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Exercise-induced arrhythmogenic right ventricular cardiomyopathy: A clinical syndrome in motion

Open AccessPublished:July 07, 2022DOI:https://doi.org/10.1016/j.hrcr.2022.07.001

      Keywords

      Exercise-induced arrhythmogenic right ventricular cardiomyopathy (ARVC), a theoretical disease entity, has an unusual history. Lacking a diagnostic gold standard, it is a diagnosis of exclusion built upon a foundation of research compiled for ARVC.
      In 2003, the first suspicion that exercise per se could cause a syndrome fulfilling 1994 ARVC criteria was described by Heidbüchel and colleagues in Belgium and the Netherlands.
      • Heidbüchel H.
      • Hoogsteen J.
      • Fagard R.
      • et al.
      High prevalence of right ventricular involvement in endurance athletes with ventricular arrhythmias: role of an electrophysiologic study in risk stratification.
      ,
      • McKenna W.J.
      • Thiene G.
      • Nava A.
      Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy.
      In a case series of “46 high-level endurance athletes, predominantly cyclists, with complex ventricular arrhythmias,” 27 (59%) met definite ARVC criteria while another 14 (30%) met some lesser criteria.
      • Heidbüchel H.
      • Hoogsteen J.
      • Fagard R.
      • et al.
      High prevalence of right ventricular involvement in endurance athletes with ventricular arrhythmias: role of an electrophysiologic study in risk stratification.
      Genetic testing was not performed and only 1 subject had a family history of ventricular arrhythmias. The importance of risk stratification was highlighted by 9 patients who died suddenly, none of whom had an implantable cardioverter-defibrillator (ICD), over a median follow-up of 2 years. Of these, 8 (89%) died during light or moderate physical activity.
      In 2021, Lie and colleagues from the “Oslo group” in Norway described 43 subjects with a history of competitive athletics for >6 consecutive years and who fulfilled 2010 ARVC criteria.
      • Lie Ø.H.
      • Klaboe L.G.
      • Dejgaard L.A.
      • et al.
      Cardiac phenotypes and markers of adverse outcome in elite athletes with ventricular arrhythmias.
      ,
      • Marcus F.I.
      • McKenna W.J.
      • Sherrill D.
      • et al.
      Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the Task Force criteria.
      Exercise-induced arrhythmogenic cardiomyopathy was considered, given absence of family history and absence of relevant genetic mutations. In multivariable logistic regression analysis, only left ventricular (LV) mechanical dispersion was a statistically significant predictor for life-threatening arrhythmic events. In light of this finding, La Gerche suggested, “perhaps it is time that the term exercise-induced ARVC is updated to exercise-induced arrhythmogenic cardiomyopathy to better reflect its various clinical expressions.”
      • La Gerche A.
      Exercise-induced arrhythmogenic (right ventricular) cardiomyopathy is real… if you consider it.
      In this issue of Heart Rhythm Case Reports, Darden and colleagues
      • Darden D.
      • Scheinman M.M.
      • Hoffmayer K.S.
      Exercise-induced arrhythmogenic right ventricular cardiomyopathy: reverse remodeling with detraining.
      report a 25-year-old man with a history of endurance exercise participation and frequent premature ventricular complexes (PVCs) who met definite diagnosis for ARVC by satisfying 1 major and 2 minor 2010 modified Task Force criteria. His primary exercise exposure was training for and participation in marathons and ultramarathons over a decade. As he was negative for significant family history and genetic screening, he was diagnosed with exercise-induced ARVC in a fashion similar to the Oslo group.
      • Lie Ø.H.
      • Klaboe L.G.
      • Dejgaard L.A.
      • et al.
      Cardiac phenotypes and markers of adverse outcome in elite athletes with ventricular arrhythmias.
      This case report has several notable features. First, it illustrates the dynamic nature of exercise-induced ARVC. Second, it suggests the role of electroanatomic voltage mapping should be revisited in the high-density mapping era. Third, it suggests that a waiting period with detraining may be useful prior to primary-prophylaxis ICD consideration. Fourth, LV involvement supports moving away from the term “exercise-induced ARVC.”
