The combination of carvedilol and digoxin appears generally superior to either carvedilol or digoxin alone in the management of AF in patients with HF.

Atrial fibrillation (AF) causes substantial morbidity and mortality. It may be triggered and sustained by either reentrant or nonreentrant electrical activity. Human atrial cellular refractory period is shortened in chronic AF, likely aiding reentry. The ionic and molecular mechanisms are not fully understood and may include increased inward rectifier K+ current and altered Ca2+ handling. Heart failure, a major cause of AF, may involve arrhythmogenic atrial electrical remodeling, but the pattern is unclear in humans. Beta-blocker therapy prolongs atrial cell refractory period; a potentially antiarrhythmic influence, but the ionic and molecular mechanisms are unclear. The search for drugs to suppress AF without causing ventricular arrhythmias has been aided by basic studies of cellular mechanisms of AF. It remains to be seen whether such drugs will improve patient treatment.

There is a paucity of controlled clinical trial data for the management of AF among patients with heart failure. The interaction between AF and heart failure means that neither can be treated optimally without treating both. Presently treatment should be on a case by case basis.

The observed atrial cellular electrophysiological changes associated with chronic beta-blockade are consistent with a long-term adaptive response, a type of 'pharmacological remodelling', and provide mechanistic evidence supportive of the anti-arrhythmic actions of beta-blockade.