Arrhythmia refers to irregularities in the rate and rhythm of the heart, with symptoms spanning from mild palpitations to life-threatening arrhythmias and sudden cardiac death (SCD). The complex molecular nature of arrhythmias complicates the selection of appropriate treatment. Current therapies involve the use of antiarrhythmic drugs (class I-IV) with limited efficacy and dangerous side effects and implantable pacemakers and cardioverter-defibrillators with hardware-related complications and inappropriate shocks. The number of novel antiarrhythmic drug in the development pipeline has decreased substantially during the last decade and underscores uncertainties regarding future developments in this field. Consequently, arrhythmia treatment poses significant challenges, prompting the need for alternative approaches. Remarkably, innovative drug discovery and development technologies show promise in helping advance antiarrhythmic therapies. Here, we review unique characteristics and the transformative potential of emerging technologies that offer unprecedented opportunities for transitioning from traditional antiarrhythmics to next-generation therapies. We assess stem cell technology, emphasizing the utility of innovative cell profiling using multi-omics, high-throughput screening, and advanced computational modeling in developing treatments tailored precisely to individual genetic and physiological profiles. We offer insights into gene therapy, peptide and peptibody approaches for drug delivery. We finally discuss potential strengths and weaknesses of such techniques in reducing adverse effects and enhancing overall treatment outcomes, leading to more effective, specific, and safer therapies. Altogether, this comprehensive overview introduces innovative avenues for personalized rhythm therapy, with particular emphasis on drug discovery, aiming to advance the arrhythmia treatment landscape and the prevention of SCD. Significance Statement Arrhythmias and sudden cardiac death account for 15-20% of deaths worldwide. However, current antiarrhythmic therapies are ineffective and with dangerous side effects. Here, we review the field of arrhythmia treatment underscoring the slow progress in advancing the cardiac rhythm therapy pipeline and the uncertainties regarding evolution of this field. We provide information on how emerging technological and experimental tools can help accelerate progress and address the limitations of antiarrhythmic drug discovery.

中文翻译：

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抗心律失常治疗未来药物发现和开发的有前途的工具。


心律失常是指心率和节律不规则，症状从轻度心悸到危及生命的心律失常和心源性猝死 （SCD）。心律失常的复杂分子性质使选择合适的治疗方法变得复杂。目前的疗法涉及使用疗效有限且副作用危险的抗心律失常药物（I-IV 类）以及具有硬件相关并发症和不适当电击的植入式起搏器和心律转复除颤器。在过去十年中，正在开发的新型抗心律失常药物的数量大幅减少，这凸显了该领域未来发展的不确定性。因此，心律失常治疗带来了重大挑战，促使需要替代方法。值得注意的是，创新药物发现和开发技术在帮助推进抗心律失常治疗方面显示出前景。在这里，我们回顾了新兴技术的独特特性和变革潜力，这些技术为从传统抗心律失常药过渡到下一代疗法提供了前所未有的机会。我们评估干细胞技术，强调使用多组学、高通量筛选和高级计算建模的创新细胞分析在开发精确针对个体遗传和生理特征的治疗方法方面的效用。我们提供对基因治疗、肽和肽体药物递送方法的见解。最后，我们讨论了此类技术在减少不良反应和提高整体治疗结果方面的潜在优势和劣势，从而获得更有效、更具体和更安全的疗法。 总而言之，本综合概述介绍了个性化心律治疗的创新途径，特别强调药物发现，旨在推进心律失常治疗前景和 SCD 的预防。意义声明 心律失常和心源性猝死占全球死亡人数的 15-20%。然而，目前的抗心律失常疗法无效且具有危险的副作用。在这里，我们回顾了心律失常治疗领域，强调了推进心律治疗管道的缓慢进展以及该领域发展的不确定性。我们提供有关新兴技术和实验工具如何帮助加快进展并解决抗心律失常药物发现局限性的信息。