Drug-coated balloon for the treatment of small vessel disease: 9 months of angiographic results and 12 months of clinical outcomes of the PEPCAD China SVD study.

BACKGROUND: Whether the drug-coated balloons (DCBs)-alone strategy was superior to plain old balloon angioplasty (POBA) in treating SVD remains unknown. AIMS: We aimed to evaluate the efficacy and safety of DCBs for the treatment of coronary de novo small vessel disease (SVD) and provide further evidence for extending the clinical indications of DCBs. (ChiCTR1800014966). METHODS: Eligible patients were randomized at a 2:1 ratio to receive DCB treatment or POBA in this prospective, multicenter clinical trial. The reference vessel diameter of lesions was visually assessed to be 2.0 to 2.75 mm. The primary endpoint of the study was angiographic in-segment late luminal loss (LLL) at the 9-month follow-up to demonstrate the superiority of DCB treatment to POBA in SVD. The composite clinical endpoints included clinically driven target lesion revascularization (CD-TLR), target lesion failure (TLF), major adverse cardiac events (MACEs), and thrombosis at the 12-month follow-up. RESULTS: A total of 270 patients were enrolled (181 for DCB, 89 for POBA) at 18 centers in China. The primary endpoint of 9-month in-segment LLL in the intention-to-treat population was 0.10 ± 0.33 mm with DCB and 0.25 ± 0.38 mm with POBA (p = 0.0027). This difference indicated significant superiority of DCB treatment (95% CI: -0.22, -0.04, psuperiority = 0.0068). The rates of the clinical endpoints-CD-TLR, TLF, and MACEs-were comparable between groups. No thrombosis events were reported. CONCLUSIONS: DCB treatment of de novo SVD was superior to POBA with lower 9-month in-segment LLL. The rates of clinical events were comparable between the two devices.

Targeted neutrophil-mimetic liposomes promote cardiac repair by adsorbing proinflammatory cytokines and regulating the immune microenvironment.

Acute myocardial infarction (MI) induces a sterile inflammatory response that may result in poor cardiac remodeling and dysfunction. Despite the progress in anti-cytokine biologics, anti-inflammation therapy of MI remains unsatisfactory, due largely to the lack of targeting and the complexity of cytokine interactions. Based on the nature of inflammatory chemotaxis and the cytokine-binding properties of neutrophils, we fabricated biomimetic nanoparticles for targeted and broad-spectrum anti-inflammation therapy of MI. By fusing neutrophil membranes with conventional liposomes, we fabricated biomimetic liposomes (Neu-LPs) that inherited the surface antigens of the source cells, making them ideal decoys of neutrophil-targeted biological molecules. Based on their abundant chemokine and cytokine membrane receptors, Neu-LPs targeted infarcted hearts, neutralized proinflammatory cytokines, and thus suppressed intense inflammation and regulated the immune microenvironment. Consequently, Neu-LPs showed significant therapeutic efficacy by providing cardiac protection and promoting angiogenesis in a mouse model of myocardial ischemia-reperfusion. Therefore, Neu-LPs have high clinical translation potential and could be developed as an anti-inflammatory agent to remove broad-spectrum inflammatory cytokines during MI and other neutrophil-involved diseases.

Targeted delivery and ROS-responsive release of Resolvin D1 by platelet chimeric liposome ameliorates myocardial ischemia-reperfusion injury.

Resolvin D1 (RvD1) has been shown to provide effective protection against ischemia-reperfusion injury in multiple vital organs such as the heart, brain, kidney. However, the clinical translational potential of systemic administration of RvD1 in the treatment of ischemia-reperfusion injury is greatly limited due to biological instability and lack of targeting ability. Combining the natural inflammatory response and reactive oxygen species (ROS) overproduction after reperfusion injury, we developed a platelet-bionic, ROS-responsive RvD1 delivery platform. The resulting formulation enables targeted delivery of RvD1 to the injury site by hijacking circulating chemotactic monocytes, while achieving locally controlled release. In a mouse model of myocardial ischemia repefusuin (MI/R) injury, intravenous injection of our formula resulted in the enrichment of RvD1 in the injured area, which in turn promotes clearance of dead cells, production of specialized proresolving mediators (SPMs), and angiogenesis during injury repair, effectively improving cardiac function. This delivery system integrates drug bio-protection, targeted delivery and controlled release, which endow it with great clinical translational value.

