The updated view on induced pluripotent stem cells for cardiovascular precision medicine

Wang, Yong; Lei, Wei; Yang, Jingsi; Ni, Xuan; Ye, Lingqun; Shen, Zhenya; Hu, Shijun

doi:10.1007/s00424-021-02530-5

Cited by 4 publications

(1 citation statement)

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“…As a result, special care should be taken when modeling cardiomyopathies caused by gene mutations that impact calcium transients, such as DMD [ 40 ]. Additionally, the immature nature of iPSC-CMs may lead to different electrophysiology, cell morphology, and metabolism [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

Verification of the Efficacy of Mexiletine Treatment for the A1656D Mutation on Downgrading Reentrant Tachycardia Using a 3D Cardiac Electrophysiological Model

et al. 2022

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The SCN5A mutations have been long associated with long QT variant 3 (LQT3). Recent experimental and computation studies have reported that mexiletine effectively treats LQT3 patients associated with the A1656D mutation. However, they have primarily focused on cellular level evaluations and have only looked at the effects of mexiletine on action potential duration (APD) or QT interval reduction. We further investigated mexiletine’s effects on cardiac cells through simulations of single-cell (behavior of alternant occurrence) and 3D (with and without mexiletine). We discovered that mexiletine could shorten the cell’s APD and change the alternant’s occurrence to a shorter basic cycle length (BCL) between 350 and 420 ms. The alternant also appeared at a normal heart rate under the A1656D mutation. Furthermore, the 3D ventricle simulations revealed that mexiletine could reduce the likelihood of a greater spiral wave breakup in the A1656D mutant condition by minimizing the appearance of rotors. In conclusion, we found that mexiletine could provide extra safety features during therapy for LQT3 patients because it can change the alternant occurrence from a normal to a faster heart rate, and it reduces the chance of a spiral wave breakup. Therefore, these findings emphasize the promising efficacy of mexiletine in treating LQT3 patients under the A1656D mutation.

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Section: Discussionmentioning

confidence: 99%