Dr Bruce L Wilkoff

Although the Pacemaker Remote Follow-up Evaluation and Review (PREFER) trial wasn't designed to show whether patients fare better clinically when their devices are remotely interrogated on a regular basis, compared with conventional transtelephonic monitoring (TTM), it shows that the strategy "has the potential to improve outcomes by reducing the time between onset and detection of clinical pathology and the indicated therapeutic options," the trial's lead investigator, Dr Bruce L Wilkoff (Cleveland Clinic Foundation, Ohio), said when presenting its results. The older TTM, he said, may be of limited value by comparison, its clinical usefulness in pacemaker follow-up perhaps restricted to detecting battery depletion.

Wilkoff noted that remote monitoring systems have already proven their value in following patients with implantable defibrillators, which, like today's pacemakers, collect copious data not available from rhythm strips. But the strategy had yet to be tested in a randomized fashion in patients with conventional pacemakers, he said.

PREFER randomized 897 patients at 50 US centers, who had been implanted with single- or dual-chamber pacemakers from Medtronic compatible with the company's CareLink Network, to be followed either that way or using standard TTM. Two patients were randomized to remote monitoring for every one assigned to the older method; the two groups were similar with respect to demographics, drug therapy, presence of bradycardia, LVEF, and mean pacemaker age.

Remote interrogations were conducted every three months until month 12, when patients went to the clinic to be evaluated in person. In the TTM group, transmissions were scheduled for every two months up to one year, when patients went to the clinic; patients with dual-chamber pacemakers, however, were evaluated at the clinic, in person, in place of a TTM transmission, at six and 12 months.

Over an average of 375 days, the identification of at least one "clinically actionable event" (CAE) was significantly more common among the 602 remotely monitored patients than the 295 followed with TTM; the rates of this primary end point were 45% and 37.6%, respectively (p<0.0001).

As described by Wilkoff, CAEs were prospectively defined events of potential clinical importance that clinicians could do something about and included nonsustained ventricular tachycardia (VT) of at least five beats, new-onset atrial tachycardia (AT) or atrial fibrillation (AF), device loss-of-capture, AT or AF lasting at least 48 hours, an increase in ventricular pacing, a heart rate exceeding 100 bpm during AF, significant changes in lead impedance, or a jump in the pacing voltage threshold.

In fact, Wilkoff reported, only three CAEs, or 2% of all that occurred over 12 months in the TTM group (as confirmed by device interrogation in the clinic), were picked up by TTM; that is, TTM missed 98% of events. Remote monitoring disclosed 446 CAEs, or 66% of those that occurred in the remote-monitoring group. "So, a very low yield for transtelephonic monitoring," he said.

In an analysis of CAE detection by individual events, significantly better detection by remote monitoring seemed driven by two CAEs in particular: new-onset AT or AF and heart-rate increase during AT or AF; rate differences for the other CAEs didn't reach significance.

"This is potentially very important," Wilkoff said, "as this earlier detection of AT/AF [could] have implied the need to give these patients Coumadin and may have prevented strokes."

On the other hand, Wilkoff said, rates at which clinicians actually responded to individual CAEs didn't differ significantly between the two monitoring groups—although, he observed, such rates trended higher in the remote-monitoring group for several of the CAEs: 24% of new-onset AT/AF events, for example, vs only 5% in the TTM group, or 10% of increases in ventricular pacing, compared with 5% in the TTM group.

The next step after PREFER, Wilkoff said, would be a trial that determines whether earlier event detection with remote monitoring compared with TTM actually cuts mortality or improves other clinical outcomes.