COMMENTARY

What Will a 'Historic Day' for TAVR Mean in Clinical Practice?

John M. Mandrola, MD; Raj R. Makkar, MD

Disclosures

March 25, 2019

This transcript has been edited for clarity.

John M. Mandrola, MD: Hi, everyone. This is John Mandrola from theheart.org | Medscape Cardiology, here at the American College of Cardiology (ACC) meeting in New Orleans. I am pleased to welcome Dr Raj Makkar, who is the associate clinical director of Cedars-Sinai Heart Institute. Welcome, Raj.

Raj R. Makkar, MD: It's a pleasure to be here, John.

Mandrola: This was a huge day for cardiology, with transcatheter aortic valve replacement (TAVR) trials in low-risk patients. What were your general impressions?

Makkar: I agree with Dr Eugene Braunwald when he commented that this was a historic day, because today we essentially changed the treatment of aortic stenosis in low-surgical-risk patients. TAVR indications have expanded now. It was approved for high-risk patients and intermediate-risk patients, and today, young, low-risk patients (which is the majority of patients) will now be preferentially treated using transcatheter techniques.

Two low-risk studies were presented today. PARTNER 3,[1] using the SAPIEN 3 valve, essentially showed that the combined endpoint of death, stroke, and rehospitalization was cut in half with the use of TAVR compared with traditional conventional surgical aortic valve replacement (SAVR). Not only did we see some reduction in mortality, but also a significant reduction in stroke rates. A lot of this was driven by rehospitalizations, but nonetheless there was a beneficial trend in all of the endpoints measured.

The Evolut trial[2] enrolled 1400 patients using a Bayesian trial design, and it was noninferior compared with surgery in terms of the endpoints of death and stroke. Stroke rates were also lower in this trial as well with TAVR than they were with SAVR. You essentially saw similar outcomes.

Evolving Use of TAVR

Mandrola: Can you speak to the whole evidence generation of TAVR from beginning to end? I think it is pretty remarkable and reminds me of the cardiology of old.

Makkar: The first time Alain Cribier did this procedure in somebody, it was a last-ditch effort and thought to be technology that would be used only in a small subset of patients who were absolutely not candidates for surgery. Now, 15 years later, this has replaced SAVR, which was the gold standard. It is an amazing thing because of the way it was done and the way leaders in the field systematically accumulated evidence by starting with inoperable patients, to high-risk patients, to intermediate-risk patients, and now the low-risk patients.

Durability

Mandrola: If we are going to be doing this in younger, lower-risk patients, I worry about valve durability. If you do this in a patient who is 88 or 90 years old, maybe durability is not such a big issue. Can you speak to that?

Makkar: You make a very important point. Are we trading some of these endpoints for long-term durability? It is good to be alive, of course, and good to have a lower incidence of stroke rates, but durability is important.

We know from small datasets up to 5 years that the durability seems to be comparable to that of SAVR.[3,4] We also know that the traditional definitions of durability with SAVR are quite flawed. Freedom from reoperation does not mean that the valve is durable. A patient who had a SAVR could be dying from valve degeneration; if they did not come back for a reoperation or TAVR, it was considered to be freedom from reoperation. That is the way it was traditionally defined.

Moving forward, we have uniform definitions of durability for surgical aortic valves and transcatheter aortic valves. I think now we will get the right answer. In the Valve-in-Valve International Data (VIVID) registry, 20% of patients had their surgical aortic valves replaced within the 5 years prior to the TAVR. It is a bell-shaped curve. Some patients [with transcatheter aortic valves] degenerate earlier, and that is true also for those with the surgical aortic valve. The data are not that good in terms of rigor when we talk about surgical aortic valves.

Pacemakers in the Evolut Trial

Mandrola: In the Evolut trial, there was a much higher rate of pacemaker [implantation]. As a pacemaker implanter, I think we should try not to put in pacemakers. Can you comment on that?

Makkar: In Evolut, pacemaker rates were higher in TAVR patients compared with surgery. That was the only big limitation. Everything else, including hemodynamics, was really good. I think some of this can be mitigated by technique. It is not uncommon for some high-volume centers to have pacemaker rates that are much lower, around 10%.

It is true that there are much lower pacemaker [implantation] rates associated with the balloon-expandable valve. In the SAPIEN 3 study, the pacemaker rates were not very different, 6% versus 4%. I think some of this will probably come down to education. It has been pointed out that half of the time, they are not using their pacemakers at follow-up. How do we better risk-stratify? Work needs to be done in that field.

Bicuspid Aortic Valve Disease

Mandrola: There were no patients with bicuspid aortic valve disease in these trials, but there are a lot of patients with bicuspid aortic valve disease. You presented a paper today; can you tell us about that?

I think we busted the myth that bicuspid aortic valves cannot be treated with TAVR.

Makkar: According to some studies, almost half of young patients may be undergoing SAVR for bicuspid aortic valve stenosis. Because all of the pivotal studies excluded this patient population, there is a paucity of data. We went to the STS/ACC TVT registry, which enrolls all consecutive patients getting TAVR in the United States. It is an amazing repository of data. There were 92,000 patients with the SAPIEN 3 valve in the 3-year period that we studied and 2700 of these had bicuspid valves.[5] We took these patients and compared them and their outcomes to the outcomes of the tricuspid aortic stenosis patients. We propensity-matched them so that they were equivalent in terms of their cohort. We found that at 30 days and at 1 year, the survival was similar. We also found that there was somewhat higher risk for aortic root injury with the bicuspid TAVR, but nonetheless, that was still less than 1%. It is statistically significantly more than tricuspid but less than 1%, so it's something that can be justifiable. We also found that stroke rates were somewhat higher: 2.4% versus 1.6%. Most of these were done without the use of cerebral protection devices. I am sure we can make a difference when doing TAVR cases by using embolic protection devices.

Hemodynamics and quality-of-life indices were similar. I think we busted the myth that bicuspid aortic valves cannot be treated with TAVR. You can get good results. It is also important to point out that not all bicuspid aortic valves are the same. Some are more hostile anatomies, and preferentially we must avoid those so that we get reasonable outcomes. It is easy to justify the use of TAVR in high-risk and intermediate-risk patients, but there are no data in low-risk patients. The right thing to do would be a randomized clinical trial.

Mandrola: This propensity-matched data are hypothesis-generating and suggest that we should do a trial on low-risk patients.

Makkar: Yes. The data we have are in high-risk and intermediate-risk patients because these are the patients being treated. Having 2700 patients is good and gives us reasonable confidence that you can treat these patients with TAVR. Realize that there was selection bias—I would not treat patients with hostile anatomies. This does not give us a blanket approval to treat every bicuspid with TAVR. We must carefully look at the anatomy on CT and then decide what to treat and what not to treat.

Mandrola: Excellent. Thank you so much for being with us.

Makkar: It's been a pleasure.

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