Literature DB >> 15851285

Genetic susceptibility to acquired long QT syndrome: pharmacologic challenge in first-degree relatives.

Prince J Kannankeril1, Dan M Roden, Kris J Norris, S Patrick Whalen, Alfred L George, Katherine T Murray.   

Abstract

OBJECTIVES: The purpose of this study was to test for a genetic component to risk for acquired long QT syndrome (LQTS).
BACKGROUND: Many drugs prolong the QT interval, and some patients develop excessive QT prolongation and occasionally torsades de pointes-the acquired LQTS. Similarities between the acquired and congenital forms of the long QT syndrome suggest genetic factors modulate susceptibility.
METHODS: Intravenous quinidine was administered to 14 relatives of patients who safely tolerated chronic therapy with a QT-prolonging drug (control relatives) and 12 relatives of patients who developed acquired LQTS, and ECG intervals between groups were compared.
RESULTS: Baseline QT and heart-rate corrected QT (QTc) were similar (QT/QTc: 394 +/- 28/410 +/- 20 ms vs 395 +/- 24/418 +/- 20 ms; control vs acquired LQTS) and prolonged equally in the two groups. The interval from the peak to the end of the T wave, an index of transmural dispersion of repolarization, prolonged significantly with quinidine in acquired LQTS relatives (63 +/- 17 to 83 +/- 18 ms, P = .017) but not in control relatives (66 +/- 19 to 71 +/- 18 ms, P = 0.648). In addition, the baseline peak to end of the T wave as a fraction of the QT interval was similar in both groups but was longer in acquired LQTS relatives after quinidine (16.3 +/- 3.5% and 19.5 +/- 3.9% in control and acquired LQTS relatives, respectively, P = .042).
CONCLUSIONS: First-degree relatives of patients with acquired long QT syndrome have greater drug-induced prolongation of terminal repolarization compared to control relatives, supporting a genetic predisposition to acquired long QT syndrome.

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Year:  2005        PMID: 15851285     DOI: 10.1016/j.hrthm.2004.10.039

Source DB:  PubMed          Journal:  Heart Rhythm        ISSN: 1547-5271            Impact factor:   6.343


  31 in total

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