Mechanistically driven transnidal hemodynamic manipulations enhance simulated endovascular transvenous treatments for brain AVMs

BACKGROUND: Treatment strategies for plexiform brain arteriovenous malformations (bAVMs) have evolved to include minimally invasive transvenous embolization. Since its conceptualization as "transvenous retrograde nidus sclerotherapy under controlled hypotension" (TRENSH), this approach has shown curative potential for highly selected small bAVMs when using adhesive embolic agents. Further innovation is required to extend safety and efficacy to larger, more complex bAVMs. We conceived and evaluated a set of theoretical hemodynamic manipulations within the venous outflow of bAVMs designed to augment nidus retropermeation during simulated TRENSH. METHODS: We used two complementary experimental platforms. First, we developed a computational bAVM model to simulate hemodynamic variations during TRENSH, including: (1) degrees of controlled arterial hypotension; (2) effects of temporary balloon occlusion of arterial feeders; (3) differing draining vein (DV) retrograde injection pressures; (4) use of alternative DVs for retroinjection; (5) elevation of central venous pressure (CVP) during injection; and (6) cardiac-cycle-synchronized diastolic retroinjection. Second, we used a carotid-jugular fistula rete mirabile AVM model in six pigs to evaluate combinations of induced hypotension and venous hypertension, simulating raised CVP to enhance retropermeation during TRENSH-like maneuvers. RESULTS: Here we show that CVP elevation, retrograde injection through dominant DVs, maximally safe transvenous injection pressures, and a distinct strategy of synchronized diastolic-phase DV retroinjection each increase nidus retropermeation in experimental simulations. CONCLUSIONS: These theoretical TRENSH-derived venous manipulation strategies may offer adjunctive benefit for future transvenous treatment of large bAVMs. The findings provide a conceptual foundation for further validation studies to determine their translational feasibility and potential incorporation into advanced clinical TRENSH paradigms.