CLEAN-TAVI: Results of Cerebral Embolic Protection in TAVR Now in Print

A study presented 2 years ago at TCT 2014 showing a reduction in ischemic cerebral lesions after TAVR with embolic protection devices is now published in the Journal of the American Medical Association.

Senior author Axel Linke, MD (University of Leipzig, Germany), told TCTMD that while the CLEAN-TAVI paper contains no new data, it does include expanded statistical analyses that gives a “much more complete picture” of how use of the Claret Montage Dual Filter System (Claret Medical) can affect TAVR patients.

CLEAN-TAVI’s results, published August 9, 2016, show a reduction in the number of lesions—not only in those regions protected by the filter but also in all regions of the brain—on diffusion-weighted magnetic resonance (MR) imaging in 100 TAVR patients at 2 and 7 days with use of the filter. Since TCTMD reported on his TCT presentation, debate has continued as to whether use of these kinds of devices is worthwhile and cost-effective.

“The scientific community is probably split into those that believe in embolic protection and those that think it’s not required,” Linke said. “In the major studies, at least in some, the stroke rate is going down, so some physicians believe there is no need for embolic protection at all. On the other hand, when patients are investigated by neurologists before and after cardiac intervention or a cath procedure, the neurological event rate is much higher as compared to the registry studies or trials.

“So it looks like that in daily clinical routine, we do not recognize all neurological deficits that the patients might have,” he noted.

Linke suspects that the “lack of evidence” proving improved outcomes with embolic protection devices is why many choose to dismiss their usefulness. Even in the study, there was no difference in clinical stroke rate between the filter and control arms (10% vs 11%), although the study was not powered to show this.

Additionally, Linke said, it’s an issue of hubris. “If we as physicians have to admit that we injure every brain when we do a TAVR, I believe people would be reluctant to undergo the procedure. I think this is part of the problem,” he commented. “It’s difficult to sell an intervention to a patient if you’re reducing the integrity of his brain. So I think this is why people are not open to communicate that we are really causing brain infarcts.”

Especially as TAVR indications expand to younger patients, “a neurologic injury as a result of a TAVR might affect a patient over the long-term and might also affect the cost for society,” Linke added. “This is the reason why it’s important to investigate.”

‘Compelling and Encouraging Start’

In an editorial accompanying the paper, Steven Messé, MD (University of Pennsylvania, Philadelphia), and Michael Mack, MD (The Heart Hospital Baylor Plano, TX), note that the CLEAN-TAVI results are “generally consistent” with the DEFLECT III study, which looked at another device in 83 patients. “Taken together, the findings from these preliminary studies suggest that embolic protection and deflection devices appear to represent a promising adjunct to improve the safety of TAVI,” they write.

Whether use of these devices “translates to a meaningful improvement in clinical outcomes will require more study, but the findings represent a compelling and encouraging start,” Messé and Mack say.

The findings also amplify concern over so-called silent strokes and their long-term clinical effects. “When identified in the general population, clinically silent cerebral infarcts have been associated with progressive dementia, future stroke, and increased mortality,” they explain.  “However, it remains unclear whether clinically silent infarcts that are acquired during a cardiovascular intervention have similar long-term adverse neurological consequences.”

The editorialists also point out that embolic protection “may not be feasible for every type of procedure” and recommend further research on other strategies including prophylactic medications, preconditioning, and selective brain cooling.

Whichever way it eventually gets done, “successfully protecting the brain from the heart during high-risk cardiovascular procedures would lead to reduced patient anxiety, improved patient outcomes, and potentially expand the number of patients eligible for the benefits of these important cardiovascular interventions,” they conclude.

Too Early for Routine Adoption

Commenting on the study for TCTMD, John Webb, MD (St. Paul’s Hospital, Vancouver, Canada), was a bit more cautious. “I think that it’s still too early to adopt this routinely,” he said, citing falling stroke rates, lack of evidence, and cost. “Use these devices routinely would be an extremely expensive proposition, so I think we’re going to have to wait for some more studies.”

For now, Webb said, clinicians need to focus more on available risk factors like age, calcification, and A-fib, whether procedures are transcatheter or surgical. With A-fib especially, “more aggressive anticoagulation periprocedurally” should be considered, he advised. Also, as newer devices are designed for easier repositionability, operators should be aware of the risks involved with taking advantage of that feature, he cautioned.

In the move toward a younger patient population, there is the possibility that the “risk of stroke will just be smaller, although the implications might be greater,” Webb acknowledged. Embolic protection may help in this regard, but “we know that many of the strokes don’t occur at the time of the procedure—they occur after. And so the window where this device would reduce stroke risk is fairly small.”

SENTINEL, the ongoing study of the Claret Sentinel system, should shed more light on this topic, as it enrolled almost four times more patients than did CLEAN-TAVI, Webb said. Beyond that, “we need some evidence that reducing MR lesions frequency and volume has a significant clinical impact. Even then I think there needs to be a cost-benefit analysis,” he concluded. “That is going to be a real problem with a low-frequency event such as strokes or events that are of unknown clinical impact such as MR lesions.”

Related Stories:

• Cerebral Protection Device Reduced Brain Lesions, Neurological Events After TAVR
• DEFLECT III: 30-Day Results Show Successful, Safe TAVR With Novel Neuroprotection Device
• Embolic Protection in TAVR: If, When, What, and How Debated as Trials Wrap Up