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(Circulation. 2004;109:1180-1185.)
© 2004 American Heart Association, Inc.

Basic Science Reports

Arrhythmogenic Right Ventricular Cardiomyopathy Causing Sudden Cardiac Death in Boxer Dogs

A New Animal Model of Human Disease

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

From the Institute of Pathology, University of Padua Medical School, Padua, Italy (C.B., F.C., G.T.); Caspary Research Institute of the Animal Medical Center, New York, NY (P.R.F.); the Ohio State University College of Veterinary Medicine, Columbus (K.M.M., A.W.S.); the Department of Pediatrics (Cardiology), Baylor College of Medicine, Houston, Tex (J.A.T.); and the Minneapolis Heart Institute Foundation, Minneapolis, Minn (B.J.M.).

Correspondence to Philip R. Fox, DVM, Caspary Research Institute, The Animal Medical Center, New York, NY 10021. E-mail philip.fox{at}amcny.org

Received July 24, 2003; revision received October 23, 2003; accepted October 28, 2003.

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.

Key Words: models, animal • cardiomyopathy • pathology • death, sudden

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