline cardiopulmonary exercise testing (CPET). Participants were instructed to maintain a moderate level of intensity. The study revealed a significant benefit in peak VO2 improvement without a difference in the occurrence of major arrhythmic events or death. A recent Korean population study of 7666 HCM patients investigated the relationship between the self-reported amount of physical activity and all-cause and cardiovascular mortality.10 All-cause mortality was found to decrease in proportion to the amount of physical activity performed. Finally, mild-to-moderate aerobic physical activity, in combination with a Mediterranean diet, has been demonstrated to be effective in determining weight loss, improvement in functional capacity and echocardiographic parameters in a single-centre study of 20 obese symptomatic patients with HCM.11 In conclusion, the evidence seems to support the beneficial role of light-to-moderate aerobic exercise in improving the clinical status and exercise tolerance in patients with HCM (Table 1).
Table 1 - Summary of the studies investigating sport activity and cardiomyopathies
| Ref. |
Cardiomyopathy |
Type of study |
Study population |
Exercise programme |
Summary of findings |
| Hypertrophic cardiomyopathy |
| Klempfner et al.8 |
HCM |
Nonrandomized intervention design |
20 patients with symptomatic (NYHA class II-III) HCM (age 62 ± 13 years) |
Supervised exercise sessions of 60 min twice a week (comprising treadmill, arm ergometer and upright cycle exercise) at an HRR of 65–85%
All sessions began with 10 min of warm-up phase (HRR of 40–50%), followed by aerobic exercise and ending with an extended 15 min of cool-down
In addition, patients were advised to complement the training with community walk, at least twice a week at a moderate pace |
Patients completed an average of 41 ± 8 h of supervised aerobic exercise training
- 80% reported subjective improvement in clinical conditions
- 50% improved NYHA class from baseline ≥1
- Functional capacity, assessed by the change in maximally attained METs, improved by 46% from 4.7 ± 2.2 to 7.2 ± 2.8 METs |
| Sheikh et al.6 |
HCM |
Observational cohort study |
106 asymptomatic athletes with HCM (age 59.9 ± 9.9 years) and 101 sedentary HCM patients (age 67.1 ± 14.3 years) |
All athletes with HCM competed at regional, national or international level and 86 (81.1%) had performed at national or international level during their career |
Compared with sedentary patients, athletes with HCM:
- exhibited a lower mean MLVWT and larger LVEDD and LV end-diastolic volumes
- were more likely to exhibit apical LVH
- showed a smaller average E/E′ ratio |
| Saberi et al.9 |
HCM |
RCT (RESET-HCM) |
136 patients with HCM (age 50.4 ± 13.3 years) randomly assigned to 16 weeks of moderate intensity exercise training (n = 67) or usual activity (n = 66) |
Unsupervised exercise programme individually prescribed based on HRR derived from the baseline CPET. Exercise was initiated at a minimum of three sessions per week, 20 min per session, at a HR corresponding to 60% of HRR. Participants were instructed to maintain a moderate level of intensity
The exercise prescription was designed to increase duration of exercise by 5--10 min every week (up to 60 min per session), four to seven sessions per week, and then incrementally increase training intensity to a goal of 70% of HRR during the first month of the study protocol
Patients were instructed to maintain their exercise regimen through to Week 16 of the protocol
Modes of exercise including cycling, walk-jog protocols and elliptical training |
At 16 weeks, mean change in peak VO2 was +1.35 ml/kg/min among participants in the exercise group and +0.08 ml/kg/min among participants in the usual-activity group
- There were no significant differences between the two groups at 16 weeks in terms of changes in any measures of cardiac morphology and function, and quality of life
- There were no occurrences of major arrhythmic events or death in either group |
| Dejgaard et al.7 |
HCM and patients genotype + and phenotype – |
Cross-sectional |
66 Genotype + LVH – (age 38 ± 15 years) and 121 HCM individuals (age 55 ± 14 years) |
PA was assessed using a questionnaire including a detailed history of exercise from school age to time of the study or to age 60 years. PA was reported as type of activity/sport, each graded as light, moderate or vigorous and duration as hours per week, months per year and years
The intensity of the reported PA was quantified in METs, and exercise intensity ≥6 METs was defined as vigorous. Patients with a history of vigorous exercise for ≥4 h/week during ≥6 years were defined as athletes |
In both genotype + LVH − and in HCM, lifetime vigorous exercise correlated moderately with left ventricular end-diastolic volume
- Lifetime vigorous exercise correlated with left ventricular mass in genotype + LVH −, but not in HCM
- HCM athletes had better NYHA class compared with HCM nonathletes
- VAs occurred in 28 (23%) of the 121 HCM patients; there were no differences in lifetime vigorous exercise between athletes with and without VAs, and the proportion of athletes was similar |
| Pelliccia et al.16 |
HCM |
Observational retrospective cohort |
88 consecutive athletes with HCM (median age 31 years, IQR 19–44)
88% of athletes had a low risk (ESC score 2.2, IQR 1.7–3), 9% moderate risk and 3% high risk |
All athletes underwent a baseline evaluation and a new clinical evaluation at a mean of 7 ± 5 years
At the time of baseline evaluation, all athletes showed an active participation in regular exercise programmes [with a weekly schedule of 7 (IQR 6–14) hours for >10 consecutive months/year] and had participated in competitive events for 14 (IQR 2–19) years
