TAVR as an Option for Intermediate-Risk Patients: Physicians Respond

The dust is settling after last week’s news that the US Food and Drug Administration (FDA) had expanded the indications for balloon-expandable TAVR into “intermediate-risk” patients with aortic valve stenosis. European regulators also recently gave CE Mark approval to a self-expanding TAVR device in this patient population. Yet while the cardiology community views this extension with much excitement, questions linger over durability data and the larger impact of procedural complications in younger patients.

Based on the trial results seen in intermediate-risk patients both with the Sapien XT and Sapien 3 valves (Edwards Lifesciences), Ted Feldman, MD, cath lab director at NorthShore University HealthSystem (Evanston, IL), told TCTMD that FDA approval of these devices “was not at all a question of if, but rather when.” Additionally, the shift from high- to intermediate-risk patients “seemed like a very natural progression,” he commented.

But Joshua Rovin, MD, a cardiothoracic surgeon and director of transcatheter and aortic therapies at Morton Plant Hospital (Clearwater, FL), was slightly more cautious. While this development “is great and gives us the green light to proceed without any angst” in elderly intermediate-risk patients, he told TCTMD, “we all need to continue with our clinical equipoise with regard to durability as the patient population gets younger and younger.”

Rovin alluded to data presented at EuroPCR in May that showed signs of valve degeneration beyond 5 years in TAVR patients who received first-generation devices. Whether those concerns transfer to newer-generation devices remains uncertain. Josep Rodés-Cabau, MD (Quebec Heart and Lung Institute, Laval, Canada), noted to TCTMD that 5-year data from the PARTNER trials “showed equivalent results in terms of structural valve failure” between TAVR and surgery.

Regardless, “we know [TAVR valves] look pretty good at 5 and maybe out to 7 years, but we don’t know beyond that,” said Michael Mack, MD (The Heart Hospital Baylor, Plano, TX), who is serving as co-principal investigator of the PARTNER 3 trial, which is randomizing patients at low risk for surgery to TAVR or surgery. He told TCTMD that durability will be an important focus of the trial and all patients will be followed through 10 years.

Rovin, however, wondered how long the FDA will wait to approve TAVR for low-risk patients, assuming the outcomes are favorable. “What kind of durability data do you need in low-risk patients?” he asked. “Is 1-year follow-up acceptable? Are you going to wait 10 years to approve it?”

“My own opinion is that durability is fundamentally different for TAVR devices than open surgical devices,” Feldman added. “That is, we know we can replace TAVR devices using a valve-in-valve approach and the impact of a redo TAVR on a patient is immensely less great than a redo traditional valve replacement operation.”

But there are other issues to consider. Mack pointed to well-established evidence showing an increased need for pacemakers in patients who receive TAVR compared with surgery. “The younger you are, the bigger deal living the rest of your life with a pacemaker is,” he said.

Other “hurdles to solve with TAVR” as it moves to lower-risk patients are dealing with complications including “embolic events/strokes, mild paravalvular aortic regurgitation, and vascular complications,” said Howard Herrmann, MD, cath lab director at the Hospital of the University of Pennsylvania (Philadelphia, PA), in an email to TCTMD.

These issues are highlighted more now because previously, interventionalists were more “willing to take risks” and perform TAVR on patients with no other feasible options, Rovin said. “As we get to this younger patient population, we do have another option. It’s a great option, and we have great data and long-term outcomes. We know very defined risks and benefits associated with the procedure, and we know its durability.”

Ultimately, as the risk level of the “TAVR population gets lower, the acceptability of complications diminishes,” Feldman said. “These are patients who should do very well with aortic valve replacement by any method, and we have a very high standard to meet set by surgery historically.”

Heart Team ‘Even More Important’

The Heart Team is going to play an even more pivotal role in deciding how to treat this new patient population, Rovin said. He likened the process of treating an intermediate-risk patient with aortic stenosis to “getting a custom-built house,” as each patient requires his or her own set of tailored decisions by a wide range of practitioners.

Rodés-Cabau agreed. As the decision-making process is “relatively straightforward” for inoperable or high-risk patients compared with that for intermediate-risk patients, the Heart Team is “even more important” now, he said. “We have to talk honestly to the patient about the risks of the two procedures.”

However, the processes of established Heart Teams should not change for intermediate-risk patients, Rovin commented. “If you have a healthy Heart Team, this should only continue to drive more volume for the team to discuss. If you have a not-so-healthy Heart Team, . . . you could start seeing people potentially jockeying for [patients].”

Even though TAVR may now be an available option for intermediate-risk patients, Isaac George, MD (Columbia University Medical Center, New York, NY), told TCTMD “there is still a population of patients who are more appropriate for surgery.” Specifically, he said, patients who are younger and more active and those who have other confounding factors “such as proximal LAD disease, extensive coronary disease, mitral valve disease, other valve disease, ascending aneurysms, [and] bicuspid valves” may do better with surgery.

“A patient’s lifespan, their comorbidities, their individual anatomic factors, their sizing—all of those considerations are going to be very important when dealing with lower-risk type patients such as intermediate-risk patients,” George added.

The Heart Team will continue to play a “critical part” in this process as treating TAVR patients becomes “much more complex . . . and it becomes less about the aortic valve and it becomes more about other things,” he said.                      

Looking to Even Lower Risk

Is it inevitable that TAVR will one day be approved for patients at even lower risk? For Feldman, the answer is yes. “We have such good trial data in the intermediate-risk group that expecting similar outcomes in lower-risk patients is completely reasonable,” he observed. “One consideration for low-risk patients is the [increasing] frequency of bicuspid aortic stenosis. We are seeing better published results with bicuspid aortic stenosis in the last year or two compared to at the very earliest part of the TAVR era. Ultimately we will learn how to treat bicuspid aortic stenosis optimally.

Patients with bicuspid aortic valves have typically been excluded from the pivotal trials of TAVR versus valve replacement surgery.

Still, “the key is to build as strong a body of evidence comparing the two therapies in low risk as we have had in intermediate and high risk,” Mack said. This approval will lead to “some creep into lower-risk” patients being treated prematurely, he predicted, but “the PARTNER 3 trial is well underway and it is important that we gather this evidence while we still can.”

On Twitter, responses to the announcement have been generally positive, with a hint of cynicism.

  • Mack reports serving as co-principal investigator for PARTNER 3 and receiving travel expenses for trial committee meetings from Edwards Lifesciences.
  • Feldman reports serving as a consultant to and receiving institutional research grants from Abbott, Boston Scientific, Edwards Lifesciences, and Gore.
  • Rodés-Cabau reports receiving grants from Edwards Lifesciences and Medtronic.
  • Rovin reports serving as a proctor and speaker for Medtronic and Abbott and a proctor for Edwards Lifesciences.
  • Herrmann reports receiving research funding to his institution from Edwards Lifesciences, Medtronic, St. Jude Medical, Boston Scientific, Abbott Vascular and serving as a consultant to Edwards Lifesciences.
  • George reports serving as a consultant to Edwards Lifesciences and Medtronic.