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Ranolazine Shortens Repolarization in Patients with Sustained Inward Sodium Current Due to Type‐3 Long‐QT Syndrome

2008; Wiley; Volume: 19; Issue: 12 Linguagem: Inglês

10.1111/j.1540-8167.2008.01246.x

1540-8167

Arthur J. Moss, Wojciech Zaręba, Karl Q. Schwarz, Spencer Rosero, Scott McNitt, Jennifer L. Robinson,

ECG Monitoring and Analysis

Introduction: One form of the hereditary long‐QT syndrome, LQT3‐ΔKPQ, is associated with sustained inward sodium current during membrane depolarization. Ranolazine reduces late sodium channel current, and we hypothesized that ranolazine would have beneficial effects on electrical and mechanical cardiac function in LQT3 patients with the SCN5A‐ΔKPQ mutation. Methods: We assessed the effects of 8‐hour intravenous ranolazine infusions (45 mg/h for 3 hours followed by 90 mg/h for 5 hours) on ventricular repolarization and myocardial relaxation in 5 LQT3 patients with the SCN5A‐ΔKPQ mutation. Changes in electrocardiographic repolarization parameters from before to during ranolazine infusion were evaluated by time‐matched, paired t ‐test analyses. Cardiac ultrasound recordings were obtained before ranolazine infusion and just before completion of the 8‐hour ranolazine infusion. Results: Ranolazine shortened QTc by 26 ± 3 ms (P < 0.0001) in a concentration‐dependent manner. At peak ranolazine infusion, there was a significant 13% shortening in left ventricular isovolumic relaxation time, a significant 25% increase in mitral E‐wave velocity, and a meaningful 22% decrease in mitral E‐wave deceleration time compared with the baseline. No adverse effects of ranolazine were observed in the study patients. Conclusion: Ranolazine at therapeutic concentrations shortened a prolonged QTc interval and improved diastolic relaxation in patients with the LQT3‐ΔKPQ mutation, a genetic disorder that is known to cause an increase in late sodium current.