Chronic myocardial and coronary arterial effects of intracoronary supersaturated oxygen therapy in swine with normal and ischemic-reperfused myocardium.

The study assessed chronic myocardial, coronary and systemic effects of intracoronary supersaturated oxygen (SSO2) therapy. Left anterior descending coronary arteries of 40 swine were stented and randomized to 90-min selective intracoronary infusion of SSO2 (pO2 760-1000 mmHg) or normoxemic saline. In 20 out of 40 animals, SSO2 delivery followed a 60-min balloon occlusion to induce myocardial infarction (MI). In both normal and MI models, intracoronary treatment with hyperoxemic SSO2 therapy showed no evidence of coronary thrombosis. There were no biologically relevant differences between treatments at either time point in regard to coronary intervention site healing and neointimal growth. No signs of any myocardial or systemic toxicity were observed after 7 or 30 days. A trend was observed toward reduced incidence of microscopic MI scars and reduced infarct size in histopathology, as well as toward better recovery of echocardiographically evaluated global and regional contractility at 30 days. No treatment related infarcts or thromboemboli were observed in the downstream organs.

Impact of Coronary Atherosclerosis on Bioresorbable Vascular Scaffold Resorption and Vessel Wall Integration.

The integration of the Absorb bioresorbable vascular scaffold (BVS) into the arterial wall has never been tested in an in vivo model of atherosclerosis. This study aimed to compare the long-term (up to 4 years) vascular healing responses of BVS to an everolimus-eluting metallic stent in the familial hypercholesterolemic swine model of atherosclerosis. The multimodality imaging and histology approaches indicate that the resorption and vascular integration profile of BVS is not affected by the presence of atherosclerosis. BVS demonstrated comparable long-term vascular healing and anti-restenotic efficacy to everolimus-eluting metallic stent but resulted in lower late lumen loss at 4 years.

Long-term performance and biocompatibility of a novel bioresorbable scaffold for peripheral arteries: A three-year pilot study in Yucatan miniswine.

AIMS: Peripheral arteries are constantly exposed to deformation (elongation, twisting, shortening, compression) making bioresorbable scaffolds (BRS) a potentially attractive therapeutic alternative to metallic stents. We conducted a long-term pilot preclinical study of a novel sirolimus-eluting BRS in peripheral arteries. METHODS AND RESULTS: Fourteen BRS were deployed in iliofemoral arteries of seven healthy Yucatan miniswine and examined with imaging, pharmacokinetic, histopathologic, and polymer degradation techniques at 0, 30, 90, 180 days, 1, 2, and 3.3 years. Angiographic late luminal loss remained unchanged at 30 and 180 days but significantly decreased from 1 to 3.3 years. optical coherence tomography (OCT) showed late increase in lumen area (1 year: 14.70 ± 3.58 mm2 , 2 years 22.04 ± 3.81 mm2 , and 3.3 years 23.45 ± 7.07 mm2 ; p < .05) primarily due to scaffold area enlargement between 1 and 3.3 years, while there was no difference in the percent area stenosis at all time points. Histologic evidence of scaffold degradation was observed starting at 2 years, with minimal inflammatory reaction. At 3.3 years, BRS struts were rarely discernible by OCT, confirmed by a nearly complete polymer degradation by molecular weight analysis. CONCLUSIONS: In this pilot study, novel sirolimus-eluting BRS showed promising acute and chronic performance in the iliofemoral arteries of Yucatan miniswine.

Two-year longitudinal evaluation of a second-generation thin-strut sirolimus-eluting bioresorbable coronary scaffold with hybrid cell design in porcine coronary arteries.

