PARIS, France -- More than one in five Acurate neo2 transcatheter heart valves (Boston Scientific) implanted in patients as part of the ACURATE investigational device exemption (IDE) study were underexpanded, a new analysis shows. In these cases, patients fared significantly worse compared with those with a fully opened valve.

At 1 year, the risk of all-cause mortality, stroke, or rehospitalization was 18.7% among patients with underexpanded valves and 11.8% in those with properly expanded devices (P = 0.04). For the harder endpoint of all-cause mortality or stroke, the rates were 13.5% and 7.3% in the two cohorts, respectively (P = 0.02).

Investigators say the findings, which were published in the Journal of the American College of Cardiology to coincide with a presentation last week at EuroPCR 2025, should be considered hypothesis-generating only.

"I think it's fair to say that valve design modification to increase radial strength and careful consideration of pre- and postdilatation may improve valve expansion," said lead investigator Raj Makkar, MD (Cedars-Sinai Medical Center, Los Angeles, CA), during the Hot Line session. Whether an improved device, or better expansion with the existing one, translates into better clinical outcomes is unknown, he said.

"It is important to have well-expanded valves, and for that, when possible, we must do effective predilatation during the procedure," he continued. "We should now start paying attention to the fluoroscopic expansion and appearance of valves, and postdilate when feasible and when it can be done safely."

The post hoc analysis is an attempt to better understand why Acurate neo2 failed to demonstrate noninferiority in the ACURATE IDE trial. The study included 1,500 patients across the spectrum of surgical risk and compared Acurate neo2, a supra-annular, self-expanding valve, to commercially available balloon-expandable Sapien valves (Sapien 3 and Sapien 3 Ultra) and self-expanding Evolut valves (CoreValve Evolut R, Evolut PRO, Evolut PRO+, and Evolut FX).

At the time of the trial's presentation last year at TCT 2024, senior investigator Michael Reardon, MD (Houston Methodist DeBakey Heart & Vascular Center, TX), said lack of familiarity with the new device may have contributed to valve underexpansion and this likely explained the higher risk of all-cause mortality, stroke, or rehospitalization with Acurate neo2. The full results of ACURATE IDE were published just last week in the Lancet.

Lower Radial Opening Force

The new analysis focuses on 624 patients randomized to Acurate neo2 in the IDE trial with procedural angiograms available for review by an independent core laboratory. Of these, 135 (21.6%) had underexpanded valves based on a visual assessment identifying angulated commissure posts. Baseline characteristics and outcomes were compared with the 489 patients who received an expanded device.

"When we looked at the baseline characteristics, essentially we did not see any differences between the underexpanded and the expanded Acurate neo2 valves," said Makkar. "We did observe that patients who had an underexpanded neo2 valve actually had somewhat tighter aortic stenosis [with] somewhat higher gradients, lower [Doppler velocity index], and they were found to have larger annular areas on CT. There was also the presence of more leaflet calcium in patients with an underexpanded valve."

An improperly expanded device in patients with greater leaflet and annular calcification is consistent with valves, like Acurate neo2, with lower radial opening force, said Makkar.

Addressing what might have contributed to underexpansion, Makkar said rates of pre- and postdilation and balloon sizing were no different between the expanded and underexpanded cohorts.

Hemodynamic outcomes at 1 year also were no different between those with an expanded and underexpanded Acurate neo2. There was no significant difference in the incidence of moderate or severe paravalvular leak between the two groups. Valve thrombosis rates were low at 1.5% in the underexpanded group and 0.4% in the expanded cohort (P = 0.16). Rates of subclinical leaflet thrombosis did not significantly differ between the two groups but were numerically higher in those with expanded valves.

"We were all very tempted to postulate, 'Oh, we are going to look at the CT substudy and we are going find dramatically higher subclinical valve thrombosis rates [with underexpanded valves],'" said Makkar. "That was not the case."

What Might Have Been?

During the presentation, Makkar presented a "what if" scenario: here, the risk of death, stroke, or rehospitalization would not have been not significantly different between those with a fully expanded Acurate neo2 versus the 730 patients in the control group of ACURATE IDE. The same would apply to the stricter endpoint of death or stroke. He acknowledged the comparison "isn't scientifically rigorous," however, because the control group also includes expanded and underexpanded Sapien/Evolut valves.

Harlan Krumholz, MD (Yale University School of Medicine, New Haven, CT), editor-in-chief of JACC, praised the researchers for attempting to understand why Acurate neo2 disappointed in its pivotal trial. With the underexpansion analysis, he was still left wondering whether the reasons can be explained by patient characteristics, operator inexperience, or the valve itself.

Makkar said understanding the failure of Acurate neo2 is a "work in progress." The valve, which is not approved in the United States, has CE Mark approval in Europe. If it is used, Makkar said it's important to "get good valve expansion." However, he also noted that the 30-day stroke rate among 517 patients (mean age 81.5 years; 50% female) treated with neo2 in the ACURATE Prime registry was 2.9% (versus 1.4% at 30 days in ACURATE IDE). In that study, postdilatation was used in 50% of cases.

"The question is: do we pay a price for [postdilatation]?" asked Makkar. "I think there's a lot more work that needs to be done." Another randomized trial with Acurate neo2, he added, isn't out of the question.