FDA Panel Weighs Leadless Pacemaker Retrieval, Perforation Concerns

Deborah Brauser

February 19, 2016

GAITHERSBURG, MD — The subject of leadless cardiac pacemakers took center stage at yesterday's meeting of the FDA's Circulatory System Devices Panel advisory committee (AdCom), with talk on adverse events, especially cardiac perforation; possible indications; long-term safety issues, including battery longevity; and postmarket surveillance.

The purpose of the all-day meeting wasn't to get a thumbs up or down from the panel members on whether to recommend the devices, which are not currently available in the US, but to discuss ways to better assess the class as a whole—a goal that AdCom chair Dr Richard Page (University of Wisconsin, Madison) said was reached.

"This is transformative technology," said Page. "Today was about how to learn more about these devices" and to provide a template to measure performance in future reviews, he added.

The day started with a presentation of the FDA executive summary memorandum, which noted that there are currently no significant data on device retrievals or any long-term data, such as at the device's end of life, and stressed the need for training.

Later, representatives from Medtronic, which has developed the Micra leadless pacemaker, and from St Jude Medical, which has developed the Nanostim leadless pacemaker, discussed trial details for their devices, laid out plans for postapproval studies, and presented ideas for physician training programs.

For the latter, St Jude discussed a seven-module mandatory program that would include focusing on patient selection, an implant demo, animal lab and/or virtual reality training, and site training.

A short presentation was also made by Boston Scientific, which is working on a leadless pacemaker to work with its subcutaneous implantable cardioverter defibrillator (S-ICD).

Perforation Concerns

Draft questions for the panel at the end of the meeting included potential concerns for possible device-related adverse events, such as cardiac perforation, pericardial effusion, dislodgement, and embolization—and whether the events should be looked at together as "overall complications" or should be evaluated separately.

"We need to look at each individual one," replied Dr Jeffrey S Borer (State University of New York Downstate Medical Center, Brooklyn). He noted that although there have been reports of groin complications, he's "not terribly worried" about that because "it's probably from the size of the catheters being used and will come down in time." He added that the rate of embolization was small and he also wasn't concerned about dislodgement.

"But cardiac perforation is a big deal to me, because it's potentially lethal and likely to lead to an additional procedure," said Borer.

"We clearly don't have enough numbers to say this with any precision, but it looks like there are 50% more perforations with leadless pacemakers currently than with the conventional approach," he said. "So I think the FDA should be looking into that and effusions."

Dr David D Yuh (Yale University School of Medicine, New Haven, CT) agreed, stressing the need to figure out perforation risk factors and ways to mitigate it. "Why do these devices perforate? If it's not technical expertise of the operator, is it a structural consideration in terms of dimensions?"

Dr Jeffrey A Brinker (Johns Hopkins Hospital, Baltimore, MD) noted that he's "amazed" there aren't more complication rates from the devices. "They're rigid by nature of their construct." And, he noted, the patient population is older and frailer.

"Although I believe perforation is a concern, I think proper training and care will decrease that rate. And I believe modifications of the devices over time will be important," said Brinker. "At the end, I think the net benefit over alternative devices in this particular group of patients needs to be the determinator, not a specific end point like the perforation data."

Lack of Long-term Data

After more adverse-event discussion, Page reported that the panel consensus was that "there is no more risk of infection from these devices, based on what we've heard, and maybe less. But robust training is needed."

As for the devices' long-term performance, he noted lack of data and that their estimated battery life has been predicted to be between 6 and 12 years.

The executive summary lists four "likely scenarios" for device end of life: explant the leadless pacemaker and implant another leadless pacemaker or a transvenous pacemaker system, or turn off the existing leadless pacemaker and implant either an adjacent leadless pacemaker or adjacent transvenous pacemaker.

"It should be noted that the [leadless pacemaker] is expected to be fully encapsulated, which differs from traditional pacemaker/lead systems," states the summary, adding that the FDA is interested in collecting postapproval data on which approach clinicians decide to use.

Several panel members also suggested the creation of a registry for all patients who receive these devices—especially to capture unpredicted complications.

In addition, the panel mostly agreed that complication-free rate should be used as an end point for long-term performance and that the postapproval sample should include at least 1741 patients (to give a 1.6% upper limit of the 95% CI).

As for recommendations for labeling regarding extractions, replacements, and best-practices, Dr Richard A Lange (University of Texas Health Science Center, San Antonio) said that "this might be more device-specific rather than for the general class."

Borer agreed. "I think this should be revisited at the time approval is being considered, and the totality of evidence available then can guide what information should be put into the label. We can't guess at what's going to happen."

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