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

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.