Clinical Outcomes of Self-Made Polyurethane-Covered Stent Implantation for the Treatment of Coronary Artery Perforations.

OBJECTIVES: The present study aimed to investigate the short- and long-term clinical outcomes of self-made polyurethane-covered stents (PU-CS) in patients for the management of coronary artery perforation (CAP) during percutaneous coronary intervention (PCI). BACKGROUND: Coronary artery perforation is reckoned as a serious complication in PCI and associated with considerable morbidity and mortality. Covered stents have been used for treating the life-threatening CAP during PCI. But in some catheterization laboratories, no commercial CS is immediately available when there is an urgent need for CS to rescue the coronary rupture site. METHODS: We retrospectively identified 24 patients who underwent 31 self-made PU-CS implantations due to CAP in Zhongshan Hospital, Fudan University, from June 2015 to January 2020. RESULTS: The total procedural success rate of CS to seal the perforation was 79.2%. Nine patients (37.5%) developed cardiac tamponade, of which 8 patients (33.3%) underwent pericardiocentesis and 4 patients (16.7%) underwent cardiac surgeries. Except for 4 cardiac death cases (16.7%), none of myocardial infarction (MI), target lesion revascularization (TLR), and stent thrombosis (ST) was reported during hospital stay. Data from 22 patients (91.7%) were available at 610.4 ± 420.9 days of follow-up. Major adverse cardiac events (MACE) occurred in 6 patients (27.3%), including 5 cases of cardiac death and one TLR case. CONCLUSIONS: Self-made PU-CS demonstrates high rates of successful delivery and sealing of severe CAP during PCI. Although the in-hospital mortality remains high after PU-CS implantation, the long-term follow-up shows favorable clinical outcomes, indicating the feasibility of PU-CS in treating CAP.

Six-month outcomes of the XINSORB bioresorbable sirolimus-eluting scaffold in treating single de novo lesions in human coronary artery.

OBJECTIVE: We aimed to investigate short-term outcomes of the XINSORB bioresorbable sirolimus-eluting scaffold in human coronary artery. BACKGROUND: Bioresorbable scaffolds are considered to be the fourth milestone in percutaneous coronary intervention. METHODS: Thirty patients with symptomatic ischemic coronary disease were enrolled and treated with the XINSORB scaffolds that were 3.0 × 12, 15, and 18 mm in size. The primary angiographic endpoint was late luminal loss (LLL), whereas the primary clinical endpoint was major adverse cardiac events (MACEs) at the 6 month follow-up. In a subset of 19 patients, intravascular ultrasound (IVUS) and optical coherence tomography (OCT) were performed at follow-up. RESULTS: The success rates of the procedure and the device were both 100%. Twenty-seven patients received angiographic follow-up. All patients were clinically assessed. Neither MACEs nor stent thrombus-related events were recorded. The percentage of diameter stenosis at follow-up was similar to that at postprocedure. In-scaffold and periscaffold LLL were 0.17 ± 0.12 and 0.13 ± 0.24 mm, respectively. No in-stent restenosis was detected. IVUS showed that the mean areas of the lumen, scaffold, and neointima at follow-up were 6.27 ± 0.69, 6.48 ± 0.70, and 0.20 ± 0.09 mm(2) , while in-device stenosis was 3.1 ± 1.3%. OCT showed that 97.9% of the struts presented a preserved box, while 2.1% had an open box after 6 months. A total of 95.9% of the struts were covered by neointima. CONCLUSIONS: This first-in-human study demonstrates the effectiveness and safety of the XINSORB scaffold in treating single de novo coronary lesions.