Individuals were classified in athletes who substantially reduced or stopped exercise and sport (n = 61, HCM-detrained) and athletes who continued with regular training and sport competitions (n = 27, HCM-trained) |
During the follow-up, two major events occurred in the HCM-detrained group outside the context of exercise
- The incidence of new symptoms was similar in patients classified as HCM-trained versus HCM-detrained. Specifically, palpitations were reported by six (10%) of detrained versus one (4%) of trained
(P = 0.346); chest pain by two (3%) versus one (4%) (P = 0.809); dyspnoea by two (3%) versus zero (0%) (P = 0.462) and syncope by five (8%) versus four (15%) (P = 0.319) |
| Kwon et al.10 |
HCM |
Observational cohort study |
7666 patients with HCM (mean age 59.5 years) |
PA was estimated based on three questions regarding PA in the survey on health behaviours provided by the NHIS. To estimate the overall grade and the amount of PA in a quantitative manner, the PA score (PAS) was used
Study populations was categorized into tertiles of PAS. In addition, PAS were converted in metabolic equivalent of tasks (METs)
Group 1 (light PA) performed 1.4 ± 0.6 METs/day
Group 2 (intermediate PA) performed 3.4 ± 0.7 METs/day
Group 3 (vigorous PA) performed 8.4 ± 3.1 METs/day |
Over a mean follow-up of 5.3 ± 2.0 years, all-cause mortality progressively decreased from group 1 to group 3: 9.1% (4.7%), 8.9% (3.8%) and 6.4% (2.7%), respectively
- Compared with group 2, group 3 did not have an increased risk for all-cause mortality [HR 0.78 (95%CI 0.63–0.95)] and cardiovascular mortality [HR 0.75 (0.54–1.03)] |
| Limongelli et al.11 |
HCM |
Nonrandomized intervention design |
20 patients with HCM and obesity (BMI >30 kg/m2) |
Patients followed a 2-year aerobic exercise protocol combined with a Mediterranean diet protocol
In the first 6 months of the training protocol, it was recommended to accumulate at least 30 min of light PA 4–5 days per week
In the following 18 months, patients followed a moderate PA programme consisting in 60 min per day for three sessions per week |
25% showed a significant weight loss (responders; ≥10% of body weight)
- Responders showed a significant reduction in left atrial diameter and volume index, E/e’ average, pulmonary artery systolic pressure and increase in VO2 max and peak workload compared with nonresponders
- 30% improved NYHA class from baseline ≥1
Two of three patients being considered for myectomy showed significant improvement of clinical-haemodynamic status and did not require surgery |
| Andreassen et al.5 |
HCM and patients genotype + and phenotype − |
Cross-sectional |
66 Genotype + LVH – (age 38 ± 15 years) and 121 HCM individuals (age 55 ± 14 years) |
PA history was assessed using a questionnaire including a detailed history of exercise (type of activity, intensity, and duration) from school age (7 years old) to the age at inclusion/study echocardiogram
The intensity of the reported PA was quantified in METs, and the average amount of exercise over 6 METs per year during childhood and adolescence (between ages 7 and 20 years) was calculated for each participant |
Exercise training during childhood and adolescence was correlated with a favourable e’, E/e’, E deceleration time and end-diastolic volume, when adjusting for the effects of age at examination, and presence of LVH
- This correlation was evident both in patients with a HCM and in individuals with an HCM-causative genotype without LV hypertrophy (genotype + LVH–) |
| Pelliccia et al.18 |
HCM |
Observational retrospective cohort |
60 patients with HCM (age 31 ± 16 years)
92% men, 85% at low risk [European Society of Cardiology score<4%) |
Baseline and follow-up (7.0 ± 4.7 years) were available
At follow-up:
43 patients (72%) had completely or substantially reduced exercise programs (HCM-detrained)
17 (28%) had continued their usual training, including participation in competitions (HCM-trained) |
Two major events occurred in the HCM-detrained group
- No differences were observed in -LV cavity size and wall thickness, regardless of patients’ sport participation
- Left atrium increased in size mildly over time in both groups
- No changes in LV filling parameters occurred
- No regression of LV hypertrophy was observed in patients who retired from exercise training |
| Basu et al.17 |
HCM |
Retrospective study |
53 athletes diagnosed with HCM (39 ± 12 years, range 19–65 years), 98% men, 53%) competed. All had ‘low’ European Society of Cardiology 5-year SCD risk score for HCM [1.9% ± 0.9% (range 0.1--3.9%)] |
During a mean follow-up of 4.5 ± 3.1 years (range 1–14 years), all athletes continued to exercise at the same level. No athlete underwent a period of detraining |
All remained free of cardiac symptoms
No deaths, episodes of SVT or syncope
Four athletes exhibited new NSVT and 1 https://www.sciencedirect.com/science/article/pii/S0735109722065263?via%3Dihub - bib3underwent ICD implant because of an increase in the European Society of Cardiology risk score
One had
>30-s episode of AF
No change in the electrical, structural, or functional phenotype as evidenced by ECG, echocardiography and cardiopulmonary exercise testing |
| Arrhythmogenic cardiomyopathy |
| James et al.30 |
Gene mutation carriers of ACM-related genes
A total of 66% fulfilled the disease diagnostic criteria |
Observational, retrospective |
87 patients (53% men, mean age 44 ± 18 years, min 11, max 88 years) carrying a pathogenic desmosomal genetic variant associated with ACM
Of these, 56 were classified as endurance athletes |
The following exercise aspects were evaluated:
1) aerobic intensity, defined as participation in vigorous-intensity endurance (aerobic) athletics
2) duration, defined as annual hours of regular exercise
