BOSTON—Dynamic Atrial Overdrive (DAO) does not prevent new-onset atrial fibrillation (AF), is often not well tolerated and increases the risk of premature battery depletion, based on the results of ASSERT, a late-breaking clinical trial presented May 11 at the 33rd annual scientific sessions of the Heart Rhythm Society (HRS). Therefore, the study authors recommended that implantable devices no longer get developed with this software.
Initially, ASSERT was conceptualized based on two hypothesis, explained principal investigator Stefan Hohnloser, MD, of the J.W. Goethe University in Frankfurt, Germany:
- Subclinical AF, detected by device memory of modern pacemakers or implantable cardioverter-defibrillators (ICDs), would predict stroke or systemic embolic events in patients without a previous history of AF.
- Continuous atrial overdrive pacing would prevent the development of AF and clinical endpoints.
For the secondary hypothesis, he explained there have been 24 previous randomized studies that assessed atrial preventive pacing with the goal of delaying or preventing AF. “These studies were relatively small with a short follow-up of three to nine months,” Hohnloser said. “Despite the use of multiple algorithms from multiple manufacturers, they failed to produce a consistent message of preventive pacing on the development of AF.”
Thus, he and colleagues sought to organize a definitive trial to answer the outstanding questions.
Of the 2,580 patients enrolled in the ASSERT trial, 2,343 were randomized and followed for an average of 2.5 years, and a maximum of five years. This trial also is unique from the previous trials because none of the patients had a prior history of AF.
The researchers prospectively enrolled hypertensive patients at least 65 years of age, who were receiving a St. Jude Medical pacemaker or an ICD for standard indications. Three months following device implantation and study enrollment, patients receiving pacemakers were randomized to have the DAO (St. Jude) algorithm turned on or off.
The primary endpoint was the development of symptomatic or asymptomatic atrial tachyarrhythmia (AT)/AF more than six minutes documented by surface ECG or surface rhythm strip.
Hohnloser et al found that the primary endpoint occurred in 60 patients in the DAO “ON” group (annual incidence 1.96 percent) compared with 45 in the DAO “OFF” group (annual incidence 1.44 percent). Also, they reported no difference in the mean atrial tachyarrhythmia burden: 2.59 percent of the time in the DAO “ON” group and 1.97 percent in the DAO “OFF” group.
Major clinical events (stroke, MI, cardiovascular death, systemic embolism and heart failure hospitalization) occurred at similar frequencies in the two treatment groups, according to the study authors. In 11.4 percent of patients assigned to DAO “ON,” the algorithm had to be turned off, primarily for intolerable side effects.
Over the course of the study, Hohnloser reported that the pacemaker generator had to be replaced for battery depletion in 4.4 percent of patients randomized to DAO “ON” as compared with 2.5 with of patients assigned to DAO “OFF.”
Inappropriate detections of AT/AF also were more common among patients assigned to DAO “ON” (23 percent) compared with DAO “OFF” (7.7 percent). “This is important to understand because this false-positive detection could lead to unnecessary anticoagulation therapy,” Hohnloser explained. “The main reason for this false-positive AF detection was the presence of repetitive non-re-entered ventricular atrial synchrony, which occurred in almost 20 percent of patients in the DAO ‘ON’ arm, compared with 4 percent in the DAO ‘OFF’ arm.”
Based on their negative results, the ASSERT researchers recommended that these software features should be removed from all future cardiac rhythm devices.
Richard I. Fogel, MD, director of the cardiovascular disease fellowship program at St. Vincent Health in Indianapolis, who chaired the late-breaking trial session, called the data “powerful and compelling.”