More Proof of Declining Paravalvular Regurgitation With Newest Balloon-Expandable TAVR Devices

Two recent, single-center studies provide reassurances that both the incidence and severity of paravalvular regurgitation are reduced among TAVR patients treated with the newest iteration of a balloon-expandable valve as compared with earlier devices. Moreover, data suggest that dwindling rates of paravalvular leak are related to device refinement, rather than differences in aortic stenosis severity or operator technique, one of the studies adds.

In the early days of TAVR, moderate or severe paravalvular leak—something seldom seen in surgical valve replacement—emerged as an important risk factor for mortality in TAVR-treated patients. The two new studies, both published online ahead of print, add to the growing body of evidence suggesting that paravalvular regurgitation, or “leak” is a diminishing problem for operators as they become more comfortable with selecting patients, CT sizing the aortic annulus, and choosing and delivering an appropriately sized valve.

“I think we’ve made great strides,” Chandan Devireddy, MD (Emory University, Atlanta, GA), who was not involved in either study, told TCTMD. “As TAVR disseminates and is being used in different centers, by different types of operators, with different levels of training and experience—to see numbers reported with paravalvular leak rate that are this low is encouraging.”

Devices Improve, Use Expands

In one study, published online ahead of print last month in Catheterization and Cardiovascular Interventions, Wolfgang Bocksch, MD, and colleagues (Eberhard-Karls-Universitaet Tuebingen, Germany) compared 30-day outcomes between 102 patients treated with Sapien XT and 107 treated with Sapien 3 (both Edwards Lifesciences) at their center. They report that none or trace aortic regurgitation was found in 34.3% of patients treated with the Sapien XT and in 89.7% of Sapien 3 patients, whereas mild aortic regurgitation was seen in 62.8% of Sapien XT patients and 10.3% of Sapien 3 patients. Higher degrees of aortic regurgitation were rare, occurring in just three Sapien XT patients and no Sapien 3 patients. Clinical events were similar between groups.

A second study, this one from the Netherlands, appeared online before print in the American Journal of Cardiology. William KF Kong, MD, and colleagues (Leiden University Medical Center, the Netherlands) reviewed echocardiographic and multidetector CT parameters, plus incidence of paravalvular regurgitation, among 272 patients treated at their center with one of the Sapien valve iterations. Kong et al report that significant paravalvular regurgitation, defined as moderate or greater, measured by echocardiography following the procedure, occurred in 14%, 10%, and 0% of patients treated with the Sapien, Sapien XT, and Sapien 3 valves, respectively. Importantly, aortic annulus size and degree of calcification were consistent across all three groups, with aortic valve calcification burden emerging as an independent predictor of paravalvular regurgitation.

Speaking with TCTMD, senior author Victoria Delgado, MD (Leiden University Medical Center), explained that selection and sizing of the prosthesis at their center has always been done by CT angiography, according to a standardized protocol. “Methodology could explain, for example, why some patients have more paravalvular regurgitation than others, but at our center, this is not a reason because we’ve always measured in the same way,” she said.

Learning curve has also been cited as a reason why paravalvular leak rates are declining as operators become more proficient, but again, said Delgado, in their series, the rates of over- or undersizing have not played a significant role. This leaves changes to the devices over subsequent iterations or in the amount and location of aortic valve calcification as the two most important factors, the authors write. Indeed, while degree of calcification emerged as an independent predictor of regurgitation, Sapien 3 was associated with less significant paravalvular regurgitation after TAVR independent of aortic valve calcification burden. The Sapien 3’s external cuff, or “skirt” as Delgado called it, “may counterbalance the effect of aortic valve calcification, reducing the risk of paravalvular regurgitation” in patients treated with this latest device.

“The most important thing is that in the current system, particularly with this balloon-expandable valve, the technology has improved and has overcome the problem of aortic valve calcification and reduced paravalvular regurgitation, so this is not a problem anymore,” she concluded.

Looking Forward

To TCTMD, Devireddy commented that it might be “premature to suggest that we’ve eliminated the problem.” These two single-center studies, he continued, are “relatively small series, and if you still want to go with the gold standard, you’re going to have to look at randomized controlled trials, or at least the large trials. The PARTNER 2-Sapien 3 study “wasn’t necessarily randomized, but it was still big numbers, core lab, echo review, and they reported trace or mild paravalvular leak in the majority of patients.”

These days, Devireddy said, an operator who sees moderate to severe leak at the end of the procedure would “see that as a treatment failure.”

He also noted that while these two studies are looking at Sapien 3 in comparison with older generation devices, other valves already being used in the United States or still in development “all have a solution for paravalvular leak in the pipeline as well. So I’m hoping this will be something that is just a rare complication that we just don’t have to worry about as often.”

As clinical trials move into younger, lower-risk patients, however, it will be important to keep an eye on paravalvular leak, he noted. “The advantage that surgery has always and currently has [over TAVR], even with the recent PARTNER 2 trial with the Sapien 3 valve, is in paravalvular leak, and if we see moderate-to-severe paravalvular leak in a low-risk population, that’s really not acceptable.”

It also remains unknown whether trace or mild paravalvular leak may be more problematic in younger, more active patients with longer life expectancy. “At least in the initial trials with shorter duration of follow-up, trace and mild paravalvular leak does not appear to confer any survival or functional disadvantage,” Devireddy said. “But now we’re [talking about] people whose regular routine is going out for a bike ride or working in the garden or going out for hikes. After 5 to 7 years, will that leak have any issues? We hope not,” he continued. “But with the data there now, we don't know.”

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