Current
pharmacologic strategies for the management of atrial fibrillation (AF) include
use of 1) sodium channel blockers, which are contraindicated in patients with
coronary artery or structural heart disease because of their potent effect to
slow conduction in the ventricles, 2) potassium channel blockers, which
predispose to acquired long QT and Torsade de Pointes arrhythmias because of
their potent effect to prolong ventricular repolarization, and 3) mixed ion
channel blockers such as amiodarone, which are associated with multi-organ toxicity. Accordingly, recent studies have focused on
agents that selectively affect the atria but not the ventricles. Several
atrial-selective approaches have been proposed for the management of AF,
including inhibition of the atrial-specific ultrarapid delayed rectified
potassium current (IKur), acetylcholine-regulated inward rectifying
potassium current (IK-ACh), or connexin-40 (Cx40). All three are largely exclusive to atria.
Recent studies have proposed that an atrial-selective depression of sodium channel-dependent
parameters with agents such as ranolazine may be an alternative approach
capable of effectively suppressing AF without increasing susceptibility to
ventricular arrhythmias. Clinical
evidence for Cx40 modulation or IK-ACh inhibition are lacking at
this time. The available data suggest that atrial-selective approaches
involving a combination of INa, IKur, IKr,
and, perhaps, Ito block may
be more effective in the management of AF than pure IKur or
INa block. The anti-AF efficacy of the atrial-selective/predominant
agents appears to be similar to that of conventionally used anti-AF agents,
with the major difference being that the latter are associated with ventricular
arrhythmogenesis and extracardiac toxicity.
Credits: Alexander Burashnikov; Charles Antzelevitch