Leadless Pacemakers Will Be Game Changers—Someday

Leadless pacemakers and implantable cardioverter defibrillators (ICDs) are expected to deliver a welcome jolt to the cardiac rhythm management (CRM) market in the coming years owing to their small profile, potential to reduce complications, and shorter recovery times. The pace at which they live up to that potential may be slower than anticipated, however.

While transvenous devices have long been the standard of care, they’re not without significant drawbacks. Several high-profile recalls during the past decade, for example, landed leads under the microscope. Medtronic recalled its Sprint Fidelis defibrillation leads in 2007 because of their potential for fracture while St. Jude Medical yanked its Riata ICD leads from the market in 2011, citing the potential for insulation failure.

Repositioning, lead fractures, pneumothorax, chronic lead perforation, and pocket infections, among other complications, also pose serious risks to patients. “The Danish Pacemaker Registry shows somewhere between 7 and 12% complication [rates] of pacemaker implants within two years. That’s quite a larger number. And because pacemakers are so common, we as physicians tend to accept this 7 to 12% complication rate,” Reinoud Knops, a cardiologist at the Academic Medical Center in Amsterdam, said during a recent conference call on leadless pacemakers hosted by BMO Capital Markets. “I really think that this leadless pacemaker technology might have an answer to really tackle some of these complications.”

The two products currently leading the way are St. Jude Medical’s Nanostim leadless pacemaker, which obtained a CE Mark last year, and Medtronic’s Micra transcatheter pacing system, which is targeting a CE Mark by the end of 2015. Initial results for these single-chamber pacemakers are relatively promising, according to Knops, who has experience implanting both pacing products and has consulted for both companies. He noted that both first-generation pacemakers have already demonstrated that their functionality and longevity are on par with those of traditional devices. 

Yet despite the truly disruptive nature of the technology, leadless pacemakers aren’t going to be a pacing panacea right from day one. There are still improvements, unanswered questions, and challenges that need to be addressed in order for leadless pacemakers to gain widespread market adoption and truly disrupt the CRM market. 

The issue of extractability is one such unanswered question. “These are devices that we currently know how to put in, but we don't know if we'll be able to get them out in a couple of years if the battery gets depleted,” Knops said. Because of this unknown, Knops and his colleagues are currently only targeting patients that are over 70, which further limits an already small pool of potential candidates for single-chamber leadless pacing. 

However, he also added that the Nantostim, because of its long, thin profile, may not require removal; experiments indicate that physicians may be able to add in a second pacemaker next to it without any negative consequences. 

As with conventional pacemakers, battery life and power management remain among the most significant obstacles for leadless pacemakers. The first-generation leadless pacemakers boast battery life relatively comparable to that of conventional pacemakers. And despite the leadless pacemakers’ dramatic size reduction compared with their transvenous counterparts, 80% of the ultrasmall Nanostim is taken up by the battery, according to Knops. 

If the extensive R&D focused on energy harvesting methods in academia and startups’ labs bears fruit, then leadless pacemakers could be further revolutionized. “If you could…get energy harvesting from the body from movement of heart or pressure differences of the heart, then you could even make the pacemaker much smaller,” Knops said. “Maybe it could last a lifetime if you can recharge the battery inside the body.”

The final major hurdle for leadless pacemakers is the steep learning curve for physicians. Knops noted that, for both systems, first-time procedures clocked in at about an hour but were reduced to just 15-20 minutes with practice. They also can be risky in the hands of the inexperienced, though. Several reports of perforations—two of which resulted in fatalities—during first-time implantations of the Nanostim resulted in a temporary cessation of a postmarketing study in Europe that has since resumed. Knops asserted his confidence in the Nanostim product, however, attributing the events to that steep learning curve coupled with poor patient selection. 

Assuming studies demonstrate the safety and effectiveness of these devices and challenges can be addressed, future generations of leadless pacemakers could be a boon for medtech companies and patients alike.

And that’s becoming increasingly evident as both technologies continue to garner positive feedback from the physician community. In fact, two recent calls with physicians on leadless pacing hosted by BMO Capital Markets and Leerink Partners, respectively, indicate that the technologies are finally also getting analysts’ attention.

“We expect the [worldwide] pacer market to be ~$3.8B by 2016, with leadless pacers representing a ~$700M market opportunity. If these physicians are right, this would imply a leadless pacer market opportunity more than 2x current expectations,” according Leerink’s write-up of its call.

Because of this growth potential, almost every company in the space in addition to savvy startups are developing leadless pacemakers, according to Knops. But the real opportunity for leadless devices lies beyond simply refining single-chamber pacing technology. Combining leadless pacemakers with ICD therapies could be a lucrative endeavor, for example.

Physicians seem to agree, though, that the Holy Grail is the development of a dual-chamber pacing device. “Ultimately, the winner in leadless pacing will be the company that launches the first dual-chamber device—a potential $3B market opportunity, according to St. Jude,” according to Leerink. “As of today, St. Jude is the only company that has gone on record to confirm a dual-chamber leadless pacer in early stages of development.” Knops predicted that a dual-chamber leadless pacemaker could be just five years away. 

“In my opinion, this is where pacing is going and I really feel like in 10 years you will see the whole pacemaker industry being shifted to these less-invasive devices, less hardware,” Knops said. “I think in 10 years’ time, transvenous pacemakers will be a rare thing.” 

 —Shana Leonard, group editorial director, medical content
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