Many commonly used antiarrhythmic drugs prolong ventricular repolarization and the qt interval on the electrocardiogram by blocking conductance of cardiac potassium channels. In a small percentage of patients receiving these drugs, a life-threatening polymorphic ventricular tachycardia called Torsades de Pointes can occur in association with excessive QT prolongation. Recently, it was found that the congenital form of this syndrome results from mutations in genes which encole voltage-gated ion channels, including K+ and Na+ channels. There is considerable precendent for genetically- determined diseases that become manifested only upon exposure to drugs. Therefore the discovery of ion channel gene mutations in the congenital long QT syndrome raises the hypothesis that some patients in the acquire long QT syndrome harbor subclinical genetic mutations in these or other genes but require drug exposure for expression of the phenotype. This study will compare drug-induced QT prolongation in first degree relatives of ALQT probands to that of non-alqt controls using the antiarrjythmic drug ibutilide. An abnormal QT response detected in the relatives of ALQT patients would provide evidence of a genetic predisposition for drug-induced long QT syndrome, and additional studies would continue in the attempt to identify candidate genes. The ultimate goal of this research is to identify susceptible genotypes which would be predictive of the development of Torsades de Pointes in patients treated with QT-prolonging drugs.

Project Start
1999-12-01
Project End
2000-11-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
40
Fiscal Year
2000
Total Cost
$592
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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