Endurance sports were activities with a high dynamic demand (>70% maximum O2) done for at least 50 h/year at vigorous intensity |
The 56 genetic carriers classified as endurance athletes:
1. Developed symptoms at a younger age
2. Had a lower lifetime event-free survival from VT/VF and from HF |
| Sawant et al.31 |
Patients diagnosed with ACM |
Observational, retrospective |
82 ACM patients (64% males, mean 43 ± 14 years, min 16 max, 76 years), fulfilling 2010 diagnostic criteria |
Endurance athletes: participants in sports with a high dynamic demand (>70% maximum O2), done for at least 50 h/year at vigorous intensity |
Top intensity exercise was associated with significantly younger age of onset, worse structural disease and shorter freedom from ventricular arrhythmias during follow-up |
| Saberniak J et al.37 |
Patients diagnosed with ACM and family members carrying genetic variants |
Observational, retrospective |
110 patients (68% men, mean age 42 ± 17 years)
Of these, 65 ACM were index patients and 45 mutation-positive family members |
Intensity of physical activity was graded as vigorous if ≥6 METs. Athlete definition: individual with a history of physical activity with intensity ≥6 METs for ≥4 h/week (≥1440 METs × min/week) for ≥6 years |
ACM patients with a history of athletic activity, compared with ACM nonathletes, had:
- reduced biventricular function
- worse outcome, with a higher
frequency and earlier onset of VAs
- need for cardiac transplantation |
| Ruwald et al.33 |
Patients diagnosed with ACM |
Observational, prospective |
108 ACM probands or family members (56% men) |
Exercise level performed by patients before and after diagnosis was divided into four groups (inactive, recreational, competitive, professional)
Sports activity was differentiated between high dynamic sports and low to moderately dynamic sports |
Competitive sports were associated with a two-fold increased risk of VT/death and earlier presentation of symptoms when compared with inactive patients and with patients who participated in recreational sport
Recreational sport was not associated with earlier onset of symptoms or increased risk of VT/death when compared with inactive group |
| Lie et al.32 |
Patients diagnosed with ACM |
Observational, retrospective |
173 ACM patients (56% men, mean age 41 ± 16 years) |
Patients were classified as regularly engaging in high-intensity exercise (>6 METs), low-intensity exercise (3--6 METs) and exercise duration was categorized as long if above median |
High-intensity exercise was a strong and independent marker of life-threatening VAs in ACM patients, independently of exercise duration |
| Ruiz Salas A et al.34 |
Patients diagnosed with ACM |
Observational, retrospective |
36 ACM patients (78% men, mean age 45 ± 18 years) |
Definition of high dynamic sports according to the guidelines on sports participation for patients with cardiovascular disease. Three groups of dynamic activity were considered: high/competitive (more than 3 h per week), moderate (1–3 h per week) and minimal/inactive (less than 1 hour per week) |
The first major arrhythmic event and occurrence of severe RV dysfunction were earlier in the high intensity exercise group, followed by the moderate intensity group and at a later age in the low intensity/inactive group |
| Müssigbrodt et al.35 |
Patients diagnosed with ACM |
Observational |
38 ACM patients (64% males, mean age 53 ± 14 years) with definite ACM and previous catheter ablation for VT |
Highly dynamic sports, defined according to the guidelines on sports participation for patients with cardiovascular disease, were distinguished from low to moderately dynamic sports |
Patients practising recreational exercise activities were not exposed to a greater risk for VT compared to patients with a sedentary lifestyle
Patients with a sedentary lifestyle or low to moderately dynamic sports activities had the same risk for VT recurrence as patients with highly dynamic sports activities |
| Paulin et al.36 |
Patients carrying TMEM43 p.S358L mutation and who had already received an ICD |
Observational |
80 patients (40% men) carrying TMEM43 p.S358L mutation |
The modified Paffenbarger Physical Activity Questionnaire was used. MET/h per day were calculated |
Exercise ≥9.0 MET-h/day (high level) in the year before ICD implantation was associated with an adjusted 9.1-fold increased hazard of first appropriate ICD discharge |
| Dilated cardiomyopathy |
| Webb-Peploe et al.43 |
DCM |
RCT |
12 patients, age 50 ± 8 years, left ventricular end-diastolic dimension was >6.5 cm and shortening fraction <25%. Stable at least 3 months before start |
5 days/week of a combination of callisthenics and bicycle ergometry, performed at home. Pts were asked to do exercises 1–9 (lasting 9 min) in the Canadian airforce XBX programme and 20 min a day on a bicycle ergometer at 50 rev/min increasing the resistance until their HR was between 70 and 80% of the maximum HR achieved on their initial maximal treadmill test |
Exercise training caused a significant decrease in left ventricular dimensions and an increased exercise capacity |
| Stolen et al.44 |
DCM |
RCT |
20 patients, age 55 ± 8 years, mean LVEF 34%, NYHA I-II, stable on medical therapy for at least 3 months |
Orientation period followed by three supervised exercise sessions/week for 5 months. Initial exercise intensity was 50% of peak VO2 –> increased during the 5-month period to 70% (45 min/session). Four weeks after the start resistance training was added |
No adverse events occurred; exercise training was associated with 27% improvement in peak VO2, stroke volume, EF and reduced the LV end-systolic diameter. QoL was significantly improved |
| Beer et al.45 |
DCM |
RCT |
