Abstract WP437: Shear-activated Nanoparticle Aggregate Lysis Combined With Temporary Stent-bypass to Treat Emergent Large Vessel Occlusions (ELVO)
Introduction: Despite the high effectiveness of stent-retrievers in ELVO, half of the patients remained functionally dependent (mRS≥3) after 90-days. Beyond futile recanalizations, variable endoluminal damage caused by stent-retrievers may contribute to reperfusion injury, and recruit iniflammatory cell infiltration. The goal of this study was to assess a less traumatic endovascular approach in combination with a novel shear activated-nanotherapeutic (SA-NT) that releases r-tPA when exposed to high levels of hemodynamic stress.
Hypothesis: SA-NT treatment coupled with temporary endovascular bypass provides high recanalization rates while reducing vascular injury.
Methods: a rabbit carotid vessel occlusion model was used. We evaluated angiographic recanalization with stent-bypass alone, intra-arterial delivery of soluble r-tPA alone, or stent-bypass combined with two doses (2 and 20 mg r-tPA) of intra-arterial infusion of either the SA-NT or soluble r-tPA. Vascular injury was compared against stent-retriever thrombectomy by assessing the level of damage on histology.
Results: Shear-targeted delivery of r-tPA using the SA-NT resulted in the highest rate of complete recanalization when compared to controls (p=0.0011). SA-NT (20mg) had a higher likelihood of obtaining complete recanalization (mTICI:3) as compared to stent-bypass alone (OR: 65.019,95%CI:[1.77,>1000], p=0.0231), intra-arterial r-tPA alone (OR: 65.019, 95% CI [1.77,>1000], p=0.0231), or stent-bypass with soluble r-tPA (2 mg) (OR: 18.78, 95%CI [1.28,275.05], p=0.0322) (Figure). Histologically, there was significantly less vascular injury using a stent-bypass as compared to stent-retriever procedure (OR 12.97, 95%CI [8.01,21.02], p<0.0001).
Conclusion: Nanoparticle-based thrombolytic therapy combined with stent-bypass achieves high rates of complete (mTICI:3) recanalization. This technology reduces vascular trauma as compared to stent-retriever thrombectomy
Author Disclosures: M.G. Marosfoi: None. N. Korin: Ownership Interest; Significant; Founder and equity holder in Dyne Therapeutics Inc. M.J. Gounis: Research Grant; Significant; Covidien/ eV3Neurovascular, Philips Healthcare. Consultant/Advisory Board; Modest; Wyss Institute/Harvard University. O. Uzun: None. S. Vedantham: None. E.T. Langan: None. A. Papa: None. O.W. Brooks: None. C. Johnson: None. A.S. Puri: None. D. Bhatta: None. M. Kanapathipillai: None. B.R. Bronstein: Ownership Interest; Significant; Founder and equity holder in Dyne Therapeutics Inc.. J. Chueh: None. D.E. Ingber: Ownership Interest; Significant; Founder and equity holder in Dyne Therapeutics Inc. A.K. Wakhoo: Research Grant; Significant; Philips Healthcare. Consultant/Advisory Board; Modest; Wyss Institute/Harvard University.
- © 2016 by American Heart Association, Inc.