sirolimus and Neointima

The present manuscript reviews the mechanism of action of drug-coated balloons (DCBs), offering a brief summary of the main clinical evidence on these devices.. DCBs are regular semi-compliant balloons coated with antiproliferative agents that are rapidly released on contact with the vessel intima, exerting an anti-restenotic effect. This technology may offer some benefits of drug-eluting stents, in particular for the treatment of restenotic lesions, small vessels, and in patients at high-bleeding risk, when the prolonged dual antiplatelet regimen should be avoided. Most recent data have pointed to a possible benefit of these devices in treating bare metal stents (BMS) or drug-eluting stents in-stent restenosis (DES ISR), effectively reducing the recurrence of restenosis and avoiding additional layers of metal in the same coronary segment. In other clinical scenarios such as bifurcations, small vessels, and de novo lesions, data is more scarce and the benefits are still unclear. There are potential benefits related to the use of DCB in selected populations. However, larger clinical trials with longer follow-up are still needed to confirm the enthusiastic initial results.

Topics: Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Equipment Failure; Foreign-Body Migration; Humans; Neointima; Paclitaxel; Prosthesis Design; Sirolimus; Stents; Treatment Outcome

Current generations of monotherapy drug-eluting stents only inhibit neointimal hyperplasia. However, these stent designs have other drawbacks such as delayed arterial healing, hypersensitivity, late stent thrombosis, and neoatherosclerosis, creating a need for a new generation of safer devices. The novel 'pro-healing' COMBOTM dual therapy stent aims to address these issues by reducing neointimal hyperplasia via an abluminal bioabsorbable polymer eluting sirolimus, and by simultaneously capturing circulating endothelial progenitor cells via luminally immobilized anti-CD34+ antibodies. Short-term preclinical data shows promising results as compared to 1st generation and 2nd generation drug-eluting stents; however long-term literature remains unavailable until now. This review aims to evaluate, histopathologically, drawbacks of the current era of stents at autopsy, review short-term preclinical and clinical data from the REMEDEE trial, and present original long-term preclinical data. To date, preclinical data shows good performance of the COMBOTM stent comparable with the safety profile of bare metal stents with minimal inflammation, increased endothelialization, and acceptable neointimal hyperplasia with no statistical evidence of late catch-up. Clinical data from the REMEDEE trial at 12 months shows non-inferiority to paclitaxel drug-eluting stents, no evidence of late stent thrombosis, and a low rate of adverse clinical events.

Topics: Antibodies, Monoclonal; Antigens, CD34; Drug-Eluting Stents; Endothelial Progenitor Cells; Humans; Neointima; Paclitaxel; Polymers; Prosthesis Design; Sirolimus; Thrombosis

Exaggerated neointimal hyperplasia is considered as the primary mechanism for increased restenosis in patients with diabetes mellitus (DM) treated with bare-metal stent. However, the vessel response in DM and non-DM treated with different drug-eluting stents (DES) has not been systematically evaluated.. We investigated 3D intravascular ultrasound (postprocedure and 6 to 9 months) in 971 patients (267 with DM and 704 without DM) treated with sirolimus- (n=104), paclitaxel- (n=303), zotarolimus- (n=391), or everolimus- (n=173) eluting stents. Volumetric data were standardized by length as volume index (VI). At postprocedure, lumen VI at the stented segment was significantly smaller in DM than in non-DM, whereas vessel VI was similar between the 2 groups. At follow-up, neointimal obstruction and maximum cross-sectional narrowing (neointimal area/stent area) were not significantly different between the 2 groups with no interaction for the DES type. Consequently, lumen VI was smaller in DM than in non-DM at follow-up. In the reference segments, residual plaque burden at postprocedure was significantly greater in DM than in non-DM, although change in lumen VI was similar between the 2 groups. The arterial responses at the reference segments also showed no interaction for the DES type.. DM and non-DM lesions showed similar vessel response in both in-stent and reference segments regardless of the DES type. In the DES era, the follow-up lumen in DM patients seems to be determined primarily by the smaller lumen at postprocedure rather than exaggerated neointima within the stent or plaque proliferation at the reference segments.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Diabetes Mellitus; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Linear Models; Male; Middle Aged; Multicenter Studies as Topic; Multivariate Analysis; Neointima; Paclitaxel; Predictive Value of Tests; Prosthesis Design; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional

The benefit of drug-eluting stents (DES) is the remarkable reduction in the rates of both restenosis and target lesion revascularization. However, the risk of thrombotic complications extends further in DES-implanted arteries compared with those treated with bare-metal stents (BMS). Moreover, in-stent thrombosis (IST) and delayed arterial healing in DES-treated arteries have been identified by histological examination. At autopsy, proliferation of a monolayer composed of endothelium-like cells over stent struts in DES receiving arteries has been observed; however, these cells are negative for well-accepted endothelial cell markers. An inflammatory reaction against the stent struts is apparent after implantation of BMS and paclitaxel-eluting stents, whereas after sirolimus-eluting stents (SES), minimal inflammation is seen up to 6 months after device implantation. IST and in-stent restenosis, both possibly related to a hypersensitivity phenomena, are peculiar to DES, albeit relatively infrequent. A case of enhanced neointimal hyperplasia at 6 months after SES implantation with massive inflammatory reaction including eosinophils, and fibrin deposition is reported here. Observation of the morphological alterations after DES implantation by imaging techniques may furnish important information, but lack of precise comparative data between vascular imaging and histopathology leads to improper interpretation of imaging. Ex vivo imaging using angioscopy, intravascular ultrasound, and optical coherency tomography of SES implantation is presented and the images are compared with the corresponding pathological section.

Topics: Coronary Vessels; Drug-Eluting Stents; Humans; Hyperplasia; Inflammation; Neointima; Paclitaxel; Risk Factors; Sirolimus; Thrombosis

This study aimed to compare the strut coverage between Orsiro ultrathin struts biodegradable polymer sirolimus-eluting stents (O-SES) and Xience thin struts durable polymer everolimus-eluting stents (X-EES) in acute coronary syndrome (ACS) patients using optical coherence tomography (OCT). In BIOSTEMI trial, O-SESs were superior to X-EESs with respect to target lesion failure in ACS patients. However, there were few reports comparing intravascular imaging between the two stents in ACS. Between August 2016 and February 2020, 49 lesions from 49 ACS patients who underwent OCT-guided percutaneous coronary intervention were enrolled. We compared vascular healing using OCT between O-SESs and X-EESs at 8 months after stenting. The protocol was approved by the Osaka Rosai Hospital ethics committee. Among 49 lesions, the X-EES group consisted of 24 lesions and the O-SES of 25 lesions. The percentage of covered strut, the percentage of malapposed strut and mean neointimal thickness at 8 months were evaluated. In the 8-month OCT analysis, the proportion of covered strut was significantly higher in the O-SES group than in in the X-EES group (97.3% vs. 92.5%; p = 0.010). On the other hand, there were no significant differences in the frequency of malapposed strut (0.4% vs 0.3%, p = 0.609). The O-SES group had the significantly thinner neointima compared to the X-EES group (60 μm vs 84 μm, p = 0.001). Compared to X-EESs, O-SESs showed better strut coverage and thinner neointima in ACS patients at 8 months follow-up. Ultra-thin strut and silicon carbide passive coating may play a key role in better vascular healing.

Topics: Absorbable Implants; Acute Coronary Syndrome; Coronary Vessels; Drug-Eluting Stents; Humans; Neointima; Percutaneous Coronary Intervention; Polymers; Sirolimus; Tomography, Optical Coherence; Treatment Outcome

The pathomechanisms underlying restenosis of the bioabsorbable sirolimus-eluting metallic scaffold (Magmaris) remain unknown. Using serial optical coherence tomography, we investigated causes of restenosis, including the contribution of late scaffold recoil versus neointimal hyperplasia.. Patients enrolled in BIOSOLVE-II undergoing serial angiography and optical coherence tomography (post-intervention and follow-up: 6 months and/or 1 year) were analyzed. Patients were divided into 2 groups according to angiographic in-scaffold late lumen loss (LLL) <0.5 or ≥0.5 mm. End points were late absolute scaffold recoil and neointimal hyperplasia area as assessed by optical coherence tomography.. In addition to neointimal hyperplasia, late scaffold recoil contributed significantly to LLL of sirolimus-eluting absorbable metal scaffolds. The extent of late scaffold recoil was dependent on the underlying plaque morphology and was the highest among fibrotic lesions. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01960504.

