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

Abstract

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.

Ranolazine: safe and effective in a patient with hypertensive cardiomyopathy and multiple episodes of electrical storm

“…In patients with long QT syndrome, ranolazine shortens the prolonged QTc and suppresses early afterdepolarizations and TdP episodes 30, 31, 32. Currently, ranolazine displays a IIb indication (as add‐on therapy to b‐blocker) in LQTS3 patients with a QTc > 500 msec, in order to shorten the QT interval 33.…”

Ranolazine in Cardiac Arrhythmia

“…2 In patients with long QT3 syndrome (LQT3), where the underlying electrophysiological mechanism of ventricular arrhythmias is secondary to increase in late I Na , ranolazine was found to suppress ventricular arrhythmias by shortening QTc in a dose-dependent pattern. 16 Ranolazine abbreviates QTc by 22 ms to 40 ms from baseline at plasma concentration of ∼ 4 μM, with more decrease in QTc duration by 24 ms with every ∼ 2 μM increase in plasma concentration. 16 This effect of ranolazine was also seen in patients with LQT1 and LQT2.…”

“…16 Ranolazine abbreviates QTc by 22 ms to 40 ms from baseline at plasma concentration of ∼ 4 μM, with more decrease in QTc duration by 24 ms with every ∼ 2 μM increase in plasma concentration. 16 This effect of ranolazine was also seen in patients with LQT1 and LQT2. 17 Ranolazine and L-Type Calcium Channel: The inhibitory effect of ranolazine on I Ca-L is minimal at concentrations ≤10 μM and mainly affects late rather than peak I Ca-L , thus ranolazine is a weak direct vasodilator and has minimal direct effect on atrioventricular nodal conduction.…”

“…Moss et al 16 Prospective cohort study 5 patients with hereditary LQT3 syndrome due to SCN5A-KPQ mutation underwent an 8-h IV ranolazine infusion (45 mg/h for 3 h followed by 90 mg/h for 5 h).…”

“…In 5 patients with LQT3, ranolazine succeeded to significantly shorten the QTc by 26 ± 3 ms (P < 0.0001). 16 In another prospective cohort study done on 12 patients with drug-refractory implantable cardioverterdefibrillator (ICD) shocks, ranolazine reduced VT burden and ICD shocks significantly in 11 out of the 12 patients without significant increase in QTc interval or QRS duration. 39 In a substudy of the MERLIN-TIMI 36 trial, Holter electrocardiographic monitoring showed that the patients who received IV ranolazine in addition to the standard therapy showed significant reduction in VT lasting ≥8 beats compared with placebo at 24 hours (2.3% vs 3.4%; RR: 0.67, 95% CI: 0.50-0.90, P = 0.008) and 48 hours (3.1% vs 4.7%; RR: 0.65; 95% CI: 0.51-0.84, P < 0.001) after randomization.…”