Repolarization dynamics during exercise discriminate between LQT1 and LQT2 genotypes

Genotype and Exercise in LQTS.

Background: Repolarization dynamics during exercise in patients with long-QT Syndrome (LQTS) may be influenced by various factors such as a patient's genotype. We sought to systematically characterize the repolarization dynamics during exercise in patients with LQTS with a particular focus on the influence of genotype.

Methods: Three groups of patients were studied on the basis of clinical status and genotype: LQT1, LQT2, and normal controls. Twenty-five age- and gender-matched patients were selected for each group. The QTc was measured during bicycle exercise testing and its dynamics were compared between the 3 groups.

Results: The degree of QTc prolongation during exercise was greater in LQTS patients (LQT1 80 ± 47 ms, LQT2 64 ± 41 ms, Control 46 ± 20 ms, P = 0.02), with significant differences between LQT1 and LQT2 patients observed at heart rates ≥ 60% of the predicted maximum (P < 0.05). LQT1 patients demonstrated progressive or persistent QTc prolongation at higher heart rates, whereas LQT2 patients demonstrated maximum QTc prolongation at submaximal heart rates (50% of the predicted maximum) with subsequent QTc correction toward baseline values at higher heart rates. Importantly, these observations were consistent regardless of age, gender, or exercise type in subgroup analyses.

Conclusions: Reduced repolarization reserve in LQTS is genotype and heart rate specific.