Topics: Absorbable Implants; Aged; Cardiovascular Agents; Coronary Restenosis; Coronary Vessels; Female; Fibrosis; Humans; Male; Metals; Middle Aged; Myocardial Ischemia; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Given the characteristic differences between intravascular ultrasound (IVUS) and optical frequency domain imaging (OFDI), their approach to therapeutic guidance during percutaneous coronary interventions (PCIs) and arterial healing response after stenting may also vary.. MISTIC-1 (The Multimodality Imaging Study in Cardiology cohort 1) is a multicenter, randomized-controlled, noninferiority trial that compared imaging end points between OFDI- and IVUS-guided PCI. Patients with stable coronary artery disease were randomly assigned to either OFDI- or IVUS-guided PCI using a Biolimus A9-eluting stent according to a prespecified protocol for imaging guidance. Stent sizing was based on external elastic lamina in IVUS-guided PCI while lumen up-size in OFDI-guided PCI. Postprocedural OFDI was investigated regardless of randomization, while operators in IVUS-guided PCI arm were blinded to the images. The primary end point was in-segment minimum lumen area assessed using OFDI at 8 months, while the secondary end point was a composite of cardiovascular mortality, target-vessel myocardial infarction, or target-lesion revascularization (device-oriented composite end point). Patients were followed up to 3 years after the index procedure.. OFDI-guided PCI was not inferior to IVUS-guided PCI in terms of in-segment minimum lumen area at 8 months. Although a small sample size was acknowledged, OFDI could be an alternative to IVUS when considering intracoronary imaging-guided PCI in selected populations with coronary artery diseases. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03292081.

Topics: Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Japan; Male; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

To show non-inferiority of the 67- or 87 µm thick, sirolimus-eluting Orsiro drug eluting stent (DES) to the 122 µm thick, biolimus-eluting Nobori DES regarding size of vessel lumen outside the stent at 13-month follow-up.. This study was a substudy to the SORT-OUT VII trial, a prospective, 1:1-randomized, comparison of the two stents in patients with stable coronary artery disease or acute coronary syndrome. Optical coherence tomography was acquired after percutaneous coronary intervention and at 13-month follow-up. The substudy was powered to access non-inferiority (Δ = 0.60 mm2) of the Orsiro DES to the Nobori DES for the primary endpoint of mean extra stent lumen (ESL) i.e. vessel lumen outside the stent at 13-month follow-up. We randomized 124 patients to Orsiro (n = 60) or Nobori (n = 64). Due to a difference in the one-sided 95%-confidence interval of 0.26 mm2, but increased to 0.82 mm2 after appropriate log-transformation, it could not be rejected that Orsiro exceeded the non-inferiority limit. Testing for superiority, Orsiro had a significantly larger mean ESL at follow-up (Orsiro: 0.11 mm2 [0.02;0.30] mm2, Nobori: 0.03 mm2 [0.00;0.17] mm2, P = 0.04). Stent strut coverage was, Orsiro: 97.6 % [93.8;99.4]%, and Nobori: 96.3 % [90.5;98,6]% (P = 0.13).. Orsiro DES had a significantly larger mean ESL at follow-up and it could not be excluded that Orsiro exceeded the limit for non-inferiority. Nobori DES had a more heterogeneous distribution of neointima but stent strut coverage did not differ significantly between the two stents.

Topics: Absorbable Implants; Angioplasty, Balloon, Coronary; Coronary Stenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Neointima; Normal Distribution; Polymers; Prospective Studies; Prosthesis Design; Reference Values; Risk Assessment; Severity of Illness Index; Sirolimus; Statistics, Nonparametric; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Vascular Patency

Drug-eluting stents with biodegradable polymer coatings have shown promising outcomes in randomised studies.. We compared neointimal healing patterns including strut coverage and assessed neointimal maturity using a novel algorithm in coronary lesions treated with sirolimus-eluting stents with biodegradable polymer coating (BP-SES) or everolimus eluting stents with permanent polymer coating (PP-EES) using optical coherence tomography after 6months.. A total of 39 patients were randomised to BP-SES (n=19) or PP-EES (n=20) for the treatment of coronary lesions. Of those, 29 patients (14 BP-SES and 15 PP-EES) underwent optical coherence tomography (OCT) and angiography at 6-month follow-up. Tissue coverage and apposition were assessed in a total of 6162 struts (BP-SES, n=2889; PP-EES, n=3273). Neointimal maturity was assessed in 3672 neointimal regions above struts using grey scale intensity analysis. OCT analysis showed neointimal coverage of 2433 (BP-SES) vs. 2702 (PP-EES) struts (84.2% vs. 82.6%, p=0.70), whereas the remainder was uncovered after 6months. Mean neointimal thickness did not differ significantly between groups (54.3±7.8μm vs. 80±14.6μm, p=0.12). The rate of malapposed struts was comparable between groups (1.3% vs. 2.2%, p=0.27). Grey scale signal intensity analysis showed mature tissue coverage of struts in 46.2% in BP-SES vs. 31.8% in PP-EES (p=0.31) of neointimal regions.. The present study showed comparable early vascular healing response characterised by neointimal coverage with mainly immature neointima in both BP-SES and PP-EES.

Topics: Absorbable Implants; Aged; Aged, 80 and over; Coronary Artery Disease; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Polymers; Sirolimus; Tomography, Optical Coherence

Durable polymers used in drug-eluting stents are considered a potential cause of hypersensitivity inflammatory response adversely affecting stent healing. Using a sequential follow-up with optical coherence tomography, we compared the differences in healing profiles of 2 drug-eluting stents with a biodegradable or durable polymer.. Sixty patients with multivessel disease were prospectively enrolled to receive both study stents, which were randomly assigned to 2 individual vessels, a Resolute Integrity zotarolimus-eluting stent with a durable BioLinx polymer and a BioMatrix NeoFlex Biolimus A9-eluting stent with a biodegradable polylactic acid polymer. Optical coherence tomography was performed at baseline, then in 5 randomly assigned monthly groups at 2 to 6 months, and at 9 months in all patients. The primary end point was the difference in optical coherence tomography strut coverage at 9 months. Key secondary end points included angiographic late lumen loss and composite major adverse cardiac events (cardiac death, myocardial infarction, target lesion revascularization, and definite or probable stent thrombosis) at 9 months. Resolute Integrity zotarolimus-eluting stent showed significantly better strut coverage than BioMatrix NeoFlex Biolimus A9-eluting stent at 2 to 6 months (. Despite having a durable polymer, Resolute Integrity zotarolimus-eluting stent exhibited better strut coverage than BioMatrix NeoFlex Biolimus A9-eluting stent having a biodegradable polymer; both showed similar antiproliferative efficacy. This novel, longitudinal, sequential optical coherence tomography protocol using each patient as own control could achieve conclusive results in small sample size.. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01742507.

Topics: Absorbable Implants; Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Hong Kong; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Durable polymer drug-eluting stents (DP-DES) may contribute to persistent inflammation, delayed endothelial healing and subsequent late DES thrombosis. The aim of this optical coherence tomography (OCT) substudy was to compare healing and neointimal coverage of a novel bioabsorbable polymer sirolimus-eluting stent (Firehawk®) (BP-DES) versus the DP-DES (XIENCE) at 90 days in an all-comers patient population.. The TARGET All Comers study is a prospective multicentre randomised post-market trial of 1,656 patients randomised 1:1 to Firehawk or XIENCE at 21 centres in 10 European countries. The TARGET OCT substudy enrolled 36 consecutive patients with 52 lesions at six centres proficient in OCT. Follow-up OCT was performed at three months or prior to revascularisation when occurring before the three-month window. The substudy was designed for non-inferiority of the primary endpoint of neointimal thickness. At follow-up, the mean neointimal thickness by OCT (52 lesions: Firehawk, n=24; XIENCE, n=28), was not significantly different between groups (Firehawk 75.5 μm vs. XIENCE V 82.3 μm) meeting the primary endpoint of non-inferiority (pnoninferiority<0.001). The percentage of stent strut coverage was high in both groups (strut level: 99.9±0.3% vs. 100±0.1%, p=0.26), and the proportion of malapposed struts (1.0±1.6% vs. 1.2±2.0%, p=0.51) was low in both groups.. Based on OCT, the Firehawk BP-DES has a similar healing response three months after implantation compared to the DP-DES, with near complete strut coverage, moderate neointima formation and minimal strut malapposition.

