The first clinical validation of the new Valve Academic Research Consortium (VARC-3) criteria reveals a significant association between neurologic events and short-term/midterm mortality post transcatheter aortic valve replacement (TAVR). Based on Neurologic Academic Research Consortium (NeuroARC) classification, the neurologic events’ negative impact on outcomes leads researchers to recommend efforts to reduce the risk of neurologic complications after TAVR. The research team also advocated for the implementation of protective measures as a major research priority to advance the care and the prognosis of TAVR candidates. “In our study, the overall incidence of neurologic complications was 16%, with over one-half occurring within the first 30 days following TAVR,” said the paper’s authors, co-led by Marisa Avvedimento, MD from Quebec Heart and Lung Institute, Laval University, Quebec City, Canada. “It is well known that the risk of stroke peaks immediately after TAVR, with up to 50% of cerebrovascular events occurring in the periprocedural period, primarily mediated by the mechanical interaction between the transcatheter valve system and the calcific native valve leading to CNS embolization.” Broad definition The research team go on to point out that even if the overall rate of neurologic events seems high, it must be highlighted that the new VARC-3 definition is quite broad, encompassing clinical events that differ markedly because of the pathophysiological mechanism. Detailed findings from the investigation, which was published Monday online and in the August 12 issue of JACC Cardiovascular Interventions revealed that after a median follow-up of 13 (7-37) months, neurologic events occurred in 471 patients (16.1%). NeuroARC type 1(stroke) occurred in 37.4% of cases, while type 2 (covert central nervous system injury) occurred in 4.7% of cases. Meanwhile, NeuroARC type 3 (transient ischemic attack and delirium) occurred in 58.0% of cases, with the majority (58.6%) noted as periprocedural. The investigation also found advanced age, chronic kidney disease, atrial fibrillation, major vascular complications and in-hospital bleeding determined an increased risk of periprocedural events (P<0.03 for all). Periprocedural time frame Additional findings revealed that neurologic events occurring during the periprocedural time frame were independently associated with a substantial increase in mortality at 1 year after the intervention (hazard ratio [HR]:1.91; 95% confidence interval [CI]: 1.23-2.97; P=0.004). The researchers added that while NeuroARC type 1 was linked to an increased mortality risk (IRR: 3.38; 95% CI: 2.30-5.56; P<0.001) for ischemic stroke and IRR: 21.7; 95% CI: 9.63-49.1; P<0.001 for hemorrhagic stroke, the occurrence of NeuroARC type 3 events had no impact on mortality. “…available evidence mostly comes from studies with a limited sample size, including patients at a higher surgical risk profile, treated with early-generation devices, and involving a high adoption of nonarterial approaches under general anesthesia,” said the paper’s authors. Increased stroke risk Commenting on the study’s implications, Vincent Auffret, MD, PhD and Maud Guillen, MD, from Rennes University Hospital in France said that the findings were consistent with a report of the SwissTAVI Registry, which demonstrated an increased risk of stroke up to 2 years post procedure. This was largely mediated by pre-existing risk factors such as dyslipidemia, a history of atrial fibrillation or a history of a cerebrovascular accident. Along with co-author Stéphane Vannier, MD also from Rennes University Hospital, the two experts added that unsurprisingly, NeuroARC type 2 events were seldom reported (0.7%) in the present observational study, capturing routine practice of TAVR. They added that this contrasted with previous reports encompassing systematic use of diffusion-weighted cardiac magnetic resonance or filter-based cerebral embolic protection devices (CEPDs) showing extremely high rates of new cerebral lesions or embolized debris. Study limitations The accompanying editorial touched on a number of study limitations, namely regarding patients who had potential neurologic complications. These patients were evaluated by a neurologist. Auffret and Guillen suggested that this might’ve resulted in an underestimation of the cerebrovascular events rate even in the rate of NeuroARC type 1, unlike what the authors state in the limitations section of the manuscript. Other limitations include the absence of data regarding neuroimaging findings in terms of lesion location and size, the presence of a proximal thrombus or signs of amyloid angiopathy as well as details regarding the immediate management of NeuroARC type 1 events. In conclusion, the experts wrote that the research team should be “commended for undertaking such a comprehensive analysis, which will undoubtedly inform patients and operators in the process of shared decision making when considering a TAVR procedure.” Study methodology The multicenter study included 2,924 patients with severe aortic stenosis undergoing TAVR. These patients had a mean age of 79.6 years ±7.4, of which 1,389 (47.5%) were female. Based on Neurologic Academic Research Consortium (NeuroARC) classification, neurologic events were classified as NeuroARC type 1 (stroke), NeuroARC type 2 (covert central nervous system injury), and NeuroARC type 3 (transient ischemic attack and delirium). Baseline, procedural and follow-up data were prospectively collected in a dedicated database. Sources: Avvedimento M, Cepas-Guillén P, Garcia CB, et al. Incidence, Predictors, and Prognostic Impact of Neurologic Events After TAVR According to VARC-3 Criteria. JACC Cardiovasc. 2024;17:1795-1807. Auffret V, Guillen M, Vannier S. TAVR-Related Cerebrovascular Events: Brand New Classification, Same Old Impact. JACC Cardiovasc. 2024;17:1808–1810. Image Credit: mehmet – stock.adobe.com