24 patients, age 56 years, LVEF <40%, on maximal medical therapy |
Five supervised training sessions/week lasting 45 min for 2 months. Dynamic exercises were included, intensity was targeted to 60–80% of maximal VO2 |
The exercise group demonstrated a 17% increase in peak VO2, a reduction in ESV and an improvement in EF. No differences in RV size or function |
| Kemps et al.46 |
DCM |
Prospective study |
14 patients, age 62 ± 9 years, NYHA II-III, LVEF < 40% in SR |
12-week training programme: cycle interval, resistance and inspiratory muscle training (1hour sessions per week). All training sessions took place in the Department of Physical Therapy and commenced with cycling training on an ergometer with a warm-up phase of 5 min, followed by 15 min of interval training with work phases of 30 s and recovery phases of 60 s. The intensity of the work phases was set at 50% of the maximum short-term exercise capacity, which was assessed by a steep ramp test (increasing the work rate by 25 W every 10 s until exhaustion) every 4 weeks |
After training, peak VO2, VO2 at VT improved significantly, with a wide variety in training responses. Using multivariate regression analyses, posttraining changes in peak VO2 could be predicted by recovery halftime of peak VO2 (T1/2), peak VO2 (percentage of predicted), and peak respiratory exchange ratio |
| Holloway et al.49 |
DCM |
Prospective study |
15 patients, age 59 ± 2 years, LVEF 38 ± 3%, NYHA I-II-III, stable on medical therapy for at least 6 months |
8-week physical training programme – 10 min of supervised cycling at a workload corresponding to 70–80% of maximal HR → 20 min of cycling per day at home |
All patients remained stable, in SR, no symptoms. 13/15 patients showed an improvement in resting LVEF from 39 to 44% after 8 weeks of training; after training there was a 28% improvement in the Minnesota HF questionnaire (QoL score) |
| Mehani et al.47 |
DCM |
RCT |
40 patients, age 56 ± 4 years, LVEF < 45%, NYHA II-III, diastolic dysfunction grade I-II-III, stable on medical therapy for at least 3 months |
Training was applied in the form of circuit-interval aerobic training using treadmill (speed 4–5 m/h at the end of 7th month), cycle ergo meter and stair master. The training HR increased gradually from 55% of HR reserve to 80% at the end of 7th month |
10 patients (25%) did not complete the study period for worsening HF > all of them had grade III diastolic dysfunction; there was a high increase in peak VO2 and EF in the training group. After training 53% of patients showed a normal diastolic function (zero before training) |
| Left ventricular noncompaction |
| De la Chica et al.56 |
LVNC (suspected) |
Community-based study |
705 middle-aged individuals participants in the PESA (Progression of Early Subclinical Atherosclerosis) study (mean age 48 ± 4 years) |
At each visit, participants were provided with a waist-secured ActiTrainer activity monitor (ActiGraph, Pensacola, Florida) to provide an objective measure of the intensity of PA over 7 consecutive days (24 h 7 days). VPA was recorded as total minutes per week. The study population was divided into six groups: no VPA and five sex-specific quintiles of VPA rate (Q1 to Q5) |
LVNC phenotype prevalence according to the Petersen criterion was significantly higher among participants in the highest VPA quintile (Q5 30.5%) than in participants with no VPA (14.2%)
VPA was associated with a higher prevalence of CMR-detected LVNC phenotype according to diverse established criteria. The association between VPA and LVNC phenotype was independent of LV volumes. According to these data, vigorous recreational PA should be considered as a possible but not uncommon determinant of LV hypertrabeculation in asymptomatic individuals |
| Woodbridge et al.60 |
LVNC (suspected) |
Cross-sectional observational study |
1030 individuals from the community-based UK Biobank study (male/female ratio: 0.84, mean age: 61 years) |
Physical activity (PA) was measured viatotal metabolic equivalent of task (Met) min/week and 7-day average acceleration, and trabeculation extent via maximal noncompaction/compaction ratio (nc/c) in long-axis images of cardiovascular magnetic resonance studies |
In a community-based general population cohort, there was no relationship at, or between, extremes, between PA and nc/c, suggesting that at typical general population PA levels, trabeculation extent is not influenced by PA changes |
| D'Silva et al.59 |
LVNC (suspected) |
Observational study |
68 novice marathon runners aged 29.5 ± 3.2 years had indices of LV trabeculation measured by echocardiography and cardiac magnetic resonance imaging 6 months before and 2 weeks after the 2016 London Marathon race, in a prospective longitudinal study |
Individuals were encouraged to follow a beginner's training plan, consisting of approximately three runs per week, increasing in difficulty over a 17-week period leading up to the London Marathon race |
After 17 weeks of unsupervised marathon training, indices of LV trabeculation were essentially unchanged. Despite satisfactory interobserver agreement in most methods of trabeculation measurement, criteria defining abnormally hypertrabeculated cases were discordant with each other. LV hypertrabeculation was a frequent finding in young, healthy individuals with no individual demonstrating clear evidence of a cardiomyopathy. Training for a first marathon does not induce LV trabeculation. It remains unclear whether prolonged, high-dose exercise can create de novo trabeculation or expose concealed trabeculation. Applying cut-off values from published LV noncompaction cardiomyopathy criteria to young, healthy individuals risks over-diagnosis |