Topics: Atherosclerosis; Chromium; Cobalt; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Europe; Humans; Neointima; Prospective Studies; Prosthesis Design; Sirolimus; Stents; Tomography, Optical Coherence; Treatment Outcome

Balloon dilatation or debulking seems to be essential to allow successful stent implantation in calcified coronary lesions. Compared with standard balloon predilatation, debulking using high-speed rotational atherectomy (RA) is associated with higher initial procedural success albeit with higher in-stent late lumen loss at intermediate-term follow-up. Whether modified (scoring or cutting) balloons (MB) could achieve similar procedural success compared with RA is not known. In addition, whether new-generation drug-eluting stents could counterbalance the excessive neointimal proliferation triggered by RA remains to be determined.. We randomly assigned patients with documented myocardial ischemia and severely calcified native coronary lesions undergoing percutaneous coronary intervention to a strategy of lesion preparation using MB or RA followed by drug-eluting stent implantation. Stenting was performed using a third-generation sirolimus-eluting stent with a bioabsorbable polymer. The trial had 2 primary end points: strategy success (defined as successful stent delivery and expansion with attainment of <20% in-stent residual stenosis in the presence of TIMI [Thrombolysis in Myocardial Infarction] 3 flow without crossover or stent failure; powered for superiority) and in-stent late lumen loss at 9 months (powered for noninferiority). Two hundred patients were enrolled at 2 centers in Germany (n=100 in each treatment group). The mean age of the study population was 74.9±7.0 years; 76% were men, and 33.5% had diabetes mellitus. Strategy success was significantly more common in the RA group (81% versus 98%; relative risk of failure with an MB- versus RA-based strategy, 9.5; 95% CI, 2.3-39.7; P=0.0001), but mean fluoroscopy time was longer (19.6±13.4 versus 23.9±12.2 minutes; P=0.03). At 9 months, mean in-stent late lumen loss was 0.16±0.39 mm in the MB group and 0.22±0.40 mm in the RA group ( P=0.21, P=0.02 for noninferiority). Target lesion revascularization (7% versus 2%; P=0.17), definite or probable stent thrombosis (0% versus 0%; P=1.00), and target vessel failure (8% versus 6%; P=0.78) were low and not significantly different between the MB and RA groups.. Lesion preparation with upfront RA before drug-eluting stent implantation is feasible in nearly all patients with severely calcified coronary lesions, is more commonly successful as a primary strategy compared with MB, and is not associated with excessive late lumen loss. A strategy of provisional MB remains feasible, safe, and effective as long as bailout RA is readily available and may offer the advantages of compatibility with smaller sized catheters and less irradiation. Both strategies are associated with excellent clinical outcome at 9 months.. URL: https://www.clinicaltrials.gov . Unique identifier: NCT02502851.

Topics: Absorbable Implants; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Atherectomy, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Germany; Humans; Male; Neointima; Percutaneous Coronary Intervention; Prosthesis Design; Risk Factors; Severity of Illness Index; Sirolimus; Time Factors; Treatment Outcome; Vascular Calcification

Polymer coatings of drug-eluting stents (DES) may induce allergic reactions and inflammation, resulting in late-acquired stent malapposition (LASM) with the risk of stent thrombosis. This study evaluated, if biodegradable polymer (BP) reduces the incidence of LASM compared to permanent polymer (PP) after treatment with newer generation DES.. Fifty patients with 59 lesions were randomized (2:1) to elective treatment with second generation PP-DES (n = 32, 39 stents), either Everolimus-eluting or Zotarolimus-eluting stents, or with BP-DES (Biolimus-eluting stents [BES]; n = 18, 20 stents) and underwent optical coherence tomography directly after implantation and after 1 year. After implantation acute stent malappositions (ASM) were documented in 30 stents (51%) distributed to 22 stents treated with PP-DES (56%) and 8 with BP-DES (40%; n.s.). After 1 year, late stent malappositions (LSM) were detected in 14 stents (24 %); ASM persisted (APSM) in 9 stents after one year (7 PP-DES-18%, 2 BES-10%), whereas ASM resolved in 21 stents. In addition, LASM was documented in nine stents including five stents without and four stents with additional APSM. All LASM were located in PP-DES (n = 9; 23%), none in BP-DES (P = 0.022). Compared to the reference lumen area, in-stent lumen area of stents without LASM was smaller due to neointimal hyperplasia (P = 0.021), whereas in-stent lumen area at maximum LASM of stents with LASM was larger due to positive remodeling (P = 0.002).. In conclusion the use of BP-DES reduced the occurrence of LASM due to positive remodeling compared to second generation PP-DES.

Topics: Absorbable Implants; Aged; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Polymers; Postoperative Complications; Prospective Studies; Prosthesis Design; Prosthesis Failure; Sirolimus; Tomography, Optical Coherence; Treatment Outcome

The aim of this study was to investigate the impact of attenuated-signal plaque (ASP) observed by intravascular ultrasound (IVUS) on vessel response after drug-eluting stent implantation.. Data were derived from the IVUS cohort of the J-DESsERT trial comparing paclitaxel- and sirolimus-eluting stents. Serial IVUS analysis (pre- and post-intervention, and 8-month follow-up) was performed in 136 non-AMI lesions. ASP was defined as hypoechoic plaque with ultrasound attenuation without calcification. Calcified plaque (CP) was defined as brightly echoreflective plaque with acoustic shadowing. ASP and CP scores were calculated by grading their measured angle as 0 to 4 for 0°, <90°, 90-180°, 180-270° and >270°, respectively. The entire stented segment was analyzed at 1-mm intervals.. At pre-intervention, ASP was observed in 40.4% of lesions, and this group had greater % neointimal volume (%NIV) at follow-up than the no-ASP group (p = 0.011). ASP score at pre-intervention positively correlated with %NIV (p = 0.023). During the follow-up, ASP score significantly decreased (p < 0.001), and CP score significantly increased (p < 0.001), with a negative correlation between them (p < 0.001). A decrease in the ASP score was associated with less %NIV in PES (p = 0.031), but not in SES (p = 0.229).. The greater extent of plaque with IVUS-signal attenuation at pre-intervention and its persistence during follow-up were associated with neointimal proliferation, possibly representing sustained inflammatory status, depending on the type of DES used.

Topics: Aged; Cardiovascular Agents; Cell Proliferation; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Japan; Male; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Predictive Value of Tests; Prospective Studies; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional; Vascular Calcification

The PRISON IV trial investigated the next-generation sirolimus-eluting stent (SES) with ultra-thin struts and biodegradable polymer against the second-generation everolimus-eluting stent (EES) with thin struts and durable polymer in patients with successfully recanalised chronic total occlusions (CTO). In this study, we examined the secondary optical coherence tomography endpoints.. The main PRISON IV trial randomised 330 patients to either SES or EES. At nine months, 281 (85%) patients underwent repeat angiography. Of these, 60 consecutive patients received optical coherence tomography divided over both stent groups. The mean number of struts analysed was 750±337 and 633±358 in SES and EES patients, respectively (p=0.07). The minimal lumen area, minimal stent area, maximal neointima area and neointimal thickness were comparable between the groups (4.8±2.1 and 4.4±1.5 mm2; 5.3±1.8 and 5.3±1.4 mm2; 2.5±2.0 and 2.2±1.5 mm2; 0.7±1.7 and 0.4±0.2 mm). The percentage of uncovered struts was higher with EES (6.2±7.5% and 11.9±13.4%, p=0.04), whereas the percentage of malapposed struts and mean number of coronary evaginations were significantly higher with SES (2.9±4.0% and 1.2±2.4%, p=0.02; 18.5±17.7 and 5.3±3.1, p=0.004).. The optical coherence tomography findings of this substudy demonstrated improved strut coverage with ultra-thin strut SES with bioresorbable polymer compared to thin-strut EES with durable polymer in CTO. On the other hand, SES showed a higher rate of stent strut malappositon and coronary evaginations. The clinical relevance of these findings remains to be demonstrated.

Topics: Absorbable Implants; Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Polymers; Sirolimus; Tomography, Optical Coherence; Treatment Outcome

This study aimed to compare very late vascular response after stent implantation between everolimus-eluting stent (EES) with a thin, non-adhesive, durable, biocompatible fluorinated polymer and biolimus-eluting stent (BES) with a biodegradable polymer by optical coherence tomography (OCT).. In the NOBORI-BES Versus XIENCE V/PROMUS-EES Trial (NEXT), a formal OCT substudy investigated 48 patients (27 EES-treated lesions in 23 patients and 28 BES-treated lesions in 25 patients) with 2-year (18-30 months) follow-up imaging at 18 centers. The percentage of uncovered strut by neointima was significantly lower in EES compared with BES (2.1±4.7% vs. 7.9±10.8%, p=0.013). The percentage of malapposed strut was not different between EES and BES (0.1±0.3% vs. 0.5±1.3%, p=0.138). The frequency of stent with evagination, which is identified as outward bulges in the luminal contour between struts, was significantly lower in EES compared with BES (22% vs. 86%, p<0.001). The frequency of neoatherosclerosis was not different between EES and BES (11% vs. 11%, p=1.000).. At 2 years after stent implantation, uncovered stent strut by neointima and evagination were less frequently observed in EES compared with BES. This OCT study suggests that the very late vascular response is different between EES and BES.

