Medtronic plc reported positive interim results on the first 171 patients implanted with Evolut transaortic valve replacement (TAVR) devices in its OPTIMIZE PRO clinical trial. The postmarket, prospective, multicenter study is assessing procedural outcomes, including pacemaker rate, associated with in-procedure techniques and post-procedure TAVR care pathways when using the self-expanding, supra-annular Evolut Pro and Pro+ TAVR systems in patients with symptomatic severe aortic stenosis.

Several approaches were used in the study to implant the Evolut TAVR system, including the cusp overlap method, which helps surgeons determine the optimal implant depth so as to reduce interaction with the heart’s conduction system.

The OPTIMIZE PRO study aims to enroll 400 patients at 46 sites in the U.S. and Canada and up to 15 sites in Europe. The primary outcome is all-cause mortality or all-stroke at 30 days. Secondary endpoints include discharge time, percentage of patients with more than moderate aortic regurgitation and the rate of pacemaker implant for new onset or worsening conduction disturbance at 30 days. The study will also consider rehospitalization rates and discharge time at 30 days and one year.

Two pathways are being employed in the study – a TAVR care pathway to assess common practices such as conscious sedation and early mobilization and a conduction disturbance pathway to further inform the management of patients with conduction disturbance who might require a pacemaker following TAVR.

Interim results

Findings from the interim analysis showed positive safety outcomes at 30 days, with no deaths or disabling strokes and a low, 8.8% pacemaker rate. Hemodynamic performance, or blood flow, was also good, with low mean gradients of 8.1 mm Hg and low rates of total aortic regurgitation at discharge – 80.4% in a majority of patients and 19.6% in the rest. The mean hospital length of stay was one day.

The interim data show that the optimized pre- and post-TAVR pathways and cusp overlap technique can produce excellent patient outcomes, Kendra Grubb, surgical director of the Structural Heart and Valve Center at Emory Healthcare in Atlanta and co-principal investigator in the OPTIMIZE PRO study, told BioWorld. “Using the cusp overlap technique, we can achieve single-digit pacemaker rates using the Medtronic Evolut valve.”

Investigators have now shown that patients with severe aortic stenosis who get the Evolut TAVR valve can be safely discharged a day later with no adverse events out to 30 days, she added. “The biggest takeaway is that the cusp overlap technique works “It’s a recipe – when you follow the recipe, you get excellent results.”

Grubb presented the data April 28 at the virtual Society for Cardiovascular Angiography and Interventions 2021 Scientific Sessions.

Confirms experience at seen at single centers

The early results confirm what surgeons are seeing in single center cases, which is very low, single-digit pacemaker rates and extremely low complication rates, Grubb said.

“The data from the interim analysis suggests that next-day discharge after TAVR is appropriate for patients who under TAVR with the Medtronic Evolut valve using the cusp overlap technique, and now single-digit pacemaker rates are expected,” she said.

“For clinicians, this means transitioning to the cusp overlap technique can provide even better outcomes for patients undergoing TAVR with the Evolut platform. The procedure changes are small but make a huge difference; using a stiffer guidewire and focusing on the depth of deployment on the lowest point in the annulus (the non-coronary cusp) and being careful to avoid any interaction with the conduction system is all that is need to achieve single-digit pacemaker rates.”

For patients, “this means lower rates of pacemakers and complications with outstanding results at 30 days.”

The OPTIMIZE PRO study has enrolled over half of the patients in the as-treated cohort in the U.S. and expects to complete enrollment later this year. The recent expansion to Europe will add another 200 patients, and the timing of the final results will depend on those patients.

Nina Goodheart, president of Medtronic’s structural heart and aortic business, stressed the need for more standardized and refined TAVR care pathways to improve patient outcomes. “In addition to helping us better understand the site-driven dynamics around conduction disturbance post-TAVR, the study also allows us to generate additional evidence around the Evolut Pro and Pro+ systems’ advanced sealing skirt and its impact on paravalvular leak,” she said.

Last fall, Dublin-based Medtronic kicked off two new trials of its Evolut TAVR system – the randomized, head-to-head SMART study comparing the self-expanding Evolut Pro and Pro+ against Edwards Life Sciences’ balloon-expanding Sapien 3 and Sapien 3 Ultra transcatheter heart valves and the Evolut EXPAND TAVR I feasibility study to explore TAVR use in patients with symptomatic moderate and asymptomatic severe aortic stenosis.

The first patients have been successfully enrolled in the SMART trial, with the first implant occurring earlier this month at the University of Pennsylvania, a Medtronic spokesperson told BioWorld. “We are also moving forward with the EXPAND studies in patients with asymptomatic and moderate AS,” the spokesperson said.