Facts and Gaps in Exercise Influence on Arrhythmogenic Cardiomyopathy: New Insights From a Meta-Analysis Approach

Abstract

Arrhythmogenic cardiomyopathy (ACM) is a genetic cardiac condition characterized by fibrofatty myocardial replacement, either at the right ventricle, at the left ventricle, or with biventricular involvement. Ventricular arrhythmias and heart failure represent its main clinical features. Exercise benefits on mental and physical health are worldwide recognized. However, patients with ACM appear to be an exception. A thorough review of the literature was performed in PubMed searching for original papers with the terms “ARVC AND sports/exercise” and “sudden cardiac death AND sports/exercise.” Additional papers were then identified through other sources and incorporated to the list. All of them had to be based on animal models or clinical series. Information was structured in a regular format, although some data were not available in some papers. A total of 34 papers were selected and processed regarding sports-related sudden cardiac death, pre-clinical models of ACM and sport, and clinical series of ACM patients engaged in sports activities. Eligible papers were identified to obtain pooled data in order to build representative figures showing the global incidence of the most important causes of sudden cardiac death in sports and the global estimates of life-threatening arrhythmic events in ACM patients engaged in sports. Tables and figures illustrate their major characteristics. The scarce points of controversy were discussed in the text. Fundamental concepts were summarized in three main issues: sports may accelerate ACM phenotype with either structural and/or arrhythmic features, restriction may soften the progression, and these rules also apply to phenotype-negative mutation carriers. Additionally, remaining gaps in the current knowledge were also highlighted, namely, the applicability of those fundamental concepts to non-classical ACM phenotypes since left dominant ACM or non-plakophillin-2 genotypes were absent or very poorly represented in the available studies. Hopefully, future research endeavors will provide solid evidence about the safest exercise dose for each patient from a personalized medicine perspective, taking into account a big batch of genetic, epigenetic, and epidemiological variables, for instance, in order to assist clinicians to provide a final tailored recommendation.

Lifestyle physical activity intensity and rapid-rate non-sustained ventricular tachycardia in arrhythmogenic cardiomyopathy

“…This provides the anatomical substrate for ventricular tachycardias and ventricular fibrillation, as well as increased risk for sudden cardiac death [2]. The underlying genetic etiology is expanding with the identification of non-desmosomal targets such as intermediate filaments, ion channels and nuclear envelope proteins, although evidence on these variants is still emerging [1,3]. The presence of rapid-rate non-sustained ventricular tachycardia (RR-NSVT) predicts appropriate future implantable cardioverter-defibrillator (ICD) shocks, interpreted as a surrogate marker for sudden cardiac death [4].…”

“…2 The underlying genetic etiology is expanding with the identification of non-desmosomal targets such as intermediate filaments, ion channels and nuclear envelope proteins, although evidence on these variants is still emerging. 1,3 The presence of rapid-rate non-sustained ventricular tachycardia (RR-NSVT) predicts appropriate future implantable cardioverter-defibrillator (ICD) shocks, interpreted as a surrogate marker for sudden cardiac death. 4 Thus, RR-NSVT has been classified as an important risk factor for sudden cardiac death in AC patients.…”

Electrocardiographic phenotype of exercise-induced arrhythmogenic cardiomyopathy: A retrospective observational study

“…Exercise exposure is known to be associated with a higher prevalence of an ACM-phenotype and VA in genotype positive family members of Gen-ACM probands ( 34 ) and clinical detraining was associated with a decrease in PVC burden in athletes with an ACM phenotype (whether Gen or ExI) ( 35 ). Continuation of exercise during the period between diagnosis and exercise testing therefore may worsen the clinical presentation, where refraining from exercise might result in a milder phenotype ( 36 ). Contrary to these findings, Costa et al ( 33 ) recently demonstrated that where non-adherence to the sports advice did associate with a decrease in physical capacity over time, there was no significant effect on VA or functional parameters.…”

Endurance Training Provokes Arrhythmogenic Right Ventricular Cardiomyopathy Phenotype in Heterozygous Desmoglein-2 Mutants: Alleviation by Preload Reduction

“…The prevalence of ARVC is estimated at 1:5000-1:1000. Notably, ARVC is a common cause of sudden death in young people, with some regional variability [10][11][12][13]. Disease diagnosis or manifestation is most common in the second to fifth decade of life, but children can also be affected by the disease [14][15][16].…”