After Some Early Successes for Bicuspid TAVR, a Randomized Trial May Be Unlikely

With proper patient selection, low-risk individuals with bicuspid aortic stenosis could undergo transcatheter aortic valve replacement (TAVR) and experience the same early benefits as their peers with tricuspid valves, two observational studies suggested.

Between the Low Risk Bicuspid Study and the randomized Evolut Low Risk Trial, propensity matching of bicuspid and tricuspid TAVR cases using Evolut valves produced 145 matched pairs sharing similar rates of death or disabling strokes at 1 year (1.4% vs 2.8%, P=0.413), according to John Forrest, MD, of Yale School of Medicine in New Haven, Connecticut.

Similarly, clinical outcomes after TAVR in the PARTNER 3 program were no different between 148 matched pairs of bicuspid and tricuspid patients in terms of all-cause death, all stroke, and cardiovascular rehospitalizations 1 year following Sapien 3 device implantation (10.9% vs 10.2%, log-rank P=0.80), reported Mathew Williams, MD, of NYU Langone Medical Center in New York City.

Forrest and Williams reported their findings at TVT: The Structural Heart Summit, an annual meeting held by the Cardiovascular Research Foundation and hosted in Miami Beach.

What's Next for Bicuspid TAVR?

The two studies provide some answers regarding TAVR in bicuspid anatomy, which had been excluded from the landmark trials that led to TAVR's FDA approval across all risk levels.

To get such good results with TAVR, bicuspid patients in both studies had undergone rigorous screening to make sure they were anatomically suitable and did not not have too much calcification for the procedure.

For example, 169 people were enrolled in the PARTNER 3 bicuspid registries (one a continued access registry with site-reported outcomes, the other a registry with core lab reporting) after 99 others failed pre-screening due to anatomical exclusions.

"Keep in mind that in the right people, this works ... The problem is do sites know the right people?" said Michael Reardon, MD, of Houston Methodist, during the panel discussion.

Moreover, given the good results so far, is a randomized trial of bicuspid TAVR the next step for the field?

Pragmatically, such a trial would be "very difficult," Reardon said. "I'm not sure my cardiology colleagues would go for it."

"Seven years ago, I thought absolutely, we need to do this. Now I'm not so sure," said Martin Leon, MD, of Columbia University Irving Medical Center/NewYork-Presbyterian Hospital in New York City, who suggested a large CT study instead to better characterize the effect of calcification patterns.

"Distribution of calcification may be one of the more important issues," Leon emphasized. "Maybe we need to have a bicuspid score that's CT-derived, that tells whether a patient is a better or worse candidate [for TAVR]."

"Regardless of the number of leaflets, vigilant case planning and focus by the Heart Team on the [CT angiogram] is critical for success," Forrest concluded.

More Details on Evolut TAVR in Bicuspid Patients

The Low Risk Bicuspid Study comprised bicuspid patients who received the self-expanding, supra-annular Evolut R or Evolut PRO valves.

Compared with the randomized tricuspid cohort from the Evolut Low Risk Trial, the bicuspid group tended to be younger and include more women, with fewer individuals with a history of prior percutaneous coronary intervention.

After matching, patients averaged approximately 70 years of age, and about half were women.

Procedural data show that over 40% of bicuspid patients received the largest 34 mm valve. This cohort had disproportionately high rates of pre-implant balloon valvuloplasty and embolic protection but less resheathing or recapturing compared with the tricuspid arm.

Good hemodynamic results were maintained out to 1 year for both bicuspid and tricuspid groups.

Notably, the former fared better in paravalvular regurgitation (PVR): 78.7% had none or trace paravalvular leak versus 57.4% of the tricuspid cohort (P<0.001).

This may be attributed to bicuspid cases being performed after some delay and refinement in technique, Forrest suggested.

Details on Sapien 3 TAVR in Bicuspid Patients

Patients in the PARTNER 3 bicuspid continued access registry and the PARTNER 3 TAVR bicuspid registry were pooled into one bicuspid TAVR group for comparison with the randomized tricuspid arm from the PARTNER 3 randomized trial.

Matched pairs had a median age of 72 years, with approximately 60% of participants being men.

Bicuspid TAVR was associated with less oversizing and longer procedural durations. In addition, operators were aggressive about pre-dilating and preferred to place Sapien 3 balloon-expandable valves higher above the annulus. There was no embolic protection offered to patients, Williams reported.

For both bicuspid and tricuspid patients, hemodynamic results showed good reductions in gradients out to 1 year. The degree of residual PVR was similar between groups as well.

Finally, Williams reported that the two cohorts shared significant quality-of-life and symptomatic improvements.