Paravalvular Regurgitation With Sapien 3 Rare but Still Can Be Deadly

(UPDATED) Transcatheter aortic valve replacement with the Sapien 3 heart valve in patients with severe aortic stenosis and at intermediate or high surgical risk results in a very low rate of paravalvular regurgitation (PVR) at 30 days, according to the results of a large, prospective registry.

Moderate or worse paravalvular regurgitation, however, remains significantly associated with an increased risk of death and rehospitalization for heart failure at 1 year, report investigators.

“In patients with moderate and more PVR, unfortunately, but as expected, there was a significant increase in all-cause mortality and cardiovascular mortality,” lead investigator Philippe Pibarot, DVM, PhD (Laval University, Quebec City, Canada), told TCTMD. “So, yes, the incidence of moderate PVR is markedly reduced with the third-generation balloon-expandable Sapien 3, but when it occurs, it still has the same impact on mortality and hospitalization outcomes.”

The magnitude of mortality risk observed—patients with “at least” moderate PVR had a 2.6-fold higher risk of all-cause mortality, a 2.9-fold higher risk of cardiovascular mortality, and a 2.3-fold higher risk of hospitalization at 1 year—is similar to that observed in the PARTNER 1 trial and other reported meta-analyses, said Pibarot.

“When it occurs, it’s bad,” he said. “Interestingly, though, among those with moderate-to-severe PVR who survived until 1 year, 73% had a regression of PVR. They had moderate or severe PVR at 30 days, but nevertheless, when we looked at these same patients, there was a regression to less than moderate PVR in about three-quarters of the patients. It’s the first time this has been reported.”

Pibarot noted, however, that the regression data is based on a small sample of patients and may reflect survivor bias.

Sapien 3 Registry Data

The new study, published online September 27, 2017, in JAMA Cardiology, includes 1,661 patients enrolled in the PARTNER 2 Sapien 3 registry and treated at 51 US hospitals. Among them, 1,592 had a transthoracic echocardiogram performed at 30 days. Approximately one-third of patients were considered high risk or were ineligible for surgery.

Speaking with TCTMD, Pibarot noted that the incidence of PVR following TAVR ranges. In one analysis of the PARTNER trial, which included both high-risk and inoperable patients, the incidence of moderate/severe PVR was 9.1%. Moderate-to-severe PVR is associated with a two- to threefold increase in mortality, he said.   

In the present study, the researchers used a grading system that classified PVR as follows: none/trace, mild, mild-to-moderate, moderate, moderate-to-severe, and severe. The five-point grading system differs from the three-point classification scheme (mild, moderate, or severe) recommended by the American Society of Echocardiography, but Pibarot said he believes it provides greater granularity and flexibility for grading PVR.

At 30 days, PVR was classified as none/trace in 55.7%, mild in 32.6%, mild-to-moderate in 8.2%, and moderate in 3.0%. Just 0.5% of patients had moderate-to-severe PVR—none were classified severe—so investigators grouped patients with moderate and moderate-to-severe PVR into one group. In total, 3.5% of patients had at least moderate PVR.

“With the new-generation transcatheter valves, such as the Sapien 3, with specific features to prevent or at least reduce PVR, we’ve seen a marked reduction in the rates, particularly PVR that is moderate or worse, which has an important clinical impact,” said Pibarot.

At 1 year, as noted, patients with at least moderate PVR had a significantly increased risk of death, cardiovascular mortality, and rehospitalization compared with individuals with no/trace PVR. These patients also had a higher risk of valve reintervention. In contrast, there was no mortality or rehospitalization risk at 1 year for those with mild or mild-to-moderate PVR. Patients with mild-to-moderate PVR did, however, have an increased risk of valve reintervention compared with those without PVR.

Getting Spoiled With New Devices

Chandan Devireddy, MD (Emory University School of Medicine, Atlanta, GA), who was not involved in the study, said that with increasing operator experience, as well as improvements with these latest-generation devices such as Sapien 3 and CoreValve Evolut R and PRO (Medtronic), the rate of PVR has declined significantly. That said, moderate leaks post-TAVR remain something to be avoided.

“This study gives us further weight that if we end up with moderate or more paravalvular leak, your outcomes are going to be the same, if not worse, than had we not done the procedure at all,” said Devireddy. “It really behooves us to pursue every strategy we have to get that [PVR] number as close to zero as possible.”

He added that these data likely reflect early experiences with Sapien 3, which includes an outer skirt designed to minimize the risk of paravalvular leak. Today, physicians have gained experience using CT imaging to plan procedures and select appropriately sized valves.

“As a result, we’re much more comfortable with ways to measure the aortic root and the associated structures to really predict the best device size possible and potentially identify some of these patients who might be at risk for leak,” he said. “I’m hoping, as we get further registry data on the incidence of paravalvular leak in patients receiving TAVR since this study, the rate will be even lower.

“We’ve kind of gotten spoiled now with our third-generation valves where if you even see a mild leak, you’re disappointed,” Devireddy continued. “We want to get it down to none or trace. It’s pretty rare to see moderate leaks in this day and age.” 

One of the controversies and debates in TAVR has been the clinical impact of mild PVR on clinical outcomes, said Pibarot. While some studies, such PARTNER 1, have shown mild regurgitation has an impact on mortality, others did not show any relationship between mild PVR and later clinical events.

In their study, said Pibarot, “even at the upper range of mild-to-moderate PVR,” at least until 1 year there was no apparent clinical impact. The findings are good news given that mild and mild-to-moderate PVR is still quite prevalent, he said.

Devireddy said the association between mild PVR and adverse clinical outcomes is going to be an area of intense focus with TAVR trials in low-risk patients, who have a longer life expectancy than high-risk/inoperable patients. “With a longer time horizon, will there be more time for a mild or mild-to-moderate leak to potentially cause clinical problems for a patient as opposed to the 1-to-5-year time horizon we’re looking at here? It may or may not,” he said. “We won’t really know until we get further data.”    

Regression Signal Observed in Moderate PVR Patients

Regarding the regression of PVR after TAVR, 24 of 33 patients with at least moderate PVR at 30 days were reclassified as having less than moderate aortic regurgitation at 1 year. The researchers did not identify any variables to predict which patients with at least moderate PVR would improve, making it important to prevent the complication given its clinical impact.   

“I think we should continue our efforts to prevent moderate PVR in the first place,” said Pibarot. “There’s still room for improvement. I think there’s some progress we can make with the skirt, for example, and I think there’s progress we can make by optimizing the positioning of the valve. In this registry, this was the first experience with the Sapien 3 and it’s a different animal compared with previous generations. It shouldn’t be sized exactly the same, it shouldn’t be positioned the same.”

As physicians begin to implant these next-generation valves into lower-risk patients, the incidence of PVR will decline even further, Pibarot predicted.