Real-world Data Support Safety of TAVR in Bicuspid Stenosis

Patrice Wendling

March 20, 2019

NEW ORLEANS — Transcatheter aortic valve replacement (TAVR) offers patients with bicuspid aortic stenosis survival similar to TAVR patients with tricuspid stenosis, albeit with an uptick in conversion to open-heart surgery, aortic root injury, and 30-day stroke risk, new registry data show.

"This analysis suggests that select bicuspid anatomy is amenable to TAVR with current-generation balloon-expandable TAVR technology with acceptable clinical outcomes," Raj Makkar, MD, Cedars-Sinai Heart Institute, Los Angeles, said here at the ACC 2019 Scientific Session (ACC.19).

"These data provide an argument for TAVR to be a reasonable alternative for bicuspid AS patients who are intermediate or high-risk for surgical aortic valve replacement" and "provide a sound basis to conduct a randomized clinical trial in young patients with bicuspid AS who are at low-risk for surgery," he concluded.

Bicuspid disease accounts for up to half of patients requiring surgical aortic valve replacement (SAVR) in the younger population and will be seen more often as TAVR becomes a therapeutic option for younger, healthier patients, Makkar observed.

The real-world study was presented during a late-breaking trial session that featured the paradigm-shifting PARTNER 3 and Evolut trials affirming the benefits of TAVR over SAVR in low-risk patients with tricuspid stenosis.

TVT Registry

For the study, the investigators identified 81,822 Sapien 3 (Edwards Lifesciences) TAVR procedures in the Society of Thoracic Surgeons/ACC TVT Registry between June 2015 and November 2018, and used 25 covariates to match 2691 patients with bicuspid stenosis to an equal number of patients with tricuspid disease.

Device success was high for both bicuspid and tricuspid patients (96.5% vs 96.6%; P = .87). Nevertheless, the bicuspid group had a higher incidence of annulus rupture (0.3% vs 0%; P = .02) and conversion to open surgery (0.9% vs 0.4%; = .03). The need for a second valve was 0.4% vs 0.2% (=.16), respectively.

At 30 days, all-cause mortality was similar, although patients with a bicuspid valve had a 50% higher risk for stroke and an increased risk for a new pacemaker.

30-Day Outcomes
End Point Bicuspid Aortic Stenosis, % Tricuspid Aortic Stenosis, % P Value
All-cause mortality 2.6 2.5 .82
Stroke 2.4 1.6 .02
Life-threatening bleeding 0.1 0.1 .99
Major vascular complication 0.9 1.0 .68
New pacemaker 9.1 7.5 .03
Aortic valve reintervention 0.2 0.3 .79

By 1 year, however, there was no difference between the bicuspid and tricuspid groups for mortality (10.5% vs 12.0%; hazard ratio [HR], 0.90; 95% CI, 0.73 - 1.10; P = .31) or stroke (3.4% vs 3.1%; HR, 1.28; 95% CI, 0.91 - 1.79; P = .16), Makkar reported.

"If you look at the timing of the strokes, more than 75% of these strokes occurred in the first 3 days after surgery," he said. "These are periprocedural strokes that are actually seen with TAVR."

During a discussion of the results, Makkar noted that cerebral embolic protection devices weren't available for roughly the first two-thirds of patients enrolled in the registry and that, even now, uptake is less than 10% nationally.

"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 who have bicuspid aortic stenosis because these valves tend to be more heavily calcified than, often, the tricuspid aortic stenosis," he said.

Paravalvular leak, a perennial Achilles heel of TAVR, was slightly increased at discharge but not significantly different between groups at 30 days or 1 year.

RCT Needed or Not?

Citing the study conclusion, panelist Mayra Guerrero, MD, Mayo Clinic, Rochester, Minnesota, asked: "Do we really need a randomized trial when we see in real-world experience in more than 2600 patients that the outcomes are fairly similar?"

Makkar replied: "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."

"For patients who are high risk and who are intermediate risk with the STS scores of what we have here — 5 and more — I think it's reasonable to consider them based on CT anatomy for TAVR procedure," he continued. "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."

Panelist Blase Carabello, MD, chief of cardiology, East Carolina Heart Institute, Greenville, North Carolina, remarked that in terms of conducting such a trial, it would be difficult to generate equipoise unless "you really have young patients where we don't know the answer."

