TAVR vs SAVR: Limitations and Risks Debated as Transcatheter Therapies Move Into Younger and Lower-Risk Patients

LONDON, England—As clinical trials testing transcatheter aortic valves against surgery in younger and lower-risk patients get underway, interventionalists and surgeons do not necessarily agree on what the limitations—and risks—of each approach will be. 

This debate was the focus of a dedicated session at PCR London Valves 2016 that pitted interventionalist Stephen Windecker, MD (Swiss Cardiovascular Center, Bern, Switzerland), against cardiothoracic surgeon Neil Moat, MBBS (Royal Brompton Hospital, London, England).

The Limitations of Surgery in Low-Risk Aortic Stenosis

Windecker was tasked with outlining the limitations of surgery in low-risk patients.

He showed data suggesting that 30-day mortality among high-risk TAVR-treated patients in the major clinical trials is already “about the same” as the 30-day rates for surgical aortic valve replacement (SAVR) patients at the lowest risk (STS score < 4%). Moreover, across the four major randomized trials of TAVR, the data point to a “modest advantage” for TAVR with respect to mortality at 2 years, an observation that is even stronger for patients treated with a transfemoral approach.

In Windecker’s opinion, the disadvantages of surgery for younger and lower-risk patients fall into three main groups: the invasiveness of the procedure, adverse events, and patient-prosthesis mismatch.

The most important consequence of surgery’s invasiveness is health resource utilization, he said, citing, for example, the 55% longer procedure times and ICU stays in PARTNER 2A. Meanwhile, index hospitalization costs for TAVR have been declining, he noted, dropping from $75,000 USD in PARTNER 1A to $45,000 using the Emory “optimized” approach.

“Whatever parameter you look at—procedure time, the mean ICU stay, median total length of stay, consummation of red blood cell products, there is always a dramatic advantage to transcatheter valve implantation,” he said.

Another issue, Windecker continued, is quality of life. He added that “recovery or restoration of normal activities” is key to patients—something that will only grow in importance for those who are younger. And while both the Sapien (Edwards Lifesciences) and CoreValve (Medtronic) high-risk trials saw similar quality of life outcomes to surgery at 1 year, “it is the early outcomes, at 30 days and 6 months, that clearly indicate that patients undergoing TAVI recuperate much more quickly than patients undergoing surgery.”

Rates of early, albeit rare, periprocedural events also favor TAVR, Windecker argued. Atrial fibrillation, major bleeding, and major kidney injury all appear to occur less commonly in TAVR-treated patients than surgery-treated patients.

Finally, there is the problem of patient-prosthesis mismatch. “It is well established that patients with severe patient-prosthesis mismatch undergoing SAVR have impaired prognosis and reduced survival,” he said. In PARTNER 1A, this was particularly pronounced for cases with smaller aortic annulus, with mismatch being more common among SAVR-treated patients. There is also mounting evidence that female patients do better with TAVR than surgery, potentially because of their lower BMI and smaller anatomy.

Windecker concluded that female patients and those suitable for a transfemoral approach, with small aortic annulus (< 25 mm), with chronic kidney disease, with prior nonaortic cardiac surgery, with reduced mobility due to orthopedic problems, and potentially patients with other hemodynamic conditions, such as low-flow/low-gradient aortic stenosis, are all likely to fare better with TAVR than surgery.

The Limitations of TAVR

Moat took the stand after Windecker, acknowledging, “It is becoming increasingly difficult to give this talk, with outcomes following TAVI improving steadily.”

Nevertheless, Moat continued, while it’s “clear” that TAVR has outperformed surgery in the recent intermediate-risk studies, the patients in the trials were “still up at the higher end of the risk echelon.”

Showing registry data from the UK-based National Adult Cardiac Surgery Audit looking specifically at all elective aortic valve replacement surgeries in patients age 65-75 with no major comorbidities, the 30-day and 1-year mortality rates were 0.1% and 2.4%, respectively. “So if we’re going to talk about low-risk patients, then this is who we are going to be talking about,” Moat said.

He believes key complications to watch for as TAVR moves into younger patients include device embolization, coronary obstruction, annular rupture, late valve thrombosis, and vascular injury—all complications that “need our attention.” In particular, coronary obstruction and annular rupture are both low-frequency events but ones that still occur and that confer very high procedural mortality, he said.

Moat also pointed to the phenomenon of early and delayed leaflet thickening. “We don't really understand this phenomenon yet, but [it] is clearly a cause for some concern,” he said. “And an important question is, will these predominantly TAVI-specific complications be less frequent or avoidable in the lower-risk patient?”

