Earlier Interventions and Later Redos? ‘Mature’ TAVI Still Has Growing Pains

LONDON, England—International faculty convening once again at PCR London Valves marked TAVI’s twentieth anniversary with some back-patting coupled with some sober reminders that for all that’s been accomplished in this space, some major holes still need to be filled.

“We now characterize [TAVI] as being in a mature state,” said Martin Leon, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY). Comoderating a main arena session reviewing the “big questions” facing the field, Leon likened TAVI to a middle-aged adult, saying: “We don't yet have the sagacity or the wisdom of an elderly reflective mode, mainly because we have many evidence gaps.”

As previously reported by TCTMD, cardiology organizations throughout the year have been celebrating the two decades of progress since Alain Cribier’s first transcatheter valve procedure in April 2002. But as multiple sessions and expert discussions here on the opening day of the conference made clear, TAVI’s success has also spurred a range of new challenges.

Some of those lie in the areas for which many hope TAVI indications can expand—less severe or asymptomatic aortic stenosis (AS), as well as aortic regurgitation. Still others are found in the techniques being pioneered to deal not only with failing surgical bioprostheses but, as the years go by, failing TAVI devices.

Kendra Grubb, MD (Emory University, Atlanta, GA), speaking with TCTMD after a morning session that addressed the latter scenario, characterized the wave of deteriorating TAVI devices as a “coming tsunami.”

“For high-volume centers, especially academic centers, it is a huge concern,” she told TCTMD. “Our heart team has evolved from treating patients who are elderly, high risk, and operable, where one valve was going to be the only valve they ever needed because the valve was going to outlast the patient. Now, as we are treating low-risk patients, which inherently are younger—we're talking about 65 year olds who are likely going to need more than one valve in their lifetime.”

Earlier Interventions and Lifetime Management

Nicolas Van Mieghem, MD, PhD (Erasmus Medical Center, Rotterdam, the Netherlands), kicked off the main arena session on Sunday by making the case for more “upstream TAVI,” potentially preventing pressure overload from transitioning to volume overload and heart failure.

“I think upstream TAVI can be treating moderate aortic stenosis,” he argued. “It can also be treating asymptomatic severe aortic stenosis.” While multiple trials are ongoing in this space, such as PROGRESS, TAVR UNLOAD, and EVoLVeD, there’s also the possibility that other trials that have proved negative in the past—he gave the example of the GALILEO and ATLANTIS anticoagulation in TAVI trials—might not deliver the same results in younger patients with lower risk of bleeding.

To successfully expand TAVI to new populations, he concluded, the field will need not only new device iterations and dedicated tools, but also a better grasp of the pathophysiology, as well as better buy-in from—and education of—physicians and patients alike.

Samir Kapadia, MD (Cleveland Clinic, OH), following Van Mieghem, had a few more additions to this wish list, noting that intervening earlier in the “lifetime management” of patient disease inevitably means a higher likelihood of encountering bicuspid valve morphology, more questions about valve durability, more potential for paravalvular leak to have an impact long-term, more implications for future coronary access pitfalls, and more risk of new pacemaker implantation if a first valve is positioned with a second valve in mind.

There's so much more information we need to acquire in order to better inform our patients and to advance this field. Martin Leon

Commenting on both presentations, panelist Hélène Eltchaninoff, MD (University Hospital Charles Nicolle, Rouen, France), noted that while she agrees with Van Mieghem there is a “physiopathologic rationale” for earlier interventions in moderate AS, this also has long-term implications, as hinted at by Kapadia.

“If you decrease pressure afterload, you feel that the patient should feel better and have a better outcome,” Eltchaninoff said, stressing that this still needs to be proven in the ongoing clinical trials. But this could also introduce a new wrinkle, she continued: “If the patients are treated earlier, they will be younger and then you have more problems for lifetime management.”

Likewise, panelist Megan Coylewright, MD (Erlanger Health System, Chattanooga, TN), who disclosed that she is leading the eligibility review committee for EXPAND TAVR II, a moderate AS study being sponsored by Medtronic, said she “liked” Van Mieghem’s point about earlier intervention but had her own caveat.

“We don't want to wait until the left ventricle is affected by the valve, but those of you that are thinking of sending your patients to a moderate AS study may be wondering if this cardiac damage that we're seeing may be just concomitant, [if] it's not actually from the valve,” said Coylewright. Moderate AS studies, she continued, “are really focusing on heart failure management of patients with moderate AS, and as that medical field progresses quickly, it's hard to predict how important early valve intervention will be if we're sophisticated in our medical management.”

When First Valves Fail

The second half of Sunday’s main arena session focused on failed bioprosthetic valves and how best to predict and avoid failures in the first place.

Thomas Modine, MD, PhD (CHRU de Lille, France), reviewed some of the recent studies showing that the number of redo TAVI procedures is rising sharply alongside TAVI-after-SAVR valve-in-valve procedures. The latter had already been a growing area of specialization, with research and innovation tackling the problems of commissure alignment, coronary access, and inadequate initial valve sizing. By contrast, he said, surgical explant of a failing TAVI valve is an area only now attracting attention, most notably for the high mortality associated with these procedures.

Smaller registries, he noted, have reported mortality rates as high as 30% at 30 days for TAVI explants, which are often being done by surgeons without much experience with this specialized procedure. Even the larger Society of Thoracic Surgeons database is pointing to mortality rates in the range of 12% for TAVI explantation, roughly double the mortality seen for TAV-in-TAV procedures.

“They are things that favor redo TAVR, and they are some other things that favor TAVR explant. We have to put them and discuss them together in a calm atmosphere,” Modine concluded cautiously, although he characterized TAVI explants as “definitely riskier” than either a first or redo surgical procedure.

