Li Qing, Wang Yi-Fei, Wang Bin, Lv Ting-Ting, Zhang Ping
School of Clinical Medicine, Tsinghua University, 100084 Beijing, China.
Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, 102218 Beijing, China.
Rev Cardiovasc Med. 2025 Apr 22;26(4):28251. doi: 10.31083/RCM28251. eCollection 2025 Apr.
Congenital long QT syndrome (LQTS) is a potentially life-threatening hereditary arrhythmia characterized by a prolonged QT interval on electrocardiogram (ECG) due to delayed ventricular repolarization. This condition predisposes individuals to severe arrhythmic events, including ventricular tachycardia and sudden cardiac death. Traditional approaches to LQTS research and treatment are limited by an incomplete understanding of its gene-specific pathophysiology, variable clinical presentation, and the challenges associated with developing effective, personalized therapies. Recent advances in human induced pluripotent stem cell (iPSC) technology have opened new avenues for elucidating LQTS mechanisms and testing therapeutic strategies. By generating cardiomyocytes from patient-specific iPSCs (iPSC-CMs), it is now possible to recreate the patient's genetic context and study LQTS in a controlled environment. This comprehensive review describes how iPSC technology deepens our understanding of LQTS and accelerates the development of tailored treatments, as well as ongoing challenges such as incomplete cell maturation and cellular heterogeneity.
先天性长QT综合征（LQTS）是一种具有潜在生命威胁的遗传性心律失常，其特征是心电图（ECG）上QT间期延长，这是由于心室复极延迟所致。这种情况使个体易发生严重的心律失常事件，包括室性心动过速和心源性猝死。LQTS研究和治疗的传统方法受到对其基因特异性病理生理学理解不完整、临床表现多变以及开发有效、个性化疗法所面临挑战的限制。人类诱导多能干细胞（iPSC）技术的最新进展为阐明LQTS机制和测试治疗策略开辟了新途径。通过从患者特异性iPSC（iPSC-CM）生成心肌细胞，现在有可能重现患者的遗传背景并在可控环境中研究LQTS。这篇综述全面描述了iPSC技术如何加深我们对LQTS的理解并加速定制治疗的开发，以及诸如细胞成熟不完全和细胞异质性等持续存在的挑战。
