Developments In Arteriovenous Malformation Models, Biomarkers, And Interventional Approaches
Yareli R Carcamo-Bahena, Maham Rahimi, Alan Lumsden, Carly S Filgueira
Houston Methodist Research Institute, Houston, TX
INTRODUCTION: Arteriovenous malformations (AVMs) are defects of the circulatory system that can arise during embryonic or fetal development or can be acquired at any stage after birth. They most commonly occur in young adults with an incidence in the United States of 1.34 per 100,000 person-years (although the actual prevalence rate is higher due to clinically silent disease) and it has a morbidity of 30-50% and mortality rate of 10-15%. AVMs may cause an individual discomfort, recurrent bleeding, hemorrhagic stroke, aesthetic or functional problems. Treatment for AVM is either surgical excision if it is small and accessible, ablation, or embolization. However, AVMs have a high rate of recurrence and progression regardless of treatment modality. Our objective was to survey various models used to study AVMs ranging from in silico, in vitro (3D printed, assembled), and in vivo (small, medium, and large animal models of both brain and peripheral malformations) and highlight the particular advantages or limitations for their use in research. METHODS: A literature search generated 158 articles ranging from 1953-2021 for AVM and models written in English. Developing reliable models of AVMs are important not only for the training of endovascular therapeutic procedures but also for applying interventions and testing the outcomes of new therapeutics, devices, and materials, such as stent-grafts, embolics, and sclerotics. We illustrate various AVM models and compose a list of relevant histological stains and biomarkers researchers have successfully used to characterize malformations and assess changes due to progression or intervention. RESULTS: Various considerations should be made when choosing a particular AVM model, as some animal species have large differences with humans in their cardiac contractile kinetics and heart rates, which can affect induction and differences in experimental outcome. Further, companion animals, such as dogs and cats, have a low frequency and unknown incidence at which arteriovenous fistulas present and, therefore, are most commonly reported as case studies. Since the AVM location should closely resemble the human hemodynamic and pathophysiologic environment for comparative assessments, choosing an appropriate model, induction approach, and site are all important parameters to consider. We propose that animals which contain a rete, can offer abundant tissue and blood sampling, and maintain compatibility with human healthcare procedures, equipment, imaging modalities, and devices, such as porcine, are excellent candidates for study. We highlight recent successes in the deployment of novel non-adhesive liquid embolics, that are rapidly accelerating the field as they provide ease of use for the operator, maintain occlusion, and prevent recanalization for successful resection to minimize intraoperative complications. We also describe the identification of certain markers shown to aid in the diagnosis and monitoring of progression or regression of vascular malformations. CONCLUSION: Notably, our literature review provides evidence that pre-operative patient imaging can aid in the generation of 3D printed AVM models, which can prove useful for patient consultation, surgical planning, and resident training. Finally, we conclude that lesions can be successful treated by multimodality therapy with combinations of endovascular embolization, radiosurgery, and surgical resection (including robotic-assisted angiographic procedures).
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