Exercise has a disproportionate role in the pathogenesis of arrhythmogenic right ventricular dysplasia/cardiomyopathy in patients without desmosomal mutations

Abhishek C. Sawant, Aditya Bhonsale, Anneline S J M te Riele, Crystal Tichnell, Brittney Murray, Stuart D. Russell, Harikrishna Tandri, Ryan J. Tedford, Daniel P. Judge, Hugh Calkins, Cynthia Anne James

Research output: Contribution to journalArticle

Abstract

Background: Exercise is associated with age-related penetrance and arrhythmic risk in carriers of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C)-associated desmosomal mutations; however, its role in patients without desmosomal mutations (gene-elusive) is uncertain. This study investigates whether exercise is (1) associated with onset of geneelusive ARVD/C and (2) has a differential impact in desmosomal and gene-elusive patients. Methods and Results: Eighty-two ARVD/C patients (39 desmosomal, all probands) were interviewed about regular physical activity from age 10. Participation in endurance athletics, duration (hours/year), and intensity (MET-Hours/year) of exercise prior to clinical presentation were compared between patients with desmosomal and gene-elusive ARVD/C. All gene-elusive patients were endurance athletes. Gene-elusive patients were more likely to be endurance athletes (P < 0.001) and had done significantly more intense (MET-Hrs/year) exercise prior to presentation (P < 0.001), particularly among cases presenting < age 25 (P=0.027). Family history was less prevalent among gene-elusive patients (9% versus 40% desmosomal, P < 0.001), suggesting a greater environmental influence. Gene-elusive patients without family history did considerably more intense exercise than other ARVD/C patients (P=0.004). Gene-elusive patients who had done the most intense (top quartile MET-Hrs/year) exercise prior to presentation had a younger age of presentation (P=0.025), greater likelihood of meeting ARVD/C structural Task Force Criteria (100% versus 43%, P=0.02), and shorter survival free from a ventricular arrhythmia in follow-up (P=0.002). Conclusions: Gene-elusive, non-familial ARVD/C is associated with very high intensity exercise suggesting exercise has a disproportionate role in the pathogenesis of these cases. As exercise negatively modifies cardiac structure and promotes arrhythmias, exercise restriction is warranted.

Original languageEnglish (US)
Article number001471
JournalJournal of the American Heart Association
Volume3
Issue number6
DOIs
StatePublished - 2014

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Arrhythmogenic Right Ventricular Dysplasia
Exercise
Mutation
Genes
Athletes
Cardiac Arrhythmias
Penetrance
Advisory Committees
Sports

Keywords

  • Arrhythmogenic right ventricular dysplasia/cardiomyopathy
  • Desmosome cardiomyopathy
  • Etiology
  • Exercise genetics-human

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Exercise has a disproportionate role in the pathogenesis of arrhythmogenic right ventricular dysplasia/cardiomyopathy in patients without desmosomal mutations. / Sawant, Abhishek C.; Bhonsale, Aditya; te Riele, Anneline S J M; Tichnell, Crystal; Murray, Brittney; Russell, Stuart D.; Tandri, Harikrishna; Tedford, Ryan J.; Judge, Daniel P.; Calkins, Hugh; James, Cynthia Anne.

In: Journal of the American Heart Association, Vol. 3, No. 6, 001471, 2014.

Research output: Contribution to journalArticle

Sawant, Abhishek C. ; Bhonsale, Aditya ; te Riele, Anneline S J M ; Tichnell, Crystal ; Murray, Brittney ; Russell, Stuart D. ; Tandri, Harikrishna ; Tedford, Ryan J. ; Judge, Daniel P. ; Calkins, Hugh ; James, Cynthia Anne. / Exercise has a disproportionate role in the pathogenesis of arrhythmogenic right ventricular dysplasia/cardiomyopathy in patients without desmosomal mutations. In: Journal of the American Heart Association. 2014 ; Vol. 3, No. 6.
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abstract = "Background: Exercise is associated with age-related penetrance and arrhythmic risk in carriers of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C)-associated desmosomal mutations; however, its role in patients without desmosomal mutations (gene-elusive) is uncertain. This study investigates whether exercise is (1) associated with onset of geneelusive ARVD/C and (2) has a differential impact in desmosomal and gene-elusive patients. Methods and Results: Eighty-two ARVD/C patients (39 desmosomal, all probands) were interviewed about regular physical activity from age 10. Participation in endurance athletics, duration (hours/year), and intensity (MET-Hours/year) of exercise prior to clinical presentation were compared between patients with desmosomal and gene-elusive ARVD/C. All gene-elusive patients were endurance athletes. Gene-elusive patients were more likely to be endurance athletes (P < 0.001) and had done significantly more intense (MET-Hrs/year) exercise prior to presentation (P < 0.001), particularly among cases presenting < age 25 (P=0.027). Family history was less prevalent among gene-elusive patients (9{\%} versus 40{\%} desmosomal, P < 0.001), suggesting a greater environmental influence. Gene-elusive patients without family history did considerably more intense exercise than other ARVD/C patients (P=0.004). Gene-elusive patients who had done the most intense (top quartile MET-Hrs/year) exercise prior to presentation had a younger age of presentation (P=0.025), greater likelihood of meeting ARVD/C structural Task Force Criteria (100{\%} versus 43{\%}, P=0.02), and shorter survival free from a ventricular arrhythmia in follow-up (P=0.002). Conclusions: Gene-elusive, non-familial ARVD/C is associated with very high intensity exercise suggesting exercise has a disproportionate role in the pathogenesis of these cases. As exercise negatively modifies cardiac structure and promotes arrhythmias, exercise restriction is warranted.",
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T1 - Exercise has a disproportionate role in the pathogenesis of arrhythmogenic right ventricular dysplasia/cardiomyopathy in patients without desmosomal mutations

