High hopes are riding on a new generation of tiny pacemakers, but the Minnesota med-tech companies that make them will be working this week to convince medical experts that the devices can be safely tested and eventually extracted from patients' hearts.
A Food and Drug Administration panel is scheduled to make recommendations Thursday about acceptable rates of patient injuries that happen during the testing and post-approval surveillance of the new pacemakers, in light of injuries reported during early implants. The panel will also hear about whether the new devices can be safely removed from the body or left in permanently.
"It's a novel technology," said Dr. Mark Carlson, St. Jude Medical's chief medical officer. "As such, it's our intent, and I'm sure it's the FDA's intent, that it be introduced in the safest and most effective way possible. And that is part of the conversation we will be having at the panel meeting."
St. Jude Medical, based in Little Canada, was first to market in Europe with its Nanostim device in 2013, but it twice halted implants there while it studied early adverse events. Trials have since resumed. Medtronic, which has major corporate offices in Fridley, got European approval to sell its slightly smaller Micra pacemaker last April. Trials are also underway for the Micra.
The FDA's action on Thursday's panel recommendations will guide that ongoing trial work, as well as the post-approval surveillance that appears certain to be required. Boston Scientific Corp., which has a substantial footprint in Minnesota, will also be governed by the FDA rules for the similarly small pacemaker it intends to publish clinical data on later this year.
"I'd hope the panel takes a measured and well-considered approach to understanding the acute safety parameters that you need to demonstrate to make this sensible, and also some of the long-term considerations," said Dr. Ken Stein, a chief medical officer with Boston Scientific. "I don't think that's throwing cold water on the field. I think that is being sort of appropriate in thinking through the risks vs. benefits for patients."
The tiny new pacemakers are novel because they touch the heart directly, avoiding the need to have thin wires called leads strung through blood vessels and across the tricuspid valve to deliver current. Such leads can become dislodged, dislocated or infected, and they can attract calcium deposits over time.
The new leadless pacemakers also eliminate the infection risk and scarring that comes from the "pocket" of tissue typically created under the skin near the shoulder to hold a traditional pacemaker.
They're implanted using a tube less than 8 millimeters wide, which is inserted in a major vein in the leg and then snaked into the heart's right ventricle. The Nanostim is mounted in the heart tissue with a helix-shaped wire, while the Micra has four flexible tines that hook into the tissue.
Early published data on the Medtronic and St. Jude leadless pacemakers show that the devices are safe and the benefits appear to outweigh the risks, the companies said in written presentations to the FDA panel, posted on the agency's website.
Questions linger, though.
Each device has been associated with at least one patient death.
Early experience shows the devices create risks for perforating heart tissue during implantation (1.6 percent of reported cases) and complications at the puncture site in the groin (fewer than 1 percent of cases), an FDA summary of available data shows.
Such figures raise questions about "the acceptability of observed learning curves" in implanting the devices, FDA officials wrote in a summary of the available clinical data. The document went on to note, however, that the 30-day implantation success rates for leadless pacemakers "seem to be quite high."
A second major question concerns whether the tiny devices can be cleanly extracted from inside the heart once their batteries die, which is expected to happen after seven to 12.5 years. Few of the earliest patients have had their devices long enough to face that issue.
The FDA observes that some doctors may opt to remove and replace a depleted device, while others may feel it safer to install a second one right next to the first. The agency isn't likely to know which route is safer when the companies eventually request full commercial approval, but "it wouldn't be in the best interest of the public health" to delay access to the devices for that reason alone.
Colorado Springs, Colo., resident Chad Stoltzfus was just 36 when he had a Nanostim pacemaker implanted in 2014 as part of a clinical trial. He intends to have it taken out and replaced when it goes.
"Being young, I'd be a little uncomfortable with that many little tiny pacemakers sitting in my right chamber, you know?" said Stoltzfus, who works as an electrocardiogram technician at Evans Army Community Hospital. "If you've ever seen the exact size of a right ventricle, it's not that big."
Back in 2014, Stoltzfus had been on the cusp of getting his fourth traditional pacemaker implanted, after the prior one had to be removed because of a stubborn infection in the lead. The older device leads collected severe calcium deposits that blocked the routes for new leads, leaving his doctors with no choice but to connect the traditional unit in an unconventional way. The idea left him nervous.
Then he heard about a new trial for leadless pacing. The new pacemaker required much less recovery time, and didn't cause him any discomfort.
"It was just night and day different," he said. "With the leadless pacemaker, I can't even tell. I don't have to change anything in my daily routine. No discomfort. And no worry about the wires."
Joe Carlson • 612-673-4779
Twitter: @_JoeCarlson
