Stroke in TAVR: Full Impact of Embolic Devices, Anticoagulants, Technique Remain Unclear

Stroke remains a problem after TAVR and continues to feed discussions around how extensively cerebral embolic protection devices and other strategies should be used.

In a session during TVT Connect, Alexandra Lansky, MD (Yale School of Medicine, New Haven, CT), noted that there was no significant movement in the post-TAVR stroke rate in the Society of Thoracic Surgery/American College of Cardiology TVT Registry between 2012 and 2017, coming in at 2.27% for any stroke and 2.05% for ischemic stroke at the end of the study period.

“Despite [greater] volume, despite improvements in TAVI devices, despite the fact that nowadays we’re looking at lower-risk patients, there’s really not been any kind of change,” she said.

A few of the discussants said they would expect the stroke rate to have come down in the last few years as use of cerebral embolic protection devices has increased, but that remains to be seen. No robust prospective studies have demonstrated that use of the devices, though they effectively capture debris headed toward the brain, drives down clinical event rates.

Despite [greater] volume, despite improvements in TAVI devices, despite the fact that nowadays we’re looking at lower-risk patients, there’s really not been any kind of change. Alexandra Lansky

The issue is an important one because the consequences of strokes can be severe. Lansky cited a study showing that disabling stroke after TAVR was associated with substantially higher risks of mortality at 1 year (67% vs 12%) and 2 years (83% vs 20%). Moreover, 40% of patients will have moderate-to-severe permanent disability following a major stroke, and 75% will have some level of residual dysfunction. Only 44% of patients will be able to return to work after a stroke. “This has tremendous implications in terms of financial strain on patients, social isolation, quality of life, etc,” Lansky said.

Hemal Gada, MD (UPMC Heart and Vascular Institute, Pittsburgh, PA), agreed, noting that stroke-related impairments would have a particularly serious impact on the younger, lower-risk patients who are increasingly undergoing TAVR. “The economic impact to those folks is going to be substantial,” he said.

What About Subclinical Infarcts?

Less clear, however, are the short- and long-term consequences of subclinical infarcts observed on brain MRI after TAVR. Lansky pointed out that there has not been a definitive link made between these covert events and subsequent neurocognitive dysfunction specifically in the TAVR population, but said the general neurology literature supports the relationship. “So I can only assume that that also applies here,” she said, noting that there are related economic costs and long-term implications. “We talk about acute silent strokes, but clearly long term there are bound to be consequences to that.”

Samir Kapadia, MD (Cleveland Clinic, OH), who moderated the discussion, was less certain. These subclinical infarcts may have different impacts depending on whether they occur as a spontaneous event or as a consequence of a medical procedure. “At least in the TAVR literature, we have not been able to find a very strong correlation with these adverse neurological consequences over time,” he said, acknowledging that “the literature is still not very convincing one way or the other.”

A key factor to consider when thinking about ways to protect the brain during TAVR is the fact that most strokes—80% according to some data—occur within the first 7 days. A full third, Lansky reported, happen on the day of the procedure. “As we look at this over time, clearly there’s a procedural risk, and we’re better understanding this risk, but it’s important to think about it particularly as you’re going into your discussion about neuroprotection. I think it really speaks to that very nicely,” she said.

Uncertain Clinical Impact of Cerebral Embolic Protection

Nicolas Van Mieghem, MD, PhD (Thoraxcenter, Erasmus MC, Rotterdam, the Netherlands), noted that there are two main types of embolic protection devices—those that are filter-based and those based on deflecting debris away from the brain. Some devices represent a combination of the two approaches.

He underscored the point that filter-based devices like Sentinel (Boston Scientific)—the only such system approved for use in the United States—capture debris in all patients undergoing TAVR, with some differences among devices in the size of debris captured. The type of debris captured varies widely and includes acute thrombus, organizing thrombus, valve tissue, arterial wall, pieces of calcium, foreign body material from delivery systems, myocardium, and necrotic core.