BACKGROUND: The first commercially available bioresorbable scaffold (BRS) had a strut thickness of 156 microns. As such, it had the potential for delivery challenges and higher thrombogenicity. The aim herein, is to evaluate biomechanical performance, pharmacokinetics and vascular healing of a novel thin strut (100 µm) sirolimus eluting BRS (MeRes-100, Meril Life Sciences, Gujarat, India) against the once clinically used BRS (Absorb BVS, Abbott, Santa Clara, CA) in porcine coronary arteries. METHODS: Following device implantation, angiographic and optical coherence tomography (OCT) evaluation were performed at 45, 90, 180 days, 1 year and 2 years. Histological evaluation was per-formed at 30, 90 and 180 days. RESULTS: At 2 years, both lumen (MeRes-100 7.07 ± 1.82 mm² vs. Absorb BVS 7.57 ± 1.39 mm2, p = NS) and scaffold areas (MeRes-100 9.73 ± 1.80 mm² vs. Absorb BVS 9.67 ± 1.25 mm², p = NS) were comparable between tested and control scaffolds. Also, the late lumen area gain at 2 years was similar in both groups tested (MeRes-100 1.03 ± 1.98 mm² vs. Absorb BVS 0.85 ± 1.56 mm², p = NS). Histologic examination up to 6 months showed comparable healing and inflammation profiles for both devices. CONCLUSIONS: The novel sirolimus-eluting BRS with thinner struts and hybrid cell design showed similar biomechanical durability and equivalent inhibition of neointimal proliferation when compared to the first-ever Absorb BVS up to 2 years in normal porcine coronary arteries.

In vitro mechanical behavior and in vivo healing response of a novel thin-strut ultrahigh molecular weight poly-l-lactic acid sirolimus-eluting bioresorbable coronary scaffold in normal swine.

BACKGROUND: New generation bioresorbable scaffolds (BRS) promise to improve the outcomes of current generation BRS technologies by decreasing wall thickness while maintaining structural strength. This study aimed to compare the biomechanical behavior and vascular healing profile of a novel thin-walled (98 µm) sirolimus-eluting ultrahigh molecular weight BRS (Magnitude, Amaranth Medical) to the Absorb everolimus-eluting bioresorbable vascular scaffold (Abbott Vascular). METHODS AND RESULTS: In vitro biomechanical testing showed lower number of fractures on accelerated cycle testing over time (at 21K cycles = 20.0 [19.0-21.0] in Absorb versus 0.0 [0.0-1.0] in Magnitude-BRS). Either Magnitude (n = 43) or Absorb (n = 22) was implanted in 65 coronary segments of 22 swine. Scaffold strut's coverage was evaluated using serial optical coherence tomography (OCT) analysis. At 14 days, Magnitude-BRS demonstrated a higher percentage of embedded struts (97.7% [95.3, 100.0] compared to Absorb (57.2% [48.0, 76.0], p = 0.003) and lower percentage of uncovered struts (0.0% [0.0, 0.0] versus Absorb 5.5% [2.6, 7.7], p = 0.02). Also, it showed a lower percent late recoil (-1.02% [-4.11, 3.21] versus 4.42% [-1.10, 8.74], p = 0.04) at 28 days. Histopathology revealed comparable neointimal proliferation and vascular healing responses between two devices up to 180 days. CONCLUSION: A new generation thin walled (98-µm) Magnitude-BRS displayed a promising biomechanical behavior and strut healing profile compared to Absorb at the experimental level. This new generation BRS platform has the potential to improve the clinical outcomes shown by the current generation BRS.

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.

