Cognitive Function After Transcatheter Aortic Valve Replacement: Reassuring Findings For Now

Transcatheter aortic valve replacement (TAVR) has become a proven therapeutic option for individuals with severe aortic stenosis at extreme, high, and intermediate risk of operative mortality. Having demonstrated the technique’s efficacy and safety with respect to mortality and morbidity, more recent attention has shifted to person-centered outcomes such as physical and cognitive functioning that are naturally relevant to the geriatricians involved in the evaluation and care of these individuals. Cognition is linked to outcomes in a variety of populations, including individuals undergoing TAVR. These individuals are typically elderly and frail, with 20–40% being cognitively impaired at baseline. The incidence of new or worsening cognitive impairment at follow-up is less established, because previous studies have been underpowered and reported conflicting results. To aggregate and harmonize these results, Khan and colleagues conducted a metaanalysis of observational studies on objective measures of cognition before and at different time points after TAVR. The metaanalysis, encompassing 18 studies and a total of 1,065 participants, did not detect a quantifiable difference in overall cognitive performance 3, 6, and 12 or more months after TAVR (with the longest follow-up being 34 months in a single study), although it detected a modest albeit statistically significant improvement in short-term cognitive performance at 1 month. The ensuing metaregression did not detect an association between changes in cognition and study-level rates of baseline cognitive impairment, perioperative embolic lesions, or incident strokes, notwithstanding the limitations of this type of analysis and the experiential evidence to the contrary at the clinical level. Regardless, given the high burden of atherosclerotic disease, atrial fibrillation, and previous stroke, optimization of comorbid conditions and prevention of cerebrovascular complications remains of fundamental importance in this vulnerable population. Knowledge from previous studies suggests at least two mechanisms by which the TAVR procedure may affect cognitive function—positively or negatively. Individuals with heart failure as a result of severe aortic stenosis may have cerebral hypoperfusion, such that relieving the stenosis improves cardiac output, cerebral perfusion, and in turn, cognition. Khan and colleagues’ finding of acutely improved cognitive performance 30 days after TAVR seems to support this hypothesis. Conversely, individuals may have cerebral ischemia due to embolic events during and after the procedure, with high embolic loads (large and micro-emboli) having a negative effect on cognition. The radiographic burden of embolic events immediately after TAVR is only weakly correlated with detectable changes in cognition, because most of these events appear to be clinically silent. The studies’ predominant use of the Mini-Mental State Examination (MMSE), which, although extensively validated as a screening tool for global cognition and Alzheimer’s disease, is less sensitive than other tools such as the Montreal Cognitive Assessment (MoCA) for detecting the deficiencies in executive function and visuospatial processing characteristic of cognitive dysfunction from vascular injury; this potential source of misclassification may in part explain the lack of detectable changes in cognition. According to one study, use of the Trail-Making and clock drawing tests identified a nonnegligible subset of individuals with vascular-type cognitive deficiencies arising after TAVR. Although not definitive, this study raises the concern that adverse cognitive effects may be underdiagnosed and underreported after TAVR. Another reason for the potential underreporting of adverse cognitive effects is the studies’ use of mean overall cognitive scores before and after TAVR as the primary outcome of interest. By using mean scores, the larger pool of individuals with cognitive stability or improvement is likely to dilute and mask the small but clinically relevant subset of individuals with cognitive decline after TAVR. Moreover, reporting mean scores at isolated time points is likely to miss individuals with early decline followed by improvement, or vice versa, underscoring the value of reporting cognitive trajectories over time, as Fanning and colleagues informatively did. Finally, individuals with cognitive decline are more likely to be censored because of death or loss to follow-up, indicating the possibility of selection bias that could lead to optimisitic estimates of cognitive function after TAVR. Yet another reason to examine these results with some caution is the emphasis on short-term cognitive function (1– 3 months), with few studies reporting mediumor long-term follow-up. Given the high baseline cognitive scores, these individuals have sufficient cognitive reserve to tolerate periprocedural cerebral ischemia without proximately manifesting overt cognitive dysfunction. Although an extensive stroke or large cumulative burden of embolic events can cause immediate cognitive dysfunction, smaller events This editorial comments on the article by Khan et al.