Early Data Support TAVR in Bicuspid Valves, but Questions Remain

Early data from a study presented today at the “virtual” American College of Cardiology 2020 Scientific Session suggest that patients with bicuspid aortic stenosis can safely be treated with a self-expandable transcatheter heart valve.  

In this small study, which was presented by Basel Ramlawi, MD (Valley Health System, Winchester, VA), as a late-breaking clinical trial, the 30-day rate of all-cause mortality or disabling stroke was 1.3%, which experts said is reassuring. The rate of nondisabling stroke was 3.3%, similar to that observed in the low-risk trials of TAVR in patients with trileaflet aortic valves, say investigators.

“Whether a randomized trial is warranted or not, I think more data is always better,” Ramlawi told TCTMD. “With regards to the self-expanding valve in bicuspid TAVR, this is clearly a multidisciplinary question based on clinical and anatomic features [as to] whether the patient goes for surgery or a transcatheter valve, especially in this low-risk population where longer-term data is going to be required. This [study] adds to the 30-day outcomes and I think more data is always welcome.”   

To TCTMD, Gilbert Tang, MD (Mount Sinai Health System, New York, NY), noted that the study included a highly selected patient population that excluded younger patients and others based on their aortic root anatomy. Additionally, the rate of permanent pacemaker implantation in this low-risk population was 14.7%, which is significantly higher than the rate of less than 5% that is typical in surgical aortic valve replacement.

“Despite cases being done in experienced centers, the 30-day outcomes in my opinion are not as good as surgery,” said Tang. “These data would be very hard to generalize to the more than 800 TAVR sites in the US, especially in lower-volume TAVR centers.”

Tang also noted that there were some “concerning” findings from the PARTNER 3 low-risk study at 2 years, also presented during the late-breaking session. While the study showed there was still a significant advantage with TAVR over surgery with respect to the primary endpoint of death, stroke, or cardiovascular hospitalizations, there were more deaths and stroke events in the TAVR arm from 1 to 2 years, as well as an increase in valve thrombosis from 1 to 2 years.

“Therefore, for bicuspid patients—remember the US FDA approval does not exclude patients based on age or bicuspid anatomy—we need to be even more thoughtful as to which patients would be appropriate for TAVR,” said Tang. What will be needed, he said, is a randomized trial comparing surgery versus TAVR in bicuspid disease, although, admittedly, any such trial would likely include some selection bias.

Similarly, Ashish Pershad, MD (Banner - University Medicine Heart Institute, Phoenix, AZ), said the present study is small, and while the results are intriguing, it is unlikely to be practice-changing. “In general, stroke and mortality at 1.3% is encouraging, but what I would want is longer follow-up,” he told TCTMD. Like Tang, Pershad said the only way to determine whether TAVR is truly comparable to surgery in patients with bicuspid aortic stenosis is a randomized, controlled study. “There’s enough anatomic differences in terms of the bicuspid valve that it’s worth looking at in a randomized trial,” he suggested.

Low-Risk Bicuspid Study

The Low-Risk Bicuspid Study was a prospective, single-arm, multicenter trial conducted across 24 experienced TAVR centers in the United States. In total, patients at low surgical risk were treated with the Evolut R or PRO (Medtronic) supra-annular, self-expanding transcatheter heart valve following a baseline CT scan to confirm bicuspid morphology. Patients younger than 60 years were excluded from the trial, as were those with an ascending aortic diameter > 4.5 cm, aortopathy requiring surgery, and prohibitive calcification in the left ventricular outflow tract (LVOT).

In total, just 9.3% of patients had a Sievers type 0 bicuspid valve and the remaining patients had type 1 valves (there were no patients with Sievers type 2 bicuspid valves).

At 30 days, there were two deaths/disabling strokes (1 death, 1 disabling stroke, or 1.3% combined). Nondisabling stroke occurred in 5 patients (3.3%) and there were 2 major vascular complications. As noted, the rate of permanent pacemaker was roughly 15%, which Ramlawi said is significantly higher than with surgery, although the rate is slightly lower than the 17.4% observed in the Low-Risk TAVR Trial of patients with trileaflet aortic valves. The device was successfully implanted in 95.3% of patients, with no patient-prosthesis mismatch reported in 87.1% of cases. There were no aortic dissections or annular ruptures.

At 30 days, valve hemodynamics were significantly improved in treated patients, including those with Sievers type 0 bicuspid valves. In total, 59.6% of patients had no/trace aortic regurgitation, and these rates were equally favorable in patients regardless of valve subtype. In fact, 84.6% of patients with Sievers type 0 valves had no/trace aortic regurgitation, although Ramlawi cautioned that their study included just 13 patients with this valve subtype.

What’s the Comparator? Surgery or Low-Risk TAVR in Trileaflet Disease

To TCTMD, Pershad said the rate of nondisabling stroke in the present study is not alarming in and of itself, but it is a factor to consider when discussing treatment options for younger TAVR patients with bicuspid disease. In the Evolut Low-Risk TAVR Trial of patients with trileaflet aortic stenosis, for example, the rate of nondisabling stroke at 30 days was 3.0% with TAVR and 1.7% in patients treated with surgery.

If a patient with a bicuspid valve requests TAVR, Pershad said their first task, before turning their attention to the CT scan, is to point out that these patients were excluded from the pivotal low-risk studies. If the patient has high-risk features, such as aortic root dilatation, low-lying coronary ostia, or LVOT calcification, or if they have anything other than a Sievers type 1 bicuspid valve, “we will make it clear to the patient that outcomes with TAVR in bicuspids are known to be inferior to the surgical outcomes," based on the registry-level data, he said. Given their young age, Pershad said, physicians must also understand there is a high probability these patients will require two interventions over their lifetimes, another factor that must be weighed during the heart-team discussions. 

Like the others, Judy Hung, MD (Massachusetts General Hospital, Boston, MA), one of the scheduled discussants, questioned to what standard TAVR should be held in bicuspid aortic stenosis, asking: what’s the comparator arm, low-risk TAVR patients with three aortic leaflets or surgery in bicuspid aortic stenosis? David Adams, MD (Icahn School of Medicine at Mount Sinai, New York, NY), made the case for surgery, noting that the 30-day rate of death/stroke, permanent pacemaker implantation, and mild aortic regurgitation—even at these high-volume, experienced centers—is much higher with TAVR than with surgery.

Adams also pointed to the hemodynamic data as a concern. “[I] keep hearing these new generations of valves are going to solve aortic regurgitation,” but the rate of mild aortic regurgitation remained relatively high at 40.4% in the study, he said. Adams questioned whether the Evolut PRO performed any better than its predecessor, but an analysis by valve type has not been performed.