AU - Sawant, Abhishek C.

AU - Bhonsale, Aditya

AU - te Riele, Anneline S J M

AU - Tichnell, Crystal

AU - Murray, Brittney

AU - Russell, Stuart D.

AU - Tandri, Harikrishna

AU - Tedford, Ryan J.

AU - Judge, Daniel P.

AU - Calkins, Hugh

AU - James, Cynthia Anne

PY - 2014

Y1 - 2014

N2 - Background: Exercise is associated with age-related penetrance and arrhythmic risk in carriers of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C)-associated desmosomal mutations; however, its role in patients without desmosomal mutations (gene-elusive) is uncertain. This study investigates whether exercise is (1) associated with onset of geneelusive ARVD/C and (2) has a differential impact in desmosomal and gene-elusive patients. Methods and Results: Eighty-two ARVD/C patients (39 desmosomal, all probands) were interviewed about regular physical activity from age 10. Participation in endurance athletics, duration (hours/year), and intensity (MET-Hours/year) of exercise prior to clinical presentation were compared between patients with desmosomal and gene-elusive ARVD/C. All gene-elusive patients were endurance athletes. Gene-elusive patients were more likely to be endurance athletes (P < 0.001) and had done significantly more intense (MET-Hrs/year) exercise prior to presentation (P < 0.001), particularly among cases presenting < age 25 (P=0.027). Family history was less prevalent among gene-elusive patients (9% versus 40% desmosomal, P < 0.001), suggesting a greater environmental influence. Gene-elusive patients without family history did considerably more intense exercise than other ARVD/C patients (P=0.004). Gene-elusive patients who had done the most intense (top quartile MET-Hrs/year) exercise prior to presentation had a younger age of presentation (P=0.025), greater likelihood of meeting ARVD/C structural Task Force Criteria (100% versus 43%, P=0.02), and shorter survival free from a ventricular arrhythmia in follow-up (P=0.002). Conclusions: Gene-elusive, non-familial ARVD/C is associated with very high intensity exercise suggesting exercise has a disproportionate role in the pathogenesis of these cases. As exercise negatively modifies cardiac structure and promotes arrhythmias, exercise restriction is warranted.

AB - Background: Exercise is associated with age-related penetrance and arrhythmic risk in carriers of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C)-associated desmosomal mutations; however, its role in patients without desmosomal mutations (gene-elusive) is uncertain. This study investigates whether exercise is (1) associated with onset of geneelusive ARVD/C and (2) has a differential impact in desmosomal and gene-elusive patients. Methods and Results: Eighty-two ARVD/C patients (39 desmosomal, all probands) were interviewed about regular physical activity from age 10. Participation in endurance athletics, duration (hours/year), and intensity (MET-Hours/year) of exercise prior to clinical presentation were compared between patients with desmosomal and gene-elusive ARVD/C. All gene-elusive patients were endurance athletes. Gene-elusive patients were more likely to be endurance athletes (P < 0.001) and had done significantly more intense (MET-Hrs/year) exercise prior to presentation (P < 0.001), particularly among cases presenting < age 25 (P=0.027). Family history was less prevalent among gene-elusive patients (9% versus 40% desmosomal, P < 0.001), suggesting a greater environmental influence. Gene-elusive patients without family history did considerably more intense exercise than other ARVD/C patients (P=0.004). Gene-elusive patients who had done the most intense (top quartile MET-Hrs/year) exercise prior to presentation had a younger age of presentation (P=0.025), greater likelihood of meeting ARVD/C structural Task Force Criteria (100% versus 43%, P=0.02), and shorter survival free from a ventricular arrhythmia in follow-up (P=0.002). Conclusions: Gene-elusive, non-familial ARVD/C is associated with very high intensity exercise suggesting exercise has a disproportionate role in the pathogenesis of these cases. As exercise negatively modifies cardiac structure and promotes arrhythmias, exercise restriction is warranted.

KW - Arrhythmogenic right ventricular dysplasia/cardiomyopathy

KW - Desmosome cardiomyopathy

KW - Etiology

KW - Exercise genetics-human

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