PDF(Pubmed)
Abstract：
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited cardiac ion channelopathy where the initial disease presentation is during childhood or adolescent stages, leading to increased risks of sudden cardiac death. Despite advances in medical science and technology, several gaps remain in the understanding of the molecular mechanisms, risk prediction, and therapeutic management of patients with CPVT. Recent studies have identified and validated seven sets of genes responsible for various CPVT phenotypes, including RyR2, CASQ-2, TRDN, CALM1, 2, and 3, and TECRL, providing novel insights into the molecular mechanisms. However, more data on atypical CPVT genotypes are required to investigate the underlying mechanisms further. The complexities of the underlying genetics contribute to challenges in risk stratification as well as the uncertainty surrounding nongenetic modifiers. Therapeutically, although medical management involving beta-blockers and flecainide, or insertion of an implantable cardioverter defibrillator remains the mainstay of treatment, animal and stem cell studies on gene therapy for CPVT have shown promising results. However, its clinical applicability remains unclear. Current gene therapy studies have primarily focused on the RyR2 and CASQ-2 variants, which constitute 75% of all CPVT cases. Alternative approaches that target a broader population, such as CaMKII inhibition, could be more feasible for clinical implementation. Together, this review provides an update on recent research on CPVT, highlighting the need for further investigation of the molecular mechanisms, risk stratification, and therapeutic management of this potentially lethal condition.
摘要：
儿茶酚胺能多形性室性心动过速（CPVT）是一种罕见的遗传性心脏离子通道病，最初的疾病表现是在儿童或青少年阶段，导致心源性猝死的风险增加。尽管医学科学和技术取得了进步，在对分子机制的理解方面仍然存在一些差距，风险预测，和CPVT患者的治疗管理。最近的研究已经确定并验证了七组负责各种CPVT表型的基因，包括RyR2，CASQ-2，TRDN，CALM1、2和3以及TECRL，提供对分子机制的新见解。然而,需要更多关于非典型CPVT基因型的数据来进一步研究潜在机制.潜在遗传学的复杂性导致了风险分层的挑战以及围绕非遗传修饰的不确定性。治疗学上,虽然涉及β受体阻滞剂和氟卡尼的医疗管理，或插入植入式心律转复除颤器仍然是治疗的主要手段，对CPVT基因治疗的动物和干细胞研究显示了有希望的结果。然而,其临床适用性尚不清楚.目前的基因治疗研究主要集中在RyR2和CASQ-2变体上，占所有CPVT病例的75%。针对更广泛人群的替代方法，如CaMKII抑制，临床实施更具可行性。一起,这篇综述提供了关于CPVT的最新研究，强调需要进一步研究分子机制，风险分层，以及这种潜在致命疾病的治疗管理。