OBJECTIVES: 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. BACKGROUND: Due to the inherent limitations of bioabsorbable polymeric materials, overexpansion/upsizing may be very limited for some BRS such as the benchmark Absorb BVS. The unique biomechanical properties of the novel S-BRS may allow it to be safely upsized. METHODS AND RESULTS: 12 coronary arteries of 4 healthy Yucatan mini-swine underwent implantation of a novel S-BRS. Upsizing by postdilation was performed up to 0.55mm (PLUS 0.55, n = 6) or 0.8 mm (PLUS 0.8, n = 6) in a manner maintaining consistent 1:1.1 stent-to-artery, thus ensuring not only the overexpansion of the scaffold but consistent level of arterial injury. Optical coherence tomography (OCT) follow-up was performed at 28 and 90-days follow-up. There was no statistical difference between the tested groups in terms of acute recoil. OCT analysis after 28 days showed numerically lower levels of neointimal formation in PLUS 0.8 compared to PLUS 0.55 group. These results were sustained at 90-days follow-up. There was no difference in late recoil between studied groups. No scaffold discontinuation, deformation or overlapping of the struts were observed. CONCLUSIONS: Overexpansion up to 0.8 mm of novel, high strength S-BRS is not associated with worse angiographic outcomes, neointimal formation or biomechanical issues such as scaffold discontinuation, deformation or overlapping of the struts, neither acutely nor chronically. © 2017 Wiley Periodicals, Inc.

Impact of bioresorbable versus permanent polymer on longterm vessel wall inflammation and healing: a comparative drug-eluting stent experimental study.

AIMS: Drug-eluting stents (DES) have evolved to using bioresorbable polymers as a method of drug delivery. The impact of bioresorbable polymer on long-term neointimal formation, inflammation, and healing has not been fully characterised. This study aimed to evaluate the biological effect of polymer resorption on vascular healing and inflammation. METHODS AND RESULTS: A comparative DES study was performed in the familial hypercholesterolaemic swine model of coronary stenosis. Permanent polymer DES (zotarolimus-eluting [ZES] or everolimus-eluting [EES]) were compared to bioresorbable polymer everolimus-eluting stents (BP-EES) and BMS. Post implantation in 29 swine, stents were explanted and analysed up to 180 days. Area stenosis was reduced in all DES compared to BMS at 30 days. At 180 days, BP-EES had significantly lower area stenosis than EES or ZES. Severe inflammatory activity persisted in permanent polymer DES at 180 days compared to BP-EES or BMS. Qualitative para-strut inflammation areas (graded as none to severe) were elevated but similar in all groups at 30 days, peaked at 90 days in DES compared to BMS (p<0.05) and, at 180 days, were similar between BMS and BP-EES but were significantly greater in DES. CONCLUSIONS: BP-EES resulted in a lower net long-term reduction in neointimal formation and inflammation compared to permanent polymer DES in an animal model. Further study of the long-term neointima formation deserves study in human clinical trials.

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.

Impact of Fluoropolymer-Based Paclitaxel Delivery on Neointimal Proliferation and Vascular Healing: A Comparative Peripheral Drug-Eluting Stent Study in the Familial Hypercholesterolemic Swine Model of Femoral Restenosis.

BACKGROUND: A polymer-free peripheral paclitaxel-eluting stent (PES, Zilver PTX, Cook, IN) has shown to improve vessel patency after superficial femoral angioplasty. A new-generation fluoropolymer-based PES (FP-PES; Eluvia, Boston Scientific, MA) displaying more controlled and sustained paclitaxel delivery promise to improve the clinical outcomes of first-generation PES. We sought to compare the biological effect of paclitaxel delivered by 2 different stent-coating technologies (fluoropolymer-based versus polymer-free) on neointimal proliferation and healing response in the familial hypercholesterolemic swine model of femoral restenosis. METHODS AND RESULTS: The biological efficacy of clinically available FP-PES (n=12) and PES (n=12) was compared against a bare metal stent control (n=12; Innova, Boston Scientific, MA) after implantation in the femoral arteries of 18 familial hypercholesterolemic swine. Longitudinal quantitative vascular angiography and optical coherence tomography were performed at baseline and at 30 and 90 days. Histological evaluation was performed at 90 days. Ninety-day quantitative vascular angiography results showed a lower percent diameter stenosis for FP-PES (38.78% [31.27-47.66]) compared with PES (54.16% [42.60-61.97]) and bare metal stent (74.52% [47.23-100.00]; P<0.001). Ninety-day optical coherence tomography results demonstrated significantly lower neointimal area in FP-PES (8.01 mm2 [7.65-9.21]) compared with PES (10.95 mm2 [9.64-12.46]) and bare metal stent (13.83 mm2 [11.53-17.03]; P<0.001). Histological evaluation showed larger lumen areas and evidence of higher biological activity (smooth muscle cell loss and fibrin deposition) in the FP-PES compared with PES and bare metal stent. CONCLUSIONS: In the familial hypercholesterolemic swine model of femoral restenosis, the implantation of an FP-PES resulted in lower levels of neointimal proliferation and sustained biological effect ≤90 days compared with a polymer-free stent-based approach.

