Kingma John, Simard Chantale, Drolet Benoît
Department of Medicine, Ferdinand Vandry Pavillon, 1050 Av. de la Médecine, Québec City, QC G1V 0A6, Canada.
Faculty of Pharmacy Ferdinand Vandry Pavillon, 1050 Av. de la Médecine, Québec City, QC G1V 0A6, Canada.
Pharmaceuticals (Basel). 2023 Jun 6;16(6):844. doi: 10.3390/ph16060844.
Maintenance of normal cardiac rhythm requires coordinated activity of ion channels and transporters that allow well-ordered propagation of electrical impulses across the myocardium. Disruptions in this orderly process provoke cardiac arrhythmias that may be lethal in some patients. Risk of common acquired arrhythmias is increased markedly when structural heart disease caused by myocardial infarction (due to fibrotic scar formation) or left ventricular dysfunction is present. Genetic polymorphisms influence structure or excitability of the myocardial substrate, which increases vulnerability or risk of arrhythmias in patients. Similarly, genetic polymorphisms of drug-metabolizing enzymes give rise to distinct subgroups within the population that affect specific drug biotransformation reactions. Nonetheless, identification of triggers involved in initiation or maintenance of cardiac arrhythmias remains a major challenge. Herein, we provide an overview of knowledge regarding physiopathology of inherited and acquired cardiac arrhythmias along with a summary of treatments (pharmacologic or non-pharmacologic) used to limit their effect on morbidity and potential mortality. Improved understanding of molecular and cellular aspects of arrhythmogenesis and more epidemiologic studies (for a more accurate portrait of incidence and prevalence) are crucial for development of novel treatments and for management of cardiac arrhythmias and their consequences in patients, as their incidence is increasing worldwide.
维持正常心律需要离子通道和转运体的协同活动,这些离子通道和转运体能够使电冲动在心肌中有序传播。这一有序过程的中断会引发心律失常,在某些患者中可能是致命的。当存在由心肌梗死(由于纤维化瘢痕形成)或左心室功能障碍引起的结构性心脏病时,常见获得性心律失常的风险会显著增加。基因多态性会影响心肌基质的结构或兴奋性,从而增加患者心律失常的易感性或风险。同样,药物代谢酶的基因多态性会在人群中产生不同的亚组,影响特定的药物生物转化反应。尽管如此,确定参与心律失常起始或维持的触发因素仍然是一项重大挑战。在此,我们概述了关于遗传性和获得性心律失常生理病理学的知识,并总结了用于限制其对发病率和潜在死亡率影响的治疗方法(药物治疗或非药物治疗)。更好地理解心律失常发生的分子和细胞方面以及更多的流行病学研究(以更准确地描绘发病率和患病率)对于开发新的治疗方法以及管理心律失常及其对患者的后果至关重要,因为心律失常在全球范围内的发病率正在上升。