Arrhythmogenic Right Ventricular Cardiomyopathy Causing Sudden Cardiac Death in Boxer Dogs

A New Animal Model of Human Disease

Cristina Basso, Philip R. Fox, Kathryn M. Meurs, Jeffrey Towbin, Alan W. Spier, Fiorella Calabrese, Barry J. Maron, Gaetano Thiene

Research output: Contribution to journalArticle

173 Citations (Scopus)

Abstract

Background-Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary familial heart muscle disease associated with substantial cardiovascular morbidity and risk of sudden death. Efforts to discern relevant pathophysiological mechanisms have been impaired by lack of a suitable animal model. Methods and Results-ARVC was diagnosed in 23 boxer dogs (12 male; 9.1±2.3 years old). Clinical events alone or in combination included sudden death (n=9; 39%), ventricular arrhythmias of suspected right ventricular (RV) origin (n=19; 83%), syncope (n=12, 52%), and heart failure (n=3; 13%). Right ventricular enlargement or aneurysms occurred in 10 (43%). Striking histopathological abnormalities were present in each boxer dog but not in controls, including severe RV myocyte loss with replacement by fatty (n=15, 65%) or fibrofatty (n=8, 35%) tissue. Focal fibrofatty lesions were also present in both atria (n = 8) and the left ventricle (LV) (n = 11). Fatty replacement occupied substantially greater RV wall area in ARVC dogs than controls (40.4±18.8% versus 13.8±3.4%, respectively) (P<0.001); residual myocardium was correspondingly reduced (56.6±19.2% versus 84.8±3.8% in controls) (P<0.001). MRI demonstrated bright anterolateral and/or infundibular RV myocardial signals, confirmed as fat by histopathology. Myocarditis appeared in the RV (n = 14, 61%) and LV (n = 16, 70%) and in each dog with sudden death, but not in controls. Familial transmission was evident in 10 of the 23. Conclusions-We describe a novel, spontaneous, and genetically transmitted animal model of ARVC associated with sudden death in the boxer dog, closely resembling the human disease. This model may aid in understanding the pathogenic mechanisms of ARVC.

Original languageEnglish (US)
Pages (from-to)1180-1185
Number of pages6
JournalCirculation
Volume109
Issue number9
DOIs
StatePublished - Mar 9 2004
Externally publishedYes

Fingerprint

Arrhythmogenic Right Ventricular Dysplasia
Animal Disease Models
Sudden Cardiac Death
Sudden Death
Dogs
Heart Ventricles
Myocardium
Animal Models
Myocarditis
Syncope
Muscle Cells
Aneurysm
Cardiac Arrhythmias
Heart Diseases
Heart Failure
Fats
Morbidity

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Arrhythmogenic Right Ventricular Cardiomyopathy Causing Sudden Cardiac Death in Boxer Dogs : A New Animal Model of Human Disease. / Basso, Cristina; Fox, Philip R.; Meurs, Kathryn M.; Towbin, Jeffrey; Spier, Alan W.; Calabrese, Fiorella; Maron, Barry J.; Thiene, Gaetano.

In: Circulation, Vol. 109, No. 9, 09.03.2004, p. 1180-1185.

Research output: Contribution to journalArticle

Basso, Cristina ; Fox, Philip R. ; Meurs, Kathryn M. ; Towbin, Jeffrey ; Spier, Alan W. ; Calabrese, Fiorella ; Maron, Barry J. ; Thiene, Gaetano. / Arrhythmogenic Right Ventricular Cardiomyopathy Causing Sudden Cardiac Death in Boxer Dogs : A New Animal Model of Human Disease. In: Circulation. 2004 ; Vol. 109, No. 9. pp. 1180-1185.
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abstract = "Background-Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary familial heart muscle disease associated with substantial cardiovascular morbidity and risk of sudden death. Efforts to discern relevant pathophysiological mechanisms have been impaired by lack of a suitable animal model. Methods and Results-ARVC was diagnosed in 23 boxer dogs (12 male; 9.1±2.3 years old). Clinical events alone or in combination included sudden death (n=9; 39{\%}), ventricular arrhythmias of suspected right ventricular (RV) origin (n=19; 83{\%}), syncope (n=12, 52{\%}), and heart failure (n=3; 13{\%}). Right ventricular enlargement or aneurysms occurred in 10 (43{\%}). Striking histopathological abnormalities were present in each boxer dog but not in controls, including severe RV myocyte loss with replacement by fatty (n=15, 65{\%}) or fibrofatty (n=8, 35{\%}) tissue. Focal fibrofatty lesions were also present in both atria (n = 8) and the left ventricle (LV) (n = 11). Fatty replacement occupied substantially greater RV wall area in ARVC dogs than controls (40.4±18.8{\%} versus 13.8±3.4{\%}, respectively) (P<0.001); residual myocardium was correspondingly reduced (56.6±19.2{\%} versus 84.8±3.8{\%} in controls) (P<0.001). MRI demonstrated bright anterolateral and/or infundibular RV myocardial signals, confirmed as fat by histopathology. Myocarditis appeared in the RV (n = 14, 61{\%}) and LV (n = 16, 70{\%}) and in each dog with sudden death, but not in controls. Familial transmission was evident in 10 of the 23. Conclusions-We describe a novel, spontaneous, and genetically transmitted animal model of ARVC associated with sudden death in the boxer dog, closely resembling the human disease. This model may aid in understanding the pathogenic mechanisms of ARVC.",
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