Topics: Aged; Biocompatible Materials; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Polymers; Sirolimus; Tomography, Optical Coherence; Treatment Outcome

To assess the vessel-healing pattern of Ultimaster drug-eluting stent using optical frequency domain imaging. Our hypothesis is that biodegradable polymer-based drug-eluting technology allows complete very early strut coverage.. The DISCOVERY 1TO3 study (Evaluation With OFDI of Strut Coverage of Terumo New Drug Eluting Stent With Biodegradable Polymer at 1, 2, and 3 Months) is a prospective, single-arm, multicenter study. A total of 60 patients with multivessel disease requiring staged procedure at 1 month were treated with Ultimaster. Optical frequency domain imaging was acquired at baseline, 1, 2, and 3 months. The primary end point is optical frequency domain imaging-assessed strut coverage at 3 months. Mean age of patients was 67.2±9.9 years, and 73.3% were male, and 36.7% presented with acute coronary syndrome. A total of 132 lesions were treated, with average 1.4 lesions per patient treated at baseline and 1.1 lesions treated at 1 month. Strut coverage at 3 months of single implanted stents (n=71, primary end point) was 95.2±5.2% and of combined single and overlapped stents was 95.4±4.9%. Strut coverage of combined single and overlapped stents at 1 (n=49) and 2 months (n=38) was 85.1±12.7% and 87.9±10.8%, respectively. The median neointimal hyperplasia thickness was 0.04, 0.05, and 0.06 mm, whereas mean neointimal hyperplasia obstruction was 4.5±2.4%, 5.2±3.4%, and 6.6±3.3% at 1, 2, and 3 months, respectively.. Nearly complete strut coverage was observed in this complex population very early after implantation of Ultimaster drug-eluting stent.. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01844843.

Topics: Absorbable Implants; Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Europe; Female; Humans; Hyperplasia; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Polyesters; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

We sought to compare, by means of IVUS and OCT imaging, the performance of a novel sirolimus-eluting drug-eluting stent (DES) with biodegradable polymer (Inspiron™) to the Biomatrix™ DES. From the DESTINY trial, a total of 70 randomized patients (2:1) were enrolled in the IVUS substudy (Inspiron™, n = 46; Biomatrix™: n = 20) while 25 patients were evaluated with OCT (Inspiron™, n = 19; Biomatrix™: n = 06) at 9-month follow-up. The main endpoints were % of neointimal tissue obstruction (IVUS) and neointimal stut coverage (OCT) at 9 months. Patients treated with both DES had very little NIH formation at 9 months either by IVUS (% of NIH obstruction of 4.9 ± 4.1 % with Inspiron™ vs. 2.7 ± 2.9 % with Biomatrix™, p = 0.03) or by OCT (neointimal thickness of 144.2 ± 72.5 µm Inspiron™ vs. 115.0 ± 53.9 µm with Biomatrix™, p = 0.45). Regarding OCT strut-level assessment, again both devices showed excellent 9-month performance, with high rates of strut coverage (99.49 ± 1.01 % with Inspiron™ vs. 97.62 ± 2.21 % with Biomatrix™, p < 0.001) and very rare malapposition (0.29 ± 1.06 % with Inspiron™ vs. 0.53 ± 0.82 % with Biomatrix™, p = 0.44). Patients with any uncovered struts were more frequently identified in the Biomatrix™ group (9.78 ± 7.13 vs. 2.29 ± 3.91 %, p < 0.001). In the present study, midterm IVUS and OCT evaluations showed that both new generation DES with biodegradable polymer were effective in terms of suppressing excessive neointimal response, with very high rates of apposed and covered struts, suggesting a consistent and benign healing pattern.

Topics: Absorbable Implants; Cardiovascular Agents; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Humans; Metals; Neointima; Percutaneous Coronary Intervention; Polymers; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

Previous studies have suggested a benefit of cilostazol in addition to standard dual-antiplatelet therapy (DAPT), reducing in-stent late luminal loss and restenosis after percutaneous coronary intervention (PCI) with bare-metal and drug-eluting stent (DES) implantation. However, there is a paucity of intravascular ultrasound (IVUS) assessment of neointimal tissue hyperplasia (NIH) after triple-antiplatelet therapy (TAPT), especially in diabetic patients treated with DES.. This prospective, placebo-controlled trial was conducted in diabetic patients randomized (1:1) to receive either standard DAPT (aspirin and clopidogrel) vs TAPT with cilostazol for a minimum of 12 months after PCI with Endeavor zotarolimus-eluting stent (E-ZES). The primary endpoint was the 9-month comparison of percentage of NIH in both groups. Additionally, we compared in-stent late lumen loss, binary restenosis, major adverse cardiac event (MACE; cardiac death, non-fatal myocardial infarction, and restenosis) rates, and the incidence of vascular/bleeding complications.. In total, 133 diabetic patients were enrolled (cilostazol cohort = 65 patients) with 56.4% male and mean age of 60.8 years. Overall, the two cohorts were comparable in terms of baseline clinical and angiographic characteristics, except for the reference vessel diameter, which was smaller among patients randomized to cilostazol (2.48 ± 0.46 mm vs 2.69 ± 0.48 mm; P=.01). At 9 months, there was a non-significant trend toward less percentage of NIH obstruction in the TAPT cohort (33.2 ± 8.29% vs 35.1 ± 8.45%; P=.07). However, this finding did not impact angiographic late-lumen loss (0.60 ± 0.46 mm cilostazol group vs 0.64 ± 0.48 mm control group; P=.30) and binary restenosis (9.8% vs 6.8%; P=.99). MACE rate also did not significantly differ between the cohorts (13.8% cilostazol group vs 8.8% control group; P=.81). Of note, the addition of a third antiplatelet agent did not increase vascular and bleeding complications.. In diabetic patients treated with E-ZES, TAPT with cilostazol did not add any significant benefit in terms of NIH suppression or MACE reduction.

Topics: Aspirin; Cilostazol; Clopidogrel; Comorbidity; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Diabetes Mellitus; Drug Therapy, Combination; Drug-Eluting Stents; Female; Hemorrhage; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Sirolimus; Tetrazoles; Ticlopidine; Treatment Outcome

The aim of the present study was to evaluate vascular healing of the bioengineered COMBO Dual Therapy Stent compared with a cobalt-chromium (CoCr) everolimus-eluting stent (EES) as assessed by optical coherence tomography in patients with acute coronary syndromes.. CD34+ cells promote endothelial repair after vascular injury. The bioengineered COMBO Dual Therapy Stent combines CD34+ cell-capturing technology with abluminal sirolimus release, but more data from clinical studies evaluating the vascular response are needed.. In a prospective randomized multicenter clinical trial, 60 patients with acute coronary syndromes were randomized 1:1 to COMBO or CoCr EES implantation. The primary endpoint was the percentage of uncovered stent struts per stent. Stent assessment by optical coherence tomography was performed at baseline and at 60 days, followed by independent core laboratory analysis.. The percentage of uncovered struts per stent was higher with the COMBO than the CoCr EES at 60 days (median 14.7% vs. 7.7%; p = 0.04). However, no significant difference in uncovered stent struts was observed in the strut level-based analysis at 60 days, which also accounted for clustering (COMBO vs. CoCr EES; 13.6% vs. 6.9%; p = 0.09; generalized linear mixed models-adjusted analysis). Neointimal thickness at 60 days was lower with the COMBO compared with the CoCr EES (median 30.17 vs. 50.26 μm; p = 0.02; stent-level analysis). There were no significant differences in the frequency of major adverse cardiac events and each component of major adverse cardiac events within the study population between the 2 groups at 30, 60, 180, 360, and 540 days post-procedure. No target vessel stent thrombosis has been documented within 540 days.. The present multicenter, prospective clinical study for the first time compared the vascular response of the bioengineered COMBO Dual Therapy Stent with a CoCr EES in patients early after acute coronary syndrome by using intracoronary optical coherence tomographic analysis. The percentage of uncovered stent struts per stent was somewhat higher after COMBO versus CoCr EES implantation as detected by optical coherence tomography, associated with reduced neointimal thickness.

