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

Kannankeril PJ, Roden DM, Norris KJ, Whalen SP, George AL, Murray KT
Heart Rhythm. 2005 2 (2): 134-40

PMID: 15851285 · DOI:10.1016/j.hrthm.2004.10.039

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.

MeSH Terms (9)

Anti-Arrhythmia Agents Electrocardiography Female Genetic Predisposition to Disease Humans Long QT Syndrome Male Middle Aged Quinidine

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