There is some evidence that atrial overdrive pacing can prevent atrial fibrillation (AF) in patients with a permanent pacemaker. However, most of the studies that have shown a benefit were modest in size, included patients with a history of prior AF, and showed only marginal benefit.
The Asymptomatic Stroke and Atrial Fibrillation Evaluation in Pacemaker Patients (ASSERT) trial was a large study that included 2,343 patients undergoing device implantation and was designed to address two questions: what is the impact of device-detected subclinical AF on the development of stroke, and what is the effect of atrial overdrive pacing in patients without prior AF? The results of the first objective have been previously published. The results of the second objective have recently been published online ahead of print.1
The ASSERT trial enrolled patients over age 65 years who were scheduled to undergo implantation of a St. Jude Medical dual-chamber pacemaker or defibrillator for standard indications and had no history of AF. Patients were randomized to continuous atrial overdrive pacing (CAOP) or standard demand pacing. The primary endpoint was the occurrence of AF that was documented electrocardiographically and lasting more than 6 minutes. After 2.5 years, there was no difference in the occurrence of AF in each group. In fact, AF occurred in 1.96% of patients per year with CAOP programmed “ON” compared to 1.44% per year of patients with CAOP programmed “OFF” (p = 0.10). Furthermore, CAOP was poorly tolerated (11% of patients had the CAOP feature deactivated during the study), led to three times the rate of false positive AF detections by the device, and was twice as likely to lead to premature battery depletion.
The ASSERT trial has taught us many lessons. Most importantly, it has taught us that atrial overdrive pacing does not prevent AF in patients who need a pacing device and have never had AF before. But it has also taught us that the incidence of AF in these patients is relatively low to begin with, affecting less than 2% of patients per year, and that any bell or whistle in a device comes at a price — energy consumption from the battery. This trial also emphasizes the power of very large randomized trials, and the importance of testing pacing algorithms after they have already become commercially available. The company should be commended for sponsoring a trial that challenged the benefit of one of their already available pacing features.
So why did overdrive pacing not prevent AF in these patients? In theory, it should have prevented sudden sinus or post-ectopic pause-related AF. Is the concept itself flawed? Is it possible that any beneficial effect that continuous pacing provides, is outweighed by the unnatural effects of pacing the right atrial appendage? Perhaps CAOP would be beneficial if the atrial pacing lead were placed on the atrial septum to decrease total atrial activation time.
Much could also be learned about the mechanisms of AF by analyzing the AF events that occurred during the study. The authors explained that the higher rate of false positive AF detection by the device when the CAOP was programmed ON, was based on a 4-fold increase in repetitive non-reentrant ventriculoatrial synchrony (RNRVAS). Is it possible that this phenomenon actually triggered AF? Did AF initiate similarly in each group? Did AF occur after an atrial paced event in both groups? There are still many unanswered questions related to the effect of pacing and AF, but after ASSERT, it appears that continuous atrial overdrive pacing does not prevent AF in patients who have never had it before.
- Hohnloser SH, Healey JS, Gold MR, et al, ASSERT Investigators. Atrial overdrive pacing to prevent atrial fibrillation: Insights from the ASSERT Trial. Heart Rhythm 2012 Jun 11. doi: 10.1016/j.hrthm.2012.06.012