ACM, arrhythmogenic cardiomyopathy; BMI, body mass index; CMR, cardiac magnetic resonance; CPET, cardiopulmonary exercise testing; DCM dilated cardiomyopathy; ESV, end-systolic volume; HCM, hypertrophic cardiomyopathy; HF, heart failure; HR, heart rate; HRR, heart rate reserve; ICD, implantable cardioverter defibrillator; IQR interquartile range; LV, left ventricular; LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction; LVH, left ventricular hypertrophy; LVNC, left ventricular noncompaction; METs, metabolic equivalent of tasks; MLVWT, maximal left ventricular wall thickness; NC/C Ratio, noncompaction/compaction ratio; NHIS, National Health Insurance Service; NYHA, New York Heart Association; PA, physical activity; QoL, quality of life; RCL, residual compacted layer; RCT, randomized controlled trial; SCA/D, sudden cardiac arrest and death; VAs, ventricular arrhythmias; VF, ventricular fibrillation; VO2, oxygen uptake; VPA vigorous physical activity; VT, ventricular tachycardia.
Despite this emerging evidence, patients with HCM tend to be less active compared with the general population mainly due to physician or self-imposed restrictions.12 This trend can be observed not only in patients with severe HCM phenotype but also in young patients with no symptoms and mild disease. Indeed, physicians are often reluctant to prescribe physical activity due to the fear of exercise-induced ventricular arrhythmias, the paucity of data and the lack of confidence with this topic. As a result, the long-term physical inactivity and weight gain are responsible for an increased risk for cardiovascular and noncardiovascular morbidity and mortality in HCM patients.13
Thus, physical exercise should be prescribed in all patients with HCM and individualized taking into account clinical characteristics, disease stage, individual response to exercise and previous training experience.14 Patients with HCM are more likely to benefit from regular aerobic exercise, and precise indication regarding the frequency, duration and intensity of exercise should be provided.15
In contrast, data on eligibility in competitive or high-intensity sports, even in patients with mild disease and low risk for SCD, are insufficient to provide a well tolerated recommendation, as studies are not randomized, limited to a small number of individuals and with low risk. An Italian study described the outcome of a cohort of 88 athletes with HCM and a low-risk profile.16 Among them, 27 patients continued to engage in competitive sports despite medical advice and, during a median follow-up of 7 years, did not experience adverse events. In addition, no differences in the prevalence of new symptoms or nonsustained ventricular tachycardia were found compared with athletes who reduced or stopped exercise and sport. More recently, another study reached the same conclusion in a group of 53 low-risk HCM athletes.17 All athletes continued to exercise at the same level (professional) for a mean follow-up of 4.5 ± 3.1 years (range 1–14 years). All remained free of cardiac symptoms: no deaths, sustained ventricular tachycardia or syncope episodes. Four athletes exhibited new nonsustained ventricular tachycardia, and one underwent an implanted cardioverter defibrillator (ICD). There was no change in the electrical, structural or functional phenotype as evidenced by ECG, echocardiography and CPET. The group of Pelliccia et al.18 also described no changes over time in those patients with HCM who did not refrain from sports participation. No changes in left ventricular cavity size, wall thickness and left ventricular filling were observed in those who continued to engage in sport participation. The left atrium increased in size mildly over time in both groups. Left ventricular regression was not observed in both groups.18 The recently published European Society of Cardiology (ESC) guidelines in sports cardiology considered light-to-moderate recreational exercise in all patients with HCM and provided tailored recommendations for high-intensity and competitive sports according to the individual risk profile of athletes.3 A comprehensive approach should be performed in any individual with HCM who requests exercise advice. The baseline evaluation should focus on the personal and family history (with a particular emphasis on the presence of a history of SCD), assessment of the severity of the HCM phenotype and presence of risk factors for SCD. According to this baseline evaluation, patients with HCM can be classified as having a low-risk or high-risk profile. Patients could be considered at low risk when asymptomatic and without any markers of increased risk: family history for SCD; exercise-induced ventricular tachycardia; left ventricular outflow tract obstruction; abnormal pressure response to exercise; ESC risk score more than 4% at 5 years. Other known markers of increased risk are severe LVH, left ventricular apical aneurysms, left ventricular ejection fraction below 50% and late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR). Thus, an asymptomatic individual with good functional capacity and a low-risk profile may engage in high-intensity and competitive sports, except those disciplines wherein the occurrence of syncope may harm others or cause a traumatic fatality. A shared decision-making approach is recommended when advising an individual with HCM wishing to participate in sport. The discussion should also underline the knowledge gaps in risk stratification and the unpredictability of SCD in athletes. On the contrary, patients with symptoms or high-risk profiles should avoid high-intensity physical exercise and competitive sports, limiting themselves to light-to-moderate aerobic exercise after a comprehensive evaluation in an experienced centre (Fig. 1).
