Good TAVI Outcomes in Young Patients, but Population Is Unique

Younger patients who are turned down for surgical aortic valve replacement and undergo TAVI instead fare just as well in medium-term follow-up as older patients who receive a transcatheter heart valve (THV), according to an observational study. 

In an analysis of patients enrolled in the Aortic+Mitral Transcatheter Registry (AMTRAC), published October 22, 2021, in EuroIntervention, investigators found that patients older and younger than 70 years with severe symptomatic aortic stenosis were equally likely to die at 5 years after TAVI.

Lead investigator Guy Witberg, MD (Rabin Medical Center, Petah-Tikva, Israel), stressed that the new data should not be construed as broadly supporting TAVI in patients younger than 70 years, because the young patients referred for a THV in the AMTRAC registry have distinct characteristics.

“At least for now, very young patients who are referred for TAVI are a very unique group, a very unique subset of the overall TAVI population,” Witberg told TCTMD. “You can’t use these patients as a justification to expand TAVI into younger patients, because they are not the average 65-year-old patient with severe AS undergoing AVR.”

At least for now, very young patients who are referred for TAVI are a very unique group, a very unique subset of the overall TAVI population. Guy Witberg

Philippe Généreux, MD (Morristown Medical Center, NJ), who wasn’t involved in the study, said the low-risk TAVI trials—PARTNER 3 and the Evolut Low-Risk Study—included very few patients this young, noting the average age in those trials was approximately 73 years. Younger, healthy patients are a different population than those studied in the AMTRAC registry, he stressed, noting that healthier patients or those with favorable anatomy have other options, such as surgery with a highly durable mechanical valve or the Ross procedure.

“It’s totally speculative to discuss the viability of TAVR in a patient younger than 65 years at this point,” Généreux told TCTMD. “Do I think one day TAVI will have a place in the lifetime management of these patients? Probably, but at this point in the game it’s premature to conclude or affirm that it does have a place in a young patient at low risk for surgical AVR.”

The AMTRAC Registry

In the AMTRAC registry, which is an investigator-initiated multicenter registry of 18 participating centers in Europe and Israel, Witberg and colleagues analyzed data from 8,626 consecutive TAVI patients, of whom 640 (7.4%) were younger than 70 years. The fraction of patients younger than 70 years steadily increased over time, from 3.9% during 2007-2010 to 9.1% during 2018-2020.

“The average age for TAVI patients is steadily decreasing,” said Witberg. “It’s a process we’ve seen throughout the development of TAVI, that things in the field precede the medical evidence. Younger and younger patients are being referred and treated with TAVI over surgery across the spectrum of surgical risk but there is basically no data on these patients.”

The new American College of Cardiology/American Heart Association (ACC/AHA) guidelines for valvular heart disease have opened up TAVI to younger patients, said Witberg, noting that those 65 years or older are “fair game” for TAVI if the heart team gives the okay. These young patients, he added, haven’t been included in any of the randomized, controlled trials, “which is what should guide our decision-making.”

In terms of patient characteristics, the mean age of those younger than 70 years referred for TAVI was 65 while the average age in the older cohort was 82 years. The mean STS score in the younger and older cohorts was 3.1 and 5.3, respectively. The younger patients were more likely to be male and to have a previous history of surgery, chronic obstructive pulmonary disease, and diabetes. The younger patients were also more likely to have a bicuspid aortic valve or require a valve-in-valve procedure.

In total, 80.7% of all patients younger than 70 years were referred for TAVI on the basis of the heart team discussion, with just 3.4% of patients declining surgery out of preference for TAVI. The reasons the heart team reclassified the patients as higher risk than indicated by the STS score included patient frailty, poor lung function precluding general anesthesia, and porcelain aorta, among other reasons. Active solid/hematologic malignancies, previous organ transplant, and indications for chronic immunosuppression were some of the other reasons patients received a THV over a surgical valve.

Mortality at 5 years was similar in the younger and older cohorts (29.4% vs 29.8%; P = 0.287). In the below-70 group, those referred for TAVI who were deemed high surgical risk by the heart team had a higher risk of death at 5 years than those referred for TAVI for other reasons (31.6% vs 24.5%; P = 0.045). Conversely, in these younger patients, there was no difference in mortality at 5 years between those considered high risk on the basis of the STS score alone versus those with lower STS scores. 

At this point in the game, it’s premature to conclude or affirm that it does have a place in a young patient at low risk for surgical AVR. Philippe Généreux

Equivalent mortality between those younger than 70 and those older than 70 years might be interpreted as a good result, but Witberg also noted there was a 17-year age difference between the two groups and the younger patients had a lower STS score at baseline. These differences would have suggested the results would be more favorable in the younger group, he said.

Généreux said interventionalists often encounter young patients at high risk for surgery, or who have been turned down for surgery. As Witberg noted, these include patients with cancer, prior cardiac surgery, or indications for immunosuppression or steroid use, among other reasons.

“These are patients considered young, say less than 70 years old, who are still high risk,” said Généreux. “They might have active cancer and a life expectancy of 3 or 4 years. TAVI is a good procedure in these younger patients and they were somewhat represented in PARTNER [cohort B] and PARTNER 2A, where they were at high or intermediate risk and surgery was not ideal.”

All told, younger patients ineligible for surgery might represent 5% to 10% of patients undergoing TAVI, said Généreux. While 5 years is not long enough in a young, healthy patient, he noted that many of them are quite sick and the life expectancy is considerably limited.

“In a lot of them, 5 years is enough [follow-up],” said Généreux. “But for a patient who has survived cancer and just has anatomical challenges for surgery, such as an excess of calcium in the aorta, obviously we want a valve that’s going to last for a long time. Five years is clearly not enough and this is why planning is important, to use the appropriate valves so you can ensure a repeat procedure in these very young patients.”

Clinical Decision-Making

In terms of clinical decision-making, Witberg emphasized that hospitals should take into account the experience of their surgical team when selecting between SAVR and TAVI. Twenty years ago, surgeons treated patients across the risk spectrum, but it’s becoming difficult to train surgeons to operate on high- and intermediate-risk patients, he noted.

“In many centers today, given the rapid expansion of TAVI, the average risk profile of patients referred for surgery is low,” Witberg explained. “If you take for granted that all high-risk patients are referred for TAVI, and most of the intermediate-risk patients are also being referred for TAVI, the risk profile of the average surgical patient is very low risk. When you’re used to treating low-risk patients, when you come across a patient who has some high-risk features, like severe lung disease, porcelain aorta, frailty, patients with previous sternotomies for previous AVR, surgeons aren’t that used to seeing [them]. It might be pretty much natural to refer these patients for TAVI.”

To TCTMD, Witberg said that before TAVI is routinely expanded into patients younger than 70 years old, there is a need for randomized, controlled data. That trial, unfortunately, is unlikely to be funded by industry. “I don’t think it’s justifiable to say, ‘OK, we have good results from PARTNER 3 and the Evolut Low-Risk Trial, and this opens the door to start sending young, low-risk, severe AS patients for TAVI.’ If we really want to base our decisions on hard evidence—and I’m not sure this will be done because it’s not in anyone’s interest to fund such a trial—[we need to do] an all-comers trial in patients under 70 years, ideally under 65 years old,” stressed Witberg.

Such a trial, he said, would require follow-up of 5 to 10 years, at a minimum, before it would be justified to expand TAVI into these younger patients.