Genetically Engineered Macrophages Co-Loaded with CD47 Inhibitors Synergistically Reconstruct Efferocytosis and Improve Cardiac Remodeling Post Myocardial Ischemia Reperfusion Injury.

Efferocytosis, mediated by the macrophage receptor MerTK (myeloid-epithelial-reproductive tyrosine kinase), is a significant contributor to cardiac repair after myocardial ischemia-reperfusion (MI/R) injury. However, the death of resident cardiac macrophages (main effector cells), inactivation of MerTK （main effector receptor), and overexpression of "do not eat me" signals (brake signals, such as CD47), collectively lead to the impediment of efferocytosis in the post-MI/R heart. To date, therapeutic strategies targeting individual above obstacles are relatively lacking, let alone their effectiveness being limited due to constraints from the other concurrent two. Herein, inspired by the application research of chimeric antigen receptor macrophages (CAR-Ms) in solid tumors, a genetically modified macrophage-based synergistic drug delivery strategy that effectively challenging the three major barriers in an integrated manner is developed. This strategy involves the overexpression of exogenous macrophages with CCR2 (C-C chemokine receptor type 2) and cleavage-resistant MerTK, as well as surface clicking with liposomal PEP-20 (a CD47 antagonist). In MI/R mice model, this synergistic strategy can effectively restore cardiac efferocytosis after intravenous injection, thereby alleviating the inflammatory response, ultimately preserving cardiac function. This therapy focuses on inhibiting the initiation and promoting active resolution of inflammation, providing new insights for immune-regulatory therapy.

Long-term clinical outcomes of drug-coated balloon for the management of chronic total occlusions.

OBJECTIVES: This study aims to compare the clinical outcomes of patients with de novo chronic total occlusion (CTO) lesions treated by hybrid strategy and drug-coated balloons (DCB)-only strategy. BACKGROUNDS: DCBs have been used as an alternative to or in combination with drug-eluting stents in CTO lesions. However, the clinical impact of DCB treatment on CTO lesion remains uncertain. METHODS: We retrospectively enrolled 154 patients with de novo CTO lesions treated by DCB, including 57 cases in hybrid group and 97 cases in DCB-only group. RESULTS: The lesions in hybrid group were more complicated than those in DCB-only group as shown by higher J-CTO score, and therefore higher percentage of retrograde approach, more IVUS guidance, more CTO guidewires, and longer procedural time were demonstrated. Although the percentage of non-flow-limiting dissection and residual stenosis of more than 30% were lower in hybrid group, TIMI flow grade, satisfactory and acceptable recanalization rate were not significantly different between two groups. During a median follow-up was 470 days, the incidence of target lesion revascularization (TLR), myocardial infarction and cardiac death was 11.0%, 1.3% and 1.9%, respectively. The long-term TLR-free survival was comparable between hybrid and DCB-only groups. By multivariate analysis, DCB length and age were predictors of TLR. CONCLUSION: DCB treatment appears effective and safe in selected de novo CTO lesions during long-term follow up. The recanalization results and long-term outcomes are comparable between hybrid and DCB-only group despite more complicated lesions in hybrid group.

Platelet Membrane-Coated Nanoparticles Target Sclerotic Aortic Valves in ApoE-/- Mice by Multiple Binding Mechanisms Under Pathological Shear Stress.

BACKGROUND: Aortic valve disease is the most common valvular heart disease leading to valve replacement. The efficacy of pharmacological therapy for aortic valve disease is limited by the high mechanical stress at the aortic valves impairing the binding rate. We aimed to identify nanoparticle coating with entire platelet membranes to fully mimic their inherent multiple adhesive mechanisms and target the sclerotic aortic valve of apolipoprotein E-deficient (ApoE-/-) mice based on their multiple sites binding capacity under high shear stress. METHODS: Considering the potent interaction of platelet membrane glycoproteins with components present in sclerotic aortic valves, platelet membrane-coated nanoparticles (PNPs) were synthetized and the binding capacity under high shear stress was evaluated in vitro and in vivo. RESULTS: PNPs demonstrated effectively adhering to von Willebrand factor, collagen and fibrin under shear stresses in vitro. In an aortic valve disease model established in ApoE-/- mice, PNPs exhibited good targeting to sclerotic aortic valves by mimicking platelet multiple adhesive mechanisms. CONCLUSION: PNPs could provide a promising platform for the molecular diagnosis and targeting treatment of aortic valve disease.