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.

Biological effect on restenosis and vascular healing of encapsulated paclitaxel nanocrystals delivered via coated balloon technology in the familial hypercholesterolaemic swine model of in-stent restenosis.

AIMS: The aim of this study was to evaluate the biological efficacy of a novel lower-dose (2.5 µg/mm2) encapsulated paclitaxel nanocrystal-coated balloon (Nano-PCB) in the familial hypercholesterolaemic swine (FHS) model of iliofemoral in-stent restenosis. METHODS AND RESULTS: Nano-PCB pharmacokinetics were assessed in 20 femoral arteries (domestic swine). Biological efficacy was evaluated in ten FHS: 14 days following bare metal stent implantation each stent segment was randomised to a clinically available PCB (IN.PACT, n=14), the Nano-PCB (n=14) or an uncoated balloon (n=12). Angiographic, optical coherence tomography and histological evaluation was performed at 28 days after treatment. Arterial paclitaxel concentration was 120.7 ng/mg at one hour and 7.65 ng/mg of tissue at 28 days with the Nano-PCB. Compared to the control uncoated group, both PCBs significantly reduced percent area stenosis (Nano-PCB: 36.0±14.2%, IN.PACT: 29.3±9.2% vs control: 67.9±15.1%, p<0.001). Neointimal distribution in the entire stent length was more homogenous in the Nano-PCB. Histological evaluation showed comparable degrees of neointimal proliferation in both PCBs; however, the Nano-PCB showed slightly higher levels of neointimal maturity and endothelialisation. CONCLUSIONS: Lower-dose encapsulated paclitaxel nanocrystals delivered via a coated balloon displayed comparable biological efficacy with superior healing features compared to a clinically validated PCB technology.

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.

In vivo delivery and long-term tissue retention of nano-encapsulated sirolimus using a novel porous balloon angioplasty system.

AIMS: Among antirestenotic compounds, sirolimus displays a superior safety profile compared to paclitaxel, but its pharmacokinetic properties make it a challenging therapeutic candidate for single-time delivery. Herein we evaluate the feasibility of delivery, long-term retention and vascular effects of sirolimus nanoparticles delivered through a novel porous angioplasty balloon in normal porcine arteries and in a swine model of in-stent restenosis (ISR). METHODS AND RESULTS: Sirolimus nanoparticle formulation was delivered via porous balloon angioplasty to 753 coronary artery segments for pharmacokinetic studies and 26 segments for biological effect of sirolimus delivery in different clinical scenarios (de novo [n=8], ISR [n=6] and following stent implantation [n=12]). Sirolimus coronary artery concentrations were above the target therapeutic level of 1 ng/mg after 26 days, and were >100-fold higher in coronary artery treatment sites than in distal myocardium and remote tissues at all time points. At 28 days, reduction in percent stenosis in formulation-treated sites compared to balloon angioplasty treatment was noted in all three clinical scenarios, with the largest effect seen in the de novo study. CONCLUSIONS: Local coronary delivery of sirolimus nanoparticles in the porcine model using a novel porous balloon delivery system achieved therapeutic long-term intra-arterial drug levels without significant systemic residual exposure.

