Three-year results from the SMART trial presented at the EuroPCR 2026 conference suggest that self-expanding transcatheter aortic valve replacement (TAVR) devices continue to deliver superior hemodynamic performance and lower rates of bioprosthetic valve dysfunction compared with balloon-expandable valves in patients with severe symptomatic aortic stenosis and small aortic annuli.
Despite these advantages, investigators reported no significant difference in major clinical outcomes between the two valve platforms at three years, underscoring the ongoing debate over whether improved valve hemodynamics ultimately translate into better long-term patient outcomes.
Presenting the findings, Howard C. Herrmann said the benefits observed with the supra-annular self-expanding valve may require more time to influence clinical endpoints.
“I think we should start to see it over the next two years,” Herrmann said. “Whether we’re going to be able to show it in the primary endpoint, or only in a secondary endpoint like cardiovascular mortality, remains to be seen.”
Clinical Outcomes Remain Comparable
The SMART trial enrolled 716 low- to intermediate-risk patients with severe symptomatic aortic stenosis and small annuli, comparing the self-expanding Evolut PRO/PRO+/FX platform with the balloon-expandable Sapien 3/3 Ultra valve. The study population had a mean age of 80 years, and women accounted for 87% of participants.
At three years, the primary composite endpoint of death, disabling stroke, or heart failure rehospitalization occurred in 25.4% of patients receiving the self-expanding valve and 22.6% of those treated with the balloon-expandable device. The difference was not statistically significant.
The findings mirror those reported at one and two years, suggesting that any clinical divergence between the valve types has yet to emerge.
Herrmann noted that the advanced age of the study population may make it difficult to demonstrate differences in composite clinical outcomes because competing risks such as non-cardiovascular death can dilute the impact of valve-related events.
Marked Differences in Valve Performance
While clinical outcomes remained similar, substantial differences were observed in valve durability and function.
The trial’s second co-primary endpoint, bioprosthetic valve dysfunction, strongly favored the self-expanding platform. Valve dysfunction occurred in 16.3% of patients treated with Evolut compared with 54.4% of those receiving Sapien valves, representing a 38.1% absolute difference.
Self-expanding valves were also associated with significantly lower rates of:
- Hemodynamic structural valve dysfunction (6.7% vs 46.4%)
- Nonstructural valve dysfunction (7.7% vs 20.4%)
- Valve thrombosis based on VARC-3 criteria (1.3% vs 6.8%)
The thrombosis advantage extended to both clinical and subclinical events.
In contrast, rates of clinical valve thrombosis, endocarditis, and aortic valve reintervention remained low and largely similar between groups, although definite endocarditis was less frequent among patients receiving self-expanding valves.
Hemodynamics Continue to Favor Self-Expanding Devices
A key finding of SMART has been the persistent hemodynamic superiority of supra-annular self-expanding valves.
At three years, patients treated with Evolut demonstrated:
- Larger effective orifice areas
- Higher Doppler velocity indices
- Lower mean transvalvular gradients
These advantages were observed regardless of annular size.
The incidence of moderate-to-severe prosthesis-patient mismatch (PPM)—a condition in which the implanted valve is too small relative to the patient’s body size—was also substantially lower with self-expanding valves. PPM occurred in 9.9% of Evolut recipients compared with 33.2% of patients receiving Sapien devices.
Importantly, PPM was linked to higher risks of both all-cause and cardiovascular mortality across the overall study population.
Patients with PPM at three years were significantly more likely to die from any cause or from cardiovascular causes than those without PPM, reinforcing concerns about the long-term impact of suboptimal valve sizing.
“We think these findings emphasize the importance of minimizing PPM whenever feasible,” Herrmann said.
Experts Await Longer-Term Data
The lack of a clinical outcome advantage despite clear hemodynamic benefits prompted discussion among conference experts.
Session moderator Martin Leon observed that there was a slight numerical advantage favoring the balloon-expandable platform for clinical endpoints despite what appeared to be “a whole variety of hemodynamic disadvantages.”
Herrmann responded that the relationship between valve hemodynamics and clinical outcomes often takes years to become apparent, citing previous studies on prosthesis-patient mismatch.
Leon suggested that even five-year follow-up may not be sufficient to fully understand the differences between valve platforms.
“We’ll anxiously await the five-year data,” he said. “It may be that we have to go even beyond five years to get a true sense as to what the clinical outcome differences are between devices.”
Thrombosis Signal Draws Attention
One of the most discussed findings during the conference was the higher rate of valve thrombosis observed with balloon-expandable devices.
Davide Capodanno noted that previous low-risk TAVR trials had hinted at numerically higher thrombosis rates with balloon-expandable valves, but SMART is among the first head-to-head studies to demonstrate the signal more clearly.
Herrmann argued that the observation is biologically plausible.
“There is a pathophysiologic rationale for it,” he said. “We know that there’s more stagnation with intra-annular valves than there is with supra-annular valves. There’s less washout.”
However, he cautioned against changing post-TAVR antithrombotic strategies based solely on these findings, emphasizing that routine anticoagulation would expose many patients to unnecessary bleeding risk.
ALL WOMEN Trial Highlights Sex-Specific Considerations
In a separate EuroPCR presentation, Ignacio Cruz-Gonzalez unveiled early results from the ALL WOMEN trial, which focused exclusively on female patients undergoing TAVR.
The study compared the self-expanding Allegra valve with balloon-expandable devices in 130 women treated at 12 European centers.
At 30 days, women receiving the Allegra valve experienced significantly lower mean aortic valve gradients, larger effective orifice areas, and lower rates of prosthesis-patient mismatch.
Moderate PPM occurred in 9.6% of Allegra recipients compared with 31.6% of patients receiving balloon-expandable valves, while severe PPM was eliminated entirely in the Allegra group.
Although safety outcomes numerically favored the self-expanding valve, the difference did not reach statistical significance.
“These findings highlight the importance of sex-specific device evaluation and may help to optimize transcatheter valve selection in women with severe aortic stenosis,” Cruz-Gonzalez concluded.
Looking Ahead
The SMART trial continues to provide some of the strongest comparative evidence in patients with small aortic annuli, a population particularly vulnerable to prosthesis-patient mismatch and elevated transvalvular gradients.
While three-year clinical outcomes remain similar between self-expanding and balloon-expandable valves, the consistent advantages in valve function, thrombosis rates, and hemodynamic performance have strengthened expectations that meaningful differences could emerge with longer follow-up.
For now, investigators and clinicians alike are focused on the next milestone: the five-year SMART results, which may determine whether superior valve hemodynamics ultimately translate into improved survival and fewer cardiovascular events.
References:
- Cruz-Gonzalez I. ALL WOMEN: multicenter randomized clinical trial ALLEGRA vs balloon-expandable valve in women. Presented at: EuroPCR 2026. May 20, 2026. Paris, France.
- Herrmann HC. Three-year outcomes of the SMART Trial. Presented at: EuroPCR 2026. May 20, 2026. Paris, France.