Topics: Acute Coronary Syndrome; Aged; Antibodies; Antigens, CD34; Cardiovascular Agents; Chromium Alloys; Coronary Vessels; Drug-Eluting Stents; Endothelial Cells; Europe; Everolimus; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; United States; Wound Healing

Incomplete neointimal coverage and malapposed struts after stenting are associated with increased risk of stent thrombosis. We aimed to evaluate neointimal coverage early after Resolute zotarolimus-eluting stent (R-ZES) implantation using optical coherence tomography (OCT). A total of 20 patients with de novo native coronary lesions with R-ZES were enrolled. Among these patients, 20 stented lesions in 19 patients were evaluated at 1, 2, and 3 months after R-ZES implantation. The strut apposition and neointimal coverage were evaluated by OCT. Neointimal hyperplasia (NIH) thickness and percentage of covered struts and the proportion of incompletely apposed struts were measured at 1-mm intervals. The mean percentages of covered stent struts were over 85 % within 3 months (88.4 ± 6.3 % at 1 month, 95.5 ± 5.5 % at 2 months, 93.6 ± 3.5 % at 3 months). The percentages of incompletely apposed struts were not significantly different among the groups (4.4 ± 4.2 % at 1 month, 1.9 ± 1.9 % at 2 months, 3.1 ± 2.2 % at 3 months, p = 0.51). Mean NIH thickness (38.9 ± 8.1 μm at 1 month, 70.6 ± 18.8 μm at 2 months, 54.1 ± 5.9 at 3 months, p = 0.0016) was thickest in the 2 months group. Most of all OCT findings within 2 months demonstrated neointimal coverage with low signal intensity. The neointimal coverage of ZES-R was over 85 % within 3 months. These data may support shorter requirement of dual antiplatelet therapy duration with R-ZES.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Japan; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Predictive Value of Tests; Prospective Studies; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

The Ultimaster bioresorbable polymer sirolimus-eluting stent (BP-SES) is a newly developed drug-eluting stent (DES) that consists of a thin-strut, cobalt chromium with bioresorbable polymer coated only albuminally. We sought to compare tissue coverage in coronary lesions treated with BP-SES with the XIENCE permanent polymer everolimus-eluting stent (PP-EES) using optical coherence tomography (OCT).. A total of 36 patients participated in the CENTURY II trial in our institution and were randomly assigned to BP-SES (n = 15) and PP-EES (n = 21). Of these, 27 patients (13 BP-SES and 14 PP-EES) underwent OCT at 9-month follow-up. Tissue coverage and apposition were assessed on each strut, and the results in both groups were compared using multilevel logistic or linear regression models with random effects at three levels: patient, lesion, and struts. A total of 6450 struts (BP-SES, n = 2951; PP-EES, n = 3499) were analysed. Thirty and 79 uncovered struts (1.02 and 2.26%, P = 0.35), and 3 and 4 malapposed struts (0.10 and 0.11%, P = 0.94) were found in BP-SES and PP-EES groups, respectively. Mean neointimal thickness did not significantly differ between both groups (110 ± 10 vs. 93 ± 10 µm, P = 0.22). No significant differences in per cent neointimal volume obstruction (13.2 ± 4.6 vs. 10.5 ± 4.9%, P = 0.14) or other areas-volumetric parameters were detected between both groups.. BP-SES shows an excellent vascular healing response at 9-month follow-up, which is similar to PP-EES.

Topics: Absorbable Implants; Aged; Aged, 80 and over; Coronary Angiography; Coronary Artery Disease; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Japan; Male; Neointima; Percutaneous Coronary Intervention; Polymers; Prosthesis Design; Single-Blind Method; Sirolimus; Tomography, Optical Coherence; Treatment Outcome

The aim of this study was to compare the efficacy of amphilimus-eluting stents (AES) with that of everolimus-eluting stents (EES) in patients with diabetes mellitus (DM).. The AES is a polymer-free drug-eluting stent that elutes sirolimus formulated with an amphiphilic carrier from laser-dug wells. This technology could be associated with a high efficacy in patients with DM.. This was a multicenter, randomized, noninferiority trial. Patients with DM medically treated with oral glucose-lowering agents or insulin and de novo coronary lesions were randomized in a 1:1 fashion to AES or EES. The primary endpoint was the neointimal (NI) volume obstruction assessed by optical coherence tomography at 9-month follow-up.. A total of 116 lesions in 112 patients were randomized. Overall, 40% were insulin-treated patients, with a median HbA1c of 7.3% (interquartile range: 6.7% to 8.0%). The primary endpoint, NI volume obstruction, was 11.97 ± 5.94% for AES versus 16.11 ± 18.18% for EES, meeting the noninferiority criteria (p = 0.0003). Pre-specified subgroup analyses showed a significant interaction between stent type and glycemic control (p = 0.02), with a significant reduction in NI hyperplasia in the AES group in patients with the higher HbA1c (p = 0.03). By quantitative coronary angiography, in-stent late loss was 0.14 ± 0.24 for AES versus 0.24 ± 0.57 mm for EES (p = 0.27), with a larger minimal lumen diameter at follow-up for AES (p = 0.02), mainly driven by 2 cases of occlusive restenosis in the EES group.. AES are noninferior to EES for the coronary revascularization of patients with DM. These results suggest a high efficacy of the AES and may support the potential benefit of this stent in patients with DM. (A Randomized Comparison of Reservoir-Based Polymer-Free Amphilimus-Eluting Stents Versus Everolimus-Eluting Stents With Durable Polymer in Patients With Diabetes Mellitus [RESERVOIR]; NCT01710748).

Topics: Aged; Biomarkers; Blood Glucose; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Diabetes Mellitus; Drug-Eluting Stents; Everolimus; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Polymers; Prospective Studies; Prosthesis Design; Risk Factors; Sirolimus; Spain; Time Factors; Tomography, Optical Coherence; Treatment Outcome

The purpose of this study was to evaluate the efficacy and long-term outcomes of a novel polymer/carrier-free drug-coated stent (DCS) in patients with de novo coronary lesions.. The BioFreedom (BFD) DCS incorporates a low-profile, stainless-steel platform, with a surface that has been modified to create a selectively microstructured abluminal surface that allows adhesion and further release of Biolimus A9 (Biosensors Europe SA, Morges, Switzerland).. A total of 182 patients (183 lesions) were randomized into a 1:1:1 ratio for treatment with BFD "standard dose" (BFD) or BFD "low dose" (BFD-LD) versus first-generation paclitaxel-eluting stents (PES) at 4 sites in Germany.. Baseline and procedural characteristics were well matched. At 4-month angiographic follow-up (Cohort 1, n = 75), in-stent late lumen loss (LLL) was significantly lower with BFD and BFD-LD versus PES (0.08 and 0.12 mm vs. 0.37 mm, respectively; p < 0.0001 for BFD vs. PES, and p = 0.002 for BFD-LD vs. PES). At 12 months (Cohort 2, n = 107), in-stent LLL (primary endpoint) was 0.17 mm in BFD versus 0.35 mm in PES (p = 0.001 for noninferiority; p = 0.11 for superiority); however, the BFD-LD (0.22 mm) did not reach noninferiority (p = 0.21). At 5 years (175 of 182), there were no significant differences in major adverse cardiac events (23.8%, 26.4%, and 20.3%) and clinically indicated target lesion revascularization (10.8%, 13.4%, and 10.2%) for BFD, BFD-LD, and PES, respectively; also, there was no definite/probable stent thrombosis reported.. The BFD, but not the BFD-LD, demonstrated noninferiority versus PES in terms of in-stent LLL, a surrogate of neointimal hyperplasia, at 12-month follow-up. At 5 years, clinical event rates were similar, without occurrence of stent thrombosis in all groups. (BioFreedom FIM Clinical Trial; NCT01172119).

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Germany; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Risk Factors; Single-Blind Method; Sirolimus; Stainless Steel; Surface Properties; Time Factors; Treatment Outcome

This registry evaluated the safety and clinical outcomes of the Combo stent in an all-comers population in routine clinical practice. We report 1-year results.. Limitations of current generation drug-eluting stents (DES) are 3-fold: stent thrombosis, neoatherosclerosis related to impaired healing, and repeat revascularization due to (late-) in-stent restenosis. The Combo stent combines an abluminal biodegradable coating eluting sirolimus and a luminal anti-CD34(+) antibody layer to attract endothelial progenitor cells in order to promote vessel healing, thus preventing neointima formation and restenosis.. The REMEDEE (Randomized study to Evaluate the safety and effectiveness of an abluMinal sirolimus coatED bio-Engineered StEnt) post-market registry was an international, multicenter, prospective trial that evaluated clinical outcomes after deployment of the Combo stent, in an all-comers population of patients treated with a Combo stent in the setting of routine clinical care. Clinical endpoints were target lesion failure (TLF), defined as a composite of cardiac death, nonfatal myocardial infarction (MI), or target lesion revascularization (TLR).. Between June 2013 and March 2014, a total of 1,000 patients were included in the registry, 49.9% of whom presented with acute coronary syndrome. Mean age was 65 ± 11 years old (range: 34 to 94 years of age), and 74% of patients were male; 58.9% of 1,255 lesions were American Heart Association type B2 or C lesions. The primary endpoints were 5.7% TLF, 1.7% cardiac death, 0.7% target vessel MI, and 4.4% TLR. Definite stent thrombosis occurred in 0.5% of subjects; no thrombosis occurred after 9 days post-stenting.. This registry showed excellent 1-year results of novel Combo bioengineered stent technology in an all-comers patient population. (Prospective Registry to Assess the Long-term Safety and Performance of the Combo Stent [REMEDEE]; NCT01874002).

