Abraham R. Tzafriri, David Marlevi, Jay Budrewicz, Lynn Bailey, Peter Markham, Mazen Albaghdadi, Farhad Rikhtegar Nezami and Elazer R. Edelman. ‘Atraumatic Endoluminal Microincisions Enhance Balloon-Based Drug Delivery in Complex Porcine Restenotic Lesions.’ Presented at: CRT Online 2021.
Background: We examined whether endoluminal microincisions could enhance arterial drug uptake and retention after paclitaxel-coated balloon (PCB) treatments of diffuse in-stent restenotic lesions (ISRLs).
Methods: Six porcine femoral arteries underwent bilateral balloon overstretch and implantation of overlapping nitinol stents at 30 days to create complex ISRLs. At 0 d, ISRLs (minimal luminal diameter = 1.0-2.7mm) were imaged by optical coherence tomography (OCT) and treated with a PCB, then re-imaged (n=3) or prepared by a retractable sheathed catheter with three radially-positioned surgical blades mounted onto protective struts (FLEX), imaged, treated with PCB and imaged with OCT. Animals survived to 1, 15, or 30 days, and arteries were processed for paclitaxel quantification. OCT frames were segmented using automated in-house algorithms to identify incision locations and quantify dimensions and percentage of circumferential coverage in prepared arteries. Tissue concentrations were fit to a model of zero-order coating depot dissolution where the intercept estimates the acute pool of tissue-delivered drug.
Results: OCT imaging of ISRLs revealed smooth stenotic surfaces, associated with remarkably low paclitaxel concentrations at 1 day in standard vessels (<0.9 ng/mL). FLEX created 9±3 micro-incisions per frame covering 36±11% of vessel arc, raising drug concentrations at all 3 time points compared to PCB alone. The mean incision depth (0.22 mm) was equal to 88% of FLEX blade thickness. Kinetic analysis inferred that microincisions facilitated 21.7-fold greater delivery of tissue-retainable paclitaxel to ISRLs compared to PCB alone (P=0.03).
Conclusions: Preclinical data illustrate that ISRLs limit drug uptake and that controlled FLEX vessel preparation establishes atraumatic endoluminal microincisions and increases the delivery of tissue-retained paclitaxel after PCB treatments.