Pacemaker Predicaments: Reining in Implantation Rates in Low-risk TAVR

The need for permanent pacemakers in patients with severe aortic stenosis who undergo transcatheter aortic valve replacement (TAVR) remains a complication, even as TAVR expands into lower-risk groups. That may prove to be a limitation, especially with younger patients who may have decades of life ahead of them.

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Valves & variations

TAVR for inoperable and higher-risk patients has been approved in the U.S. for two different types of devices: Edwards Lifesciences’ balloon-expandable valves and Medtronic’s self-expanding valves. Edwards, consistently the front runner in the U.S. for TAVR approvals, also won the FDA’s blessing in August 2016 for its newer-generation Sapien XT and Sapien 3 valves in intermediate-risk patients.

In the randomized trial for intermediate-risk patients, the XT showed similar rates to surgery for permanent pacemaker implantation at 30 days, one year and two years (N Engl J Med 2016;374[17]:1609-20). But a registry study assessing the newer Sapien 3 found an unexpectedly higher 30-day pacemaker rate of 13.3 percent in high-risk patients and 10.1 percent in intermediate-risk patients (Eur Heart J 2016;37[28]:2252-62). In addition, a propensity score analysis reported about a 3 percentage point difference between Sapien 3 and surgery for pacemakers at 30 days and one year, but it also found TAVR to be superior for overall outcomes that included death, stroke and moderate or severe aortic regurgitation (Lancet 2016;387[10034]:2218-25).

The risk of needing a permanent pacemaker was significantly higher with Medtronic’s CoreValve in its clinical trial in patients considered at increased surgical risk from 30 days out to three years (N Engl J Med 2014;370[19]:1790-8; J Am Coll Cardiol 2016;67[22]:2565-74).  CoreValve also conferred a significant survival benefit compared with surgery. 

Medtronic’s Evolut R, an iteration that allows physicians to reposition the self-expanding valve, knocked the 30-day permanent pacemaker rate down from CoreValve’s 19.8 percent to 16.4 percent in a single-arm, nonrandomized study (JACC Cardiovasc Interv 2017;10[3]:268-75). A registry study based on cases in the U.K. and Ireland placed the rate even lower, at 14.7 percent (JACC Cardiovasc Interv 2017;10[3]:276-82). The FDA approved the 34 mm Evolut R for high- and extreme-risk patients in October 2016.  

But SURTAVI, the clinical trial evaluating Medtronic’s TAVR valves in intermediate-risk patients, reported a 30-day rate of permanent pacemaker implantation of 25.9 percent vs. 6.6 percent for surgery, with no increased risk of all-cause mortality at two years. The results, which established TAVR’s noninferiority, were presented at the 2017 American College of Cardiology Scientific Session and published in the New England Journal of Medicine (2017;376[14]1321-31).

“This is the reality,” says Josep Rodés-Cabau, MD, a researcher at the Quebec Heart and Lung Institute at Laval University in Quebec City who studies TAVR-related conduction disturbances. “Valve type is a very important factor and nowadays it is not only related to balloon-expandable vs. self-expandable. In the past, it was [Sapien] vs. CoreValve. Now there are many kinds of valves, and we have seen significant differences.”

For instance, a single-arm multicenter trial evaluating Boston Scientific’s Lotus mechanically expanded system reported a one-year permanent pacemaker rate of 31.9 percent for the repositionable and fully retrievable device, along with improved health and quality of life (JACC Cardiovasc Interv 2016;9[4]:376-84). (Boston Scientific voluntarily recalled all of the Lotus valves in February after problems were reported with the device’s locking mechanism.) The 30-day rate for pacemaker implantation in a nonrandomized multicenter evaluation of Direct Flow Medical’s inflatable and repositionable TAVR device was 17 percent (J Am Coll Cardiol 2014;63[8]:763-8). Although the devices received CE mark in Europe, the company reportedly shut down in 2016.

Some of the published data may underestimate the incidence of pacemaker implantations by including patients with prior pacemakers who undergo TAVR in their calculations, according to a study by Rodés-Cabau and colleagues (J Am Coll Cardiol 2016;68[21]:2387-9).

Excluding those patients resulted in a higher incidence rate, with balloon-expandable and self-expanding valves reaching mean estimated upper limits of 8.4 percent and 29.9 percent, respectively (see figure above).

Rodés-Cabau points out that the earlier TAVR studies enrolled older patients, with a sizable number who already had pacemakers. “Probably when we move to younger patients, the number of pacemakers [at baseline] will decrease,” he says. “Still, I think it is pertinent to provide this insight about the real risk patients have instead of including those patients with a prior pacemaker.”

