Background: It is unknown whether direct oral anticoagulant edoxaban can reduce leaflet thrombosis and the accompanying cerebral thromboembolic risk after transcatheter aortic-valve replacement (TAVR). Also, the causal relationship of subclinical leaflet thrombosis with cerebral thromboembolism and neurological or neurocognitive dysfunction remains unclear. Methods: We conducted a multicenter, open-label randomized trial comparing edoxaban with dual antiplatelet therapy (DAPT; aspirin plus clopidogrel) in patients who had undergone successful TAVR and did not have an indication for anticoagulation. The primary end point was an incidence of leaflet thrombosis on four-dimensional computed tomography (CT) at 6-month. Key secondary end points were the number and volume of new cerebral lesions on brain magnetic resonance imaging (MRI) and the serial changes of neurological and neurocognitive function between 6-month and immediate post-TAVR. Results: A total of 229 patients were included in the final intention-to-treat population. There was a trend toward a lower incidence of leaflet thrombosis in the edoxaban group than in the DAPT group (9.8% vs. 18.4%; absolute difference, −8.5%; 95% confidence interval [CI], −17.8% to 0.8%; P=0.076). The percentage of patients with new cerebral lesions on brain MRI (edoxaban vs. DAPT; 25.0% vs. 20.2%; difference, 4.8%; 95% CI, −6.4% to 16.0%) and median total new lesion number and volume were not different between two groups. Also, the percentages of patients with worsening of neurological and neurocognitive function were not different among the groups. The incidence of any or major bleeding events were not different between two groups. We found no significant association of the presence or extent of leaflet thrombosis with new cerebral lesions and a change of neurological or neurocognitive function. Conclusions: In patients without an indication for long-term anticoagulation after successful TAVR, the incidence of leaflet thrombosis was numerically lower with edoxaban than with DAPT, but this was not statistically significant. The effect on new cerebral thromboembolism and neurological or neurocognitive function were also not different between two groups. Because the study was underpowered, the results should be considered hypothesis-generating, highlighting the need for further research.

Background Various ECG criteria for left ventricular hypertrophy (LVH) have been proposed, but their association with clinical outcomes in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement is unknown. We investigated the prevalence of ECG LVH according to different criteria and its prognostic impact on clinical outcomes after transcatheter aortic valve replacement. Methods and Results In this prospective observational cohort, we evaluated 700 patients who underwent transcatheter aortic valve replacement between March 2010 and December 2019. Baseline preprocedural LVH was defined by 3 ECG criteria—Sokolow‐Lyon, Romhilt‐Estes, and Cornell voltage criteria. The primary outcome was major adverse cardiac or cerebrovascular event (MACCE; composite of death, myocardial infarction, stroke, or rehospitalization from cardiovascular cause); the key secondary outcome was all‐cause and cardiovascular mortality. Among 596 eligible patients, the prevalence of LVH was determined as 56.3% by Sokolow‐Lyon, 31.1% by Romhilt‐Estes, and 48.1% by Cornell criteria. Regardless of the criteria, patients with ECG LVH had more severe aortic stenosis hemodynamics and higher left ventricular mass index. After multivariate adjustment, the presence of LVH by the Cornell criteria was significantly associated with lower risks of MACCE (adjusted hazard ratio [HR], 0.68; 95% CI, 0.51–0.91; P =0.009), all‐cause mortality (adjusted HR, 0.55; 95% CI, 0.34–0.90 [ P =0.017]), and cardiovascular mortality (adjusted HR, 0.40; 95% CI, 0.20–0.79 [ P =0.008]). However, this association was absent with the Sokolow‐Lyon and Romhilt‐Estes criteria. Conclusions ECG LVH by Cornell criteria only was significantly associated with lower risks of MACCE and all‐cause or cardiovascular mortality. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03298178.