Evolut TAVI Shows Promise in Low-risk Bicuspid Patients at 3 Years

Patients with bicuspid aortic stenosis at low risk for surgery who underwent TAVI with an Evolut (Medtronic) bioprosthesis have low rates of all-cause mortality or disabling stroke as well as good hemodynamic outcomes at 3 years, according to findings from a small, multicenter study.

In an area with a paucity of data, lead author Firas Zahr, MD (Oregon Health & Science University, Portland), said, the results are encouraging. “In this case, the Evolut valves have done well in terms of hemodynamic durability,” he told TCTMD. “The patients have done well in terms of their outcome and their rate of reinterventions for various reasons. So it is reassuring that at least we're not doing the wrong things for those patients.”

The study, published in the July 22, 2024, issue of JACC: Cardiovascular Interventions, comes on the heels of the randomized NOTION-2 trial presented earlier this year, whose results left some arguing that TAVI should only be performed in patients with bicuspid anatomy if surgery is not an option. NOTION-2 compared TAVI to SAVR in low-risk patients, and while there was no difference in the primary endpoint, the 26% of patients with bicuspid anatomy tended to have worse outcomes: a nearly fourfold higher risk of death, stroke, or rehospitalization compared with those treated surgically (14.3% vs 3.9%; P = 0.07) and a threefold higher risk of death or disabling stroke (6.1% vs 2.0%; P = 0.3).

Lead investigator of NOTION-2, Ole De Backer, MD, PhD (University of Copenhagen, Denmark), told TCTMD the new findings are good news. “The clinical outcomes are really excellent with low mortality and disabling stroke at 3 years, and also if you then look at the hemodynamic valve performance, it is really stable from discharge up to 3 years,” said De Backer, who was not involved with this latest analysis. “That's what this paper really adds. It shows that the valve performance remains really excellent, with single-digit mean transprosthetic gradients with nice, large, effective orifice areas of above 2 cm². Also, [it shows] really good outcomes, with actually no cases with moderate or severe paravalvular leakage and reintervention in only two patients.”

However, while valve performance was similar in the two studies, the patients here were subject to greater selection bias than those in NOTION-2, which might account for the differences seen in clinical outcomes, De Backer suggested.

3-year Outcomes

The Evolut Low Risk Bicuspid study included 150 patients (mean age 70.3 years; 48% women) with bicuspid anatomy undergoing TAVI with a self-expanding, supra-annular Evolut R or Evolut PRO valve at one of 25 US centers between December 2018 and October 2019. Mean STS predicted risk of mortality score was 1.3%, and 90.7% had Sievers type 1 bicuspid morphology. Three-year follow-up data were complete in 85.3% of patients.

The primary endpoint of all-cause mortality or disabling stroke was 1.3% at 1 year, 3.4% at 2 years, and 4.1% by 3 years.

About one in five patients (19.4%) needed a new permanent pacemaker at 3 years. None reported moderate or severe paravalvular aortic regurgitation at 2 and 3 years post-TAVI, and 85.0% had none or trace paravalvular aortic regurgitation at 3 years. Both endocarditis (1.4%) and bioprosthetic thrombosis (2.0%) happened infrequently.

Mean aortic valve mean gradient remained low from discharge through 3 years (9.0 vs 9.1 mm Hg), and mean effective orifice area was stable, measuring 2.2 cm² at both time points.

What we have learned is, at least in our clinical practice, the patients that we are selecting for TAVR are doing well and the long-term data for those patients is encouraging. Firas Zahr

Quality of life remained consistently high over the study period, with mean KCCQ overall summary scores of 91.0 at 1 month and 92.2 at 3 years. At baseline, 70.7% of patients had symptoms consistent with NYHA functional class II, but by 3 years, 81.1% had NYHA functional class I symptoms.

In the absence of a randomized clinical trial comparing TAVI to surgery in patients with bicuspid anatomy, Zahr said these findings can’t yet impact practice. However, “what we have learned is, at least in our clinical practice, the patients that we are selecting for TAVR are doing well and the long-term data for those patients is encouraging,” he said. “Obviously there are still patients who will benefit from surgery, and we have to consider patient as well as anatomical variables very carefully.”

Additionally, Zahr acknowledged that the patients included in the study were all 60 years and older, and as such, he said, the findings cannot be applied to those younger or with anatomies like significant ascending aortopathy requiring surgical repair that were excluded.

“Surgery will remain an important therapy for those patients, especially when coronary artery disease is present, where aortic disease is present, and those patients are young and they need a concomitant aortic or bypass surgery at the time of their aortic valve,” he said. “But for those who do not, TAVR, at least with this data that follow them respectively to 3 years, appears to be safe and effective with low risk of adverse events or reinterventions or mortality.”

Zahr said his team plans to follow patients out to 10 years to have a better idea of what the valve durability outcomes will be. “We'll be very eager to see what the longer-term follow-up data look like,” he said.

‘Too Little Evidence’

Compared with the NOTION-2 population, De Backer stressed, the patients included here were “highly selected.” He argued that the results cannot necessarily be applied to, say, patients with Sievers type 0 bicuspid morphology.

As for where the totality of data stands now, De Backer said “we simply have too little evidence” to make any strong statements about how patients with bicuspid anatomy should be treated.

“On one hand, for example, we have this low-risk, single-arm bicuspid study . . . in which there are reported excellent outcomes up to 3 years, but everybody knows that these are highly selected patients,” he said.  While in NOTION-2 there’s a “small first signal” that TAVR should be offered as a first therapy for some, it’s still uncertain whether this extends to an all-comers population, De Backer continued. “But I think it's too early to make a really strong call on this. We need more studies, we need more data, we need more evidence, ideally from either randomized controlled trials or even much larger all-comers registries. We need just simply more data.”

Also, 3-years of data is “still nothing,” De Backer said. “I would almost call this short- to intermediate-term results. These are not long-term results.”

We need just simply more data. Ole De Backer

In an accompanying editorial, Stephan Windecker, MD, and Daijiro Tomii, MD (both Inselspital, University of Bern, Switzerland), write that while this study represents the longest follow-up available for a population of low-risk patients with bicuspid aortic valve stenosis, several questions remain unanswered, including “1) the definitions of favorable and unfavorable bicuspid aortic valve morphology; 2) the optimal device selection and sizing strategy; 3) long-term TAVR durability and the evolution of aortopathy after TAVR; and 4) safety and efficacy compared with SAVR.”

While longer-term data are awaited, the editorialists suggest that heart teams “provide a tailored approach for individual patients with bicuspid aortic valve stenosis on the basis of their risk profiles, comorbidities, anatomical considerations, and life expectancies.”