France: A new study published in the journal Circulation reveals that about one in four patients undergoing transcatheter aortic valve replacement (TAVR) develop new cerebral microbleeds (CMBs). These are the results from a small, observational METHYSTROKE study.
In healthy elderly people undergoing systematic brain magnetic resonance imaging (MRI), cerebral microbleeds have been observed. There is no information on the potential role of acute triggers in the appearance of CMBs. Eric Van Belle and researchers from France aimed to describe the incidence of new CMBs after TAVR and to identify clinical and procedural factors linked with new CMBs including hemostatic measures and anticoagulation management.

For this purpose, the researchers evaluated a prospective cohort of patients with symptomatic aortic stenosis referred for TAVR for CMBs (METHYSTROKE [Identification of Epigenetic Risk Factors for Ischemic Complication During the TAVR Procedure in the Elderly]). Before and after TAVR, the researchers performed brain magnetic resonance imaging, standardized neurologic assessment, and analysis of hemostatic measures including von Willebrand factor.
Two independent neuroradiologists blinded to clinical data reported numbers and location of microbleeds on preprocedural MRI and of new microbleeds on postprocedural MRI. Measures associated with new microbleeds and postprocedural outcomes including neurologic functional outcome at 6 months were also examined. A total of 84 patients were included in the study.
Key findings of the study include:
On preprocedural MRI, 26% patients had at least 1 microbleed.
After TAVR, new microbleeds were observed in 23% patients.
The occurrence of new microbleeds was independent of the presence of microbleeds at baseline and of diffusion-weighted imaging hypersignals. In univariable analysis, a previous history of bleeding, a higher total dose of heparin (P=0.02), a prolonged procedure, absence of protamine reversion, higher final activated partial thromboplastin time, lower final von Willebrand factor high-molecular-weight:multimer ratio, and lower final closure time with adenosine–diphosphate were associated with the occurrence of new postprocedural microbleeds.
In multivariable analysis, a prolonged procedure (odds ratio, 1.22 for every 5 minutes of fluoroscopy time) and postprocedural acquired von Willebrand factor defect (odds ratio, 1.42 for every lower 0.1 unit of high-molecular-weight:multimer ratio) were independently associated with the occurrence of new postprocedural microbleeds.
New CMBs were not associated with changes in neurologic functional outcome or quality of life at 6 months.
To sum up the findings, about 1 patient of 4 has CMBs before transcatheter aortic valve replacement and nearly 1 of 4 develops new microbleeds after transcatheter aortic valve implantation.
"The occurrence of new postprocedural CMBs could be due to anticoagulation management and an acquired von Willebrand factor multimer defect, particularly when this defect persists at the end of the procedure," the researchers wrote. They explained that a prolonged procedure increases exposure to anticoagulation and favors the appearance of new CMBs.
The researchers conclude, "We report a high incidence (23%) of new CMBs following TAVR. Anticoagulation management and persistence of acquired VWF defect were associated with development of new CMBs. Further study is required for the pathophysiologic mechanisms of CMBs and their role on long-term outcomes."
Reference:
Van Belle E, Debry N, Vincent F, Kuchcinski G, Cordonnier C, Rauch A, Robin E, Lassalle F, Pontana F, Delhaye C, Schurtz G, JeanPierre E, Rousse N, Casari C, Spillemaeker H, Porouchani S, Pamart T, Denimal T, Neiger X, Verdier B, Puy L, Cosenza A, Juthier F, Richardson M, Bretzner M, Dallongeville J, Labreuche J, Mazighi M, Dupont-Prado A, Staels B, Lenting PJ, Susen S. Cerebral Microbleeds During Transcatheter Aortic Valve Replacement: A Prospective Magnetic Resonance Imaging Cohort. Circulation. 2022 Aug 2;146(5):383-397. doi: 10.1161/CIRCULATIONAHA.121.057145. Epub 2022 Jun 20. PMID: 35722876; PMCID: PMC9345525.