Twelve-month angiographic and clinical outcomes of the XINSORB bioresorbable sirolimus-eluting scaffold and a metallic stent in patients with coronary artery disease.

BACKGROUND: Recent studies showed bioresorbable scaffold (BRS) increased risks of late target lesion failure (TLF) and thrombosis. XINSORB scaffold is a poly-L-lactic acid based BRS. METHODS: The study included randomization and registry parts. Eligible patients with one or two de novo lesions were randomly 1:1 assigned to XINSORB scaffold and sirolimus-eluting stent (SES) in randomization part. These patients were clinically and angiographically assessed. In registry part, patients were treated with XINSORB scaffold only and were clinically assessed. The primary endpoint was in-segment late luminal loss (LLL) at 12-month in randomization part. The secondary endpoint was 12-month TLF in all XINSORB-treated patients. RESULTS: Total 395 and 798 patients were enrolled in randomization and registry part, respectively. Device success was 98.0% (1069/1091) in all XINSORB-treated and 100% (221/221) in SES-treated lesions. The primary endpoint of in-segment LLL at 12-month was 0.19 ±â€¯0.32 mm in XINSORB and 0.31 ±â€¯0.41 mm in SES (P = 0.003), which met the noninferior margin of 0.195 mm (95% CI: -0.20, -0.04, P ≪ 0.0001). No difference was found in TLF between two devices. In all XINSORB-treated patients, 12-month TLF was 0.8% (8/998), which also met the noninferior margin of 9.0% (95% CI: 0.3%, 1.4%, P ≪ 0.0001). Only one device thrombosis was recorded in all XINSORB-treated patients while none in SES. CONCLUSIONS: In the multicenter clinical trial, XINSORB BRS was noninferior to sirolimus-eluting stent for the primary endpoint of in-segment LLL at 12-month in patients with simple and moderate complex de novo coronary lesions. TLF at 12-month was low and comparable.

A head to head comparison of XINSORB bioresorbable sirolimus-eluting scaffold versus metallic sirolimus-eluting stent: 180 days follow-up in a porcine model.

We aimed to investigate the safety and efficacy of XINSORB bioresorbable sirolimus-eluting scaffold in porcine model. XINSORB scaffolds and metallic Firebird2™ stents were randomly implanted into minipigs' coronary arteries. Angiography, optical coherent tomography (OCT) and histopathological analyses were performed at post-procedure and 14-, 28-, 90-, 180-day follow-up. Thirty-two minipigs were enrolled. Eight XINSORB scaffolds and 8 Firebird2 stents were examined at each time point. Quantitative coronary angiography showed that in-scaffold late luminal loss (LLL) of XINSORB scaffold was 0.26 ± 0.13, 0.50 ± 0.16, 0.88 ± 0.29 and 0.43 ± 0.24 mm at 14-, 28, 90-, and 180-day follow-up respectively, and the corresponding diameter stenosis (DS) was 7.3 ± 4.7, 12.0 ± 9.5, 22.1 ± 8.0, and 16.0 ± 9.5%. Neither in-scaffold LLL nor DS of XINSORB scaffold was significantly different in comparison with Firebird2 stent. No difference of luminal area, device area, neointimal hyperplasia, and area stenosis was detected between two devices under OCT. Scaffold area of XINSORB remained steady through the observation. Histopathology revealed the similar findings. The greatest late recoil of XINSORB scaffold was about 4.12% at 90-day follow-up, which was comparable to Firebird2 stent. Both devices showed low injury or inflammation of vessel wall. XINSORB scaffold showed early neointimal coverage on struts within 28 days under scanning electron microscopy. XINSORB scaffold suppressed neointimal hyperplasia as effectively as Firebird2 did without obvious late device recoil during the 180 days follow-up. It is feasible to carry out clinical trial to investigate the safety and efficacy of XINSORB scaffold for patients with coronary artery diseases.