Cardiovascular surgeon Hendrik Treede, MD, PhD (University Heart Center Bonn, Germany), reacting to Modine’s numbers, urged caution in interpreting the TAVI explant data Modine provided. Most of these failed TAVIs, Treede noted, were due to endocarditis, which “is a totally different animal” than other forms of TAVI valve failure.

According to Treede, most TAVI explantations would involve a Bentall procedure for aortic root replacement, which many surgeons would be familiar with. “Root replacement has a risk of 2%, not 12%,” he said. “What we shouldn't do now is to speak so badly about surgery because we overestimate the risk. When it comes to TAVR degeneration, it's a much easier procedure [than in the setting of endocarditis]. Comparing apples to oranges doesn't help us a lot in this field.”

Danny Dvir, MD (Hebrew University, Jerusalem, Israel), who was one of the first to raise questions about TAVI valve durability, as well as pioneer solutions to protect coronary access during valve-in-valve procedures, spoke with TCTMD about initial device selection. “The most important thing by far, to me, is that the operator that implants a device needs not only to think about the success of the device, but what will happen in a couple of years if that device fails. They can choose a specific device, in a specific size, and a specific location, doing commissural alignment. These are the type of things that may help the lifetime management.”

Understanding which of the devices today may be best in younger patients more likely to require repeat procedures remains an area of active investigation, he added. Most operators would choose a shorter device, with the least risk of coronary obstruction, but there are some signs that the shorter valves in use today, though easiest for valve-in-valve down the road, may not be as durable. “Obviously we want devices that last, but if they fail, we want them to be easy to treat,” he said. “But there is a balance between those that are treatable but not as durable, and those that are durable but not as treatable—it's not so easy to decide.”

What About Imaging?

Concluding his talk, Modine stressed the need for “meticulous fluoro and CT planning,” both for valve-in-valve TAVI and for TAVI explantation, and when deciding between the two.

Grubb, to TCTMD, made the same argument. Earlier in the day, she presented an analysis of 204 post-TAVI CT scans to identify factors worth considering at the time of an initial TAVI implant: to reduce the risk of coronary flow obstruction and to preserve future coronary access while avoiding conduction disturbances.

“These issues start to become more and more important,” said Grubb, “and so not only identifying those patients ahead of time from the initial implant, but also looking at their CT scan and saying, ‘This is going to be the best valve in this position so that we can use another valve with the tools that we have,’” if a repeat intervention is warranted.

While the coming “tsunami” might not benefit from that foresight in the immediate future, she acknowledged, “we have an opportunity to change our behaviors now, not just be happy that we got a valve in, but be very precise in our implantation to get surgical-like results in our old and young patients.”

The most important thing by far, to me, is that the operator that implants a device needs not only to think about the success of the device, but what will happen in a couple of years if that device fails. Danny Dvir

Christopher Meduri, MD (Karolinska University Hospital, Stockholm, Sweden), whose talk followed Modine’s in the main arena, also called for high-quality multimodality imaging to optimize valve-in-valve procedures. To make this point, he showed a number of side-by-side case examples where imaging results might tilt the decision-making in favor of a percutaneous or surgical approach.

“It's critically important that we start thinking now about independently reviewing, understanding, and using all of the imaging available,” he said.

Speaking with TCTMD after the session, Leon picked up on the same point, calling imaging “a fundamental, central piece of the entire procedure.”

Importantly, said Leon, it’s not enough to have a specialized imager on the team—operators themselves should themselves have these skills. “Right now, it is done ad hoc, it's more of an apprenticeship than it is a scholarly exercise,” he told TCTMD. “I'm hoping in the future that [advanced CT imaging] will become not something that people view in a cavalier way, but take as seriously as the procedure itself. . . . I think there has to be at least one key operator who's involved in the procedure who personally has the experience to interpret and to view the studies, and to be able to share that information with the rest of the team.”

Conversations With Patients

With all that information in hand, it will be important to make sure patients, too, understand the implications of valve choices both at the time of their initial procedure and for any subsequent do-overs.

“These are difficult discussions, particularly with younger patients who are active and want an immediate return to normal lifestyle,” Leon noted during the session he chaired. Putting the question to Coylewright he asked: how much of this can patients understand?

In response, Coylewright said she’ll continue to advocate for data and shared decision-making, agreeing that these conversations may not come easily for some physicians. “It's not something that we are just all born doing, being able to talk to patients in sophisticated ways and engage their preferences,” she said.

I think there's still a long way to go to bring the science of shared decision-making to our clinical practice, but it will be more important than ever before as we extend into new patient populations. Megan Coylewright

Coylewright recently wrapped up a multicenter trial of a decision aid to use with patients with aortic stenosis and observed that when patients first see their doctors, they “do not have informed preferences, they have uninformed preferences.”

Physicians typically tell her that they can’t do shared decision making, because their patients come in with their minds made up—they want a TAVI.

“But what we found in the study was that with the use of a well-designed decision aid and a shared decision-making process, we were able to increase patient knowledge and improve decisional quality,” Coylewright said. “And patients did change their mind about the therapy that they thought they wanted, based on clear identification of their goals and values. So I think there's still a long way to go to bring the science of shared decision-making to our clinical practice, but it will be more important than ever before as we extend into new patient populations.”

Wrapping up the session, Leon called it “exciting to see the last 20 years evolve to a point where we can talk about relative stability and maturity.”

But work remains, he reiterated. “When I see the number of still unanswered questions and the potential for the future, I'm hoping that the next generation of you in the audience will consider this challenge, because there's so much more information we need to acquire in order to better inform our patients and to advance this field.”