Can progression to permanent atrial fibrillation be prevented by pacing?

The optimal pacing mode in patients with bradycardia has been searched for through a series of randomized controlled trials performed within the last two decades. It is well documented, and easy to understand, that single lead ventricular pacing disrupting the normal atrioventricular synchrony is associated with a higher incidence of atrial fibrillation (AF) than dual chamber pacing (DDD) preserving atrioventricular synchrony. Furthermore, in patients with sinus node dysfunction, prevention of AF seems to depend on a delicate balance between the avoidance of excess ventricular pacing and the avoidance of excessively long atrioventricular intervals, both factors promoting the occurrence of AF. Some previous studies have indicated an effect of atrial pacing algorithms in preventing AF. However, the majorityof randomized trials investigating these algorithms showed no convincing effect on reducing AF, and the use of such algorithms is not recommended in the most recent guidelines on cardiac pacing. The MINERVA randomized trial investigated the effect of a combination of preventive atrial pacing algorithms, different antitachycardia atrial pacing algorithms, and managed ventricular pacing (MVP) to minimize ventricular pacing in the subgroup of patients with bradycardia and indication for DDD pacing, who had paroxysmal or persistent atrial tachyarrhythmia without complete atrioventricular block. Using this combination of algorithms was associated with a lower risk of progression from paroxysmal or persistent atrial tachyarrhythmia to permanent AF during follow-up of almost 3 years. The effect on progression to permanent AF was statistically and clinically significant, with a hazard ratio of 0.39 when compared with normal DDD pacing. The investigators should be credited for performing a large multicentre randomized controlled trial with aclinically relevant follow-up period investigating this topic, and for using a design with three treatment arms, two of which represented the pacing modes recommended in the current guidelines and used by most physicians—DDD pacing with a moderately prolonged atrioventricular interval or DDD pacing with MVP. In the light of previous findings, it is no surprise that incidences of death and stroke, and the hospitalization rate did not differ between treatment arms in the MINERVA trial. Few deaths and strokes were observed during the study, and the difference observed in the composite primary endpoint of permanent AF, death, or cardiovascular hospitalization was carried exclusively by a difference in progression to permanent AF. The finding that use of MVP alone had no effect on progression to permanent AF is in agreement with the results of the Danish Multicenter Randomized Trial on Single Lead Atrial Pacing versus Dual Chamber Pacing in Sick Sinus Syndrome as well as with the findings from the recent Prefer for Elective Replacement Managed Ventricular Pacing randomized (Prefer-MVP) trial. One important limitation of the MINERVA trial needs to be considered. The study was performed as a single-blinded trial where the investigators, who were responsible for assessing the primary endpoint—including permanent AF, defined as ‘long AF duration coupled with decision not to convert the patient’—were aware of the assigned treatment of the patients. The lower incidence of cardioversions in the interventiongroup,withthepacingalgorithmsactivated, supports that this treatment truly reduces progression to permanent AF. It cannot be excluded, however, that the single-blinded design may have introduced a bias in differentiated use of antiarrhythmic drug therapy and catheter ablation for atrial tachyarrhythmias in the three treatment arms during the conduct of the study. The results of the MINERVA trial raise some important questions. Which pacing intervention is effective for different patient groups in preventingprogression topermanent AF? Previous trials indicate that simple overdrive pacing or the combination of atrial preventive pacing algorithms used in the present study is not highly effective. Antitachycardia atrial pacing has been found to be moderately effective in terminating slow regular arrhythmias, but does not reduce AF burden. It is hard to believe that antitachycardia pacing delivered in the right atrial appendage is effective for terminating mostepisodesof AF, originating from the left atrium, and often with very high rate atrial activity (Figure 1). A subgroup of patients included in the MINERVA