What is the clinical evidence from this study?

Study design: Other. Population: Type 3 long QT syndrome (LQT3) (n=23). Intervention: Mexiletine vs. Wild-type (WT) hiPSC-CMs. Primary outcome: Action potential duration (APD90) reduction (p=<0.05).

January 23, 2016Basic Research in CardiologyOpen Access

Human iPS cell model of type 3 long QT syndrome recapitulates drug-based phenotype correction

Q: What are the key findings of this study?

Mexiletine significantly reduced action potential duration by 25.8% in LQT3 hiPSC-CMs and suppressed early afterdepolarizations, recapitulating the clinical response of the patient.

View Full Paper

Ask AI

Bookmark

Key result

Mexiletine significantly reduced action potential duration by 25.8% in LQT3 hiPSC-CMs and suppressed early afterdepolarizations, recapitulating the clinical response of the patient.

Why the study?

Does administration of sodium channel inhibitors correct the electrophysiological phenotype in LQT3 hiPSC-CMs?

Population

Human induced pluripotent stem cell-derived cardiomyocytes generated from a patient with type 3 long QT…

Comparison

Sodium channel inhibitors vs Wild-type (WT) hiPSC-CMs and untreated baseline

Design

Preclinical

Authors

DMDaniela MalanUniversity of Bonn MZMiao ZhangQingdao University BSBirgit StallmeyerUniversity of Münster

Discussion

Member takes

Implication

May inform personalized LQT3 therapy selection; leaves open prospective outcome validation.

Structured PICO

Does administration of sodium channel inhibitors correct the electrophysiological phenotype in LQT3 hiPSC-CMs?

Population

In vitro disease model using human induced pluripotent stem cell-derived cardiomyocytes from a patient with type 3 long QT syndrome carrying the SCN5A p.R1644H mutation, supported by clinical data from 23 family members.

Intervention

Sodium channel inhibitors (mexiletine 5-100 µM, ranolazine 20 µM, phenytoin 10 µM)

Comparator

Wild-type (WT) hiPSC-CMs and untreated baseline

Outcome

Electrophysiological features including action potential duration (APD), field potential duration (FPD), and early after depolarizations (EADs)surrogate

Main Result

Absolute Event Rate: -25.8% vs -3.2%

p-value: p=<0.05

Patient-specific LQT3 hiPSC-CMs recapitulate the disease phenotype, including early after depolarizations, and demonstrate phenotype correction with sodium channel inhibitors, validating their utility for drug screening.

Limitations

hiPSC-CMs present a heterogeneous mixture of cardiac subtypes
Early hiPSC-derived cardiomyocytes tend to be immature in their physiological properties
Clinical interpretation of family data is complicated by patients receiving both antiarrhythmics and beta blockers

Cite This Study

Malan et al. (2016) studied Type 3 long QT syndrome (LQT3) (n=23). Mexiletine vs. Wild-type (WT) hiPSC-CMs was evaluated on Action potential duration (APD90) reduction (p=<0.05). Mexiletine significantly reduced action potential duration by 25.8% in LQT3 hiPSC-CMs and suppressed early afterdepolarizations, recapitulating the clinical response of the patient.

synapsesocial.com/papers/6a71b7c1abc331a85807af29 https://doi.org/10.1007/s00395-016-0530-0

View Full Paper

Ask AI

Bookmark

Human iPS cell model of type 3 long QT syndrome recapitulates drug-based phenotype correction

Discussion

Member takes

Implication

Structured PICO

Main Result

Limitations

Cite This Study

Human iPS cell model of type 3 long QT syndrome recapitulates drug-based phenotype correction

Discussion

Member takes

Implication

Structured PICO

Main Result

Limitations

Cite This Study

Also Consider

Also Consider