Reed Miller

May 03, 2012

May 2, 2012 (San Francisco, California)— Too many patients who cannot benefit from aortic-valve replacement are being treated with transcatheter valve implants, according to Dr Craig Miller (Stanford University, CA), one of the surgeon investigators of the pivotal PARTNER trial.

"When it was new and we were experimenting, then you can do [transcatheter aortic-valve implantation (TAVI) in] anybody and you figure out if it's going to work and how to do it, but we know from all of these registries and the PARTNER trial, both cohort A and cohort B, that we're overextending the envelope on the older and sicker 'cohort C' side," Miller told heartwire . "These are patients who are so sick and so old that they're not going to benefit."

On April 29 at the American Association of Thoracic Surgery 2012 Annual Meeting, Miller gave a presentation entitled "[Transcatheter aortic-valve replacement] TAVR has a limited role in the treatment of patients with severe aortic stenosis" [1]. He argues that the PARTNER B results support the role of TAVI as the standard of care for symptomatic patients with aortic stenosis who are not surgical candidates. But he cautioned that there is an "upper limit" to how sick these patients can be. In his presentation, Miller favorably quoted PARTNER B lead investigator Dr Raj R Makkar (Cedars-Sinai Heart Institute, Los Angeles, CA), who said that "the ultimate value of TAVR in 'inoperable' patients will depend on careful selection of patients who are not surgical candidates and yet do not have extreme comorbidities that overwhelm the benefits of TAVR and render the intervention futile."

Miller pointed out that in the latest one-year data from 3195 patients in theFRANCE 2TAVI registry, published today in the New England Journal of Medicine,18.6% of patients died within six months and 24% died within one year of implant [2]. Multivariate analysis by the FRANCE 2 investigators, led by Dr Martine Gilard (Université de Bretagne Occidentale, Brest, France), found that the factors significantly linked to one-year mortality were a high logistic EuroSCORE (hazard ratio of 1.37 for every 1% increase in EuroSCORE), NYHA functional class 3 or 4 vs 1 or 2 (hazard ratio 1.49), implant via the transapical approach vs the transfemoral approach (hazard ratio 1.45), and periprosthetic regurgitation of grade 2 or higher vs a grade <2 (hazard ratio 2.49). At one year, 89.5% of the patients were asymptomatic or only mildly symptomatic (NYHA class 1 or 2).

Miller points out that the mortality rates in FRANCE 2 are similar to that shown in the UK TAVI registry and PARTNER A (eligible for surgery) and a bit better than in PARTNER B (surgery ineligible). "The valve isn't killing them; all of these other [comorbidities] are killing them," Miller said. "Why are we losing a quarter of them if they're getting a perc valve and everything is hunky-dory? That represents an error in judgment by who we did the procedure on?

"Where are these patients coming from, and how much money are we going to squander if we're still losing a quarter or so at one year? [These patients are] the 'cohort C' whom we shouldn't touch. The potential benefit of [TAVI] is overwhelmed by the other comorbidities," Miller told heartwire . "Society cannot afford this amount of money on them. As [Dr Michael Mack (Baylor Health Care System, TX)] said, 'They're not dying of their aortic stenosis, they're dying with it.' So patient selection is key."

Miller explained that this so-called "cohort C" that is too sick to benefit from aortic-valve replacement includes patients with a Society of Thoracic Surgeons score over 20, forced expiratory volume over 40%, long-term oxygen dependence with a history of cigarette smoking, pulmonary hypertension, chronic kidney or liver disease, extreme obesity, neuromuscular disease, extreme frailty, or dementia.

Miller pointed out that the Centers for Medicare & Medicaid Services' new Medicare coverage policy for TAVI precludes coverage of TAVI for patients whose comorbidities would preclude the expected benefit from correction of the aortic stenosis. 

Still Giving TAVI to People Not Sick Enough

While Miller and other experts are concerned about the costs of TAVI in patients who are unlikely to benefit, the latest registry data show that many patients who may be better suited to surgical replacement are getting TAVI. In the paper on FRANCE 2, Gilard et al report that although too many patients with high EuroSCOREs are getting TAVI, the average EuroSCORE of TAVI patients in the registry is declining.

Between 2010 and 2011, patients in FRANCE 2 were more likely to choose TAVI (from 14.4% to 17.1%, p=0.04), while the proportion of patients who declined surgical-valve replacement even though they were candidates for surgery also increased. This pattern "is a reflection of real-life practice, despite the national recommendations. The rapid increase in the use of TAVI entails a risk that candidates for conventional aortic-valve replacement will be treated percutaneously," Gilard et al report.

German registry data show that 13% of patients had opted to undergo TAVI rather than conventional aortic-valve surgery, "a rate that is alarming and clearly a case of off-label use of the procedure if the EuroSCORE is below 20%," Gilard reports. In 2011, 30% of all aortic-valve repairs in Germany were TAVI procedures, vs 24% in 2010, Miller told heartwire.

Commenting on the FRANCE 2 results, Dr Grayson Wheatley (Arizona Heart Institute, Phoenix) agreed that the "most interesting aspect of the data was the significant increase in patient choice in favor of TAVI in patients who were a candidate for surgical aortic-valve replacement.

"This trend suggests that, even though the surgical outcomes in the lower-risk patients are improving and perhaps better than TAVI, patients are choosing TAVI. It is unclear what specific factors are influencing patient choices, but further insight into this process is warranted," Wheatley told heartwire . "We need to understand the specific factors that are leading patients with a EuroSCORE below 20% to choose TAVI. Perhaps future registries will capture that information. This information has global implications, since the TAVI procedure is still indicated for prohibitive-surgical-risk patients."

Miller is an investigator for the PARTNER trial sponsored by Edwards Lifesciences and is a consultant to Abbott Vascular Structural Heart, Medtronic, and St Jude Medical. FRANCE 2 is supported by Edwards Lifesciences and Medtronic. Both Gilard and Wheatley say they have no conflicts of interest. Disclosures for the coauthors of the Gilard et al paper are listed on www.nejm.org .

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