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Lifetime burdens 

Some elderly patients with aortic stenosis may be destined to need a pacemaker, says Vinod H. Thourani, MD, co-director of the Structural Heart and Valve Center at Emory University School of Medicine in Atlanta, an investigator in the PARTNER 2 trial that evaluated the second-generation Sapien valves and the lead author of the propensity analysis. The mean age in that study was 82. “Their conduction system is fragile to start off with,” he says.

Implanting a permanent pacing device in a younger patient raises more concerns. Thourani, a member of the executive committee for a trial designed to evaluate Sapien 3 in low-risk patients, says that is a point of discussion for the PARTNER 3 panel.  

“If a 60-year-old gets a pacemaker, that is very different from an 80-year-old getting a pacemaker,” he says. “In a 60-year-old getting a pacemaker, are you going to deal with tricuspid issues down the road? A lot of people who have long-term pacemakers end up having tricuspid regurgitation, so that needs to be monitored very carefully. That is why in the PARTNER 3 study we will be monitoring them for a decade.”

Over their lifetimes, younger patients implanted with a permanent pacemaker also will more likely need generator replacements than octogenarians, says Edward J. Schloss, MD, an electrophysiologist at The Christ Hospital in Cincinnati who works with the hospital’s heart team on pacemaker-related TAVR protocols.

“Each one of those generator replacements will add an infection risk,” Schloss says. In addition, there is “long-term risk to the lead, both based on the dwell time in the body for many, many years and also the fact that younger patients tend to have more lead failures,” possibly because they are more active.

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Reducing complications & inconsistencies

Patient factors such as existing right bundle branch block or calcium burden are known to increase the risk of needing a TAVR-related permanent pacemaker, Rodés-Cabau and Thourani say. Identifying those factors in potential TAVR candidates can help to stratify patients before a procedure.

Technique and the device itself also play a role, and the two can go hand-in-hand. For instance, the Sapien 3 has a longer stent than its older siblings. Initially some physicians positioned it too low, which may have caused conduction disturbances. The depth and sizing protocols were adjusted during enrollment in the Sapien 3 registry study, a change the authors say may explain the lower incidence of pacemakers in the intermediate-risk cohort. Other studies with before-and-after comparisons also found that positioning the valve higher reduced the permanent pacemaker rate.

Physicians can turn to growing evidence to help them select patients, devices and techniques for optimal outcomes but when it comes to the management of conduction issues, there’s a gap. In a survey of 250 TAVR centers in 38 different countries, Rodés-Cabau and colleagues found wide variability in postprocedural monitoring and pacemaker implantation practices (Int J Cardiol 2017;228:640-7).

About one-fifth of respondents reported using no standard protocol for maintaining temporary pacemakers after TAVR. The majority of centers did not continuously monitor patients using EKG for at least 48 hours; only 6 percent and 30.7 percent waited that long after implanting balloon-expandable and self-expanding valves, respectively. In cases of transient atrioventricular block during the procedure, most chose to extend the time for a temporary pacemaker and wait for an indication for permanent pacemaker implantation, but 12.6 percent that used a self-expanding valve and 7.2 percent with a balloon-expandable valve implanted a permanent pacemaker then.

In the absence of strong evidence to inform recommendations, centers may be relying on their own experiences or industry guidance, says Rodés-Cabau. “This reflects very well that there is a need for more data in this field, data that could provide more insights,” he says.

Electrophysiologists who respond to emergencies when conduction problems arise during TAVR, monitor patients afterwards and must determine whether they need a pacemaker or can be safely discharged feel this void, too. “Talk to anybody in my situation and they will tell you that they are vexed by this,” Schloss says. “Why don’t we have a standard of care?”

He and his colleagues at The Christ Hospital initiated a protocol at their institution that guides monitoring for conduction disturbances and specifies that permanent pacemaker implantation during TAVR should be rare and only in the highest-risk patients. They designed the protocol to be straightforward and useful for a range of caregivers.

“We were trying to structure something that could be implemented by nurse practitioners or general cardiologists, a whole wide range of TAVR-implanting physicians,” he says. “Then if we weren’t available for call, they would not do something that would remove our options.”

The Christ Hospital is not alone in its efforts to set up guidelines to ensure proper care. Other electrophysiologists have reached out to Schloss to share their approaches. Their hope is to foster consensus on best practices and prompt research to guide evidence-based recommendations.

Conduction disturbances can occur even if the TAVR was performed perfectly, Rodés-Cabau notes. As TAVR edges into lower-risk patients, it will be important to educate patients about options and possible complications, he says. “If the patient is aware, it also in the end will be a patient’s decision,” he says. “You have pros and cons. Nothing is perfect.”