Conduction defects, stroke and cerebral emboli, and durability each require close scrutiny as new data comes in. “Permanent pacemaker implantation in the young is not benign,” he warned. Considerations include the incidence of lead infection and endocarditis, lead-induced tricuspid regurgitation, perforation, and long-time effects on left ventricular function.

The effects of cerebral emboli during transcatheter valve implantation are also a great unknown, although preliminary, nonrandomized data suggest that the emboli caused by TAVR as opposed to surgery may have more severe and longer lasting effects on the brain.

Durability remains the biggest question mark for TAVR, said Moat. “We’re not going to see durability as an issue in high-risk elderly patients, but it is absolutely going to be an issue in the younger patients. We had a number of surgical devices that looked very good out to 5 or 6 years, then suddenly fell off a cliff.”

The fact is all valves eventually fail, Moat noted. “The mode of failure is key. We know some surgical valves fail catastrophically—if TAVI valves do the same, it will cause much more of a problem than if it is a slow degradation.”

Last but not least, Moat countered Windecker’s resource utilization argument with some numbers of his own. He pointed out that TAVR device costs have actually been increasing, with second- and third-generation devices costing more than the original devices. In the United Kingdom, the total hospitalization costs for a surgical valve replacement are less than the cost of a TAVR device, he reported. “In many healthcare systems, this is going to stop the growth of TAVI into low-risk patients.”

For his concluding remarks, Moat quoted Windecker himself, who was the senior author on an editorial published online last week in EuroIntervention. “Full-scale expansion into low-risk younger patients remains inappropriate beyond the setting of a randomized trial,” Moat recited, adding: “It’s always good to call on my interventional colleagues to help me out.”

Knowns and Unknowns

Following Windecker and Moats’ presentations, an expert panel debated just how much data and observations from high-risk patients can be extrapolated to younger patients.

Session moderator Darren Mylotte, MD (Galway University Hospital, Ireland), asked Windecker whether some of the comorbidities that cause the problems he discussed among the surgically treated patients in high-risk trials and registries will still be an issue in younger and lower-risk patients. In response, Windecker acknowledged that while event rates for certain complications may be lower in younger patients, there are other things “that are not going to disappear.” New-onset atrial fibrillation, for example, will still occur in the order of 20-30% of patients. Likewise, patient sex and annulus size won’t change.

Others questioned whether pacemaker implantation rates can be expected to decline in younger patients and with newer devices—a position supported by session co-moderator Jonathan Byrne, MB ChB, PhD (London Bridge Hospital, London, England), and panelist Ajay Sinhal, MD (Heart and Vascular Institute, Fullarton, Australia), but contested by cardiothoracic surgeon Olaf Wendler, MD, PhD (London Bridge Hospital), who pointed out that there has not been much of a shift downward in pacemaker use in recent registry reports and clinical trials.

There’s also the fact that patients themselves are requesting less invasive procedures, something Alain Cribier, MD (Charles Nicolle Hospital, Rouen, France), called “absolutely normal.” The fact remains, he continued, “our role, as clinicians is to be reasonable” and “we don’t need to rush to treat younger patients” with TAVR when the excellent results of surgery are already well established in this group. This is particularly true while the valve durability question is still being resolved.

On this point, Rüdiger Lange, MD (German Heart Centre Munich), who acknowledged that his hospital is already treating some patients in the 65- to 75-year-old range, noted that durability concerns prompted his center to review outcomes in the first 300 patients treated there. “Up to 7 years’ follow-up, we did not see—in terms of valve gradients and effective orifice area—any signs of degeneration.”

Panelist Martin Leon, MD (Columbia University Medical Center, New York, NY), also reminded the audience that younger and low-risk are not necessarily the same thing. PARTNER 3, for which he is co-principal investigator, has no maximum age cutoff.

“But many of the patients that are currently not being treated are patients over the age of 80 with low STS scores,” Leon pointed out. “So from the standpoint of being able to get good evidence in those patients to allow the FDA to approve a lower-risk group and for CMS to reimburse, we have to cover the older patients who are low risk as well. Ideally, yes, it would have been nice to have age cutoffs, but I have to tell you the FDA frowns on this. And we’ve eliminated the lower age cutoff as well, which is going to be helpful because to get the late data you have to have younger patients.”

Indeed, Lars Sondergaard, MD (Rigshospitalet, Copenhagen, Denmark) called it a Catch-22: “We [could] wait for long-term durability data before we go to lower risk, younger patients, but if we don't go to younger patients we won't have long-term durability data.”