Need for rhythm control in atrial fibrillation (AF)
The potential advantages of rhythm control (achievement and maintenance of sinus rhythm) may include improved cardiac function, better quality of life, prevention of thromboembolism and possible increase in life expectancy . Though the well known AFFIRM trial (The Atrial Fibrillation Follow-Up Investigation of Rhythm Management) as a whole did not show advantage with the rhythm control option in atrial fibrillation, forty seven percent lower mortality in sinus rhythm was noted with on treatment analysis of AFFIRM [Circulation. 2004; 109, 1973–1980]. Hence the ideal strategy may be to maintain sinus rhythm without anti arrhythmic drug therapy because most of the benefits of maintaining sinus rhythm are lost due to the adverse effects of the currently available anti arrhythmic therapy.
Dronedarone is an amiodarone analogue without the iodine moiety and hence without the adverse effects on thyroid or pulmonary function. It has multiple effects on cardiac ion channels like amiodarone. ATHENA trial has documented benefits of dronedarone compared with placebo [N. Engl. J. Med. 2009; 360, 668–678]. The primary end point of the trial was cardiovascular hospitalization or death and a significant reduction was noted. A post hoc analysis of the trial showed reduction of stroke with use of dronedarone [Circulation. 2009; 120, 1174–1180]. ATHENA was the first trial to show beneficial effect on important cardiovascular outcomes in atrial fibrillation with anti arrhythmic therapy.
Pharmacological or ablation therapy for atrial fibrillation?
The need for anticoagulation based in on stroke risk and not whether sinus rhythm is maintained or not. Available anti arrhythmic drug therapy has poor efficacy and significant drawbacks. In one study, anti arrhythmic drug adverse effects increased mortality by forty nine percent offsetting the fifty three percent decrease in mortality obtainable by maintaining sinus rhythm. Circumferential pulmonary vein ablation which is an important mode of rhythm control in atrial fibrillation has been shown to be effective in nearly ninety percent in certain studies, though most other studies have shown modest results of about two thirds. Mechanism of therapeutic effect of circumferential pulmonary vein ablation would include pulmonary vein trigger elimination, electrophysiological substrate modification as well as transient vagal denervation. A study by Papone et al published in 2003 using circumferential pulmonary vein ablation reported sinus rhythm in seventy eight percent compared with thirty seven percent in control group. The results of Stabile et al (2006) was fifty six percent versus nine percent and that of Papone et al in 2006 was eighty six percent versus thirty five percent. Wazni and colleagues reported similar results of eighty seven percent versus thirty seven percent for pulmonary vein isolation, in 2005. ThermoCool AF study by Wilber DJ et al (2010) enrolled patients with symptomatic atrial fibrillation who failed a single antiarrhythmic drug. They could document better intermediate outcomes with catheter ablation compared with anti arrhythmic therapy. CABANA trial is currently enrolling high-risk patients with atrial fibrillation who are being randomized to catheter ablation or medical management with rate or rhythm-control strategy. The primary end point of the study is all-cause mortality. The results are expected in 2015.
Till the new trials are completed, an individualized approach may be better in managing atrial fibrillation. For example, in a young healthy patient with atrial fibrillation, a strategy to achieve and maintain sinus rhythm with cardioversion, anti arrhythmic drug therapy or catheter ablation may be considered rather than rate control. In contrast, an older patient may have minimal or no symptoms with atrial fibrillation, especially if they have underlying conduction system disease which leads to a moderate ventricular rate and may need only anticoagulation.
A challenging group to manage would be those with atrial fibrillation and heart failure. Rhythm control options are mostly limited to amiodarone and dofetilide in this group. Dronedarone use has to be limited for only those without any recent decompensation of heart failure.