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The introduction into clinical practice of intravascular imaging, including intravascular ultrasound (IVUS), optical coherence tomography (OCT) and their derivatives, allowed for the in vivo assessment of coronary atherosclerosis in humans, including insights into plaque evolution and progression process. Intravascular ultrasound, the most commonly used intravascular modality in many countries, due to its low resolution cannot assess many features of vulnerable plaque such as lipid plaque or thin-cap fibroatheroma. Thus, novel methods were introduced to facilitate this problem including virtual histology intravascular ultrasound and later on near-infrared spectroscopy and OCT. Howbeit, none of the currently used modalities can assess all known characteristics of plaque vulnerability; hence, the idea of combining different intravascular imaging methods has emerged including NIRS-IVUS or OCT-IVUS imaging. All of those described methods may allow us to identify the most vulnerable plaques, which are prone to cause acute coronary syndrome, and thus they may allow us to introduce proper treatment before plaque destabilization.

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 per­formed at 30, 90 and 180 days. Results: At 2 years, both lumen (MeRes-100 7.07 ± 1.82 mm 2 vs. Absorb BVS 7.57 ± 1.39 mm 2 , p = NS) and scaffold areas (MeRes-100 9.73 ± 1.80 mm 2 vs. Absorb BVS 9.67 ± 1.25 mm 2 , 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 mm 2 vs. Absorb BVS 0.85 ± 1.56 mm 2 , 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.

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.

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.

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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

AIMS The Mitra-Spacer (Cardiosolutions, Bridgewater, MA, USA) is designed to treat mitral regurgitation by introducing a dynamic spacer that constantly adapts to the changing haemodynamic conditions during the cardiac cycle. We aimed to evaluate the performance and safety of this device in the chronic ovine model. METHODS AND RESULTS Eight sheep were enrolled in this study. Through a left thoracotomy, the Mitra-Spacer was inserted via the transapical approach and advanced into the left atrium (LA) under imaging guidance. Device performance and safety were evaluated up to 90 days using fluoroscopy, echocardiography and histopathology. The volume within the balloon spacer shifted during the cardiac cycle in all cases. Seven animals survived up to 90 days for terminal imaging and tissue harvest. Echocardiography showed no change in left ventricle (LV) ejection fraction from baseline to 90 days. There were no observations of changes in LV diastolic function, pulmonary vein inflow, or tricuspid valve function. Histological analysis demonstrated no significant injury to the mitral apparatus. CONCLUSIONS In the healthy ovine model, Mitra-Spacer implantation was feasible and safe. At 90 days, no evidence of structural damage to the mitral apparatus or deterioration of cardiac performance was demonstrated.

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.

Introduction. Syncope is a transient loss of consciousness due to a decrease in cerebral perfusion. The aim of the study is to evaluate the incidence of syncope within 2 years before the finding of significant carotid stenosis and to seek the relationship between syncope occurrence and clinical and ECG parameters. Material and methods. The study group consisted of 78 patients (31 women and 47 men aged 65.4 ± 7.7 years) admitted to the Department of Vascular Surgery in order to perform the surgery because of significant carotid stenosis. The studied patients were interviewed for syncopal history and risk factors for cardiovascular diseases. Moreover, a 12-lead resting electrocardiogram was performed. Results. In the study group 20 (25.6%) patients reported at least one faint, 7 (9%) patients reported a faint in the past 2 years. The subgroups distinguished in the basis of syncopal history in the past 2 years did not differ significantly in terms of the assessed demographic and clinical parameters. In the group of patients with syncope in the past 2 years, there was significantly more patients with QRS ≥ 120 ms than the other patients. Logistic regression analysis showed that the only parameter associated with syncope in the past 2 years has been QRS width ≥ 120 ms odds ratio (OR): 18.9; 95% confidence interval (CI) 2.4–147.4 (p = 0.005). Conclusions. 1. Syncope during the past 2 years occurs in almost 10% of patients qualified for carotid artery surgery. 2. The parameter associated with syncope in the past two years is widened QRS complex indicating a cardiac cause of syncope. 3. Gathering information about recent loss of consciousness in patients qualified for vascular surgery on the carotid arteries can have important implications for the planning further cardiological diagnostics.