      On baseline evaluation, features satisfying the major criterion were regional right ventricular (RV) dyskinesis of the basal to mid free wall and a ratio of RV end-diastolic volume to body surface area of 134.8 mL/m2 on cardiac magnetic resonance imaging (MRI). Two minor criteria included a terminal activation duration of the QRS complex measured at 60 milliseconds in electrocardiogram lead V1 in the absence of complete right bundle branch block and 807 PVCs per hour on 14-day ambulatory monitoring.
      After a 6-month detraining period, the cardiac MRI abnormalities and the PVC burden improved such that they no longer met thresholds for ARVC criteria. This was accomplished by transitioning from endurance running, with an estimated metabolic equivalents (METs) of 9.8, to golf and yoga, with estimated METs of 4.8 and 2.5, respectively.
      • Towbin J.A.
      • McKenna W.J.
      • Abrams D.J.
      • et al.
      2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy.
      Thus, the patient could be considered to have “resolved exercise-induced ARVC.” A compelling question becomes, “How many patients with suspected exercise-induced ARVC can achieve disease resolution with detraining?” In addition, whether disease manifestations can identify when resolution or regression is no longer possible is of interest.
      Programmed electrical stimulation and voltage mapping via electrophysiology study for sudden death risk stratification were given class IIa and IIb recommendations, respectively, in the 2015 International Task Force consensus statement.
      • Corrado D.
      • Wichter T.
      • Link M.S.
      • et al.
      Treatment of arrhythmogenic right ventricular cardiomyopathy/dysplasia: an International Task Force consensus statement.
      Voltage mapping was not recommended as a “routine diagnostic tool,” as it was recognized to be “an invasive, expensive, and highly operator-dependent technique.”
      • Corrado D.
      • Wichter T.
      • Link M.S.
      • et al.
      Treatment of arrhythmogenic right ventricular cardiomyopathy/dysplasia: an International Task Force consensus statement.
      The only study cited used an older system with point-by-point acquisition such that RV voltage maps were created with a mean average ± standard deviation of 195 ± 22 points.
      • Migliore F.
      • Zorzi A.
      • Silvano M.
      • et al.
      Prognostic value of endocardial voltage mapping in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia.
      Abnormal bipolar voltage maps, but not abnormal unipolar voltage maps, were associated with major arrhythmic events on multivariable analysis.
      In the 2019 Heart Rhythm Society arrhythmogenic cardiomyopathy consensus statement, VT inducibility, but not an abnormal voltage map, was listed under primary-prophylaxis ICD recommendation criteria.
      • Towbin J.A.
      • McKenna W.J.
      • Abrams D.J.
      • et al.
      2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy.
      The role of voltage mapping in the current, high-density era should be studied, as it may be faster, more affordable, and more reproducible than earlier techniques.
      In the case report by Darden and colleagues, VT inducibility would have raised the recommendation for a primary-prophylaxis ICD from class IIb to IIa.
      • Towbin J.A.
      • McKenna W.J.
      • Abrams D.J.
      • et al.
      2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy.
      However, the dynamic nature of exercise-induced ARVC should also be considered, as the patient no longer met ICD recommendation after detraining (Table 1). In addition, if the diagnosis of exercise-induced ARVC excludes those with genetic causes, as the Oslo group supports, then proband status and desmosomal variants criteria would not apply.
      • Lie Ø.H.
      • Klaboe L.G.
      • Dejgaard L.A.
      • et al.
      Cardiac phenotypes and markers of adverse outcome in elite athletes with ventricular arrhythmias.
      ,
      • Towbin J.A.
      • McKenna W.J.
      • Abrams D.J.
      • et al.
      2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy.
      Thus, extrapolation of these criteria to the exercise-induced ARVC population deserves scrutiny. Even those with a number of risk factors for sudden death may benefit from reevaluation after a waiting period of detraining, rather than proceeding immediately with ICD placement. A wearable cardioverter-defibrillator could offer temporary protection.