Impact of Paclitaxel Dose on Tissue Pharmacokinetics and Vascular Healing: A Comparative Drug-Coated Balloon Study in the Familial Hypercholesterolemic Swine Model of Superficial Femoral In-Stent Restenosis.

OBJECTIVES: This study sought to compare the effect of paclitaxel-coated balloon (PCB) concentration on tissue levels and vascular healing using 3 different PCB technologies (In.Pact Pacific = 3 µg/mm(2), Lutonix = 2 µg/mm(2) and Ranger = 2 µg/mm(2)) in the experimental setting. BACKGROUND: The optimal therapeutic dose for PCB use has not been determined yet. METHODS: Paclitaxel tissue levels were measured up to 60 days following PCB inflation (Ranger and In.Pact Pacific) in the superficial femoral artery of healthy swine (18 swine, 36 vessels). The familial hypercholesterolemic swine model of superficial femoral artery in-stent restenosis (6 swine, 24 vessels) was used in the efficacy study. Two weeks following bare-metal stent implantation, each in-stent restenosis site was randomly treated with a PCB or an uncoated control balloon (Sterling). Quantitative vascular analysis and histology evaluation was performed 28 days following PCB treatment. RESULTS: All PCB technologies displayed comparable paclitaxel tissue levels 4 h following balloon inflation. At 28 days, all PCB had achieved therapeutic tissue levels; however, the In.Pact PCB resulted in higher tissue concentrations than did the other PCB groups at all time points. Neointimal inhibition by histology was decreased in all PCB groups compared with the control group, with a greater decrease in the In.Pact group. However, the neointima was more mature and contained less peri-strut fibrin deposits in both 2-µg/mm(2) PCB groups. CONCLUSIONS: Compared with the clinically established PCB dose, lower-dose PCB technologies achieve lower long-term tissue levels but comparable degrees of neointimal inhibition and fewer fibrin deposits. The impact of these findings in restenosis reduction and clinical outcomes needs to be further investigated.

Early feasibility evaluation of thoracoscopically assisted transcatheter ventricular reconstruction in an experimental model of ischaemic heart failure with left anteroapical aneurysm.

AIMS: To test the feasibility of a thoracoscopically assisted, off-pump, transcatheter ventricular reconstruction (TCVR) approach in an ovine model of left ventricular (LV) anteroapical aneurysm. METHODS AND RESULTS: Myocardial infarction (MI) was induced by coil occlusion of the middle left anterior descending artery and diagonals. Two months after MI creation, TCVR was performed via a minimal thoracotomy in eight sheep. Under endoscopic and fluoroscopic guidance, trans-interventricular septal puncture was performed from the LV epicardial scar. A guidewire was externalised via a snare placed in the right ventricle from the external jugular vein. An internal anchor was inserted over the wire and positioned on the right ventricular septum and an external anchor was deployed on the LV anterior epicardium. Serial pairs of anchors were placed and plicated together to exclude the scar completely. Immediately after TCVR, echocardiography showed LV end-systolic volume decreased from pre-procedure 58.8±16.6 ml to 25.1±7.6 ml (p<0.01) and the ejection fraction increased from 32.0±7.3% to 52.0±7.5% (p<0.01). LV twist significantly improved (3.83±2.21 vs. pre-procedure -0.41±0.94, p=0.01) and the global peak-systolic longitudinal strain increased from -5.64% to -10.77% (p<0.05). CONCLUSIONS: TCVR using minimally invasive access techniques on the off-pump beating heart is feasible and resulted in significant improvement in LV performance.

Optimizing flushing parameters in intracoronary optical coherence tomography: an in vivo swine study.

