ABC | Volume 114, Nº5, May 2020

Arq Bras Cardiol. 2020; 114(5):943-987 Guidelines Brazilian Cardiovascular Rehabilitation Guideline – 2020 heart disease in the general population, caused by a range of mutations in genes which encode the cardiac sarcomere proteins. 268 HCM has a characteristically heterogeneous clinical expression, with unique pathophysiological changes and a variable natural history. Up to 10% of cases are caused by other genetic disorders, including hereditary metabolic and neuromuscular disorders, chromosomal abnormalities, and genetic syndromes. 272 Some patients have other disorders that can mimic HCM, such as amyloidosis. 273 The population-wide prevalence is estimated at around 0.2% or 1 in 500. 268 However, this estimate appears to differ in clinical practice, which allows us to infer that a portion of the affected individuals are asymptomatic. Various patterns of asymmetric hypertrophy of the left ventricle are commonly seen in HCM, and there may be different phenotypes in first‑degree relatives. Typically, one or more regions of the left ventricle exhibit increased wall thickness when compared to others; transitions and variations in thickness may occur in adjacent or noncontiguous areas. However, although asymmetric septal hypertrophy is the most common finding, there is no “classic” HCM pattern, and virtually all possible patterns of left ventricular hypertrophy can occur. Hypertrophy may even be absent in genetically affected individuals, in what is known as a negative phenotype. Several multicenter retrospective and observational cohort studies, conducted in different populations, have elucidated the natural history and clinical course of HCM. Recent studies have reported an annual mortality of around 1%, much lower than in older surveys. 274 Notably, only a small subgroup of patients with HCM experience significant complications and premature death; these complications can occur due to obstruction of the left ventricular outflow tract, HF with diastolic and/or systolic dysfunction and sudden cardiac death (SCD), or cardiac arrhythmias (atrial fibrillation and ventricular tachycardia or fibrillation). 275 In HCM, SCD can occur at any age, although it is most common in adolescents and young adults; therefore, identification of individuals at the highest risk is an essential component of the pre-exercise evaluation, especially in patients who may want to engage in competitive sports. 276 In many cases, SCD can be the first manifestation of the disease; indeed, it occurs most commonly in those without warning symptoms and who had not been diagnosed prior to the event. Nevertheless, most patients with HCM have a normal or near-normal life expectancy, with mortality usually attributable to other causes, some even of non‑cardiovascular etiology. 277-279 Therefore, encouraging a healthy lifestyle for HCM patients is essential to reducing the overall risk of morbidity. 6.6.1.1. Therapeutic Benefits of Physical Exercise In the general population, cardiorespiratory fitness is a determinant of the risk of cardiovascular and all-cause mortality. 19 In patients with obstructive and minimally symptomatic HCM, an association of mortality with aerobic fitness has also been observed. 280,281 Patients with a VO 2 peak below 18 ml.kg -1 .min -1 on CPET had higher mortality and were more symptomatic compared to those who achieved values equal to or greater than this threshold. A VO 2 peak below 60% of predicted was associated with worse 4-year survival (as low as 60%). 280 Myocardial fibrosis and myofibrillar derangement may underlie the increased risk of SCD in HCM, as these structural changes act as a substrate for fatal arrhythmias. 271 Evidence does suggest that high-intensity physical training could accelerate these changes, but this is still a controversial topic. However, it is well established that the increase in myocardial fibrosis is associated with a lower VO 2 peak in this population. 282 Therefore, assessing aerobic fitness – preferably through CPET – is essential in patients with HCM. 281 When there is a reduction in VO 2 peak, physical exercise can help increase functional capacity. To date, only one randomized controlled trial has examined the effect of physical training on patients with HCM (RESET‑HCM). This study, which included 136 patients, demonstrated an increase in VO 2 peak after 16 weeks of a moderate-training intervention (+1.35 ml.kg -1 .min -1 or < 0.5 MET). 266 Another prospective, non-randomized study included 20 patients with HCM and found a significant increase in treadmill test duration, as well as in estimated functional capacity (+2.5 MET). 267 In this study, patients completed a CVR programwhich consisted of 60-minute sessions of moderate to vigorous exercise, performed on a treadmill or cycle ergometer, twice a week. The intensity of exercise progressed from 50 to 85% of HR reserve, which resulted in a gradual increase in conditioning and may have minimized the risk of adverse events, such as exercise-induced arrhythmias. Serious adverse events, such as death, aborted SCD, implantable cardioverter- defibrillator (ICD) activation, or sustained ventricular tachycardia, did not occur in any of these studies. 266,267 Table 8 – Indications for physical exercise in cardiomyopathy Indication Recommendation Level of evidence Moderate aerobic exercise is recommended for selected patients with HCM 266,267 IIa B Vigorous or competitive physical exercise in patients with HCM 268,269 III C Moderate aerobic exercise for selected patients 3 to 6 months after acute myocarditis IIb C Light to moderate aerobic exercise for selected patients with ARVC 270 IIb B Vigorous or competitive physical exercise in patients with ARVC 268,269 III C HCM: hypertrophic cardiomyopathy; ARVC: arrhythmogenic right ventricular cardiomyopathy. 965