Be ‘Mindful’ of TAVI Unknowns in Younger Patients, Experts Urge

Transcatheter aortic valve implantation is approved in the United States for low-risk patients with severe aortic stenosis, without an age threshold. As the authors of a new review point out, though, much is still unknown about how youth can impact outcomes and future options.

Low risk and younger age are categories that should not be conflated, they urge. “The pivotal TAVR trials in low-risk patients have, so far, demonstrated excellent clinical outcomes. However, these results should be extrapolated to younger patients with caution.”

Toby Rogers, MD, PhD (MedStar Washington Hospital Center, Washington, DC, and National Institutes of Health, Bethesda, MD), who led the paper along with Charan Yerasi, MD (MedStar Washington Hospital Center), stressed a similar point to TCTMD.

“TAVR is now approved theoretically across the board for low-, intermediate-, high-, and extreme-risk patients,” Rogers said, “and that raises the potential for every patient with aortic stenosis either being offered or coming and requesting TAVR. We thought it was important to summarize all the evidence, just to be very mindful that we still don’t have good data in younger patients—and that just because it’s approved doesn’t mean it’s the right treatment for everyone.”

Current US guidelines for valvular heart disease say that most patients younger than 50 are best served by a surgically implanted mechanical valve, while “uncertainty and debate continue about which type of AVR is appropriate for patients 50 to 65 years of age.” US Food and Drug Administration approval for TAVI does not specify an age cutoff.

The state-of-the-art review, published online yesterday in JACC: Cardiovascular Interventions, discusses factors that influence decision-making below the age of 65 years—the need for anticoagulation but durability with mechanical valves, for instance, versus the freedom from long-term anticoagulation but need for reintervention with bioprosthetic valves, as well as the risks and benefits seen with various sequences of surgical and transcatheter redo procedures.

It’s ‘very important that we don’t jump on the bandwagon of TAVR is the treatment for everyone, regardless of age.’ Toby Rogers

Flexibility allows for tailored treatment in specific scenarios, said Rogers. For instance, TAVI could be the right choice in a young patient who has undergone radiation therapy for cancer but isn’t a surgical candidate. That said, it’s “very important that we don’t jump on the bandwagon of TAVR is the treatment for everyone, regardless of age,” he added.

Indeed, the main message from their review is that “these decisions have to be individualized. There is no single strategy that fits all,” Rogers commented. Their review calls for lifetime management to be guided by the heart team, with an eye toward tailored care.

Commenting on the review for TCTMD, surgeon Kendra Grubb, MD (Emory University, Atlanta, GA), said it addresses “where the thinking is right now today” when it comes to choosing the first step in younger patients with severe aortic stenosis.

“When we sit in our heart team meetings and we discuss each individual patient, this is the conversation we have every single week. And this is the conversation everybody should be having about these patients,” Grubb said. “Because patients don’t want a sternotomy, they don’t. And patients don’t really want mechanical valves. So if we’re going to put in a tissue valve—whether it’s a surgical valve or a transcatheter valve—we need to be individualizing that.”

The strength of this paper, she said, is that “it really does lay out ‘we don’t know what we don’t know.’”

Low Risk Didn’t Equal Young

The review begins with a summary of existing evidence. For low-risk patients, that comes from three randomized controlled trials (NOTION, PARTNER 3, and Evolut Low Risk) as well as three nonrandomized prospective studies (LRT, LRT Bicuspid, and Evolut Low Risk Bicuspid).

All-cause mortality and stroke trended lower with TAVI versus SAVR, while moderate/severe paravalvular leak (PVL) rates largely were similar; mild PVL was more common with TAVI, which also had higher need for permanent pacemaker implantation. SAVR, on the other hand, was more likely to result in new-onset atrial fibrillation. “Consolidating all this information from the low-risk trials, the overwhelming message is that TAVR has acceptable clinical outcomes compared with SAVR and can be the preferred option in low-risk patients,” the authors write.

Outstanding issues include a lack of data on bicuspid aortic stenosis with Sievers type 0 morphology, the implications for future coronary access after TAVI, unknown long-term durability of transcatheter heart valves (THVs), technical challenges related to their surgical removal, the safety and feasibility of TAVI-in-TAVI, and how best to manage concomitant conditions (eg, aortopathy, mitral valve disease, and CAD). Additionally, patients with bicuspid valves are a key area of interest, since they tend to present when they are younger and often receive surgically implanted mechanical valves.

It’s also important to note, Yerasi et al say, that patients in the low-risk trials had a mean age between 68 and 79 years, with few comorbidities. “So when we say low risk in terms of the clinical trial data, we’re not talking about 50- and 60-year-olds, because those are not the patient populations that were in the trials,” Rogers noted.

Benoy Shah, MBBS, MD (Southampton General Hospital, England), who praised the review for taking a systematic approach to unanswered questions, raised a similar point when speaking with TCTMD: “The randomized trials obviously have quite strict inclusion and exclusion criteria, and so the patients they recruit are quite specific, they’re really quite selected.” Nor did the trials consider frailty, said Shah, president of the British Heart Valve Society. “And so extrapolating those results to everyone else is fraught with difficulty.”

Real-world outcomes may not live up to what’s obtained in the trial setting, he cautioned, citing data from the TVT Registry presented during EuroPCR 2021. In that instance, patients with tricuspid valve disease had a 1-year mortality rate that reached 6.6%, as opposed to the 2.1% seen in PARTNER 3 and 2.4% seen in Evolut Low Risk. Admittedly, these registry patients had been propensity matched to patients with bicuspid valve disease, said Shah, but the disparity is hard to overlook.