Intracoronary optical frequency domain imaging (OFDI), requires the displacement of blood for clear visualization of the artery wall. Radiographic contrast agents are highly effective at displacing blood however, may increase the risk of contrast-induced nephropathy. Flushing media viscosity, flow rate, and flush duration influence the efficiency of blood displacement necessary for obtaining diagnostic quality OFDI images. The aim of this work was to determine the optimal flushing parameters necessary to reliably perform intracoronary OFDI while reducing the volume of administered radiographic contrast, and assess the influence of flushing media choice on vessel wall measurements. 144 OFDI pullbacks were acquired together with synchronized EKG and intracoronary pressure wire recordings in three swine. OFDI images were graded on diagnostic quality and quantitative comparisons of flushing efficiency and intracoronary cross-sectional area with and without precise refractive index calibration were performed. Flushing media with higher viscosities resulted in rapid and efficient blood displacement. Media with lower viscosities resulted in increased blood-media transition zones, reducing the pullback length of diagnostic quality images obtained. Flushing efficiency was found to increase with increases in flow rate and duration. Calculations of lumen area using different flushing media were significantly different, varying up to 23% (p < 0.0001). This error was eliminated with careful refractive index calibration. Flushing media viscosity, flow rate, and flush duration influence the efficiency of blood displacement necessary for obtaining diagnostic quality OFDI images. For patients with sensitivity to contrast, to reduce the risk of contrast induced nephrotoxicity we recommend that intracoronary OFDI be conducted with flushing solutions containing little or no radiographic contrast. In addition, our findings show that careful refractive index compensation should be performed, taking into account the specific contrast agent used, in order to obtain accurate intravascular OFDI measurements.

First in vivo evaluation of a flexible self-apposing left atrial appendage closure device in the canine model.

OBJECTIVES: Aimed to evaluate the feasibility of deployment and healing response of a novel transcatheter left atrial appendage (LAA) occlusion device in the canine model BACKGROUND: LAA occlusion is proposed to reduce the risk of stroke in atrial fibrillation patients METHODS: Transseptal puncture and device deployment was guided under fluoroscopy and transesophageal echocardiography (TEE) in five dogs. First, a distal cylindrical bulb occluder was released and secured to the appendage wall with hooks. Subsequently, a proximal sail was unfolded, covering the LAA ostium. Rotational angiography, TEE, and histology outcomes were assessed 30 days following implantation RESULTS: Pre-operative TEE revealed the mean diameter of the LAA ostium to be 17.2 ± 1.6 mm with a depth of 18.5 ± 1.7 mm. The landing zone for the distal bulb was measured to be 12.8 ± 1.3 mm. The mean bulb diameter at implant was 16.8 ± 1.8 mm. Post-operative TEE showed adequate positioning and successful LAA occlusion with all implanted devices. Pericardial effusion requiring pericardiocentesis was seen in one animal following device implantation. At 30 days, TEE revealed full occlusion of all LAA ostia with the exception of a minimal peri-device leak (<3 mm) observed in one animal. No pericardial effusion or device-related thrombus formation was found at termination. Histological analysis confirmed circumferential occlusion of all appendages and complete neointimal coverage on the luminal aspect of the occluder CONCLUSION: The percutaneous delivery of a novel self-positioning LAA occlusion device is feasible and safe in a canine model. At 30 days, all devices displayed complete healing and occlusion of the LAA without any device related adverse events.

Neointimal patterns obtained by optical coherence tomography correlate with specific histological components and neointimal proliferation in a swine model of restenosis.

