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In patients with severe aortic stenosis who are at prohibitive risk for surgery, transcatheter implantation of a self-expanding valve substantially reduces all-cause death and stroke at 1 year, according to a prospective nonrandomized study published online March 19, 2014, ahead of print in the Journal of the American College of Cardiology. While the device also appears to yield low rates of stroke and paravalvular regurgitation, more than 1 in 5 patients undergoing the procedure require a permanent pacemaker.

Results of the CoreValve Extreme Risk Pivotal Trial were initially presented at the Transcatheter Cardiovascular Therapeutics scientific session in San Francisco, CA, in October 2013.  The data formed the basis for approval of the device by the US Food and Drug Administration in January 2014.

For the prospective, single-arm study, investigators led by Jeffrey J. Popma, MD, of Beth Israel Deaconess Hospital (Boston, MA), analyzed outcomes of 489 patients with symptomatic severe aortic stenosis who were at extreme surgical risk and scheduled for treatment with the CoreValve self-expanding nitinol bioprosthesis (Medtronic, Minneapolis, MN) at 41 US centers from February 2011 to August 2012. All procedures were performed via the iliofemoral route.

All but 3 patients underwent implantation. The device success rate was 84.6%; procedural success (device success in the absence of in-hospital MACCE) was achieved in 77.6%.

CoreValve Easily Beats ‘Objective Performance Goal’

At 12 months, the Kaplan-Meier rate of all-cause mortality or major stroke (primary endpoint) in the as-treated cohort was 26.0%, with an upper 2-sided 95% confidence interval of 29.9%. The latter was lower than the prespecified objective performance goal of 43% (P < 0.0001). According to the authors, the 1-year mortality rate was similar to that seen in the PARTNER B trial of inoperable patients treated with the Sapien valve (30.7%; Edwards Lifesciences, Irvine, CA). However, the 30-day stroke rate was roughly half that of PARTNER B (5.0%). Importantly, the need for permanent pacemaker implantation was markedly higher than with the Sapien valve (4%; table 1).

Table 1. Clinical Outcomes

 

At 12 months, mean aortic valve gradient and effective orifice area were both substantially improved over baseline (by 39.8 ± 14.8 mm Hg and 1.2 ± 06 cm², respectively; both P < 0001). LVEF increased from 54.5 ± 14.4% to 57.3 ± 11.6% over the same period. At discharge, 9.1% of patients had moderate paravalvular regurgitation, while 1.6% had severe regurgitation (the only level associated with late mortality). However, among patients with paired echocardiograms, 82.8% of those with moderate regurgitation at discharge showed improvement by 12 months. The study authors say this suggests “ongoing remodeling of the annular-bioprosthesis interface with the self-expanding device.”

In a telephone interview with TCTMD, Dr. Popma pointed out that the CoreValve investigators had no transcatheter valve experience before they started the trial, although they underwent an intensive training process. “We were very pleased that [such] investigators … had very acceptable outcomes with low procedural complications.” 

Lessons Learned

“We learned several lessons early on,” Dr. Popma reported. First, device sizing is critical, and for that reason all patients had CT assessment of the aortic annulus to guide valve selection. “I think that speaks to … the low rate of paravalvular regurgitation and the improvement in regurgitation over time,” he said

Another important technical strategy, Dr. Popma observed, was implanting the valve as high in the aortic annulus as possible. “That allowed us to capitalize on the diameter of the inflow portion of the CoreValve frame in an effort, again, to minimize the degree of paravalvular regurgitation,” he explained.

Finally, the investigators learned the importance of assessing the immediate post-implantation results using echocardiography, hemodynamics, and aortography. “We made certain to treat patients if they had moderate or severe aortic regurgitation,” Dr. Popma commented.

Furthermore, he noted, the rate of permanent pacemaker implantation seen in the trial represents a reduction from the early European experience, and key to the improvement was the somewhat higher valve implantation, to avoid the conduction system. “We looked on [the current pacemaker rate] as an acceptable trade-off to have very low rates of moderate or severe paravalvular regurgitation and good clinical outcomes,” he said, adding that even when it was necessary, pacemaker implantation had no impact on 1-year mortality.   

As to how the availability of CoreValve will impact the TAVR field, Dr. Popma said, “This is all an evolution, but right now there is certainly a broader range of annular diameters that can be treated with CoreValve rather than the currently available commercial valve.” In addition, the 18 F delivery system can accommodate smaller iliofemoral diameters. “What that does is shift more patients form alternative access with the commercially available device into a transfemoral approach. We think the results are just a little more favorable with transfemoral access.”

When it comes to choosing among bioprostheses, Dr. Popma said, “We’ll have to see how this plays out over the long term. Certainly we’re thrilled to have 2 valves available, and we’re looking for more. It allows us to provide more options to our patients, and that’s a good thing.” He added that valve selection will likely be “an individual institution decision about which device they’re going to be more comfortable with in terms of implantation, ease of use, and sizing.”

PARTNER Comparison Misguided

In a telephone interview with TCTMD, Peter C. Block, MD, of Emory University School of Medicine (Atlanta, GA), said comparison of the CoreValve results with those from PARTNER B, though tempting, is ill advised. However, he added, “results from the randomized CHOICE trial pitting CoreValve against Sapien, which is scheduled to be presented at the upcoming 2014 ACC/i2 Scientific Sessions, may provide some insight in that regard.

Overall, the introduction of CoreValve will probably expand the pool of patients who receive a new valve and thus potentially reap better outcomes, Dr. Block said. Moreover, each device has advantages and disadvantages, he observed, and “now we have the luxury of making a decision about which valve is best for a specific patient.”  

For example, for a patient who already has a pacemaker, the CoreValve might be a good choice because that contingency is already covered, Dr. Block commented. For someone with tortuous vasculature, likewise CoreValve may be preferred because it is “a little slicker and more user-friendly to the arteries, and the vascular complications are low,” he added. “For a patient at very high risk of stroke, perhaps I would choose CoreValve, too, because the stroke rate seems to be extremely low.”

In the end, however, he said the paper shows that “the 3 major issues that all of us in TAVR worry about—paravalvular leak, pacemaker rate, and stroke—are still with us.”  

In particular, he observed, the poor prognosis for severe paravalvular leak “indicates that this issue needs to be solved. We have learned … that to leave the lab with a significant paravalvular leak is just not acceptable. You either have to post-dilate or put in a second valve.”  

Study Details

Overall, patients were elderly (83.2 ± 8.7 years). About half (52.1%) were women and most were severely symptomatic (91.8% NYHA class III/IV). The mean STS score was 10.3%, with 17.2% of patients having a score greater than 15%. Almost half of patients (46.8%) had A-fib.

Bioprostheses with diameters of 23, 26, 29, and 31 mm were used to treat patients with an annulus size ranging from 18 to 29 mm; the valve size selected was based on a pre-enrollment CT angiogram. All valves were delivered via an 18 Fr catheter.

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Source:
Popma JJ, Adams DH, Reardon, MJ, et al. Transcatheter aortic valve replacement using a self-expanding bioprosthesis in patients with severe aortic stenosis at extreme risk for surgery. J Am Coll Cardiol. 2014;Epub ahead of print.

 

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