Atrial-selective pharmacologic approaches targeting specific ionic currents and connexins offer promising therapeutic potential for atrial fibrillation with reduced ventricular side-effect liability.
Atrial-selective antiarrhythmic drugs targeting specific atrial ion channels and connexins offer a promising strategy to treat atrial fibrillation while minimizing ventricular proarrhythmic risks.
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.
Ehrlich et al. (Fri,) conducted a review in Atrial fibrillation. Atrial-selective pharmacologic approaches was evaluated. Atrial-selective pharmacologic approaches targeting specific ionic currents and connexins offer promising therapeutic potential for atrial fibrillation with reduced ventricular side-effect liability.