2.3 Stroke Prevention in TAVR—What’s Missing

These proceedings summarize the educational activity of the 16th Biennial Meeting of the International Andreas Gruentzig Society held January 31-February 3, 2022 in Punta Cana, Dominican Republic

Faculty Disclosures     Vendor Acknowledgments

2022 IAGS Summary Document

Statement of the problem or issue

Despite improvements in devices and techniques, while most complications of TAVR have declined, stroke unfortunately remains prevalent, and improvement in stroke event rates has reached a plateau. Contemporary clinical trials and large registries consistently show rates of 1%-2% for major stroke. If minor strokes are included, events which may be equally consequential to patients, then the rates are even higher, particularly when adjudicated by a neurologist. Additionally, virtually all TAVR procedures are associated with magnetic resonance imaging evidence of cerebral infarction despite a lack of acute symptoms, and emerging data suggest these microinfarcts may be associated with progressive cognitive decline. While relatively low in prevalence, given its severe consequences, stroke remains a significant problem in TAVR.

Gaps in knowledge

Since most emboli occur during the TAVR procedure itself, cerebral protection (CEP) devices have been proposed to help mitigate stroke. While numerous CEP devices are under investigation, the Sentinel device is the most extensively studied, it has received FDA approval, and is in current clinical use. Existing data remain controversial though. The Sentinel IDE Trial showed numerically fewer strokes at the 30-day endpoint, but this was not statistically significant. However, a post hoc analysis of strokes within the 72-hour periprocedural window did show statistically fewer events. Several registries suggest fewer event rates with CEP, although an analysis of the TVT registry showed only a trivial reduction in stroke. All registries may be subject to bias and confounding. Thus, use of CEP remains highly variable in clinical practice, with only 5% of institutions in the US using CEP routinely, and no more than one-half using CEP selectively. An ongoing clinical trial, PROTECTED TAVR, should add insights. Yet, if PROTECTED TAVR is negative, how will that change this field? Do we move on to other technologies or would this severely diminish further interest? How positive would PROTECTED TAVR have to be to change CEP usage? Will PROTECTED TAVR have enough statistical power to identify subgroups that do and do not benefit from CEP? How can we better study long-term cognitive effects of “silent emboli,” and their prevention? Are better technologies than Sentinel needed? Is arch manipulation for TAVR deployment causing more harm than benefit? Is radial access required or is large bore femoral access acceptable given its bleeding risks? Is there any role for pharmacology in stroke prevention, for example, with different drug agents or activated clotting time (ACT) targets? Is air embolism a significant contributor to stroke, or is this a red herring distraction?

Possible solutions and future directions

Mechanistically, Sentinel CEP should work, with virtually all baskets retrieving embolic material regardless of estimated surgical risk profile. But it is possible that the filters miss material, or the process of placing filters itself results in cerebral emboli. Other investigational devices attempt to mitigate these potential shortcomings with more complete arch coverage or less manipulation, but whether these different designs will result in meaningful improvements in stroke remains to be studied. Finally, recent data question the role of air embolism generated by TAVR device preparation and the deployment procedure, where embolic protection filters would be less effective, as contributors to stroke. The recently completed PROTECTED TAVR randomized trial of Sentinel CEP should provide critical data that, if positive, may show improved outcomes, or, on the other hand, if negative, might result in reassessment of the entire field of CEP.