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Europe; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Neointima; Percutaneous Coronary Intervention; Product Surveillance, Postmarketing; Prospective Studies; Prosthesis Design; Registries; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Wound Healing

The aim of this study was to analyze the difference in neointima pattern assessed by intravascular ultrasound (IVUS) between two dedicated bifurcation stents, BiOSS® Expert and BiOSS® LIM at 12-month follow-up. This manuscript reports IVUS findings obtained from the analysis of patients enrolled into first-in-man registries initially assessing the BiOSS Expert® (paclitaxel) and BiOSS LIM® (sirolimus) stents. Quantitative angiographic analysis was performed pre, post-stenting, and at follow-up. IVUS examination was performed at 12 months. There were analyzed 34 cases (BiOSS Expert® 11 patients, BiOSS LIM® 23 patients). Procedural characteristics in the two groups were similar, except for rates of main vessel predilatation and FKB/POT, which were higher in BiOSS® LIM group, 54.5 % vs 73.9 % (P < 0.05) and 0 % vs 39.1 % (P < 0.05), respectively. When comparing late lumen loss (LLL) for both stents there were significantly bigger values for main vessel and main branch in the BiOSS® Expert group, but not in side branch. Intravascular ultrasound examination showed that in the BiOSS LIM® group comparing with the BiOSS Expert® group there was lower neointima burden in the whole stent (24.7 ± 7.5 % vs 19.4 ± 8.6 %, P < 0.05) as well as in main vessel (22.8 ± 5.6 % vs 16.9 ± 6.1 %, P < 0.05) and main branch (36.1 ± 6.5 % vs 27.6 ± 8.7 %, P < 0.05), but not at the level of bifurcation (15.1 ± 3.8 % vs 13.6 ± 5.4 %, P = NS). In addition, we found that final kissing balloon/proximal optimization technique (FKB/POT) was associated with significantly smaller value of LLL in main vessel (0.24 ± 0.09 mm vs 0.32 ± 0.14 mm, P < 0.05), which in IVUS analysis resulted in smaller neointima burden in main vessel (13.7 ± 3.9 % vs 18.9 ± 4.45 %, P < 0.05) as well as at the bifurcation site (12.6 ± 4.1 % vs 14.1 ± 2.4 %, P < 0.05). The obtained results suggest that neointima proliferation was the largest in main branches of both stents assessed in quantitative angiography (LLL) as well as in IVUS (neointima burden) and the neointima increase was smaller in BiOSS LIM® stents than in BiOSS Expert® stents. Moreover, the middle part of the stent seems to not to be associated with excessive neointima proliferation and more aggressive protocol of implantation with the use FKB/POT seems to decrease this process.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cell Proliferation; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Non-ST Elevated Myocardial Infarction; Paclitaxel; Predictive Value of Tests; Prosthesis Design; Registries; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Current monotherapy drug-eluting stents are associated with impaired healing, neoatherosclerosis, and late stent thrombosis. The healing profile and neointimal transformation of the first dual-therapy endothelial progenitor cell-capturing sirolimus-eluting stent are unknown.. In this prospective, single-center study, 61 patients treated with the Combo stent had optical coherence tomography at baseline, early follow-up (4 monthly groups in a 1:2:2:1 ratio from 2 to 5 months), 9 months, and 24 months. Optical coherence tomography early strut coverage increased from 77.1% to 92.5% to 92.7% to 94.9% between 2 and 5 months. At 9 months, the major adverse cardiac event rate was 1.64%, and angiographic in-stent late loss was 0.24 mm (0.08-0.40). The 36-month major adverse cardiac event rate was 3.3%. From 9 to 24 months, neointimal regression was confirmed by optical coherence tomography: neointimal thickness (median [first quartile and third quartile]), 0.14 mm (0.08 and 0.21) versus 0.12 mm (0.07 and 0.19), P<0.001; neointimal volume, 29.9 mm(3) (22.1 and 43.2) versus 26.2 mm(3) (19.6 and 35.8), P=0.003; and percent neointimal volume, 17.8% (12.2 and 21.2) versus 15.7% (11.2 and 19.4), P=0.01. No definite or probable late stent thrombosis was recorded.. With additional endothelial progenitor cell-capturing technology, the Combo stent exhibits a unique late neointimal regression (from 9 to 24 months) that has not been reported in any drug-eluting stents, translating into good 36-month clinical results with minimal restenosis and no late stent thrombosis. This is the first study testing the concept of using a longitudinal sequential optical coherence tomography protocol to continuously document early healing profile and late neointimal transformation, predicting long-term outcomes of a new novel stent platform.. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01274234, NCT01756807, and NCT02263313.

Topics: Aged; Cardiovascular Agents; Combined Modality Therapy; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Endothelial Progenitor Cells; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

To compare the efficacy and safety of the MiStent absorbable polymer sirolimus-eluting stent (APSES) with a zotarolimus-eluting stent (ZES).. The trial was a 2:1 randomisation at 26 sites of 184 patients implanted with an APSES (n=123) versus a ZES (n=61). Following stent implantation, all patients underwent quantitative coronary angiography at baseline and at nine months of follow-up, while a select subgroup also underwent optical coherence tomography (OCT). The primary efficacy hypothesis was superiority of in-stent late lumen loss (LLL) of APSES compared to ZES. At nine months, the primary endpoint was met, with a mean in-stent LLL of 0.27±0.46 mm in 103 APSES patients versus 0.58±0.41 mm in 52 ZES patients (p<0.001). The proportion of uncovered stent struts by OCT at nine months was very low in both groups. The mean neointimal thickness of covered struts (p=0.002) and percent net volume obstruction (p≤0.003) were significantly lower in the APSES than in the ZES group. Major adverse cardiac event and stent thrombosis rates were low and comparable between groups.. The DESSOLVE II trial demonstrated superiority in the primary efficacy endpoint of nine-month mean LLL for APSES compared to ZES. Strut coverage by OCT was high with both stents and the clinical safety endpoints including stent thrombosis were equally low in both groups. ClinicalTrials.gov Identifier: NCT01294748.

Topics: Absorbable Implants; Aged; Antibiotics, Antineoplastic; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Polymers; Single-Blind Method; Sirolimus; Tomography, Optical Coherence; Treatment Outcome

The aim of this study was to evaluate the extent of neointimal response after the implantation of a second-generation drug-eluting stent, zotarolimus-eluting stent (ZES-ER, Endeavor Resolute) or everolimus-eluting stent (EES, Xience V), using intravascular ultrasound (IVUS) in diabetic patients.. In all, 154 diabetic patients with de-novo coronary lesions were randomized to be implanted with a ZES-ER or EES, and the angiographic follow-up at 9 months combined with a complete IVUS study was available for 96 patients with 101 lesions.. Baseline demographic and lesion parameters were similar in both groups at index percutaneous coronary intervention. On follow-up angiography, in-stent late lumen loss and minimal lumen diameter were not different between the two groups. On IVUS study, neointimal hyperplasia volume [median (interquartile range): ZES-ER vs. EES; 2.25 mm (0.57-6.25) vs. 1.59 mm (0.45-8.37), P=0.615] and in-stent percentage of volume obstruction [median (interquartile range): ZES-ER vs. EES; 1.16% (0.33-3.61) vs. 0.77% (0.29-4.01), P=0.615] showed similar results between the two groups.. In diabetic patients, the second-generation drug-eluting stents, ZES-ER and EES, were comparable in inhibiting neointimal proliferation.

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Pilot Projects; Predictive Value of Tests; Prosthesis Design; Republic of Korea; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Patients at high bleeding risk would benefit from a shorter dual antiplatelet therapy after PCI. Compared to first-generation devices, the design of newer generation drug-eluting stents may facilitate more rapid anatomical and functional healing of stented vessel based on thinner stent platforms, biodegradable/biocompatible polymers and rapid drug elution.. Forty-four non-diabetic patients with acute coronary syndrome (ACS) and culprit lesion in the LAD were randomized to receive either biodegradable polymer sirolimus-eluting stent (BP-SES) or durable polymer zotarolimus-eluting stent (DP-ZES). Neointimal strut coverage was examined using optical coherence tomography, and vasodilator response on invasive thermodilution-derived coronary flow reserve (CFR) at 3-month follow-up. The primary endpoints were percent uncovered struts and CFR. A total of 425 cross-sections (4,897 struts) were analyzed in the BP-SES group, and 425 cross-sections (5,467 struts) in the DP-ZES group. The percent uncovered struts was lower in the BP-SES group compared with the DP-ZES group, both at strut level (3.9% vs. 8.9%, respectively, P<0.001), and stent level (3.9 ± 3.2% vs. 8.9 ± 6.9%, respectively, P=0.019). No significant difference was found between the 2 groups regarding CFR (3.0 ± 1.3 vs. 3.2 ± 1.0, respectively, P>0.05).. In non-diabetic patients with ACS, BP-SES provided slightly better stent strut coverage at 3 months compared with DP-ZES, but neither stent was fully covered. No difference in vasodilator response was seen.