The beating human cadaver heart biosimulator (BHCHB) model resolves discrepancies between bench/animal models and human anatomy in evaluating transcatheter mitral valve repair (TMVR) technologies in this laboratory. Significant valve area and tricuspid regurgitation reductions achieved clinically

Anchoring transcatheter aortic valves in an orthotopic position in the absence of native valve calcification has been historically a challenge. This preclinical study aimed to evaluate the anchoring, retention, hemodynamics, and biocompatibility of the new-generation self-expandable, fully

Objectives The aim of the study was to capture the evolution of neointima after implantation of a biodegradable polymer–coated, sirolimus–eluting, cobalt–chromium coronary stent system (BP-DES). Background Optical coherence tomography (OCT) suggests that in-stent neointimal morphology influences clinical outcomes after DES implantation. Methods Sixty patients treated with single BP-DES implantation were examined by quantitative coronary angiography (QCA) and OCT at 3, 6, and 12-month follow-up. Results Median late lumen loss by QCA (mm) was 0.04 (IQR 0, 0.08), 0.17 (IQR 0, 0.32), and 0.14 (IQR 0.07, 0.31) at 3, 6, and 12-month follow-up respectively (P = 0.03). OCT cross-section multilevel analysis showed uncovered struts in 3.90%, 1.78%, and 0.02% of struts respectively (P = 0.03). The corresponding malapposition rates were 0.12%, 0.04%, and 0%. Lipid-rich neointima was observed only at 12-month follow-up in one restenotic lesion (0.77% cross-sections) that was accountable for the only target vessel revascularization. The homogeneous pattern was prevalent at all three time points, but its incidence displayed an upward trend (3 months: 59%; 6 months: 71%; 12 months: 88%) despite no difference in neointimal volume between 6 and 12 months. Conversely, a trend could be observed of decreasing incidence of heterogeneous pattern as the follow-up length increased. Conclusions In this study of a single-type BP-DES, the majority of stent struts were covered within 3 months from implantation. While the quantitative neointimal accumulation plateaued at 6 months with no further significant increase beyond 6 months, the neointima continued to evolve qualitatively and mature along with better strut coverage between 6 and 12 months after implantation.

Optical coherence tomography (OCT) has opened new horizons for intravascular coronary imaging. It utilizes near-infrared light to provide a microscopic insight into the pathology of coronary arteries in vivo. Optical coherence tomography is also capable of identifying the chemical composition of atherosclerotic plaques and detecting traits of their vulnerability. At present it is the only tool to measure the thickness of the fibrous cap covering the lipid core of the atheroma, and thus it is an exceptional modality to detect plaques that are prone to rupture (thin fibrous cap atheromas). Moreover, it facilitates distinguishing between plaque rupture and plaque erosion as a cause of acute intracoronary thrombosis. Optical coherence tomography is applied to guide angioplasties of coronary lesions and to assess outcomes of percutaneous coronary interventions broadly. It identifies stent malapposition, dissections, and thrombosis with unprecedented precision. Furthermore, OCT helps to monitor vessel healing after stenting. It evaluates the coverage of stent struts by the neointima and detects in-stent neoatherosclerosis. With so much potential, new studies are warranted to determine OCT's clinical impact. The following review presents the technical background, basics of OCT image interpretation, and practical tips for adequate OCT imaging, and outlines its established and potential clinical application.

Objectives The aim of the study was to evaluate the healing process at 12 months after ABSORB™ bioresorbable vascular scaffold (BVS) implantation in patients with ST-segment elevation myocardial infarction (STEMI). Background There is currently no data on long-term BVS performance in the acute thrombotic setting. The underlying altered plaque pathomorphology may impact the neointima healing pattern, potentially making it different to that observed in stable coronary artery disease (CAD). Methods We have performed an angiographic and optical coherence tomography (OCT) 12-month follow-up of 19 STEMI patients who were treated with a BVS implantation (23 scaffolds). An independent core laboratory performed a paired analysis of the corresponding frames at baseline and follow-up. Results At 12 months, the OCT follow-up showed a decrease in the mean lumen area (8.29 ± 1.53 mm2 vs. 6.82 ± 1.57 mm2, P

There is a continued need for a reproducible preclinical large animal model of coronary chronic total occlusion (CTO) adequately mimicking human CTO pathology and biomechanics for testing of CTO-targeting therapies. A novel calcific plug model was created using powder calcium, cholesterol esters

Endoleak is defined as persistent flow of blood into the abdominal aortic aneurysm (AAA) sac after endograft placement and signifies a failure to completely exclude the aneurysm. It is present in 20-50% of patients treated with endograft implantation and is associated with continued risk for

