Arrhythmias & electrophysiology
Therapeutic Efficacy of Mexiletine for Long QT Syndrome Type 2: Evidence From Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes, Transgenic Rabbits, and Patients
Main findingResult — go to the resultIncidence rate ratio 0.40 95% CI 0.16–0.84Authors' conclusion
Mexiletine significantly shortens cardiac repolarization in LQT2 human induced pluripotent stem cells, in the LQT2 rabbit model, and in the majority of patients with LQT2. Furthermore, mexiletine showed antiarrhythmic efficacy.
Study context
- Population
- Long QT syndrome type 2 (LQT2): patient-specific hiPSC-derived cardiomyocytes, transgenic LQT2 rabbits and patients with LQT2patients with LQT2
- Participants
- 96 participants
- Comparison
- Mexiletine vs no mexiletine
- Mexiletinen = 96
- Outcome
- Antiarrhythmic efficacy (yearly event rate, Poisson regression) and QTc shortening (responders: QTc shortening ≥40 ms)
Methodological detailshiPSC-derived cardiomyocytes, transgenic LQT2 rabbit model, patient cohort
- hiPSC-derived cardiomyocytes
- Transgenic LQT2 rabbit model
- Patient cohort
Main finding
As reported in the abstract
Incidence rate ratio
0.40
95% CI 0.16–0.84
P = 0.01
By group
Baseline
0.10
mean yearly event rate · 95% CI 0.07–0.14
Mexiletine
0.04
mean yearly event rate · 95% CI 0.02–0.08
Mexiletinevs Baseline
IRR 0.40 (95% CI 0.16–0.84); P = 0.01
- LQT2 rabbit cardiomyocytes: APD90 shortened
- 113 ms
Further findings
Responders (QTc shortening ≥40 ms)
- Responders (QTc shortening ≥40 ms): chronic n=60; acute oral test n=36
Basal QTc vs ∆QTc during test
- Correlation r
- −0.8
- P
- P < 0.001
Oral drug test predicting long-term effect
- Correctly predicted
- 93%
Original publication
Therapeutic Efficacy of Mexiletine for Long QT Syndrome Type 2: Evidence From Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes, Transgenic Rabbits, and Patients. Circulation. Published 28 June 2024. doi:10.
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