AIMS: Although optical coherence tomography (OCT) is capable to detect microscopic peri-strut changes that seem to be related to neointimal inhibition and healing, its ability to characterize these components is still limited. In this study, we aimed to compare different OCT morphological characteristics with different in-stent neointimal tissue types analysed by histology. METHODS: A total of 69 stents (39 drug eluting and 30 bare metal stents) were implanted in coronary arteries of 27 swine. By OCT, neointimal type was classified as homogeneous, heterogeneous, or layered according to its pattern of backscatter and optical intensity. The resulting optical patterns were correlated with several histological findings [external elastic lamina (EEL) disruption, fibrin deposition, circumferential rim of peri-strut inflammatory cell infiltration, and fibrous connective deposition] in every single cross-section (CS) analysed. RESULTS: A total of 197 matched OCT and histological CS were analysed. The heterogeneous (0.44 ± 0.21 mm) and layered (0.65 ± 0.16 mm) patterns had a significantly higher degree of neointimal thickness compared with the homogeneous pattern (0.25 ± 0.16 mm, P < 0.001). Fibrous connective tissue deposition was more frequently present in the homogeneous pattern (71.6%, P < 0.001), whereas significant fibrin deposits were more commonly seen in the heterogeneous pattern (56.9%, P = 0.007). Peri-strut inflammation was less frequently found in the homogeneous pattern (19.8%, P < 0.001) in comparison with the layered (73.9%) or heterogeneous patterns (43.1%). The presence of EEL rupture was also more commonly seen in layered (73.9%) and heterogeneous (46.6%) patterns than in the homogeneous pattern (22.4%, P < 0.001). CONCLUSION: The optical characteristics of neointimal formation seen in OCT properly correlated with the presence of several histological findings involved in stent healing. The biological implications of these findings in clinical outcomes require further investigation.

Stent healing response following delivery of paclitaxel via durable polymeric matrix versus iopromide-based balloon coating in the familial hypercholesterolaemic swine model of coronary injury.

AIMS: The routine use of paclitaxel-coated balloons (PCB) in combination with bare metal stents (BMS) in de novo coronary lesions has been questioned. In this study, we aimed to compare the vascular response of BMS implanted using a second-generation PCB (BMS+PCB) with the TAXUS stent (PES) and a BMS control (BMS) in the familial hypercholesterolaemic swine (FHS) model of coronary injury. METHODS AND RESULTS: A total of 17 stents (PES=6, BMS+PCB=6, and BMS=5) were implanted in the coronary territory of 10 FHS using a 20% overstretch injury ratio. Imaging evaluation (QCA and IVUS) was conducted in all animals at baseline and 28 days following stent implantation. Following terminal imaging all animals were euthanised and stented coronary segments harvested for histological evaluation. At 28 days, the lowest degree of percentage diameter stenosis by QCA was achieved by the PES (2.9 ± 9%) followed by the BMS+PCB (9.5 ± 16.4%) and the BMS group (25.65 ± 18.7%, p<0.05). In histology, percentage area of stenosis (BMS+PCB=29.6 ± 6.4% vs. PES=21.5 ± 3.3% vs. BMS=55.2 ± 12.9%; p<0.01) and neointimal thickness (BMS+PCB=0.26 ± 0.1 mm vs. PES=0.21 ± 0.1 mm vs. BMS=0.59 ± 0.2 mm; p<0.01) were significantly reduced in both paclitaxel groups in comparison to BMS controls. Both BMS+PCB and BMS groups had higher endothelialisation scores (PES=1.50 ± 0.9 vs. BMS+PCB=2.73 ± 0.4 vs. BMS=3.00; p<0.05) and lower peri-strut inflammatory scores (PES=0.83 ± 0.4 vs. BMS+PCB=0.20 ± 0.2 vs. BMS=0.43 ± 0.6, p<0.05) when compared to PES. Neointima maturity (PCB+BMS: 2.00 [2-2.4] vs. PES: 1.00 [0.3-1] vs. BMS: 3.00, p<0.05) and fibrin deposition (PCB+BMS: 1.40 ± 0.3 vs. PES: 2.17 ± 0.7 vs. BMS: 0.27 ± 0.3, p<0.05) scores in PCB+BMS appeared to fall between the PES and the BMS ranges. CONCLUSIONS: In the FHS coronary injury model, BMS implantation using a PCB yields a degree of neointimal inhibition comparable to the PES. The BMS+PCB combination presented lower degrees of inflammation and fibrin deposition; however, signs of delayed healing were still present.