Mechanical strength of Bioresorbable Scaffolds (BRS) is highly dependent on strut dimensions and polymer features. Thicker struts have the potential for delivery challenges and higher thrombogenicity. Due to the inherent limitations of the first-generation PLLA, reduction of wall thickness of BRS is

During the development of novel transcatheter mitral valve replacement (TMVR) technology, the discrepancy between benchtop models (i.e. silicone), animal models, and human anatomy may be overcome by using human cadaveric hearts, preferably under realistic hemodynamic conditions. The aim of this

Owing to robust inflammatory and neointimal response and exceedingly high cholesterol levels, the familial hypercholesterolemic swine (FHS) model has been very successful in predicting efficacy of peripheral antirestenotic therapies. It clearly differentiates the antiproliferative effects of drug

The speed and quality of stent/scaffold strut coverage by tissue are strongly impacted by strut thickness and shape, which influence shear stress and blood flow dynamics, affecting platelet accumulation and endothelial cell growth. In this study, we aimed to evaluate the short-term healing response

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.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.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.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.

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 2 [7.65–9.21]) compared with PES (10.95 mm 2 [9.64–12.46]) and bare metal stent (13.83 mm 2 [11.53–17.03]; P 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.

An occlusion or severe stenosis (angiographic culprit lesion) of the infarct-related artery is frequently located at the site of the maximum thrombus burden, whereas the origin of the plaque rupture (the true culprit) can be situated proximal or distal to it. The aim of this study was to examine stent coverage of true culprit lesions in 20 patients who underwent primary percutaneous coronary intervention and had Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow restored in the infarct-related artery by angiographically guided direct stenting. Images of lesions were obtained using virtual histology-intravascular ultrasound before and after intervention (blinded to the operator). Plaque rupture sites were identified by intravascular ultrasound in 12 lesions (60%), 11 proximal and 1 distal to the minimum luminal area (MLA). Maximum necrotic core sites were found proximal to the MLA in 16 lesions, at the MLA in 3 lesions, and distal to the MLA in 1 lesion. Plaque rupture sites were fully covered by stents in 11 lesions. Virtual histology-intravascular ultrasound-derived thin-cap fibroatheroma longitudinal geographic misses were found in 10 lesions, 7 in the proximal reference segment and in 3 patients in the proximal and distal reference segments. In conclusion, in about 50% of patients who undergo primary percutaneous coronary intervention for ST-segment elevation myocardial infarction with optimal angiographic results, the stent does not fully cover the maximum necrotic core site related to the culprit lesion.

Aim: To determine if three-dimensional quantitative coronary angiographic analysis (3D QCA) provides an advantage over twodimensional (2D QCA) by increasing accuracy and precision of length measurements through compensating for foreshortening inherent to 2D images. Material and methods: A total of 800 inter-marker length measurements were performed (8 per wire, 5-40 mm) with novel 3D software and standard 2D software and compared with the true lengths of the inter-marker distances on the wire in coronary vessels of 21 patients recruited. Results: 2D QCA generally underestimated true length in comparison to 3D, and the discrepancy increased with absolute length. In contrast, 3D QCA showed a minimal difference from true length over the examined range of lengths. Conclusions: 3D QCA minimizes errors in length measurements associated with foreshortening, shows minimal difference from true length, and performs significantly better in comparison to 2D QCA. The advantage of 3D QCA is more pronounced at longer lengths.

Aims: Despite recent abundance of data on drug-coated balloon technology, the biological effects of paclitaxel coated balloon (PCB) treatment followed by bare metal stent (BMS) implantation in peripheral arteries (simulating bail-out stenting, a common clinical scenario), have not been published. Methods and results: PCB technology containing a paclitaxel-iopromide coating and identical iopromide-coated controls (without paclitaxel) were used in 16 porcine ilio-femoral arteries. The biological effects of inflating one (PCBxl) or two sequential (PCBx2) paclitaxel coated balloons before BMS implantation were compared to the single application of a control balloon (CCBx1; contrast coated balloons). At 30 days PCBx2 displayed significantly reduced late lumen loss by angiography (58% reduction vs. CCBx1; p=0.04) and neointimal area by histomorphometry (35% reduction vs. CCBx1 and 30% vs. PCBx1; p-0.02). Similarly, percent area stenosis in the PCBx2 group was reduced by 45% as compared to CCBx1 and PCBx1 (p=0.04). At this time, all parameters of vessel wall healing (including injury score, inflammation, and endothelialisation) following drug coated balloon treatment were comparable to the control group. Conclusions: Paclitaxel delivery to porcine ilio-femorals using PCB followed by BMS implantation effectively decreased neointimal proliferation. More extensive and prolonged proliferative response of the vessel after stenting (necessitating higher drug dose) could potentially explain the undetectable effect of PEBx1 relative to CCBx1 in this pilot study. Histological analysis confirmed the safety and biocompatibility of PCB technology.

