Experimental Cardiology, Department of Cardiovascular Sciences, KU Leuven, 3000 Leuven, Belgium.
Division of Cardiology, University Hospitals Leuven, 3000 Leuven, Belgium.
Cells. 2021 Oct 1;10(10):2629. doi: 10.3390/cells10102629.
Ischemic heart disease is the most common cause of lethal ventricular arrhythmias and sudden cardiac death (SCD). In patients who are at high risk after myocardial infarction, implantable cardioverter defibrillators are the most effective treatment to reduce incidence of SCD and ablation therapy can be effective for ventricular arrhythmias with identifiable culprit lesions. Yet, these approaches are not always successful and come with a considerable cost, while pharmacological management is often poor and ineffective, and occasionally proarrhythmic. Advances in mechanistic insights of arrhythmias and technological innovation have led to improved interventional approaches that are being evaluated clinically, yet pharmacological advancement has remained behind. We review the mechanistic basis for current management and provide a perspective for gaining new insights that centre on the complex tissue architecture of the arrhythmogenic infarct and border zone with surviving cardiac myocytes as the source of triggers and central players in re-entry circuits. Identification of the arrhythmia critical sites and characterisation of the molecular signature unique to these sites can open avenues for targeted therapy and reduce off-target effects that have hampered systemic pharmacotherapy. Such advances are in line with precision medicine and a patient-tailored therapy.
缺血性心脏病是致命性室性心律失常和心源性猝死（SCD）的最常见原因。在心肌梗死后处于高风险的患者中，植入式心脏复律除颤器是降低 SCD 发生率的最有效治疗方法，消融治疗对于可识别的罪犯病变引起的室性心律失常也可能有效。然而，这些方法并不总是成功的，而且成本相当高，而药物治疗通常效果不佳且无效，有时甚至有致心律失常作用。心律失常机制见解的进步和技术创新导致了改进的介入方法正在进行临床评估，但药物治疗的进展却落后了。我们回顾了当前管理的机制基础，并提供了一个视角，以获得新的见解，这些见解以心律失常性梗死和存活心肌的交界区的复杂组织架构为中心，作为触发和折返环中心参与者的来源。识别心律失常关键部位和这些部位特有的分子特征可以为靶向治疗开辟途径，并减少阻碍系统性药物治疗的脱靶效应。这些进展符合精准医学和个体化治疗的理念。
