Atrial-selective approaches for the treatment of atrial fibrillation

被引:68
作者
Ehrlich, Joachim R. [1 ]
Biliczki, Peter [1 ]
Hohnloser, Stefan H. [1 ]
Nattel, Stanley [2 ,3 ]
机构
[1] Goethe Univ Frankfurt, Div Cardiol, Sect Electrophysiol, D-60590 Frankfurt, Germany
[2] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada
[3] Univ Montreal, Montreal, PQ, Canada
关键词
D O I
10.1016/j.jacc.2007.08.067
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Atrial-selective pharmacologic approaches represent promising novel therapeutic options for the treatment of atrial fibrillation (AF). Medical treatment for AF is still more widely applied than interventional therapies but is hampered by several important weaknesses. Besides limited clinical efficacy (cardioversion success and sinus-rhythm maintenance), side effects like ventricular proarrhythmia and negative inotropy are important limitations to present class I and III drug therapy. Although no statistically significant detrimental survival consequences have been documented in trials, constitutional adverse effects might also limit applicability. Cardiac targets for novel atrial-selective antiarrhythmic compounds have been identified, and a large-scale search for safe and effective medications has begun. Several ionic currents (I-KACh,I-Kur) and connexins (Cx-40) are potential targets, because atrial-selective expression makes them attractive in terms of reduced ventricular side-effect liability. Data on most agents are still experimental, but some clinical findings are available. Atrial fibrillation generates a specifically remodeled atrial milieu for which other therapeutic interventions might be effective. Some drugs show frequency-dependent action, whereas others target structurally remodeled atria. This review focuses on potential atrial-selective compounds, summarizing mechanisms of action in vitro and in vivo. It also mentions favorable interventions on the milieu in terms of conventional (such as antifibrotic effects of angiotensin-system antagonism) and innovative gene-therapy approaches that might add to future AF therapeutic options.
引用
收藏
页码:787 / 792
页数:6
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