Few methods exist to noninvasively study in vivo gastrointestinal motility in animal models of enteric infections. None have been used on mouse pups, which often display more severe symptoms during enteric infections than adult mice. This study sought to determine whether digital fluoroscopy could be used to evaluate gastrointestinal motility in mouse pups as well as adult mice.Fluoroscopic imaging studies were performed on normal 6- to 8-week-old adult mice and 12-day-old pups to develop protocols for evaluating gastric and intestinal wall movements and changes in stomach sizes. These protocols were then applied to evaluate motility in an established rotavirus mouse model. Imaging studies were performed on adult mice at 0, 2, and 4 days postinfection and on 12-day-old pups at 2 days postinfection.Fluoroscopic studies revealed postnatal differences of gastric peristalsis and rates of intestinal contractions between normal mouse pups and adult mice. Studies of the rotavirus mouse model revealed that differences in gastric function occur between rotavirus-infected and control mouse pups, but no discernible difference occurs between infected and control adult mice. In contrast, there were no detectable differences in rates of intestinal wall movements between control pups with normal stools and infected pups with loose stools.These results demonstrate that fluoroscopy can evaluate in vivo motility in mouse pups and by doing so provide findings that are clinically relevant to the study of enteric infections in young.

Accurate sizing and stent apposition are of paramount importance to achieve an optimal stenting result. Bioresorbable scaffolds (BRS), in particular, require more rigorous implant optimization than drug eluting stent (DES) and bare metal stents (BMS) to achieve a favorable outcome. We investigated

First generation Bioresorbable Scaffolds (BRS) are more prone to mechanical failure and vascular recoil despite their redundant surface area and wall thickness (∼157-microns). The development of DES-like BRS is key for the future of this field. In this study, we tested the biological performance

Peripheral arteries are constantly exposed to external forces (elongation, twisting, shortening, compression) making this vascular territory particularly suitable for bioresorbable scaffolds (BRS). We evaluated the performance of a novel sirolimus-eluting balloon-expandable BRS (Credence BRS, Meril

Objectives: The purpose of the present study was to evaluate the efficacy and safety of a biodegradable polymer coated, paclitaxel eluting stent (Luc-Chopin2) based on 9-months angiographic and 12-months clinical follow-up results. Background: First-generation drug-eluting stents utilize nonbioabsorbable polymeric coatings, whose persistent presence in the arterial wall may negatively affect long-term outcomes. Bioabsorbable coatings with a degradation period matched to that of the drug elution may be a better alternative, clinically and economically. Methods: We conducted a prospective, multicenter first-in-man registry of a novel, locally developed, bioabsorbable-coated, paclitaxel-eluting coronary stent in 116 patients with single-lesion de novo coronary disease. Results: Major adverse cardiac events occurred in 7.8% patients within 12 months. There were no late thrombotic events, death, stroke, or surgical revascularization in that period. There were two myocardial infarctions, one related to recent subacute stent thrombosis and another associated with restenosis. By 12 months, target vessel revascularization was performed in 7.8%; 2.9% were ischemia-driven and the rest were mandated at 9 months in accordance with a control angiography protocol. Core-lab assessed binary in-stent restenosis (≥50% DS) was noted in 11.9% patients and mean late loss was 0.46 ± 0.47 mm. Conclusions: This first-in-man experience obtained in a multicenter registry of real-world de novo lesions (almost half of lesions were class B2 or C by AHA classification) showed a favorable safety profile and acceptable efficacy through 12 months. Randomized comparison with a benchmark nonbioabsorbable polymer coated paclitaxel eluting stent should be undertaken to validate this initial positive experience. © 2008 Wiley-Liss, Inc.