      Table 12019 Heart Rhythm Society arrhythmogenic cardiomyopathy consensus statement
      • Towbin J.A.
      • McKenna W.J.
      • Abrams D.J.
      • et al.
      2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy.
      criteria for primary-prophylaxis implantable cardioverter-defibrillator consideration at baseline and after a 6-month detraining period in the patient reported by Darden and colleagues
      • Darden D.
      • Scheinman M.M.
      • Hoffmayer K.S.
      Exercise-induced arrhythmogenic right ventricular cardiomyopathy: reverse remodeling with detraining.
      CriteriaBaselineAfter detraining
      Major
       Nonsustained ventricular tachycardiaNoNo
       Inducibility to ventricular tachycardia at electrophysiology studyNoNot assessed
       Left ventricular ejection fraction ≤49%YesNo
      Minor
       Male sexYesYes
       >1000 premature ventricular contractions/24 hNoNo
       Right ventricular dysfunctionYesNo
       Proband statusN/AN/A
       ≥2 desmosomal variantsN/AN/A
      N/A = not applicable.
      The real-life impact of detraining and ICD placement should not be underestimated. Individuals devoted to endurance athletics, many of whom are young, are likely committed for more than general health purposes. These pursuits may be intricate facets of their personal identities and social circles. The addition of an ICD on top of exercise restrictions may be psychologically challenging.
      • Dunbar S.B.
      • Dougherty C.M.
      • Sears S.F.
      • et al.
      Educational and psychological interventions to improve outcomes for recipients of implantable cardioverter defibrillators and their families: a scientific statement from the American Heart Association.
      The disconnect between the patient presented by Darden and colleagues and using terminology derived from the ARVC population is also highlighted by LV involvement. The only major criterion for ICD consideration in the patient was the LV ejection fraction of 49% (Table 1) on cardiac MRI, which improved to 61% after detraining.
      • Darden D.
      • Scheinman M.M.
      • Hoffmayer K.S.
      Exercise-induced arrhythmogenic right ventricular cardiomyopathy: reverse remodeling with detraining.
      ,
      • Towbin J.A.
      • McKenna W.J.
      • Abrams D.J.
      • et al.
      2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy.
      Moreover, our review of the cine MRI videos suggests a subtle regional hypokinesis in the mid to apical lateral walls. If this were to be corroborated by review of short-axis imaging (not provided in the case report), the possibility of biventricular involvement would be raised. We agree that the current definition appears to be RV-“centric” and that the more general term of “arrhythmogenic cardiomyopathy” may be a more accurate description of the clinical phenomenon.
      • La Gerche A.
      Exercise-induced arrhythmogenic (right ventricular) cardiomyopathy is real… if you consider it.
      In conclusion, using comprehensive evaluation and reporting of a single patient, Darden and colleagues compel the cardiology community to rethink the existing paradigm of exercise-induced ARVC. The time appears ripe for moving toward a set of recommendations specific to this dynamic clinical syndrome, perhaps under the name of exercise-induced arrhythmogenic cardiomyopathy.
      • La Gerche A.
      Exercise-induced arrhythmogenic (right ventricular) cardiomyopathy is real… if you consider it.

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      Linked Article

      • Exercise-induced arrhythmogenic right ventricular cardiomyopathy: Reverse remodeling with detraining
        HeartRhythm Case ReportsVol. 8Issue 9
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          Long-term exercise training leads to structural cardiac adaptations, collectively referred to as the “athlete’s heart.” While the ventricles both undergo dilation and eccentric hypertrophy, it has been shown that the right ventricle (RV) experiences disproportionate remodeling under intense sports activity.1 Occasionally, the remodeling that occurs in the athlete’s heart may resemble arrhythmogenic right ventricular cardiomyopathy (ARVC), a pathologic cardiomyopathy associated with sudden death.
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