Topics: Absorbable Implants; Acute Coronary Syndrome; Aged; Biodegradable Plastics; Double-Blind Method; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Prospective Studies; Sirolimus; Vasodilation

To evaluate the preliminary safety and efficacy of the EXCEL II stent system.. Although the first biodegradable polymer drug-eluting stent (BP-DES), EXCEL, was launched nearly a decade ago, in-stent restenosis and stent thrombosis remain pertinent clinical problems in practice. A new cobalt-chromium BP-DES EXCEL II has been developed with the aim of improving stent safety and efficacy.. Forty-five patients with single de novo native coronary lesions were enrolled and randomized to two groups in a 2:1 ratio, the 4-month follow-up group (n = 30) and the 12-month follow-up group (n = 15). All patients underwent percutaneous coronary intervention (PCI) with the EXCEL II stent system. Quantitative coronary angiography (QCA) and optical coherence tomography (OCT) were used to assess coronary vasculature at the designated 4- or 12-month follow-up. The primary outcome was major adverse cardiac events (MACE) at 30 days post-PCI.. No MACE, thrombotic events, or target lesion failure was found in the 45 patients during the 12-month follow-up. There was no significant difference (P > 0.05) between the two groups in terms of in-stent and in-segment late lumen loss (LLL). No in-stent and in-segment restenosis was found in either group. At follow-up, the ratio of >10% uncovered struts per lesion was 26.67% in the 4-month group and 0% in the 12-month group (P < 0.05). Neointimal coverage in the 12-month group was significantly better than in the 4-month group (98.58% vs. 93.51%, P < 0.01).. This first-in-man study demonstrates promising feasibility, safety, and efficacy of EXCEL II stents. These stents were found to have rapid endothelialization and low LLL rates at 4 and 12 months after implantation.

Topics: Absorbable Implants; Aged; Cardiovascular Agents; China; Chromium Alloys; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Polymers; Predictive Value of Tests; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Biodegradable polymers for release of antiproliferative drugs from drug-eluting stents aim to improve vascular healing. We assessed noninferiority of a novel ultrathin strut drug-eluting stent releasing sirolimus from a biodegradable polymer (Orsiro, O-SES) compared with the durable polymer Xience Prime everolimus-eluting stent (X-EES) in terms of the primary end point in-stent late lumen loss at 9 months.. A total of 452 patients were randomly assigned 2:1 to treatment with O-SES (298 patients, 332 lesions) or X-EES (154 patients, 173 lesions) in a multicenter, noninferiority trial. The primary end point was in-stent late loss at 9 months. O-SES was noninferior to X-EES for the primary end point (0.10±0.32 versus 0.11±0.29 mm; difference=0.00063 mm; 95% confidence interval, -0.06 to 0.07; Pnoninferiority<0.0001). Clinical outcome showed similar rates of target-lesion failure at 1 year (O-SES 6.5% versus X-EES 8.0%; hazard ratio=0.82; 95% confidence interval, 0.40-1.68; log-rank test: P=0.58) without cases of stent thrombosis. A subgroup of patients (n=55) underwent serial optical coherence tomography at 9 months, which demonstrated similar neointimal thickness among lesions allocated to O-SES and X-EES (0.10±0.04 mm versus 0.11±0.04 mm; -0.01 [-0.04, -0.01]; P=0.37). Another subgroup of patients (n=56) underwent serial intravascular ultrasound at baseline and 9 months indicating a potential difference in neointimal area at follow-up (O-SES, 0.16±0.33 mm(2) versus X-EES, 0.43±0.56 mm(2); P=0.04).. Compared with durable polymer X-EES, novel biodegradable polymer-based O-SES was found noninferior for the primary end point in-stent late lumen loss at 9 months. Clinical event rates were comparable without cases of stent thrombosis throughout 1 year of follow-up.. http://www.clinicaltrials.gov. Unique identifier: NCT01356888.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Europe; Everolimus; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neointima; Polymers; Predictive Value of Tests; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

The purpose of the present study was to investigate the relationship between in-stent neoatherosclerosis (NA) and native atherosclerosis progression of untreated coronary segments.. In-stent NA was assessed by optical coherence tomography (OCT) among patients included in the SIRTAX-LATE OCT study 5 years after drug-eluting stent (DES) (sirolimus-eluting and paclitaxel-eluting stents) implantation. Neoatherosclerosis was defined as the presence of fibroatheroma or fibrocalcific plaque within the neointima of stented segments with a longitudinal extension >1.0 mm. Atherosclerosis progression in untreated native coronary segments was evaluated by serial quantitative coronary angiography (QCA). The change in minimal lumen diameter (MLD) was serially assessed within matched segments at baseline and 5-year angiographic follow-up. The key clinical endpoint was non-target lesion (non-TL) revascularization throughout 5 years. A total of 88 patients with 88 lesions were available for OCT analysis 5 years after DES implantation. In-stent NA was observed in 16% of lesions with the majority of plaques being fibroatheromas (11.4%) followed by fibrocalcific plaques (5.7%). A total of 704 non-TL segments were serially evaluated by QCA. Between baseline and 5-year follow-up, the reduction in MLD was significantly more pronounced in patients with NA (-0.25 mm, 95% CI -0.36 to -0.17 mm) when compared with patients without NA (-0.13 mm, 95% CI -0.17 to -0.10 mm, P = 0.002). Similarly, non-TL revascularization was more frequent in patients with NA (78.6%) when compared with patients without NA (44.6%, P = 0.028) throughout 5 years.. In-stent NA is more common among patients with angiographic and clinical evidence of native atherosclerosis progression suggesting similar pathophysiological mechanisms.SIRTAX trial is registered at http://www.clinicaltrials.gov/ct2/show/NCT00617084.

Topics: Aged; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Disease Progression; Drug-Eluting Stents; Female; Graft Occlusion, Vascular; Humans; Male; Middle Aged; Neointima; Paclitaxel; Prosthesis Failure; Sirolimus; Tomography, Optical Coherence; Tubulin Modulators

The early phase arterial reaction after implantation of second-generation drug-eluting stents (2nd DES) and baremetal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI) remains unclear.The MECHANISM pilot study is a multi-center prospective registry that enrolled 24 STEMI patients (from 11 centers) who had undergone implantation of everolimus-eluting (n = 6), biolimus A9-eluting (n = 6) or zotarolimus-eluting stents (n = 6), or BMS (n = 6). Scheduled optical coherence tomography (OCT) was performed 2 weeks after implantation, and images were independently analyzed at a core laboratory in a blinded fashion. Intra-stent thrombus was quantitatively analyzed in terms of the maximal area and the percentage of cross-sections with thrombus (the numbers of cross-section with thrombus × 100 divided by total number of cross-sections within the stented segment). More than 90% of struts were already covered 2 weeks after the index procedure, regardless of the stent type. There were no differences in stent diameter, minimal lumen diameter, minimal lumen area, neointimal thickness, or the frequencies of malapposed and uncovered struts among the 4 groups. The quantity of intra-stent thrombus also did not differ among the 4 groups.The results of this pilot study suggest that the 2-week vascular responses seem to be similar among 2nd DES and BMS in STEMI patients. Considering the possible advantage of 2nd DES in the prevention of restenosis, 2nd DES are a feasible option for the treatment of patients with STEMI.

Topics: Aged; Angioplasty, Balloon, Coronary; Antineoplastic Agents; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Neointima; Pilot Projects; Prospective Studies; Sirolimus; Thrombosis; Time Factors; Tomography, Optical Coherence

The aim of the present study was to compare vascular healing response between the first-generation sirolimus-eluting stent (SES) and the second-generation everolimus-eluting stent (EES) by using optical coherence tomography (OCT).. The RESET was a prospective, multicentre, randomised, open-label trial comparing EES and SES. Of the 3,197 patients enrolled in the RESET, nine-month follow-up OCT after stent implantation was performed in 100 patients (48 EES-treated lesions in 44 patients and 62 SES-treated lesions in 56 patients), thus constituting the OCT substudy population. The percentage of uncovered struts per lesion (8±15% vs. 14±19%, p=0.031) and cross-sections with >30% uncovered struts per lesion (6±14% vs. 18±29%, p=0.009) was significantly lower in EES compared with SES. The frequency of DES-treated lesions with incomplete stent apposition (8 [17%] vs. 29 [47%], p<0.001) was significantly lower in EES compared with SES. Intra-stent thrombus was comparably observed between EES and SES (1 [2%] vs. 5 [8%], p=0.229).. Compared with SES, EES was associated with a favourable vascular response at nine months after stent implantation.