;)
Fig. 1:
Schematic representation of sport participation recommendation in hypertrophic cardiomyopathies. CMR, cardiac magnetic resonance; ESC, European Society of Cardiology; HR, heart rate; LGE, late gadolinium enhancement; LVEF, left ventricular ejection fraction; LVH, left ventricular hypertrophy; LVOTO, left ventricular outflow tract obstruction; SCD, sudden cardiac death.
Arrhythmogenic cardiomyopathy
Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac disease clinically characterized by ventricular morpho-functional abnormalities and the presence of ventricular arrhythmias that can even lead to SCD.19,20 The ACM prevalence is difficult to estimate due to the frequent misdiagnoses, but it reasonably ranges from 1 : 1000 to 1 : 5000.19–21 The pathologic basis consists of myocyte necrosis followed by fibro-fatty tissue replacement.20 Even though in the first descriptions, the disease was characterized by an exclusive or at least predominant right ventricular involvement, in the following years, CMR studies demonstrated that left ventricular is frequently involved.22 Furthermore, a phenotypic variant with a predominant left ventricular involvement and minor or no right ventricular abnormalities, also known as ‘arrhythmogenic left ventricular cardiomyopathy (ALVC)’, has recently been described.23 Since the first descriptions, an inheritable disease pattern in ACM with familial recurrence has been demonstrated.19,20 Genetic studies found that approximately 30–50% of ACM patients carry a pathogenic mutation in a desmosomal gene, although genetic variants in nondesmosomal genes have also been identified.24 Sports activity has been proven to constitute an arrhythmic trigger in ACM.19,25–28 In 1988, Thiene et al.20 described a series of 60 young SCD victims (>35 years) and found that among the 12 patients with ACM diagnosis at autopsy, 10 had died during exertion. The disease was later recognized as one of the leading causes of SCD in athletes of the Veneto region of Italy (14% of cases), and athletes with ACM were found to have a 5.4 times higher risk of dying suddenly than their sedentary counterparts.29 Furthermore, intense exercise has been recognized as a modulating factor promoting phenotypic penetrance and disease progression in animal studies and carriers of ACM gene variants.30–37 Systematic preparticipation screening for sports activity reduces the risk of SCD associated with ‘classic’ ACM variants (right dominant or biventricular) due to its capability to identify asymptomatic patients by abnormal ECG or ventricular arrhythmias.38 For this reason, the incidence of SCD from ‘classic’ ACM has decreased in the last few years. At the same time, at the moment, the ALVC phenotype constitutes an increasingly reported substrate of SCD due to the frequent diagnostic problems in these forms.23 On the contrary, there is no evidence that low-to-moderate intensity exercise may be detrimental in patients with ACM or genetic positive/phenotypic negative family members. Thus, recent recommendations suggest not depriving these individuals entirely of the many benefits of physical activity.25 In conclusion, in recent years, several studies have provided convincing evidence that exercise constitutes an important modulating factor in ACM that may favour disease penetrance in positive genetic carriers, worsen ventricular dysfunction and trigger ventricular arrhythmias. Thus, there is a unanimous consensus that ACM patients should be advised against participation in competitive sports and high-intensity leisure-time physical activity. On the contrary, ACM patients, particularly young individuals with mild disease, should not be deprived of the many health benefits of low-to-moderate intensity personalized leisure activity prescribed by experienced physicians.