"It will be really hard considering the [tricuspid] data that have been presented and the data you just presented to take an even intermediate-risk surgical patient just because they were bicuspid and not do TAVR," he said. "I think that would be very hard to swallow."

Asked for comment, session cochair John Jarcho, MD, Brigham and Women's Hospital and Harvard Medical School, Boston, said: "I agree with Dr Makkar in principal that a randomized trial is the right way to go in terms of confirming definitively the answer to the question, but I also agree with Dr Carabello that it's going to be hard to enroll that trial because clinicians are not going to be willing to randomize their patients to surgery."

"Maybe very young patients with severe bicuspid aortic stenosis would be a candidate for a trial like that, but for a lot of bicuspid patients who are older, I think people are going to do them," he said, observing that the registry numbers would suggest operators already are.

At a press conference here, PARTNER 3 coprincipal investigator Martin Leon, MD, Columbia University Medical Center, New York City, said: "The majority of bicuspid patients I think would be good candidates for TAVR, but not all. I think we need to be aware of that and I would hate for the message to be that all bicuspid disease can now be treated with equal outcomes with TAVR. We need to be selective and there needs to be more studies."

Press conference discussant John Cleveland, MD, University of Colorado, Aurora, however, said even though some patients with bicuspid disease have anatomic factors that are not fully understood, "I'm not sure that we still need a randomized trial."

"A lot of selection process will go on with the heart team concept" and in low-risk patients with select anatomy, "I can be convinced that this could be an alternative to surgery," he said.

Coauthor of the Evolut study, Michael Reardon, MD, Houston Methodist DeBakey Heart & Vascular Institute, told theheart.org | Medscape Cardiology: "I would have loved to have done a randomized trial when we started low risk. I lobbied very hard; Medtronic didn't want to do it."

Nevertheless, he said, "it would be very hard pragmatically and ethically for me to randomize anymore and I also think we have enough data on surgical bicuspid valves in this lower-risk group that we can draw on for objective performance criteria."

Reardon is currently enrolling his low-risk patients with bicuspid stenosis in a nonrandomized trial with Medtronic's Evolut PRO and Evolut R valves, with preliminary results expected sometime next year. "We're going to learn a lot because we're going to have a core lab looking at the CTs. We need to learn more about sizing and how to pick valves in bicuspid," he said.

During his formal presentation, Makkar noted that the TVT Registry does not collect anatomic data that would tell if there was a wide range of aortic dilatation, nor does it have information on whether patients had previous balloon valvuloplasty.

"Moving forward, I think there's a need to incorporate more anatomic fields in this dataset, 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 actually give us more information on this," he said.

Speaking to the press, Makkar echoed Leon's concerns that the inference from the three late-breaking trials is that TAVR should be used for all bicuspid stenosis.

"I think what we need to do is balance," he said. "A lot of people actually considered that bicuspid anatomy was a relative contraindication to TAVR and I think we can blow that myth away if we carefully select our patients. At the same time, I don't think we can say that the 60-year-old bicuspid patient with a heavily calcified valve is a candidate for TAVR. That would be a disservice."

Statistical analyses were performed by Edwards Lifesciences. Makkar reports receiving grant/research support and consulting fees/honoraria from Edwards, Abbott, Medtronic, and Boston Scientific; and holding a major stock shareholder/equity position in Entourage Medical.

Carabello reports serving on a data safety monitoring board for Edwards. Guerrero reports receiving consulting fees/honoraria and research/research grants from Edwards Lifesciences and serving on the speaker's bureau for Abbott Vascular and Boston Scientific. Jarcho is deputy editor of the New England Journal of Medicine. Leon reports receiving consultant fees/honoria from Boston Scientific, Gore Medical, and Medtronic; and research/research grants from Edwards Lifesciences. Cleveland reports receiving consulting fees/honoraria from Bayer, Biotronik, GSK, Johnson & Johnson, Medtronic, MSD, MyoKardia, St. Jude Medical, Stealth Biotherapeutics, Zoll, ZS Pharma; and research/research grants from Amgen, Bayer, Biosense-Webster, Biotronik, Bristol-Myers Squibb, MSD, Novartis, Philips, Roche, and Servier. Reardon reports research/research grants from Boston Scientific and Medtronic.

American College of Cardiology (ACC) 2019 Scientific Session: Abstract 404-15. Presented March 16, 2019.

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