Subclinical Leaflet Thrombosis After Transcatheter Aortic Valve Replacement and Risk of Cerebrovascular Events: An Updated Systematic Review and Meta-Analysis of 12 Studies Comprising 13,592 Patients

Abstract

Background: Subclinical leaflet thrombosis (SLT), characterized by hypoattenuated leaflet thickening (HALT) and/or reduced leaflet motion on 4D-CT, occurs in 6-30% of patients following TAVR. Its association with cerebrovascular events remains debated.

Objectives: To quantify the association between SLT after TAVR and risk of stroke or TIA, while exploring heterogeneity, valve-type effects, anticoagulation responses, and silent brain injury.

Methods: PubMed/MEDLINE, Embase, Cochrane CENTRAL, and Web of Science searched through December 2024. DerSimonian-Laird random-effects pooling. Primary endpoint: composite stroke or TIA.

Results: 12 studies (13,592 patients; 1,923 with SLT [14.1%]). Pooled RR for stroke/TIA: 2.28 (95% CI 1.62-3.21; I²=27%; p<0.0001). SLT strongly associated with TIA (RR 3.12; CI 1.84-5.30). Oral anticoagulation resolved SLT in 100% vs. 9% spontaneously. HALT independently predicted white matter hyperintensities on MRI. GALILEO trial: rivaroxaban reduced HALT but increased adverse clinical events (HR 1.35; CI 1.01-1.81).

Conclusion: SLT after TAVR confers a >2-fold increased cerebrovascular risk. The GALILEO paradox underscores the need for SLT-targeted randomized trials with individualized antithrombotic strategies.

Keywords: Subclinical leaflet thrombosis; TAVR/TAVI; Hypoattenuated leaflet thickening; HALT; Stroke; TIA; Meta-analysis; Anticoagulation