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

Objectives The purpose of this study was to assess the role of oral rapamycin in decreased restenosis after bare metal stent implantation. Background Small observational studies suggest that the administration of oral rapamycin reduces angiographic restenosis after bare metal stent implantation. Methods Between September 2003 and September 2004, 100 patients were randomized to either oral rapamycin (6-mg loading dose given 2.7 h before intervention followed by 3 mg/day for 14 days) plus diltiazem 180 mg/day or no therapy after the implantation of a coronary bare metal stent design. The primary study end point was incidence of angiographic binary restenosis and late loss at nine months. The secondary end points were target lesion revascularization, target vessel revascularization, and incidence of major adverse cardiovascular events at 1 year. Results Angiographic follow-up was completed in 87% of patients. In the rapamycin group, the drug was well tolerated (26% minor side effects) and was maintained in 96% of patients. At 9 months, the in-segment binary restenosis was reduced by 72% (11.6% rapamycin vs. 42.8% no-therapy group, p = 0.001) and the in-stent binary restenosis was reduced by 65% (12% rapamycin vs. 34.6% no-therapy group, p = 0.009). The in-segment late loss was also significantly reduced with oral therapy (0.66 vs. 1.13 mm, respectively; 43% reduction, p Conclusions This randomized, controlled, and unblinded study showed that the administration of oral rapamycin during 14 days after stent implantation significantly reduces angiographic and clinical parameters of restenosis.

Objective— Mitomycin C (MMc) is an antibiotic that exerts a potent antiproliferative effect in tumor cells. Because the proliferation of vascular smooth muscle cells (VSMCs) plays a prominent role in the development of restenosis after percutaneous coronary interventions, the present study examined the effect of MMc on VSMC proliferation and on neointima formation after arterial balloon injury. Methods and Results— Treatment of cultured rat aortic VSMCs with MMc (1 nmol to 30 μmol/L) inhibited VSMC proliferation in a concentration-dependent manner. Whereas high concentrations of MMc (1 to 30 μmol/L) induced VSMC apoptosis, as reflected by DNA laddering and caspase-3 activation, lower concentrations of MMc (1 to 300 nmol/L) directly inhibited VSMC growth by arresting cells in the G 2 /M phase of the cell cycle. The antiproliferative action of MMc was associated with a selective increase in the expression of the cyclin-dependent kinase inhibitor p21, and with a decrease in cyclin B1-cyclin-dependent kinase-1 complex activity. Finally, the local perivascular delivery of MMc immediately after balloon injury of rat carotid arteries induced p21 expression and markedly attenuated neointima formation. Conclusion— These studies demonstrate that MMc exerts a potent inhibitory effect on VSMC proliferation and neointima formation after arterial injury. MMc represents a potentially new therapeutic agent in treating and preventing vasculoproliferative disease.

Background Numerous medical and surgical options exist for the treatment of vessel ischemia, which some patients fail or cannot tolerate. These investigations were designed to determine the effects of lentiviral-delivered vascular endothelial-derived growth factor (VEGF) and angiopoietin-2 (Ang-2) on collateralization in a rabbit model of hindlimb ischemia. Materials and methods Self-inactivating human immunodeficiency virus (HIV)-based vectors were constructed encoding VEGF or Ang-2, co-transfected with vesicular stomatitis virus glycoprotein (VSV G) into 293T cells, and vector supernatants (1 × 10 8 IU/ml after concentration) were harvested. New Zealand white rabbits had ligation of either the right or left external iliac artery and excision of the ipsilateral femoral artery. Ten days later, empty, VEGF, or VEGF+Ang-2 vector supernatant was injected intramuscularly (IM) into the ipsilateral thigh. Ankle systolic blood pressure (SBP) ratios were recorded and venous blood samples collected on postoperative days (POD) 10, 25, and 40. On POD 40, run-off angiography was performed to measure vessel collateralization. Capillary density was determined by thin sectioning of muscle. Results A significant increase was noted in SBP in the VEGF-treated animals over time. Capillary density was not elevated despite significantly increased large vessel collateralization in rabbits receiving VEGF, which was counteracted by Ang-2. Antibodies against vector components were detected in exposed serum. Conclusions Arterial collateralization and SBP increased significantly following VEGF vector administration, which was reversed by the Ang-2 vector. Development of antibody against VSV G can limit repeated injections of vector. Future experiments will involve the addition of other pro-angiogenic factors, repeated vector administration, and alternative routes of vector delivery.