This application is part of a clustered proposal consisting of three components: an application by Dr. Frank Marcus describing the overall scientific program, an application by Dr. Jeffrey Towbin describing the genetic analyses for the study, and a proposal by Dr. Wojciech Zareba describing the organization and operation of the Coordination and Data Center (CDC) for the study. The proposed five-year research plan is a multi-disciplinary, multicenter, collaborative study to investigate the cardiac, clinical, and genetic aspects of arrhythmogenic right ventricular dysplasia (ARVD), a progressive disorder that predominantly affects the right side of the heart and causes ventricular arrhythmias. In many patients the disease is familial. ARVD may account for as many as 5% of unexpected sudden deaths under the age of 65 and 3-4% of sudden death during sports. There can be considerable difficulty in diagnosing this disease with certainty, and there is incomplete information on the pathogenesis, natural history, and treatment of the patients and affected members. The overall objective of the Multidisciplinary Study of Right Ventricular Dysplasia is to characterize the genetic and clinical features of arrhythmogenic right ventricular dysplasia (ARVD).
The specific aims are: 1) to establish a North American ARVD Registry enrolling ARVD patients and their family members, based on standardized diagnostic test criteria, in a prospective longitudinal follow-up study; 2) to determine the genetic background of ARVD by identifying chromosomal loci and specific gene mutations associated with this disorder; 3) to determine the influence of the genotype on the clinical course of patients with ARVD and explore phenotype-genotype associations that will contribute to improved diagnosis, risk stratification, and therapy; and 4) to develop quantitative methods to assess right ventricular function in order to enhance the specificity and sensitivity of ARVD diagnosis. This integrated research grant proposal offers a substantial prospect of expanding the fund of clinical knowledge regarding ARVD and of localizing the gene(s) responsible for this disorder.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL065691-03
Application #
6662553
Study Section
Special Emphasis Panel (ZHL1-CSR-A (F3))
Program Officer
Hoke, Tracey R
Project Start
2001-09-27
Project End
2006-07-31
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
3
Fiscal Year
2003
Total Cost
$511,082
Indirect Cost
Name
University of Rochester
Department
Internal Medicine/Medicine
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
Kamath, Ganesh S; Zareba, Wojciech; Delaney, Jessica et al. (2011) Value of the signal-averaged electrocardiogram in arrhythmogenic right ventricular cardiomyopathy/dysplasia. Heart Rhythm 8:256-62
Morin, Daniel P; Mauer, Andreas C; Gear, Kathleen et al. (2010) Usefulness of precordial T-wave inversion to distinguish arrhythmogenic right ventricular cardiomyopathy from idiopathic ventricular tachycardia arising from the right ventricular outflow tract. Am J Cardiol 105:1821-4
Marcus, Frank I; McKenna, William J; Sherrill, Duane et al. (2010) Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the Task Force Criteria. Eur Heart J 31:806-14
Xu, Tianhong; Yang, Zhao; Vatta, Matteo et al. (2010) Compound and digenic heterozygosity contributes to arrhythmogenic right ventricular cardiomyopathy. J Am Coll Cardiol 55:587-97
Marcus, Frank I; McKenna, William J; Sherrill, Duane et al. (2010) Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria. Circulation 121:1533-41
Marcus, Gregory M; Glidden, David V; Polonsky, Bronislava et al. (2009) Efficacy of antiarrhythmic drugs in arrhythmogenic right ventricular cardiomyopathy: a report from the North American ARVC Registry. J Am Coll Cardiol 54:609-15
Marcus, Frank I; Zareba, Wojciech; Calkins, Hugh et al. (2009) Arrhythmogenic right ventricular cardiomyopathy/dysplasia clinical presentation and diagnostic evaluation: results from the North American Multidisciplinary Study. Heart Rhythm 6:984-92