Pacemaker Implantation Still Risky, Not Rare With Self-Expanding TAVI Devices

Around one in every nine patients who undergo TAVI with a new-generation self-expanding device will need permanent pacemaker implantation (PPI) within the next 30 days, according to an analysis of registry data. These patients who require a PPI face a higher mortality risk at 1 year, particularly if their baseline left ventricular ejection fraction (LVEF) was lower than 40%.

“Despite major improvements in TAVR outcomes during the last years, conduction disturbances requiring new PPI still represent a major issue, carrying a non-negligible risk of pacemaker-related complications and potentially impacting on patients’ morbidity and mortality,” the investigators note in their paper, published online this week in JACC: Cardiovascular Interventions.

However, evidence has been conflicting as to whether patients who require a PPI are actually at risk for worse outcomes, they point out, and not enough is yet known about next-generation self-expanding transcatheter heart valves (THVs).

For this analysis, which looked at PPI after use of Acurate neo/neo2 (Boston Scientific) and Evolut PRO/PRO+ (Medtronic), the goal wasn’t to rank one device’s performance above another. Rather, said senior author Antonio Mangieri, MD (Humanitas University, Pieve Emanuele-Milan, Italy, and IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy), “the main focus was essentially to investigate what the prognosis was for different types of patients who underwent pacemaker implantation in a broad spectrum of patients who received a self-expanding valve.”

Much of the data showing PPI has a negative impact came from studies of “older and more fragile populations,” he told TCTMD, so it was surprising to see that new PPI continues to so adversely affect prognosis in a younger population with fewer risk factors.

What they learned can help guide management, especially in the patients with low ejection fraction, Mangieri said. The study also confirmed prior reports showing baseline right bundle branch block (RBBB) and implantation depth as important predictors of PPI.

Hasan Jilaihawi, MD (Cedars-Sinai Medical Center, Los Angeles, CA), who wrote an editorial accompanying the paper, said its results are “meaningful.”

“There’s been some disparity in the literature on the prognostic significance [of PPI],” he commented to TCTMD, noting that the new paper is concordant with a 2022 meta-analysis. “This paper reemphasizes that it certainly is prognostically important.” This is especially true for patients with LV dysfunction: in this study, those with LVEF < 40% had more than triple the risk of 1-year mortality with versus without PPI, Jilaihawi added.

The registry data also are “timely,” he said, in that they provide US operators with a look at how the Acurate neo/neo2 performs in real-world use—the devices have yet to garner US Food and Drug Administration approval, but are sold in Europe.

NEOPRO and NEOPRO-2

Led by Matteo Pagnesi, MD (University of Brescia, Italy), the researchers analyzed data on 3,211 patients (mean age 81.6 years; 35.7% male) from the multicenter NEOPRO and NEOPRO-2 registries without prior pacemaker or implantable cardioverter-defibrillator. All underwent transfemoral TAVI between 2012 and 2021 using a self-expanding valve: Acurate neo (n = 1,090), Acurate neo2 (n = 665), Evolut PRO (n = 1,312), or Evolut PRO+ (n = 144).

Overall, 11.3% of patients needed new PPI within 30 days of TAVI. Rates were similar between the Acurate neo and Acurate neo2 (8.8% and 7.7%), and similar between Evolut PRO and Evolut PRO+ (15.7% and 10.4%). While there was a significant difference between Acurate neo and Evolut PRO, this was not seen for Acurate neo2 versus EvolutPRO+.

STS-PROM and EuroSCORE II values were higher in the PPI group. Patients who received a pacemaker were more apt to be male and to have diabetes mellitus, previous CABG, NYHA functional class III or IV, and RBBB at baseline. They also had worse renal function, though the proportion with LVEF values that fell below 50% or 40% didn’t differ between the PPI and no-PPI groups. And while the degree of aortic valve calcification was similar irrespective of PPI, patients in the PPI group had a higher frequency of severe calcification in the left ventricular outflow tract.

Compared with those who didn’t need a pacemaker, the patients who required PPI tended to have larger valves, were less likely to undergo predilatation, more often had their valves repositioned, and had lower mean implantation depth. Both groups had similar VARC-3 technical success, though the pacemaker-treated patients tended to have longer hospital stays. On predischarge echocardiography, the PPI group had lower mean LVEF.

The investigators identified three independent predictors of new PPI that applied to all four devices: STS-PROM score (per 1-percentage point increase), baseline RBBB, and implantation depth (per 1-mm increase).

Independent Predictors of New PPI

By 1 year, patients had higher mortality if they’d received a new PPI than if they had not (16.9% vs 10.8%; adjusted HR 1.66; 95% CI 1.13-2.43). Subgroup analysis showed that this increase was significant among patients with baseline LVEF < 40% (40.7% vs 14.6%; adjusted HR 3.67; 95% CI 1.37-9.83), but not in those with LVEF ≥ 40% (15.1% vs 10.4%; adjusted HR 1.50; 95% CI 0.98-2.23). Similar patterns were seen for the composite of 1-year mortality or CV hospitalization.

For the patients most at risk for receiving new PPI, what “we should do is select a valve with a low probability of pacemaker implantation and we should work [to ensure] the implantation depth is perfect and everything around the procedure is perfect,” said Mangieri, who urged operators to look at the whole patient’s medical needs, not just the intervention itself.

Jilaihawi also emphasized the importance of standardizing procedural technique, the topic being explored by Medtronic’s OPTIMIZE PRO study. Exactly how best to deploy a given THV depends upon its design, he noted. “It’s a combination of knowing that particular device and how to optimize the technique that can further reduce the rate of that complication.”

For patients who do need a pacemaker, there are ways to lessen the chance for harm. “Frequency of RV pacing is relevant. If you can program with our electrophysiologists the settings of the pacemaker such that, for instance, AV delay is optimized so the pacing burden is lower, perhaps that can influence prognosis,” he explained.

One reason why PPI-treated patients face worse outcomes may be because the pacemaker can worsen tricuspid regurgitation, Jilaihawi pointed out. “The question is, does having a right ventricular pacing lead contribute to tricuspid regurgitation and can it influence prognosis, particularly in patients who already have LV dysfunction?” The mechanism isn’t yet clear, but it’s possible that leadless pacemakers could reduce risk, he suggested.

Cardiac resynchronization therapy (CRT), too, could play a role as an alternative in the most vulnerable patients, Jilaihawi observed. In those with PPI, “it’s important to look post-TAVR at this population and assess systematically in clinic what their pacing burden is. If their pacing patient is more than half or more than 40%, . . . then perhaps you should very seriously consider CRT. I think it’s highly relevant to look at that.”