Bone marrow CD34+ cell subset under induction of moderate stiffness of extracellular matrix after myocardial infarction facilitated endothelial lineage commitment in vitro.

BACKGROUND: The stiffness of the myocardial extracellular matrix (ECM) and the transplanted cell type are vitally important in promoting angiogenesis. However, the combined effect of the two factors remains uncertain. The purpose of this study is to investigate in vitro the combined effect of myocardial ECM stiffness postinfarction with a bone marrow-derived cell subset expressing or not expressing CD34 on endothelial lineage commitment. METHODS: Myocardial stiffness of the infarct zone was determined in mice at 1 h, 24 h, 7 days, 14 days, and 28 days after coronary artery ligation. Polyacrylamide (PA) gel substrates of different stiffnesses were prepared to mechanically mimic the myocardial ECM after infarction. Mouse bone marrow-derived CD34+ and CD34- cells were seeded on the flexible PA gels. The double-positive expression for DiI-acetylated low-density lipoprotein (acLDL) uptake and fluorescein isothiocyanate-Ulex europaeus agglutinin-1 (FITC-UEA-1) binding, the endothelial lineage antigens CD31, von Willebrand factor (vWF), Flk-1, and VE-cadherin, as well as cytoskeleton were measured by immunofluorescent staining on day 7. Cell apoptosis was evaluated by both immunofluorescent staining and flow cytometry at 24 h after culture. RESULTS: We found that the numbers of the CD34+ cell subset adherent to the flexible substrates (4-72 kPa) was much larger than that of the CD34- subset. More double-positive cells for DiI-acLDL uptake/FITC-UEA-1 binding were seen on the 42-kPa (moderately stiff) substrate, corresponding to the stiffness of myocardial ECM at 7-14 days postinfarction, compared with those on substrates of other stiffnesses. Similarly, the moderately stiff substrate showed benefits in promoting the positive expressions of the endothelial lineage markers CD31, vWF, Flk-1, and VE-cadherin. In addition, the cytoskeleton F-actin network within CD34+ cells was organized more significantly at the leading edge of the adherent cells on the moderately stiff (42 kPa) or stiff (72 kPa) substrates as compared with those on the soft (4 kPa and 15 kPa) substrates. Moreover, the moderately stiff or stiff substrates showed a lower percentage of cell apoptosis than the soft substrates. CONCLUSIONS: Infarcted myocardium-like ECM of moderate stiffness (42 kPa) more beneficially regulated the endothelial lineage commitment of a bone marrow-derived CD34+ subset. Thus, the combination of a CD34+ subset with a "suitable" ECM stiffness might be an optimized strategy for cell-based cardiac repair.

Delivery of alginate-chitosan hydrogel promotes endogenous repair and preserves cardiac function in rats with myocardial infarction.

The regenerative potential of alginate-chitosan composite in bone and cartilage tissue has been well documented, but its potential utility in cardiac tissue engineering has remained unknown. This study sought to determine whether early intramyocardial injection of alginate-chitosan could prevent left ventricular (LV) remodeling after myocardial infarction (MI), leading to a more favorable course of tissue restoration. In a rat model of acute MI, local injection of alginate-chitosan hydrogel into the peri-infarct zone preserved scar thickness, attenuated infarct expansion, and reduced scar fibrosis after 8 weeks, concomitantly with promoting increased angiogenesis and greater recruitment of endogenous repair at the infarct zone. Furthermore, this treatment prevented cell apoptosis, induced cardiomyocyte cell cycle re-entry. The cardiac function of the control-injected animals deteriorated over the 8-week course, while that of the hydrogel-injected animals did not.In addition, the hydrogel did not exacerbate inflammation in the heart. Intramyocardial injection of alginate-chitosan hydrogel represents a useful strategy to treat MI. It demonstrated marked therapeutic efficacies on various tissue levels after extensive MI, as well as potential to induce endogenous cardiomyocyte proliferation and recruit cardiac stem cells.

