Longer-Term LRT Results ‘Encouraging’ for TAVI in Low-risk Patients

TAVI provides low rates of adverse clinical outcomes and excellent hemodynamic results through at least 4 years in low-risk patients with symptomatic severe aortic stenosis, extended follow-up from the single-arm LRT trial shows.

By that time point, 12.1% of patients had died from any cause, with a 3.4% cardiovascular death rate, and 2.0% had had a disabling stroke, Ron Waksman, MD (MedStar Washington Hospital Center, Washington, DC), one of the national principal investigators of the trial, reported yesterday at CRT 2022 in Washington, DC.

And in a reassuring finding, Waksman said, the reduction in aortic valve area observed early on in patients with hypoattenuated leaflet thickening (HALT) at 30 days was no longer apparent with longer-term follow-up. Also, HALT was not associated with poorer clinical outcomes.

“The results are really outstanding,” Waksman told TCTMD. He acknowledged that LRT was not a randomized trial—so no comparison with surgery was possible—and that even longer follow-up is necessary to determine how TAVI performs in low-risk populations. On the other hand, there were broad inclusion criteria and a period of 4 years represents the longest follow-up of any US trial of low-risk TAVI at this point, he said.

More information is forthcoming from continuing follow-up of the randomized trials from Edwards Lifesciences and Medtronic that supported the US Food and Drug Administration’s addition of a low-risk indication for TAVI. But right now, Waksman said, TAVI should be the default option for patients with severe symptomatic aortic stenosis who meet low-risk criteria, rather than surgery.

Benoy Shah, MBBS, MD (Wessex Cardiac Centre, University Hospital Southampton, England), however, would not go that far in his interpretation of the data on TAVI in low-risk patients that have accumulated up to this point.

“I’m not sure on what basis we can say that, to be honest, mainly because we don’t have the data for the low-risk patients,” Shah commented to TCTMD, alluding to the lack of details on what happens after 10 or 15 years, which is how long a prosthetic heart valve is expected to last. He described the initial data from this and other studies as promising and encouraging, but said longer-term follow-up is critical to determine whether there’s a difference between transcatheter and surgical valves.

“I am pro-TAVI in the right patients,” said Shah, who is president of the British Heart Valve Society. “I wouldn’t consider it the default yet. Could it be the default once we have that data? Without question, it could well be, but I’m not sure we’ve got enough to say that just yet.”

Valve Hold Up Through 4 Years

The LRT trial, performed at 11 US sites, included 200 patients (mean age 73.6 years; 61.5% men) who had symptomatic severe aortic stenosis, had an STS PROM score no higher than 3%, and were considered by a heart team to have low surgical risk. All patients underwent a transfemoral procedure, mostly with a balloon-expandable valve (88.2%).

Waksman presented preliminary data from the study at CRT 2018, revealing good overall results but with more than 10% of patients with subclinical leaflet thrombosis at 30 days. One-year data released the following year at CRT 2019 provided additional reassurance about the safety of performing TAVI in this population. Now, 4-year data on a total of 174 patients, including 76 with follow-up CT scans to provide information on HALT, are available.

The rate of all-cause mortality remained low through 4 years, with a particularly low rate of CV death, Waksman said. Though the overall stroke rate crept up to 7.9%, only three patients had a disabling stroke by the end of follow-up. Rehospitalization rates for heart failure were 6.1% and no patients had greater than mild paravalvular leak (based on an analysis of 72 patients). Endocarditis was seen in 2.7%, but none of the four patients had had HALT detected at 30 days.

A new permanent pacemaker implant was required in 12.3% of patients by 4 years, up from 6.5% at 30 days. This should be watched, particularly in a population like this, Waksman said. “When you’re looking at low-risk patients, and usually they are younger, one thing that bothers them is a pacemaker.”

Though the analysis of HALT was limited in that it involved only seven patients with the finding and 67 without it—due to loss to follow-up and the fact that not every patient underwent CT at their 4-year visit—it was not associated with differences in any hemodynamic measures over longer-term follow-up. Moreover, there was no severe structural valve deterioration detected during the trial.

“The valve integrity, including the hemodynamics, seems to be very stable through the duration of the follow-up,” Waksman said, pointing out that devices have improved since the trial was conducted and results should be even better for procedures performed now.

As such, Waksman said, “we should not be that alarmed” by early HALT—a position backed up by other studies, too. HALT “is a finding that I would say right now is creating noise in the system, but we don’t have any signs or signals . . . that this is really making any clinical difference.”

Shah agreed that HALT is not a major concern at this point, noting that physicians are not performing routine CT scans to check for the issue. That said, he cautioned against reading too much into the HALT findings from LRT due to the small number of patients who had it detected and were included in the 4-year analysis. “With the numbers so small, we shouldn’t really be trying to hang our hat on this,” he said.

Of note, centers that participated in the LRT trial had low TAVI volumes and were not experienced in participating in clinical trials, Waksman observed. “It tells you that these results in the hands of real-world, not necessarily . . . high-volume centers are excellent and are as good if you compare those results to the studies from the pivotal trials.”

No Worrying Signals

Shah agreed that the results obtained in LRT are comparable to those seen in the randomized low-risk TAVI trials. “They are encouraging, there’s no doubt about that. These are 4-year outcomes now. I don’t see any signal in the results that is a major cause for concern,” he said. He added, however, that even within the larger low-risk population, the LRT participants were particularly low risk and would be expected to have excellent outcomes.

It will be important to see what happens over the next several years to ensure that the TAVI valves continue to last, Shah indicated. “My take on TAVI in low-risk patients is simply so far, so good, in that the data so far are encouraging. But I still think it’s early days.” Long-term results of the STICH trial, albeit from a different patient population, highlight the need to track patients over longer periods of time to assess the safety and efficacy of an intervention, he said.

Although there’s no reason to expect that the 10-year results of TAVI in low-risk patients will be terrible, physicians need to be honest about the lack of data when counseling patients, Shah said.