Arteriovenous Malformations (AVMs): Molecular Pathogenesis, Clinical Features, and Emerging Therapeutic Strategies

Area of Science:

• Vascular biology and medicine
• Genetics and molecular mechanisms of vascular disease
• Medical imaging and interventional radiology

Background:

• Arteriovenous malformations (AVMs) are direct artery-to-vein shunts lacking capillaries, posing risks of hemorrhage and organ damage.
• AVMs develop from a complex interplay of genetic susceptibility, somatic mutations, signaling pathway dysregulation, hemodynamic stress, and inflammation.
• Recent scientific synthesis highlights the multifaceted etiology of AVMs.

Purpose of the Study:

• To synthesize recent advances in understanding the pathogenesis of AVMs.
• To review current diagnostic and risk stratification imaging modalities.
• To outline contemporary and emerging management strategies, including interventional and precision medicine approaches.

Main Methods:

• Comprehensive review and synthesis of current literature on AVMs.
• Analysis of multimodal imaging techniques for diagnosis and hemodynamic assessment.
• Evaluation of interventional (embolization, surgery, radiosurgery) and emerging pharmacotherapy strategies.

Main Results:

• AVMs arise from germline and somatic genetic factors, perturbed signaling pathways, hemodynamic stress, and inflammation.
• Multimodal imaging, including DSA, MRI/MRA, CTA, and ultrasound, is crucial for diagnosis and risk assessment.
• Innovations in embolization devices and precision medicine offer improved treatment options, with ongoing development in genomic-imaging risk scores and targeted therapies.

Conclusions:

• Management of AVMs is individualized, multidisciplinary, and evolving with technological and therapeutic advancements.
• Precision medicine strategies targeting specific genetic pathways show promise for syndromic and mutation-driven AVMs.
• Future priorities include integrated genomic-imaging risk scores, genotype-informed therapies, and standardized long-term outcome measures focused on hemorrhage prevention and quality of life.