PARTNER Data Back 5-Year Durability of Sapien 3 TAVR

Five years after implantation, the Sapien 3 TAVR device—but not the Sapien XT—holds up just as well as surgical bioprostheses, according to durability details from the PARTNER trials.

Philippe Pibarot, DVM, PhD (Québec Heart & Lung Institute, Laval University, Canada), and colleagues combined data on nearly 3,000 intermediate-risk patients from the PARTNER 2A randomized trial and the SAPIEN 3 intermediate-risk observational study in order to compare the two Sapien valves (Edwards Lifesciences) with each other and individually against SAVR.

“Everybody is waiting for good data about durability,” Pibarot told TCTMD, especially in light of TAVR’s shift toward lower-risk, younger patients with longer expected life spans.

Rishi Puri, MD, PhD (Cleveland Clinic, OH), commenting on the analysis for TCTMD, described it as “really what we need right now,” in terms of its event adjudication, sample size, and echocardiographic core lab.

“There’s something in it for everyone, I think the surgeons can take some confidence that at least in [PARTNER 3] compared to [PARTNER 2], they’ve really upped their game and put in larger valves and the surgical results are excellent. And we can be confident about TAVR being a very good therapy in low-to-intermediate-risk patients,” he said. “Sometimes we get carried away about TAVR, TAVR, TAVR, but I think we have to give credit to the surgeons for doing a really good job.”

Notably, the researchers used the “very comprehensive” Valve Academic Research Consortium 3 (VARC-3) definition for structural valve deterioration (SVD), Puri pointed out. “It takes prosthesis-patient mismatch out of the equation . . . and really homes in in a granular way on structural valve degeneration, both from a stenotic perspective [and] also a paravalvular leak perspective.” These standardized definitions help to “create a level playing field” between TAVR and SAVR, he added.

Historically, SAVR’s durability has been defined according to death/reintervention, Puri and Pibarot both observed.

This approach, said Pibarot, only captures the “tip of the iceberg,” since older patients with comorbidities may not be candidates for repeat procedures. The current study offered a “good opportunity to apply and validate this new VARC-3 definition that we proposed. I am very proud of the paper for this, because it is important from a scientific standpoint,” he added.

As to the results themselves, he also was positive. “So far so good,” Pibarot said. “Five years is an important milestone.”

For Puri, the data are reassuring that, at least until the 5-year mark, later-generation TAVR devices are as durable as SAVR. There’s the question, though, of whether TAVR will be able to match the resilience of surgical bioprostheses through 10 to 15 years. It can’t be taken for granted that the 5-year similarity will hold in the longer term, Puri cautioned. “We have to wait and see. . . . This story is still playing out.”

We have to wait and see. . . . This story is still playing out. Rishi Puri

Pibarot et al looked at 1,069 patients who received a Sapien 3 valve, 936 who underwent SAVR, and 974 who received a Sapien XT valve. Among them, 78% had full echocardiographic data. SVD, the study’s primary endpoint, was defined as the composite of SVD-related hemodynamic deterioration during echocardiographic follow-up and/or SVD-related bioprosthetic valve failure (BVF).

There are a few differences between the VARC-3 definitions and those outlined in a 2017 paper, Pibarot noted, most salient being a threshold for aortic gradient. Mean aortic gradient ≥ 20 mm Hg, featured in the European definition for SVD, when used as a snapshot can inadvertently identify people who have prosthesis-patient mismatch early after intervention. “These are patients with normal valve function—there is no SVD, but the valve is a little bit too small for the patient for the size of the cardiac output required,” he explained. Since SAVR patients are more at risk of such mismatch than TAVR patients, this misclassification can make it seem like surgery is associated with a higher risk of SVD than is actually the case. VARC-3 also considers not just hemodynamic, but also morphological changes.

On Kaplan-Meier analysis, the 5-year estimated rates of SVD were 9.5% for Sapien XT, 3.9% for Sapien 3, and 3.5% for surgery. Compared to SAVR, the Sapien XT carried higher risk (HR 2.61; 95% CI 1.45-4.69). For Sapien 3, risk was similar to that of surgery (HR 1.16; 95% CI 0.60-2.24).  Five-year estimated rates of SVD-related BVF, meanwhile, were 3.7%, 1.1%, and 0.8%, respectively. Again, Sapien XT was associated with higher risk versus surgery (HR 4.73; 95% CI 1.38-16.20).