“The million dollar question is: when we use these cerebral embolic protection devices will we then see a clinical benefit?” Van Mieghem said. “I think the jury is still out. We don’t have robust prospective randomized trial data to back up that statement.” Real-world data suggest that protection devices reduce rates of clinical events, but those retrospective analyses are subject to selection bias, Van Mieghem said.

Axel Linke, MD (Heart Center Dresden, Germany), said he’s a believer in the technology, but also pointed to the limitations of studies evaluating the clinical impact of its use. “The problem is we are comparing people that were treated in the early phase of TAVR without embolic protection and now we are comparing it to patients that are at lower risk and we use embolic protection,” he said. “So scientifically, this is not fair. And I think this is the reason why we need PROTECTED TAVR to close the deal.”

The ongoing PROTECTED TAVR trial, headed by Kapadia, will enroll a planned 3,000 patients who are undergoing transfemoral TAVR with or without cerebral protection with the Sentinel device, with neurological examinations performed before and after the procedure. The primary endpoint is stroke at 72 hours or discharge.

Kapadia said that even though he uses embolic protection in every patient, equipoise exists to perform the trial because only 21% to 25% of TAVRs in the United States are currently done with protection. Linke put the figure at about 20% in Europe.

While awaiting those results, the discussants felt embolic protection devices should be used routinely based on the knowledge that filters capture debris bound for the brain in all TAVR patients.

Linke noted that good predictors of stroke have not been identified in the embolic protection trials performed thus far. “As long as we don’t have these working predictors of stroke, I think it should be used in all of our patients,” he said.

Stroke Reduction Beyond Embolic Protection

The TVT discussion turned to other ways of reducing stroke risk in the TAVR population, alone or on top of embolic protection, touching first on possible changes in pharmacological management before shifting to procedural modifications.

Kapadia pointed to use of deflectable catheters, not postdilating the valves, and being more careful in certain situations (using the BASILICA procedure, for instance). “There can be some procedural things that we can potentially do that makes the procedure safer,” he said. “I’m not so sure that [by prescribing] pharmacological therapy for stroke prevention after we place the valve, we have sorted it out completely. There are a lot of unknowns.”

One factor known to increase stroke risk is procedure time, Gada noted, stressing the need to get procedures done quickly in order to achieve the best neurologic outcomes.

An additional talk centered on how to lower the persistent risk of stroke beyond the periprocedural period in patients with both severe aortic stenosis and A-fib. Amar Krishnaswamy, MD (Cleveland Clinic), pointed out that A-fib is common in the TAVR population and that TAVR patients often present with a high stroke risk according to the CHA₂DS₂-VASc score. TAVR patients, however, are poor candidates for oral anticoagulation, and those who do receive an anticoagulant have a heightened risk for complications.

One possible approach to lower stroke risk in these types of patients is to perform left atrial appendage closure with the Watchman device (Boston Scientific) along with TAVR, an idea being evaluated in the ongoing WATCH-TAVR trial. That study will randomize an estimated 312 patients at 25 US centers to TAVR plus Watchman implantation or TAVR alone. The primary endpoint is a composite of all-cause mortality, stroke, or bleeding through 1 year.

“The combined procedure appears to be safe based on some small studies that have been performed in the past and we’re all, I think, anxiously awaiting the results of WATCH-TAVR,” Krishnaswamy said.

Not to be lost in all of this discussion of stroke after TAVR, Kapadia and Lansky both noted, is that risk has been shown to be consistently lower with TAVR versus SAVR.

“The best way a patient can reduce their risk of stroke is actually having TAVR as opposed to SAVR,” Lansky said. “In the very early randomized clinical studies, clearly TAVR had a heightened stroke rate but ever since then we’ve seen time and time again in all these trials really showing low stroke rates with TAVR compared to surgical AVR. And I think that’s key to keep at the front of our minds because we’re so focused on this issue. Clearly TAVR is the way to go.”