Dilated cardiomyopathy
Dilated cardiomyopathy (DCM) describes a condition characterized by left ventricular or biventricular dilatation accompanied by systolic dysfunction not caused by abnormal loading conditions or coronary artery disease and may recognize a genetic or nongenetic substrate, such as in the case of inflammatory, toxic or peripartum DCM.39 The prevalence of nonischemic DCM varies according to geographical and ethnical factors and, despite being underestimated, ranges between 7 and 14/100 000.40 Although 12-lead ECG is usually abnormal and, in some circumstances, may also suggest specific genotypes, echocardiography is crucial for initial diagnosis and follow-up. CMR has gained a pivotal role in the structural and functional evaluation of DCMs, thanks to its capability to describe tissue characteristics, including fibrosis. Indeed, in a proportion of cases, DCM shows mid-wall fibrosis carrying prognostic information.41 CPET represents a precious tool to assess functional capacity in DCM and may both suggest physical activity capability and guide treatments. Exercise echocardiography can be helpful to discriminate between an athlete's heart and DCM by detecting the contractile reserve.42 The DCM clinical trajectory is mainly driven by the development of heart failure, but arrhythmic events may change the disease course or lead to SCD. The role of physical activities in this setting is only partially understood, given the absence of adequate prospective studies. If, on the one hand, adrenergic activation may promote arrhythmias, it appears that regular exercise may be beneficial. Webb-Peploe et al.43 performed a crossover study on 24 ischemic and nonischemic DCM in a home-based exercise programme showing how only among nonischemic DCM did training increase peak oxygen consumption (pVO2) and improve symptoms and exercise time, while decreased left ventricular dimensions came at the cost of a higher incidence of exercise-induced ventricular arrhythmias. The group of Stolen44 randomized 20 stable DCM patients to training (three supervised exercise sessions/week for 5 months, initial exercise intensity 50% pVO2 up to 70% pVO2) demonstrating how trained DCM improved pVO2, stroke volume, ejection fraction and quality of life with no adverse events during follow-up. Several other small studies confirmed the results of the aforementioned trials.45,46 More recently, Mehani47 showed how aerobic training (starting from 55% of HRR to achieve 80% for a period of 7 months) enhances the quality of life, particularly by improving diastolic function, but patients with a grade III diastolic dysfunction bore a higher risk of developing worsening heart failure. Less is known about the effect of training on patients with genotype-positive but phenotype-negative DCM. On the basis of these data, the Italian and the European Society of Cardiology have proposed recommendations for athletes with DCM, mostly based on expert consensus (level of evidence C).2,48 Neither leisure activities nor competitive sports should be discouraged in people with left ventricular dilatation but preserved left ventricular function in the absence of a family history of DCM, abnormal ECG patterns or history of tachyarrhythmias. In the case of certain DCM, there might be two scenarios: asymptomatic athletes with LVEF at least 45% and no history of unexplained syncope or any documentation of ventricular tachyarrhythmias on ECG-monitoring or CPET may compete in sports whether they have no family history of SCD; competitive sports should be avoided if LVEF is less than 45% and in case of symptomatic patients, extensive fibrosis on CMR, documented ventricular tachyarrhythmias, history of unexplained syncope or ascertained presence of high-risk mutations (e.g. Lamin A/C or Filamin C mutation). These patients should be limited to leisure-time activities and undergo periodical follow-up (Figure 2). Leisure-time activities in confirmed DCM should be individualized. Aerobic training and dynamic exercises should be preferred, 1–5 days per week. On the basis of the few data available, initial exercise intensity should be limited to 50% of pVO2 at basal CPET, with a progressive increase of up to 70%.44 The training HR should increase gradually from 55 to 80% of the HR reserve.47,49
Fig. 2:
Schematic representation on sport participation recommendation in dilated cardiomyopathy. CMR, cardiac magnetic resonance; CPET, cardiopulmonary exercise test; HR, heart rate; LGE, late gadolinium enhancement; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; pVO2, peak oxygen consumption.
Left ventricular noncompaction
Left ventricular noncompaction (LVNC) is a rare cardiomyopathy characterized by a thin epicardial layer and an extended noncompact endocardial portion with prominent trabeculae and deep recesses. Its prevalence ranges from 0.014 to 1.3%.50,51 The prognosis of the LVNC is related to the potential development of heart failure, ventricular arrhythmias and thromboembolism. Cardiac structural abnormalities such as those of LVNC were described in other cohorts, including pregnant women and athletes (up to 8%), suggesting that increased trabeculation represents an epiphenomenon in such patients.52–54 In a study of 1146 healthy athletes, trabeculations were found in 18.3% with 8.1% fulfilling traditional criteria for LVNC, suggesting that further assessment of such athletes should be confined only to the small minority who demonstrate low indices of systolic function and marked ECG repolarisation changes.55 Another study on 2501 highly trained athletes found that 1.4% had a marked left ventricular trabecular pattern. However, only a small group of these athletes (0.1%) showed familial, clinical or morphological changes supporting the diagnosis of LVNC.54 It is hypothesized that an increased cardiac preload may unmask left ventricular trabecular morphology. In this case, the LVNC would represent the epiphenomenon of a physiological process. Although it is essential to identify carriers of the disease who have an increased risk of cardiac events early on, it is equally important to avoid an incorrect diagnosis of an LVNC, which would lead to exclusion from competitive activity, with economic and psychological repercussions.54 This hypothesis is supported by a study reporting higher LVNC phenotype prevalence among participants with the highest vigorous recreational physical activity.56,57 Although several studies report the effect of physical activity on trabeculation expression, the data on the effect of sport on LVNC disease progression and outcome are lacking and limited to single cases.58–60 European Guidelines emphasize that no adverse events are reported in the absence of left ventricular dysfunction and that the clinical outcome is also guided by atrial/ventricular arrhythmias and thromboembolic events. Consequently, the European Society of Cardiology recommends that no restrictions on physical activity be placed on athletes with incidental discovery of left ventricular hyperbeculation in the absence of symptoms, family history of LVNC or cardiomyopathies, ECG abnormalities, frequent and/or complex ventricular arrhythmias and left ventricular systolic and diastolic dysfunction.3 Participation in high-intensity exercise and all competitive sports may be considered in asymptomatic individuals with LVNC, preserved systolic function and absence of frequent and/or complex ventricle arrhythmias (Fig. 3).3
Fig. 3:
Schematic representation of sport participation recommendation in left ventricle noncompaction. LVEF, left ventricular ejection fraction; LVNC, left ventricular noncompaction; Vas, ventricular arrhythmias; VT, ventricular tachycardia.
