Novel anti-arrhythmic drugs for atrial fibrillation management

Abstract

Atrial fibrillation (AF) is a highly prevalent arrhythmia and responsible for significant morbidity, mortality and health care cost. Considerable work has been performed to improve medical options but treatment success still remains suboptimal. The use of conventional anti-arrhythmic agents has been limited by potentially fatal ventricular proarrhythmia. Thus, novel drug targets have been characterised and are currently being tested in experimental and clinical studies. The atrially (but not ventricularly) expressed ion channel subunit Kv1.5 (conducting the ultra-rapid delayed rectifier, I(Kur)) is a prominent candidate. A variety of drugs that inhibit this current is being evaluated. Human experience with these agents is limited. Atrial expression of connexin 40 and downregulation of this protein in AF turn its modulation into a potential therapeutic approach. The acetylcholine-activated current (I(KACh)) is another novel candidate target for drug therapy. The constitutively active form of this current is increased in human AF and pharmacological inhibition might be of therapeutic value. Certain drugs have I(KACh) blocking properties, but as for I(Kur)-blockers none to date has shown pure selectivity for this current. This article summarizes relevant aspects of the cellular electrophysiology of AF and reviews the actions of pharmacological agents presently available or in development as novel anti-arrhythmic therapy.