Heart rate dependence of the QT interval duration: Differences among congenital long QT syndrome subtypes

Introduction: The heart rate dependence of QT interval duration is abnormal in patients with congenital long QT syndrome. Patients with LQT1 have a defective I_KS current, a major determinant of QT response to heart rate. Methods and Results: We studied the heart rate dependence of QT interval duration in different long QT syndrome genotypes and control subjects using computerized QT measurements obtained from Holter recordings. The dependence of QT duration on heart rate is steeper in long QT syndrome than in control subjects (0.347 ± 0.263 vs 0.162 ± 0.083 at heart rate 100 beats/min; P < 0.05). In addition, QT interval is significantly longer in LQT2 and LQT3 than in LQT1 patients at slow (533 ± 23 ms vs 468 ± 30 ms at heart rate 60 beats/min; P < 0.0001) but not at rapid heart rate. The heart rate dependence of QT interval is steeper in LQT2 and LQT3 than in LQT1 (0.623 ± 0.245 vs 0.19 ± 0.079 at heart rate 100 beats/min; P < 0.05). For a given heart rate, the QT intervals vary more in LQT2 and LQT3 than in LQT1 patients (25.98 ± 11.18 ms vs 14.39 ± 1.55 ms; P < 0.01). Conclusion: Individual long QT syndrome genotypes differ with respect to QT interval dependence on heart rate. These differences may relate to the propensity of LQT2 and LQT3 patients to develop arrhythmias during bradycardia.