An Eye Toward Lifetime Management

Another widely discussed issue is how long the devices will last, and here, too, there are knowledge gaps. “Available data on the durability of surgical bioprosthetic valves are more extensive than those for THVs, as it has almost been six decades since the first SAVR, but these data are disparate and of varying quality,” Yerasi and colleagues point out. Moreover, the tendency to gauge durability by reintervention rates in the surgical sphere may lead to an underestimate of structural valve degeneration (SVD) post-SAVR.

 “So far,” said Rogers, “there’s been no signal that [transcatheter valves] will fail prematurely . . . . But nonetheless you can’t put a TAVR valve in a 60-year-old and promise them [it will be] 25 years before they need another procedure, because we just don’t have the data for that.”

Moreover, the surgical literature suggests bioprosthetic valves deteriorate more rapidly in younger versus older patients, both Rogers and Shah noted. This may be because of the “sheer number of heartbeats,” Shah suggested. “Younger people tend to be more active. They push their heart rates up more, so the wear and tear on the valve is greater.” It also may relate to stronger immune systems, Rogers said. “These are all just theories.”

For the review’s authors, “the totality of the data so far suggest that in terms of SVD, TAVR valves are as durable as SAVR valves, if not more so, as evidenced by the NOTION and CoreValve high-risk long-term follow-up studies.” While 10-year data from the low-risk trials will provide “definitive information,” they say, “we do not believe that patients and physicians will wait for 10 years before offering TAVR to young patients, so interim looks into the data will be invaluable to inform patient discussions.”

Extrapolating [trial] results to everyone else is fraught with difficulty. Benoy Shah

Most interesting to Shah is the paper’s take on repeat valve interventions. It lists several scenarios that might occur in young patients: SAVR followed by TAVI then another TAVI, an initial TAVI followed by SAVR then TAVI, as well as three TAVIs, the latter option being least desirable at the moment.

Although a TAVI-only approach has the advantage of being minimally invasive, it carries higher risk of coronary obstruction, may present difficulties for future coronary access, and is feasible in only a few patients, Yerasi at al note.

“A ‘surgery first,’ or SAVR-TAVR-TAVR, strategy has the benefit of performing surgery at a young age, which carries less risk and is associated with lower morbidity and mortality and feasibility of coronary access in case of percutaneous coronary intervention,” they write, adding elsewhere that “a ‘TAVR first’ strategy of TAVR-SAVR-TAVR has a potential advantage of offering a minimally invasive procedure with rapid recovery and no need for anticoagulation when patients are young, of working or childbearing age.” On the downside, surgical explantation of THVs is complex and risky.

What’s not mentioned in these scenarios, Shah said, is the “obvious fourth option” of SAVR-SAVR-TAVI, which might be possible in young patients whose second intervention would occur when they still are surgical candidates.

Rogers emphasized that, at least for now, these conversations with patients are largely based on hypotheticals: “We don’t know what the right option or the right sequence is. The likelihood is that there isn’t one perfect solution for everyone.”

Cost, too, could be a factor, Shah observed. In North America and Europe, “a multivalve strategy is perfectly affordable or reasonable. But there are many parts of the world where people would say, ‘You know what, if we put a mechanical valve into a 60-year-old [that costs] $1,500, that’s going to see them through for the next 20 or 30 years.” . . . Warfarin costs pennies. If you put a $20,000 TAVR valve into a 65-year-old, and then when that fails at 10 years when they’re 75 you put another [one in], it can become very costly.

“It’s not really something we tend to talk about, because of course we like to be guided by the science principally,” he continued. “But I think it would be naive to think that there are not parts of the world where they will look at cost and they will look at whether that multivalve strategy is realistic in their healthcare system.”

Unknowns and Knowns

Young people being treated for severe aortic stenosis, for their part, will want to know not only how their first procedure will go but also what to expect in the decades to come, Rogers said. What would increase confidence in a transcatheter approach irrespective of age are durability data from ongoing studies as well as improved technologies and techniques for TAVI-in-TAVI. For Grubb, the main gaps in knowledge relate to TAVI versus SAVR in bicuspid aortic valves, techniques for commissure alignment, and tools for modifying leaflets of implanted TAVI devices.

Rogers said he’s not aware of any ongoing randomized controlled trials of TAVI dedicated to young patients, perhaps “because the majority of physicians would still feel uncomfortable about it.” Yet there will always be some people below 65 who, for specific reasons, are best treated by TAVI. “Those patients are being done out there,” Rogers observed. “I suspect every TAVR operator you speak to will have a story of a 50-year-old they did a TAVR in, but that’s the exception not the rule.”

Discussions such as these serve as a reminder for clinicians to “be aware of the unknowns as well as the knowns,” Rogers concluded.

Despite the unknowns, patients themselves are nudging TAVI toward younger ages, said Grubb, and this fits with the shared decision-making that’s integral to the current guidelines. This isn’t necessarily a bad thing, she said. “I do think that patients are going to ask for it—and again, I’m not opposed to young patients having a TAVR first, as long as they know that we don’t know durability in their demographic.”

Ten-year data from the low-risk trials will add clarity, and 15 years would be even better, said Grubb, “so that we can really start to say to our patients: ‘We really do believe this is the right thing for you.’”

For now, honesty about what the data say—and don’t say—is the best policy, she noted.