Provocative Cases -> Teaching Case Reports D-PO01 - Featured Poster Session (ID 11) Poster

D-PO01-102 - Non-precision Medicine: Mexiletine Useful For More Than Just Long QT Syndrome Type 3 (ID 91)

 J. Ashouri: Nothing relevant to disclose.


Background: Long QT syndrome (LQTS) is a potentially lethal condition with β-blockers as the mainstay of therapy. Genotype targeted therapy with concomitant use of sodium channel blockers (i.e. mexiletine) has been shown to reduce events and QT interval in LQTS3 and recently, in potassium channel mediated LQTS2.
Objective: We present a case showing the effective use of mexiletine in a high-risk patient with potassium channel mutations for LQTS2 and 5.
Results: A 12 year-old female presented after recurrent syncope and prolonged QTc interval of 482 msec. Further evaluation revealed maximal QTc of 520 msec during the recovery phase of exercise testing (EST) and pathogenic mutations in KNCH2 associated with LQTS2 (heterozygous mutation, c.3003G>A) and KCNE1 associated with LQTS5 (heterozygous mutation, c.226G>A). Initially trialed on nadolol, she transitioned to propranolol due to side effects and nonadherence, but had a breakthrough syncopal event with a QTc >500 msec prompting ICD placement. She continued to have non-sustained ventricular arrhythmias and syncopal events with appropriate ICD shocks, so was transitioned back to nadolol (1.4 mg/kg/day). Due to events occurring with pre-event resting heart rates of 90 to 110 bpm, prolonged QTc >500 msec, and prior EST with rare isolated PVCs, mexiletine (10 mg/kg/day) was added. Follow up evaluation has shown no events after 3 months, a shortened baseline QTc of 452 msec, and a maximal QTc of <500 msec in the recovery phase of EST.
Conclusion: Concomitant use of mexiletine for compound potassium channel mutations in LQTS2 and 5 was effective in shortening the QT interval and may provide an adjunctive approach to reduce clinical events.