Nine-month angiographic and two-year clinical follow-up of novel biodegradable-polymer arsenic trioxide-eluting stent versus durable-polymer sirolimus-eluting stent for coronary artery disease.

BACKGROUND: Despite great reduction of in-stent restenosis, first-generation drug-eluting stents (DESs) have increased the risk of late stent thrombosis due to delayed endothelialization. Arsenic trioxide, a natural substance that could inhibit cell proliferation and induce cell apoptosis, seems to be a promising surrogate of sirolimus to improve DES performance. This randomized controlled trial was to evaluate the efficacy and safety of a novel arsenic trioxide-eluting stent (AES), compared with traditional sirolimus-eluting stent (SES). METHODS: Patients with symptoms of angina pectoris were enrolled and randomized to AES or SES group. The primary endpoint was target vessel failure (TVF), and the second endpoint includes rates of all-cause death, cardiac death or myocardial infarction, target lesion revascularization (TLR) by telephone visit and late luminal loss (LLL) at 9-month by angiographic follow-up. RESULTS: From July 2007 to 2009, 212 patients were enrolled and randomized 1:1 to receive either AES or SES. At 2 years of follow-up, TVF rate was similar between AES and SES group (6.67% vs. 5.83%, P = 0.980). Frequency of all-cause death was significantly lower in AES group (0 vs. 4.85%, P = 0.028). There was no significant difference between AES and SES in frequency of TLR and in-stent restenosis, but greater in-stent LLL was observed for AES group (0.29 ± 0.52 mm vs. 0.10 ± 0.25 mm, P = 0.008). CONCLUSIONS: After 2 years of follow-up, AES demonstrated comparable efficacy and safety to SES for the treatment of de novo coronary artery lesions.

Anti-inflammatory effects of arsenic trioxide eluting stents in a porcine coronary model.

Previous research from our group has demonstrated arsenic trioxide eluting stents significantly reduced neointimal area and thickness compared with bare metal stents. In the present study, the anti-inflammatory effects of arsenic trioxide in vitro and arsenic trioxide eluting stents in a porcine coronary model have been explored. Sixty-five pigs underwent placement of 139 oversized stents in the coronary arteries with histologic analysis, endothelial function analysis, and immunohistochemical and western blot analyses. Arsenic trioxide eluting stents effectively inhibited local inflammatory reactions, while no significant difference in endothelialization and endothelial function between arsenic trioxide eluting stents and bare metal stents was observed. Arsenic trioxide eluting stents favorably modulate neointimal formation due to less augmentation of early inflammatory reactions, and quick endothelialization of the stent surface, which might contribute to long-term safety and efficacy of drug eluting stents.

Real-world use of the second-generation cobalt-chromium sirolimus-eluting stents: 12-month results from the prospective multicentre FOCUS registry.

AIMS: The FOCUS registry is a prospective, multicentre, web-based programme designed to collect clinical outcome data from real-world patients receiving the second-generation cobalt-chromium sirolimus-eluting stent (CoCr-SES). METHODS AND RESULTS: From March 2009 to February 2010, a total of 5,084 patients from 83 centres who were eligible to receive CoCr-SES were enrolled in the FOCUS registry. The primary endpoint was 12-month major adverse cardiac events (MACE, defined as the composite of cardiac death, myocardial infarction [MI], and target vessel revascularisation [TVR]). One-year data were available for 5,013 (98.6%) of the 5,084 patients enrolled. The primary endpoint occurred in 174 (3.47%) of 5,013 patients, consisting of 43 (0.86%) cardiac deaths, 132 (2.63%) MI, and 46 (0.92%) TVR. According to the Academic Research Consortium definition, definite and probable stent thrombosis (ST) occurred in 0.52% (26/5,013) of patients, including 19 cases of early ST and 7 of late ST. The 12-month MACE rates were 3.73% and 2.60% for extended-use and standard-use patients, respectively (p=0.065). CONCLUSIONS: The second-generation CoCr-SES was associated with low rates of 12-month MACE and ST in a broad spectrum of patients, thereby confirming the clinical safety and efficacy of this stent in a real-world setting.

