TAVR in Bicuspid Aortic Stenosis Safe, Feasible in Selected Real-World Patients

Experts disagree on whether a randomized trial is needed as a next step, but are aligned that TAVR is an option only for those with certain anatomies.

TAVR in Bicuspid Aortic Stenosis Safe, Feasible in Selected Real-World Patients

NEW ORLEANS, LA—TAVR in real-world patients with bicuspid aortic stenosis (AS) is associated with largely similar outcomes for key metrics of success at 30 days and 1 year compared with a cohort of TAVR-treated patients with tricuspid disease, according to new registry data. Notably, though, bicuspid patients are at a slightly higher risk of aortic-root injury, conversion to surgery, and stroke.

“This analysis suggests that select bicuspid anatomy is amenable to TAVR with current-generation balloon-expandable TAVR technology with acceptable clinical outcomes,” said Raj R. Makkar, MD (Cedars-Sinai Heart Institute, Los Angeles, CA), who presented the findings here today at the American College of Cardiology (ACC) 2019 Scientific Session. “These data provide an argument for TAVR to be a reasonable alternative for bicuspid AS patients who are at intermediate or high-risk for surgical aortic valve replacement, which are the patients that are enrolled in this registry, and provide a sound basis to conduct a randomized clinical trial in young patients with bicuspid AS who are low risk for surgery.”

TVT Registry Data

For the study, Makkar and colleagues looked at 2,691 propensity-matched patients each with bicuspid or tricuspid aortic stenosis who underwent TAVR with the Sapien 3 valve (Edwards Lifesciences) as part of the Society of Thoracic Surgeons/American College of Cardiology TVT Registry between June 2015 and November 2018. Before matching, bicuspid disease patients had a larger mean annular size and a greater LVEF than those with tricuspid disease.

More patients in the bicuspid arm required conversion to open surgery (0.9% vs 0.4%; P = 0.03) and had more annular rupture (0.3% vs 0; P = 0.02). Numerically but not significantly, they also were more likely to need a second valve (0.4% vs 0.2%; P = 0.16) compared with those with tricuspid aortic stenosis. At 30 days, there was no difference in all-cause mortality, life-threatening bleeding, major vascular complications, and aortic valve reintervention between the study groups, but bicuspid disease increased the risk of all stroke (2.4% vs 1.6%; P = 0.02) and need for new pacemaker (9.1% vs 7.5%; P = 0.03).

In the matched 1-year analyses, there were no differences in mortality (HR 0.90; 95% CI 0.73-1.10), stroke (HR 1.28; 95% CI 0.91-1.79), or mortality and stroke (HR 0.97; 95% CI 0.81-1.16) between the bicuspid and tricuspid cohorts.

The vast majority of all strokes occurred within 3 days, Makkar reported, meaning that most were periprocedural.

The rate of paravalvular leak trended higher at discharge in bicuspid patients (P = 0.08) but was equivalent at 30 days and 1 year compared with the tricuspid cohort. Valve hemodynamics were also comparable as measured by mean gradient and aortic valve area, and NYHA class and improvements in Kansas City Cardiomyopathy Questionnaire score were matched between the study groups at baseline, 30 days, and 1 year.

Randomized Trial Needed?

In a panel discussion following the presentation of the results, Eugene Braunwald, MD (Brigham and Women's Hospital, Boston, MA), said, “This is a very important registry. Congenital bicuspid valve is probably the most frequent congenital cardiac anomaly.” He asked if the researchers collected data on whether any patients had earlier balloon valvuloplasties as well as regarding the wide range of dilatation of the aorta in the study population, “which of course is quite common and could be quite problematic.”

Because of the nature of the registry, none of these data were collected Makkar said. “[But] moving forward, I think there is need to incorporate more anatomic fields in this data set, which are actually based on CT, because CT is routinely done in all of these patients, and I think it would actually be very helpful to incorporate more fields that will give us more information on this.”

Responding to a panel question about the use of cerebral embolic protection devices in patients with bicuspid aortic stenosis, Makkar said that these devices weren’t yet available for almost the first two-thirds of patients enrolled in the registry.

“Even now, the penetration of the cerebral protection devices is less than 10% nationally,” he noted. “There were only a minority of patients, 5% or less, in this registry that actually had the use of cerebral protection devices. In fact, I would argue that based on these data, it would be wise for us to use cerebral protection devices especially when we are doing TAVR in patients with bicuspid aortic stenosis because these valves tend to be more heavily calcified than often the tricuspid aortic stenosis.”

Looking forward, panelist Mayra Guerrero, MD (Mayo Clinic, Rochester, MN), questioned Makkar’s comment about needing a future randomized trial of TAVR in bicuspid patients “when we see in real \-world experience of more than 2,600 patients [that] the outcomes are fairly similar.”

Indeed we do, Makkar responded. “I think these data are reassuring and encouraging but we must not get carried away. I think that would be the important message that I must give,” he said. “I think for patients who are high-risk and who are intermediate-risk with the STS scores of what were here 5 and more, I think it’s reasonable to consider them based on CT anatomy for TAVR procedure. For young patients, as I concluded, I think we must do a randomized clinical trial to definitely establish the safety and efficacy of TAVR in these patients.”

This kind of study would be challenging to conduct, commented panelist Blase Carabello, MD (East Carolina Heart Institute, NC). “It will be difficult to generate equipoise unless you really have young patients where we don't know the answer,” he said. “It will be really hard considering the data that have been presented [today] and the data that you just presented to take an even intermediate-risk surgical patient just because they were bicuspid and not do TAVR. That would be very hard to swallow.”

Additionally, in a media briefing Joseph Cleveland, MD (University of Colorado Anschutz Medical Center, Aurora), said that even though some patients with bicuspid aortic stenosis have anatomic features “that we still don’t understand,” in which the circular transcatheter valves don’t conform, “I’m not sure that we still need a randomized trial.” Heart teams will continue to refine their selection processes, and so long as there is a consensus of appropriate anatomy, “I can be convinced that this could be an appropriate alternative to surgery,” he added.

  • Makkar RR. Outcomes of transcatheter aortic valve replacement with balloon-expandable Sapien 3 valve in bicuspid aortic stenosis: an analysis of the STS/ACC TVT registry. Presented at: ACC 2019. March 17, 2019. New Orleans, LA.

  • Makkar reports receiving grant/research support and consulting fees/honoraria from Edwards Lifesciences, Abbott, Medtronic, and Boston Scientific and holding stock/equity in Entourage Medical.