What TAVR Needs Next . . . and What It’s Getting

CHICAGO, IL—The clinical data are robust, efficacy is through the roof, adverse events are declining, and the innovation pipeline is plump and thriving; all of these factors support the “relentless march” of TAVR into lower and lower risk patients, one expert said here. So what’s needed next in the transcatheter aortic valve arena, at least in the mind of Ian Meredith, MD (Monash Medical Center, Melbourne, Australia), who was tasked with providing an opinion in the opening session at TVT 2016?

The answers may surprise you.

Number one, he told TCTMD following his talk: “Device wars don’t help us, and they don’t help the field. What we really have to do is see what’s good in each device and force other valve makers and innovators to come to the party.”

Number two, he continued: investigators and operators alike need to adopt some universal standards when it comes to reporting details of key complications—stroke rates, pacemaker implantation, and vascular complications.

‘Aren’t We Lucky’

Meredith began his talk by joking that this was the first time he’d been invited to an international meeting to provide a “thoughtful synthesis” of the data. But his tone swiftly turned serious. “Aren’t we lucky,” he said. “Aren’t we incredibly lucky to work in this field, which has seen such a remarkable flow of sophisticated and impactful studies.”

Meredith reviewed 10 approved or close-to-approved TAVR devices in his talk, noting that there are many more at an earlier stage in the development pathway. As he pointed out, together the devices represent a surprisingly diverse combination of design components, materials, positioning/recapturing technology, delivery methods, sealing strategies, and more.

What’s worth acknowledging, Meredith stressed to TCTMD, is that “any time a new iteration comes out, it pushes the field to actively do more. And in pushing the field to do more, that’s better for all our patients.”

More importantly, he said, “We shouldn’t be focusing on which device is the best, which features are best. [We should be talking about] which novel devices can be used appropriately for different patients. You know the expression ‘horses for courses.’ I think at the moment, having this diverse number of devices, means that we do have horses for courses—different devices for different patients—and that’s a huge advantage.”

Challenges remain, he noted, and innovative strategies are needed to tackle issues related to valve positioning and repositioning, hemodynamics, mobility, durability, and paravalvular regurgitation. All of these are reflected in the wide variety of devices gushing through the pipeline.

What TAVR Needs

But the TAVR field has other needs as it moves into lower risk patients—needs that have nothing to do with the technology itself, Meredith pointed out.

“The three things we need to focus on now are stroke, vascular complications, and pacemaker implantations, ” he said. Not only are further studies needed to understand the true incidence of these adverse events, but operators implanting the valves now need to do a better job with standardized reporting.

Meredith would like to see stroke rates reported more “honestly” with records detailing whether the stroke was diagnosed by the operator, or with independent neurological assessment and imaging. For vascular complications, he wants manufacturers to agree on universal sheath size measurements so that when complications occur, sheath sizes can be accurately compared with other systems. As it stands today, maximal and minimal dimensions are typically measured at different points in the different catheters, he said. “I have more of a chance of understanding gravitational waves than I do of understanding this.”

Finally, Meredith called for a rethink on how new pacemaker implantation rates are reported. Most studies report these implantations using the entire trial population as the denominator, he noted. To get a better sense of the true rate of new pacemaker needs across different devices, said Meredith, studies should report new pacemaker implantations post-TAVR as compared with the study population at risk of needing one—excluding any patients with pacemakers prior to their procedures.

Following Meredith’s presentation, several panel members picked up on the same themes, shifting the onus for improved outcomes away from device innovation and onto operators themselves.

“How do we get smarter at doing TAVR?” Howard Hermann, MD (Perelman School of Medicine at the University of Pennsylvania, Philadelphia), asked rhetorically. “We’ve learned so much over the last 8 to 9 years [from] 15,000 patients in trials, but we are not uniformly applying that information the same way in every person. There still is a lot of clinical variability in care, from who we select, to how we do the procedure, to how we manage the patients postprocedure.”

Bernard Prendergast, MD (Guy’s and St. Thomas’ Hospitals, London, England), pointed to another battle on the horizon as an increasingly transfemoral procedure moves into younger, lower-risk patients traditionally the purview of cardiothoracic surgeons.

 “If we take a broader view of this, I think a bigger problem we’re facing is how we’re going to move forward together as a community of physicians and surgeons who look after patients with aortic stenosis,” Prendergast commented. “We need to learn the lessons of coronary artery disease where we had 5 to 6 years of turf wars over evidence and guidelines. And avoid a confrontation in the interests of patients. And as we move forward, we have to move forward together and we need to think about how to train the next generation of cardiologists and surgeons to treat these patients collectively.

What TAVR Is Getting Next

Later in the day, TVT attendees got their first detailed glimpse of what the big, US Food and Drug Administration-approved clinical trials testing the two leading devices in low-risk patients will look like. Jeffrey Popma, MD (Beth Israel Deaconess Medical Center, Boston, MA), presented the plan for the Medtronic-sponsored EVOLUT R low-risk trial and Martin Leon, MD (Columbia University Medical Center, New York, NY), who earlier in the day characterized the progression to low-risk TAVR as “relentless,” presented the design of the Edwards Lifescience-sponsored PARTNER 3 trial using the Sapien 3 device. Both studies are randomizing patients 1:1 to the newest generation TAVR devices or the surgeon’s choice of surgical bioprosthesis. Both trials have a number of similarities, but also some important differences.

Leon’s closing slide had a blazing orange banner that read “The Final Frontier,” but both Popma and Leon stressed the need for rigorously designed studies to “get this right” as TAVR moves into what Leon called “the surgeon’s sweet spot.” Leon predicted that enrollment will go slowly, hinting that many patients will have a hard time stomaching randomization to surgery, hoping they could just find another center willing to treatment with a transcatheter approach.

Of note, while Popma made no mention of the age of patients eligible to participate in the EVOLUT R trial, Leon stated that younger age will not be among the exclusion criteria for PARTNER 3. This speaks to a point made by many presenters throughout day one of TVT, namely that low risk is not the same thing as younger age. Revealing plans for the NOTION II “all-comers” randomized controlled trial now launching in Scandinavia, Lars Sondergaard, MD (Rigshospitalet, Copenhagen, Denmark), pointed out that in all of the major randomized controlled trials of TAVR versus SAVR to date, including NOTION I, STS scores have steadily declined, but the average patient age has remained the same, at 80 years. In NOTION II, patients will need to be 75 years or younger to be admitted into the trial. 

---

Source: