Chang Lee

Four-year polymer biocompatibility and vascular healing profile of a novel ultrahigh molecular weight amorphous PLLA bioresorbable vascular scaffold: an OCT study in healthy porcine coronary arteries

AIMS The vascular healing profile of polymers used in bioresorbable vascular scaffolds (BRS) has not been fully characterised in the absence of antiproliferative drugs. In this study, we aimed to compare the polymer biocompatibility profile and vascular healing response of a novel ultrahigh molecular weight amorphous PLLA BRS (FORTITUDE®; Amaranth Medical, Mountain View, CA, USA) against bare metal stent (BMS) controls in porcine coronary arteries. METHODS AND RESULTS Following device implantation, optical coherence tomography (OCT) evaluation was performed at 0 and 28 days, and at one, two, three and four years. A second group of animals underwent histomorphometric evaluation at 28 and 90 days. At four years, both lumen (BRS 13.19±1.50 mm2 vs. BMS 7.69±2.41 mm2) and scaffold areas (BRS 15.62±1.95 mm2 vs. BMS 8.65±2.37 mm2) were significantly greater for BRS than BMS controls. The degree of neointimal proliferation was comparable between groups. Histology up to 90 days showed comparable healing and inflammation profiles for both devices. CONCLUSIONS At four years, the novel PLLA BRS elicited a vascular healing response comparable to BMS in healthy pigs. Expansive vascular remodelling was evident only in the BRS group, a biological phenomenon that appears to be independent of the presence of antiproliferative drugs.

Comparative Characterization of Biomechanical Behavior and Healing Profile of a Novel Ultra-High-Molecular-Weight Amorphous Poly-l-Lactic Acid Sirolimus-Eluting Bioresorbable Coronary Scaffold

Background—Clinically available bioresorbable scaffolds (BRS) rely on polymer crystallinity to achieve mechanical strength resulting in limited overexpansion capabilities and structural integrity when exposed to high-loading conditions. We aimed to evaluate the biomechanical behavior and vascular healing profile of a novel, sirolimus-eluting, high-molecular-weight, amorphous poly-L-lactic acid–based BRS (Amaranth BRS). Methods and Results—In vitro biomechanical testing was performed under static and cyclic conditions. A total of 99 devices (65 Amaranth BRS versus 34 Absorb bioresorbable vascular scaffold [BVS]) were implanted in 99 coronary arteries of 37 swine for pharmacokinetics and healing evaluation at various time points. In the Absorb BVS, the number of fractures per scaffold seen on light microscopy was 6.0 (5.0–10.5) when overexpanded 1.0 mm above nominal values (≈34%). No fractures were observed in the Amaranth BRS group at 1.3 mm above nominal values (≈48% overexpansion). The number of fractures was higher in the Absorb BVS on accelerated cycle testing over time (at 24K cycles=5.0 [5.0–9.0] Absorb BVS versus 0.0 [0.0–0.5] Amaranth BRS). Approximately 90% of sirolimus was found to be eluted by 90 days. Optical coherence tomography analysis demonstrated lower percentages of late scaffold recoil in the Amaranth BRS at 3 months (Amaranth BRS=−10±16.1% versus Absorb BVS=10.7±13.2%; P=0.004). Histopathology analysis revealed comparable levels of vascular healing and inflammatory responses between both BRSs up to 6 months. Conclusions—New-generation high-molecular-weight amorphous poly-L-lactic acid scaffolds have the potential to improve the clinical performance of BRS and provide the ideal platform for the future miniaturization of the technology.

First in human evaluation of the vascular biocompatibility and biomechanical performance of a novel ultra high molecular weight amorphous PLLA bioresorbable scaffold in the absence of anti‐proliferative drugs: Two‐year imaging results in humans

In this first‐in‐human study, we prospectively studied the vascular compatibility and mechanical performance of a novel bare ultra‐high molecular weight amorphous PLLA bioresorbable scaffold (BRS, FORTITUDE®, Amaranth Medical, Mountain View, California) up to two years after implantation using multimodality imaging techniques.

Novel ultrahigh molecular weight amorphous PLLA bioresorbable coronary scaffold upsized up to 0.8 mm beyond nominal diameter: An OCT and histopathology study in porcine coronary artery model

The aim of the study was to evaluate the biomechanical properties and healing pattern of novel sirolimus‐eluting, ultrahigh molecular weight amorphous poly‐L‐lactic acid bioresorbable scaffolds (S‐BRS) that have been postdilated by 0.55 and 0.8 mm beyond the nominal diameters within the pressure‐diameter compliance chart range.