Also, per 100 patient-years, the 5-year exposure-adjusted incidence rates for SVD were higher with Sapien XT than with SAVR (mean 1.61% vs 0.63%), as were SVD-related BVF (mean 0.58% vs 0.12%; both P < 0.001). Propensity-matched risks were similar with Sapien 3 and SAVR.

All-cause BVF—including both structural and nonstructural endpoints—was more common with Sapien XT than with surgery, both at 5 years (4.7% vs 1.3%) and per 100 patient-years (mean 0.81% vs 0.27%). These all-cause events also trended higher for Sapien 3 (2.6% and mean 0.56%, respectively) versus SAVR, though their etiologies differed.

“In the SAVR cohort, most BVFs were related to endocarditis (50%), followed by SVD (37.5%). In the Sapien XT TAVR cohort, BVF was related to SVD in 64% of the cases and paravalvular regurgitation in 20%. In the SAPIEN 3 TAVR cohort, BVF was related to paravalvular regurgitation in 58% of the cases and SVD in 32%,” the study authors note. Much more rare were valve thrombosis and valve migration, each seen in three patients. In the SAVR group, most reinterventions were surgical, whereas in the TAVR groups, most patients underwent valve-in-valve procedures.

‘Ball Is in the Court of the Heart Team’

Puri said that, all in all, the data for Sapien 3 are good news. However, “perhaps not unexpectedly, given what we’ve seen with some other analyses and what we see perhaps brewing with the 2-year data from PARTNER 3—with there being more valve thrombosis from the 1- to 2-year mark for the balloon-expanding valve driving structural valve degeneration and the need to reintervene—we’re kind of seeing the same patterns in this analysis,” he observed.

A key takeaway for operators, then, is the need to be careful with balloon inflation, Puri noted. “Perhaps balloon dilatation, especially postdilatation, may fissure or injure the leaflets and make cause a nidus for thrombosis and accelerated valve degeneration. It’s a hypothesis that I think is evolving. We’re going to learn more and more as these patients are continually followed over time.”

Puri also cautioned that there are some caveats to the analysis itself. For instance, 22% of eligible patients were excluded from the SVD analysis due to missing echocardiographic results, and the Sapien 3 comparisons stemmed from a nonrandomized study. Additionally, he found the complete lack of TAVR-related endocarditis to be curious.

As to why Sapien 3 performed so much better than the XT, Puri said this was related both to the introduction of a skirt on the device frame, meant to mitigate paravalvular leak, and increased use of CT sizing. Sapien 3 Ultra, the latest generation, features an even taller, textured outer skirt.

Sapien XT is no longer on the market, but what of the thousands of people who’ve already received the device? To TCTMD, Pibarot acknowledged that this is a valid question. Luckily, with TAVR it’s relatively easy to address SVD with a repeat TAVR valve-in-valve, he said. “It’s like giving a second life to the valve.”

Eric Van Belle, MD, PhD, Cédric Delhaye, MD, and Flavien Vincent, MD, PhD (CHU Lille, France), writing in an accompanying editorial, say that better prevention of paravalvular leak (eg, newer devices, higher valve position, CT fusion) will soon lessen the need for reintervention after TAVR. As the data roll in regarding TAVR’s long-term performance, “it seems too early to recommend TAVR for all the youngest and lower-risk patients,” they advise. “Conversely, the body of favorable data for TAVR in addition to the present reassuring data for TAVR durability support the fact that SAVR should not be proposed as the go-to treatment for all young candidates for a bioprosthetic valve.”

The “ball is in the court of the heart team,” Van Belle et al conclude. “Overall, a lifetime plan of care should be discussed with the patient to put in perspective that both techniques are complementary and could be required during his or her lifespan, in the same way that percutaneous coronary intervention and coronary artery bypass graft surgery can be used at different moments for a given patient.”