Safety and efficacy of cobalt chromium alloy based sirolimus-eluting stent with bioabsorbable polymer in porcine model.

BACKGROUND: First generation drug-eluting stents (DESs) were based on 316L stainless steel and coated with a permanent polymer. The vessel wall of these DESs was inflammatory and late in-stent thrombosis was reported. Hence, cobalt chromium based DES coated with a bioabsorbable polymer was an alternate choice. METHODS: Cobalt chromium based DES with bioabsorbable polymer (Simrex stent) as well as control stents (Polymer stent and EXCEL(TM) stent) were implanted into porcine arteries. At a designated time, angiography, quantitative coronary angiography (QCA) analysis, histomorphometry, and electron-microscopical follow-up were performed. RESULTS: A total of 98 stents of all the three groups were harvested. At week 24, percent diameter stenosis (%DS), late loss (LL), and percent area stenosis (%AS) of Simrex was (12.9 ± 0.4)%, (0.35 ± 0.02) mm, and (24.5 ± 4.2)%, respectively, without significant difference in comparison to commercialized EXCEL(TM) stent. Slight inflammatory reaction was seen around the stent strut of Simrex, just as in the other two groups. Electron-microscopical follow-up suggested that it might take 4 - 12 weeks for Simrex to complete its re-endothelialization process. CONCLUSIONS: Cobalt chromium based, bioabsorbable polymer coated sirolimus-eluting stent showed excellent biocompatibility. During 24 weeks observation in porcine model, it was proved that this novel DES system successfully inhibited neointima hyperplasia and decreased in-stent stenosis. It is feasible to launch a clinical evaluation to improve the current prognosis of DES implantation.

Assessment of an asymmetrical coating stent with sirolimus released from ablumial matrix in porcine model.

BACKGROUND: Delayed endothelialization contributes to stent thrombosis of current drug-eluting stents. The asymmetrical coating technique provides an anti-proliferative effect abluminally without affecting luminal endothelialization. Layer-by-layer self-assembled chitosan/heparin (C/H LBL) has been proved to promote re-endothelialization. A novel stent system, C/H LBL coated luminally and sirolimus released abluminally (C/H LBL-SES), was fabricated. METHODS: Bare metal stents (BMS), traditionally circumferential sirolimus-eluting stents (SES), and C/H LBL-SES were implanted into porcine coronary arteries. At the 7, 14 and 28 days follow-up (FU), angiography, intravascular ultrasound (IVUS), vasomotor function induced by acetylcholine (Ach), scanning-electron microscopy and histopathology were performed. Remodeling index (RI) was based on IVUS and defined as cross-sectional area (CSA) of vessel at in-stent segment divided by CSA of reference vessel and expressed as a percentage with a normal range from 0.95 to 1.05. RESULTS: Thirty-eight mini pigs were enrolled and 74 stents (BMS = 23, C/H LBL = 28, SES = 23) were implanted in this study. At 28 days after implantation, the diameter stenosis of C/H LBL-SES by quantitative coronary angiography was 18.8 ± 2.5 %, the area stenosis by histomorphometry was 24.2 ± 2.9 %, which were comparable to that of SES and superior to BMS. At 14 days, re-endothelialization of C/H LBL-SES was almost completed, while only about 50 % of surface of SES was covered by endothelium. At 7, 14 and 28 days FU, although C/H LBL-SES suffered a greater vasoconstriction induced by Ach infusion than BMS (P < 0.05), it behaved better than SES (P < 0.01). No sign of stent malapposition was detected, while RI was within the normal range by IVUS. No acute or subacute thrombotic events occurred in all three groups. CONCLUSIONS: The asymmetrically designed C/H LBL-SES successfully inhibited neointima hyperplasia, while diminishing vasoconstriction after Ach-stress. Endothelialization of C/H LBL-SES was less affected compared with traditionally circumferentially coated SES.