WASHINGTON, D.C.—Boston Scientific’s long-awaited transcatheter aortic heart valve missed its mark in a head-to-head study aimed at bringing the implant to the U.S.—but the company believes it has a fix.
The Acurate neo2 TAVR system reported a higher rate accounting for all-cause deaths, strokes or rehospitalizations after one year, failing the trial’s test for noninferiority against the two main replacement valves on the market. Half of the study’s participants received the physician’s choice of either Edwards Lifesciences’ Sapien 3 or Medtronic’s Evolut family.
The trial was the largest to date of Acurate neo2, enrolling 1,500 patients with severe aortic stenosis at all risk levels for open surgery. The valve delivered a composite rate of 16.16% versus the control group’s 9.53%. The results were presented as a late-breaking trial at the Cardiovascular Research Foundation’s Transcatheter Cardiovascular Therapeutics conference in Washington, D.C.
However, an interesting finding led Boston Scientific to dig deeper into the trial data.
Typically, a major design issue with the valve would result in more adverse events sooner, such as following implantation or within the first month after the procedure—for example, if the problem was related to paravalvular leaks, or blood escaping around the sides of the implant. But the neo2 was specifically designed to address that, with the addition of a sealing skirt around its edges compared to its predecessor.
Instead, the paths of the study’s two arms only began to diverge much later.
“Once we got all our data together, we saw that our procedure results were great and our 30-day results were great,” the Acurate IDE study’s co-principal investigator, Michael Reardon, M.D., said in an interview with Fierce Medtech. “It was only the one-year results—that we didn't even find out about until the data monitoring committee pointed out that we were going to miss our endpoint—only the one-year results were out of line. So we started looking for reasons why that might be.”
The company conducted a post hoc review of each case and found that in many Acurate neo2 procedures—about 20%—the valve was not fully expanded during its placement.
“If you don’t fully expand the valve, then there’s several things we can see,” said Reardon, the Allison Family Distinguished Chair In Cardiovascular Research at Houston Methodist and Weill Cornell Medical College. “First off, the expanded valve has better, cleaner flow and lower velocities, and it has laminar flow. An under-expanded valve has higher velocities and non-laminar flow.”
He said that difference offers up a plausible explanation: Faster, more turbulent blood flow can lead to more platelet activation and clumping—forming floating clots that could then trigger more heart attacks or strokes.
Reardon also noted that, while many clinicians reported that the valve was easy to safely deploy during a procedure—through a two-step process that first extends stabilizing arms to help slot it into place within the aortic valve before finally expanding and securing the main column of the implant—with the trial spread out across 71 sites and four years spanning the COVID pandemic, individual locations went three months between implanting Acurate valves, on average.
And, while the neo2 has been available in Europe since early 2020, with more than 80,000 patients treated globally, many users in the U.S. may not have been totally familiar with its workings. That may have led to clinicians missing a telltale sign that the valve was not fully expanded—which Boston Scientific said is easily correctable.
“You can tell valve under-expansion by looking at how parallel the commissure posts are” under angiographic imaging in real time during the procedure, said Reardon, adding that the waist of the implant should also be as wide as the valve is tall. If the struts in the implant’s frame are not in alignment, it’s a clear sign that a balloon should be used to further expand the valve, he said.
In addition, the company emphasized that the patient’s natural aortic valve should be properly dilated before inserting the self-expanding implant.
“Every TAVR valve is a little bit different, and with Acurate it is super crucial that you do what we call an effective pre-dilatation, at 1 millimeter less than the perimeter-derived diameter,” Boston Scientific’s chief medical officer for interventional cardiology therapies, Janar Sathananthan, M.D., said in an interview. “So you want a balloon, very simplistically speaking, that's pretty close to the size of the landing zone where you're going to put the valve. That's very important for the expansion of the valve.”
Reardon said this pre-dilation was not correctly performed in about 80% of cases, with some balloons 4 millimeters or 5 millimeters smaller than the valve’s diameter. Going forward, the company said spotting and correcting under-expansion would improve Acurate neo2’s performance.
“We looked at all the cases, and we found that using a very simple method, it can be identified by any operator—a very binary method, yes or no. We basically had a small proportion of the cases that were severely under-expanded, but they contributed to quite a significant number of events,” said Sathananthan.
According to the study, under-expansion was associated with a twofold increase in risk of death and a threefold increase in risk of stroke. By separating out that 20% of cases and focusing only on patients who had a properly implanted valve replacement, the primary endpoint composite rate dropped to 12.4%.
In measures of death and stroke in the post hoc analysis specifically, the rates from fully expanded Acurate neo2 valves aligned almost perfectly with the control group’s at the one-year time point, according to Reardon. Sathananthan said the company is actively communicating with the FDA on the next steps for the valve.
“Once you see this, you cannot unsee this … the posts [not being parallel] lights up the screen like a Christmas tree,” Reardon said. “I would say that across the field, TAVR under-expansion has been becoming more recognizable, among all the valves—and in this particular valve, we just didn't know how to see it.”