Variants classified as of uncertain significance
Nowadays, the increasing use of genetic testing through next-generation sequencing (NGS) has given a better insight into the pathogenesis of cardiomyopathies (CMPs). However, the massive use of genetic testing leads also to the identification of results of uncertain significance, whose clinical relevance is unknown and may create confusion in patients and clinicians with a possible negative impact on sports participation. According to the Standards and Guidelines of the American College of Medical Genetics and Genomics (ACMG), a variant is defined as a permanent change in nucleotide sequence.61 Most inherited heart diseases are associated with sequence variants, which can alter the structure or function of a protein encoded by a gene. Less frequently, copy number variation (CNVs), consisting of loss or additional copies of genetic material, may be associated with inherited heart disease.62 CMPs are considered monogenic disorders with dominant inheritance, even if some patients with inherited cardiomyopathy may have more than one disease-causing variant, which may act as a modifier of phenotype along with causative ones.63–67 Not all variants identified through genetic testing have clinical relevance. In fact, according to current ACMG guidelines, variants can be distinguished based on a five-tier classification system into benign (I), likely benign (II), of uncertain significance (III), likely pathogenic (IV) and pathogenic (V).61 Variants belonging to the first two classes, that are benign (B) and likely benign variants, are considered not causative or likely not causative of disease, and their identification at genetic testing does not assume clinical relevance. Pathogenic (P) and likely pathogenic variants are considered, respectively, causative or with a high likelihood to be causative of disease according to available data. Identifying likely pathogenic or P variants in genes related to the primary indications can confirm clinical diagnosis and should lead to a cascade of genetic testing in available first-degree relatives or other symptomatic relatives to offer the best clinical management.68 Variants classified as of uncertain significance, also referred to as VoUS, fall in a grey zone, as there are no sufficient data to estimate the likelihood of the variant to be pathogenic or benign and molecular consequences and thus to evaluate clinical relevance. To reduce the identification of VoUS the indiscriminate use of genetic testing, such as multigene panel testing, including genes with poorly established associations with the disease, should be avoided.69,70 A clinical diagnosis of CMP and/or strong familiarity with CMPs or SCD in absence of other causes, which can explain myocardial alteration, is the leading indication to perform genetic testing. It is recommended to try to reclassify VoUS as likely benign or likely pathogenic through segregation analysis of family members and/or experimental studies to evaluate molecular consequences of the variant identified.61,70,71 Of note, segregation analysis should not only when it is plausible lead to a reassessment of the variant identified in the proband. A proactive dialogue between genetics clinical laboratories and clinical specialists may help the process of variant reclassification.70 When it is not possible due to insufficient or inconclusive data, it is still strongly suggested to periodically reassess VoUS classification based on new scientific evidence.61 It is important to underline that the identification of a VoUS such as the finding of a B or likely benign variants does not exclude a clinical diagnosis. When available, further larger genetic testing may be considered in the presence of strong clinical suspicion of inherited cardiac disease. Therefore, the finding of VoUS in genes related to the primary indication does not affect sports activity and carriers of VoUS should undergo clinical management according to their diagnosis similarly to those resulting as negative to genetic testing.
Limitations
First, the present review is narrative; thus, the literature research was not structured as for a systematic one. Despite this, we showed a great number of studies summarizing evidence from literature and limits of the management of physical exercise in patients with cardiomyopathies. Second, we did not include studies on paediatric populations due to the existence of poor data, on small cohorts of children that gave contrasting results showing how, in the absence of specific guidelines, physical activity prescription in children is driven by the physician's background and experience.72 Lastly, providing specific and standardized indications is challenging due to the existence of national protocols that could be more stringent in comparison with the international recommendations. Future research with a focus on larger cohorts and including longer follow-up periods is needed to ensure the safety of physical activity in patients with cardiomyopathies.
Conclusion
Over recent decades, an accumulating proportion of studies have reported that low and moderate exercise does not accelerate disease progression in patients with inherited cardiomyopathies and does not affect the outcome, except for ACM. Data are still limited to small cohorts and patients with low-risk profiles. Considering the detrimental effect of a sedentary lifestyle, the recommendation for exercise in patients with cardiomyopathies has been implemented. The most important aspect to recognize is the wide spectrum of cardiomyopathy phenotypes with the different risk profiles and the important role of genetic profiles. As a consequence, exercise prescriptions should be tailored on individual bases in centres with specific expertise. Future research could explore this aspect, expanding the limited experience of dedicated gyms/sport centres where patients with chronic diseases can perform supervised and tailored physical activity.73 Moreover, there is the need for studies with larger cohorts and longer follow-up to ensure the safety of practising sport in patients with cardiomyopathies and contrast the risks related to a sedentary lifestyle.
Acknowledgements
Conflicts of interest
There are no conflicts of interest.
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