Comparative Biomechanical Behavior and Healing Profile of a Novel Thinned Wall Ultrahigh Molecular Weight Amorphous Poly-l-Lactic Acid Sirolimus-Eluting Bioresorbable Coronary Scaffold

Background— Mechanical strength of bioresorbable scaffolds (BRS) is highly dependent on strut dimensions and polymer features. To date, the successful development of thin-walled BRS has been challenging. We compared the biomechanical behavior and vascular healing profile of a novel thin-walled (115 µm) sirolimus-eluting ultrahigh molecular weight amorphous poly-L-lactic acid-based BRS (APTITUDE, Amaranth Medical [AMA]) to Absorb (bioresorbable vascular scaffold [BVS]) using different experimental models. Methods and Results— In vitro biomechanical testing showed no fractures in the AMA-BRS when overexpanded 1.3 mm above nominal dilatation values (≈48%) and lower number of fractures on accelerated cycle testing over time (at 21 K cycles=20.0 [19.5–20.5] in BVS versus 4.0 [3.0–4.3] in AMA-BRS). In the healing response study, 35 AMA-BRS and 23 BVS were implanted in 58 coronary arteries of 23 swine and followed-up to 180 days. Scaffold strut healing was evaluated in vivo using weekly optical coherence tomography analysis. At 14 days, the AMA-BRS demonstrated a higher percentage of embedded struts (71.0% [47.6, 89.1] compared with BVS 40.3% [20.5, 63.2]; P=0.01). At 21 days, uncovered struts were still present in the BVS group (3.8% [2.1, 10.2]). Histopathology revealed lower area stenosis (AMA-BRS, 21.0±6.1% versus BVS 31.0±4.5%; P=0.002) in the AMA-BRS at 28 days. Neointimal thickness and inflammatory scores were comparable between both devices at 180 days. Conclusions— A new generation thinned wall BRS displayed a more favorable biomechanical behavior and strut healing profile compared with BVS in normal porcine coronary arteries. This novel BRS concept has the potential to improve the clinical outcomes of current generation BRS.

TCT-31 Impact of Strut Thickness on Short-Term Healing Response after Bioresorbable Scaffold Implantation: Serial OCT Evaluation of Novel Thin Strut Sirolimus Eluting BRS Versus Thick Strut Everolimus Eluting BRS in Porcine Coronary Arteries.

The most widely commercially available bioresorbable scaffold (BRS) Absorb has strut thickness of 165 microns. Therefore, it has potential for higher thrombogenicity, especially in the early phase of vessel healing. As such, decreasing the BRS strut thickness with no adverse effect on its

TCT-831 Novel Thin Strut (100 μm) Ultra-High Molecular Weight PLLA Sirolimus-Eluting Bioresorbable Scaffold: A Comparative Preclinical Evaluation in Porcine Coronary Arteries

RESULTS The median of ESS per scaffold group is as follows; Absorb BVS:0.57(0.29-0.99) Pa, MMSES(125mm):0.68(0.35-1.18)Pa, MMSES (150mm):0.85(0.49-1.40)Pa. In linear mixed-effects analysis,ESS was significantly higher in MMSES(150mm) compared to Absorb BVS. The percentages of recirculation area were as follows; Absorb BVS:3.26 2.07, MMSES(150mm):3.17 1.97 and MMSES(125mm): 2.71 1.32.At device level,there was no statistical difference between the scaffold groups for the recirculation area.

TCT-832 In Vivo Biomechanical Performance of Thin Strut Sirolimus-Eluting Coronary Scaffold, Regular-Strut Scaffolds and Bare Metal Stents in Normal Porcine Coronary Arteries.

RESULTS The median of ESS per scaffold group is as follows; Absorb BVS:0.57(0.29-0.99) Pa, MMSES(125mm):0.68(0.35-1.18)Pa, MMSES (150mm):0.85(0.49-1.40)Pa. In linear mixed-effects analysis,ESS was significantly higher in MMSES(150mm) compared to Absorb BVS. The percentages of recirculation area were as follows; Absorb BVS:3.26 2.07, MMSES(150mm):3.17 1.97 and MMSES(125mm): 2.71 1.32.At device level,there was no statistical difference between the scaffold groups for the recirculation area.

TCT-776 Vascular Healing Response after Implantation of a Novel Fluoropolymer-Coated Paclitaxel-Eluting Peripheral Stent: a Comparative Drug-Eluting Stent Study in a Familial Hypercholesterolemic Swine Model of Balloon-Injured Femoral Arteries.

Key processes of restenosis occur weeks or months following stent implantation. Sustained drug release over time may be crucial to achieve long term vessel patency. This study compared the efficacy of a novel fluoropolymer-coated nitinol self-expanding paclitaxel-eluting stent (PES) with a

TCT-829 Biomechanical Behavior and Healing Response of a Novel Thin Strut Sirolimus Eluting Bioresorbable Scaffold Overexpanded up to 0.75 mm Beyond Nominal Compliance Chart Diameters in Porcine Coronary Artery Model

Esha Singhal, Don P. Giddens, Alessandro Veneziani, Richard Rapoza, Spencer King III, Hanjoong Jo, Habib Samady Emory University School of Medicine, Atlanta, Georgia, United States; igic, patna, Bihar, India; Abbott Vascular, Santa Clara, California, United States; Emory Healthcare, Atlanta, Georgia, United States; Emory University Hospital, Lawrenceville, Georgia, United States; Decatur, Georgia, United States; Emory University School of Medicine; Emory University School of Medicine; Emory University; Emory University Department of Biomedical Engineering, Atlanta, Georgia, United States; Emory University, Atlanta, Georgia, United States; Abbott Vascular, Santa Clara, California, United States; Emory University, Atlanta, Georgia, United States; Emory University Department of Biomedical Engineering; Emory University Hospital, Atlanta, Georgia, United States