Investigational antiarrhythmic agents: promising drugs in early clinical development.
Investigational antiarrhythmic agents: promising drugs in early clinical development.
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DOI：
10.1080/13543784.2017.1353601
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发表时间：
2017-08
影响因子：
6.1
通讯作者：
Dobrev D
中科院分区：
文献类型：
--
作者：
Heijman J;Ghezelbash S;Dobrev D
尽管在心律失常治疗方面已经取得了重要的技术进步（如导管消融技术），但抗心律失常药物（AADs）仍然是大多数心律失常患者的基础治疗方法。目前大多数可用的aad是偶然发现的，不是基于已知心律失常机制和特定靶点的系统发展过程的结果。在过去的20年里，我们对心脏电生理学和心律失常基本机制的理解有了显著的提高，从而确定了基于机制的抗心律失常治疗的新潜在靶点。在这里，我们回顾了心律失常发生机制和AAD治疗的最新进展。此后，我们将重点关注最近受到显著关注的一些抗心律失常靶点：心房特异性K+通道、晚期Na+电流、心脏红嘌呤受体通道2型和小电导Ca2+激活的K+通道。我们重点介绍了这些靶点的抗心律失常药物及其在动物模型和早期临床发展中的抗心律失常作用的证据。将AADs靶向于表型良好的患者的特定亚组可能是必要的，以检测可能在整个人群中模糊的改善结果。此外，选择性AADs的特定组合可能具有协同效应，并可能实现基于机制的定制抗心律失常治疗。
Although there have been important technological advances for the treatment of cardiac arrhythmias (e.g., catheter ablation technology), antiarrhythmic drugs (AADs) remain the cornerstone therapy for the majority of patients with arrhythmias. Most of the currently available AADs were coincidental findings and did not result from a systematic development process based on known arrhythmogenic mechanisms and specific targets. During the last 20 years, our understanding of cardiac electrophysiology and fundamental arrhythmia mechanisms has increased significantly, resulting in the identification of new potential targets for mechanism-based antiarrhythmic therapy. Here, we review the state-of-the-art in arrhythmogenic mechanisms and AAD therapy. Thereafter, we focus on a number of antiarrhythmic targets that have received significant attention recently: atrial-specific K+-channels, the late Na+-current, the cardiac ryanodine-receptor channel type-2, and the small-conductance Ca2+-activated K+-channel. We highlight for each of these targets available antiarrhythmic agents and the evidence for their antiarrhythmic effect in animal models and early clinical development. Targeting AADs to specific subgroups of well-phenotyped patients is likely necessary to detect improved outcomes that may be obscured in the population at large. In addition, specific combinations of selective AADs may have synergistic effects and may enable a mechanism-based tailored antiarrhythmic therapy.
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影响因子：
5.8
作者：
Bartos DC;Grandi E;Ripplinger CM
通讯作者：
Ripplinger CM
影响因子：
5.5
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
37.8
作者：
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通讯作者：
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影响因子：
6.1
作者：
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通讯作者：
Nattel, S