Recipient Organization
TUFTS UNIVERSITY
200 WESTBORO ROAD
N. GRAFTON,MA 01536
Performing Department
Clinical Sciences
Non Technical Summary
Cardiomyopathy, a disease of the heart muscle, is a common affliction of the Boxer breed. The arrhythmic form of the disease bears a striking resemblance to arrhythmogenic right ventricular cardiomyopathy (ARVC) in people, characterized by replacement of the normal heart muscle by fat, scar tissue, and inflammation. The recent discovery of a gene mutation allows us to identify carrier animals that are at increased risk for developing the disease. However, genetic tests are imperfect and ARVC screening usually entails a combination of family history, genetic testing, 24h ECG, and echocardiographic findings. The development of blood-based cardiac biomarkers has revolutionized the way in which we screen for certain types of heart disease. These markers may also aid in our understanding of the causes of cardiac disease and improve our ability to offer prognostic and therapeutic recommendations. Elevated markers of inflammation have also been identified in the bloodstream of people with ARVC, implicating a possible role of systemic inflammation in the progression of the disease. The results of this study are anticipated to improve our understanding of cardiomyopathy, and to open exciting new avenues for screening and treatment.
Animal Health Component
20%
Research Effort Categories
Basic
60%
Applied
20%
Developmental
20%
Goals / Objectives
Cardiomyopathy is a common affliction of the Boxer manifested by malignant right ventricular-origin arrhythmias, left ventricular myocardial dysfunction, or both. The arrhythmic form of the disease closely resembles arrhythmogenic right ventricular cardiomyopathy (ARVC) in people; characterized by replacement of normal myocardium by fibrofatty infiltrates and myocarditis, the degree of which correlates with clinical disease severity. The recent discovery of a mutation in the striatin gene has aided our ability to identify carrier animals; however ARVC is characterized by incomplete penetrance and variable disease expressivity. Thus, ARVC screening usually entails a combination of family history, genetic testing, Holter, and echocardiographic data. N-terminal pro B-type natriuretic peptide (NT-proBNP) serves as a circulating marker of increased cardiac wall stress or myocardial dysfunction. Cardiac biomarkers such as NT-proBNP may aid in the diagnosis and prognostication of cardiomyopathy; offer insight into disease pathophysiology; and allow for improved treatment recommendations. Elevated inflammatory marker concentrations have also been identified in people with ARVC, implicating a possible role for systemic inflammation in the etiopathogenesis of this disease. We hypothesize that Boxers with ARVC will have increased circulating concentrations of NT-proBNP and plasma markers of inflammation relative to healthy controls, and that these changes will be more profound in dogs with myocardial dysfunction. These findings are anticipated to result in new screening and treatment options for affected dogs.
Project Methods
We will measure plasma levels of NT-proBNP and inflammatory markers in Boxers with the arrhythmic and structural forms of ARVC compared to healthy age- and breed-matched controls. Correlations between plasma markers, striatin status, and clinical markers of disease severity (including Holter and echocardiographic data) will be determined.