Topics: Aged; Angina, Unstable; Antineoplastic Agents; Coronary Angiography; Coronary Artery Disease; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Myocardial Infarction; Neointima; Percutaneous Coronary Intervention; Sirolimus; Tomography, Optical Coherence

The aim of this study was to assess the safety and the efficacy of the novel sirolimus-eluting Prolim® stent with a biodegradable polymer in the all-comers population.. We prospectively enrolled all patients with stable coronary artery disease or acute coronary syndrome treated with Prolim® stent between January and December 2013 in two interventional cardiology centers in Poland. Angiographic control was planned at 12 months, in which 15 % of patients (randomly chosen) underwent optical coherence tomography imaging. The primary end-point was the cumulative rate of cardiac death, myocardial infarction, and target lesion revascularization at 12 months.. There were 204 patients enrolled, in whom 238 Prolim® stents were deployed (1.17 stent per patient). The mean age was 68 ± 10 years and 32.8 % were females. The examined stent was implanted in 5.9 % in STEMI patients, in 21.6 % - in NSTE-ACS and in 72.5 % - in patients with stable coronary artery disease. The Prolim® stent was most frequently implanted in right coronary artery (38.2 %) followed by left anterior descending artery (34.0 %). The cumulative major adverse cardiovascular events rate at 12 months was 6.9 %, and the clinically-driven target lesion revascularization rate - 5.4 %. At 12 months in quantitative coronary angiography the late lumen loss was 0.21 ± 0.18 mm, and in optical coherence tomography the mean neointima burden was 24.6 ± 8.6 %.. Sirolimus-eluting Prolim® stent with a biodegradable polymer is a feasible device with a very good safety profile and long-term clinical effectiveness.. ClinicalTrials.gov NCT02545985 .

Topics: Absorbable Implants; Acute Coronary Syndrome; Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Neointima; Percutaneous Coronary Intervention; Poland; Polymers; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Registries; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

The aim of this study was to evaluate the Sparrow sirolimus-eluting stent (Sparrow-SES) against the Sparrow bare-metal stent (Sparrow-BMS) and conventional balloon-expandable bare-metal stent (BMS: Driver/Micro-Driver stent, Medtronic Vascular, Santa Rosa, CA).. The Sparrow stent (Biosensors International, Singapore) consists of a guide wire-based, self-expandable, ultra-thin nitinol stent. The performance of this device with sirolimus in a fully biodegradable polymer has not been determined.. A total of 74 patients were included in this intravascular ultrasound (IVUS) sub-study of the CARE II trial, which was a prospective, randomized, multicenter trial in the treatment of single de novo native coronary artery lesions in vessels ranging from 2.0 mm to 2.75 mm in diameter (Sparrow-SES: n = 31, Sparrow-BMS: n = 22, BMS: n = 21).. Stent volume index (VI) was significantly increased 8-month later in Sparrow-SES and Sparrow-BMS, but not in BMS (4.0 ± 1.0 to 4.6 ± 1.0 mm(3) /mm, p<0.0001, 4.0 ± 0.6 to 4.4 ± 0.8 mm(3) /mm, p<0.05, and 5.2 ± 1.0 to 5.1 ± 0.9 mm(3) /mm, p=0.421, respectively). % neointimal obstruction in Sparrow-SES was significantly smaller than those in Sparrow-BMS and BMS at follow-up (17.6 ± 9.4 vs. 36.2 ± 13.8 and 39.9 ± 11.1%, p<0.001). Sparrow-SES showed a mean 15% stent expansion and good suppression of neointimal proliferation, resulting in a significantly lower percentage of change in lumen VI during follow-up period (Sparrow-SES: -6.2 ± 16.2%, Sparrow-BMS: -30.4 ± 11.6%, BMS: -40.4 ± 10.0%, p<0.001).. The self-expanding Sparrow-SES demonstrated chronic stent expansion, good suppression of neointimal proliferation and resulted in a more preserved lumen in stented small vessels compared with the Sparrow-BMS and conventional balloon expandable BMS.

Topics: Aged; Alloys; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cell Proliferation; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Stents; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Persistence of stent polymer coating has been associated with incomplete endothelialization, expansive vessel remodeling, neoatherosclerosis, and delayed healing associated with inflammation that may contribute to late adverse events.. The BICARE (Lepu Medical, Beijing, China) stent is a novel polymer-free, nanotechnology-based stent eluting sirolimus and probucol. As a first in human feasibility study, patients with a single de novo native coronary stenosis <30 mm in length and with reference vessel diameter from 2.5 to 4.0 mm underwent revascularization with the BICARE stent. The primary endpoint of target lesion failure (TLF) was assessed at 30 days. Secondary endpoints included in-stent late lumen loss and proportion of uncovered or malapposed stent struts by optical coherence tomography at 4-month angiographic surveillance.. Among 32 consecutive patients (age, 55.7 ± 8.7 years; men, 62.5%; diabetes, 18.8%), the average baseline reference vessel diameter and lesion length were 2.85 ± 0.48 mm and 15.0 ± 5.6 mm, respectively. At 30 days there was no occurrence of TLF. At 4 months (angiographic follow-up, N=32), angiographic in-stent late loss was 0.14 ± 0.19 mm, and the in-stent binary restenosis rate was 3.1%. Complete strut coverage was 98.2% with 0.2% malapposition among 16,751 analyzed struts. At 18 months, TLF occurred in 3 (9.4%) patients related to repeat revascularization with no adverse safety events identified.. The preliminary feasibility and safety of a polymer-free, dual-drug eluting stent are demonstrated by absence of early adverse safety events and favorable angiographic suppression of neointimal hyperplasia. Stent imaging suggests favorable healing with extensive stent strut coverage and very low malapposition. These findings further inform comparison with biopermanent polymer DES.

Topics: Cardiovascular Agents; China; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug Combinations; Drug-Eluting Stents; Feasibility Studies; Female; Humans; Hyperplasia; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Probucol; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

To evaluate the effects of the everolimus-eluting Xience™/Promus™ stent (EES) and the sirolimus-eluting Cypher™ stent (SES) on intimal hyperplasia (IH) in diabetic patients.. Patients with diabetes mellitus have increased risk of in-stent restenosis after coronary stent implantation due to intimal hyperplasia (IH).. In a sub study of the Randomized Comparison of Everolimus-Eluting and Sirolimus-Eluting Stents in Patients Treated with Percutaneous Coronary Intervention (SORT OUT IV trial), serial intravascular ultrasound (IVUS) 10-month follow-up data were available in 88 patients, including 48 EES and 40 SES treated patients. IVUS endpoints included IH volume, in-stent % volume obstruction and changes in external elastic membrane (EEM) volume.. Compared with the SES group, IH volume was increased in the EES group [median (interquartile range): 2.8 mm(3) (0.0-12.6) vs. 0.0 mm(3) (0.0-1.1), P = 0.001]. In-stent % volume obstruction was increased in EES compared to SES [median (interquartile range): 1.6% (0.0-8.2) vs. 0.0% (0.0-1.0), P = 0.001]. Peri-stent external elastic membrane (EEM) volume: (post procedure vs. follow-up EES [300 mm(3) (219-491) vs. 307 mm(3) (223-482), P = 0.73] and SES [316 mm(3) (235-399) vs. 323 mm(3) (246-404), P = 0.05]) and peri-stent plaque volume: EES [163 mm(3) (103-273) vs. 184 mm(3) (115-291), P = 0.18] and SES [186 mm(3) (139-248) vs. 175 mm(3) (153-243), P = 0.26]) were unchanged in both groups. In the proximal reference segment a significant increase in plaque area was seen in the EES group only, without vascular remodeling.. In diabetic patients, EES stent implantation was associated with increased IH volume obstruction without involvement of vascular remodeling.

Topics: Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional; Vascular Remodeling

This study sought to assess device-specific outcomes after implantation of bare-metal stents (BMS), zotarolimus-eluting Endeavor Sprint stents (ZES-S), paclitaxel-eluting stents (PES), or everolimus-eluting stents (EES) (Medtronic Cardiovascular, Santa Rosa, California) in all-comer patients undergoing percutaneous coronary intervention.. Few studies have directly compared second-generation drug-eluting stents with each other or with BMS.. We randomized 2,013 patients to BMS, ZES-S, PES, or EES implantation. At 30 days, each stent group received up to 6 or 24 months of clopidogrel therapy. The key efficacy endpoint was the 2-year major adverse cardiac event (MACE) including any death, myocardial infarction, or target vessel revascularization, whereas the cumulative rate of definite or probable stent thrombosis (ST) was the key safety endpoint.. Clinical follow-up at 2 years was complete for 99.7% of patients. The MACE rate was lowest in EES (19.2%; 95% confidence interval [CI]: 16.0 to 22.8), highest in BMS (32.1%; 95% CI: 28.1 to 36.3), and intermediate in PES (26.2%; 95% CI: 22.5 to 30.2) and ZES-S (27.8%; 95% CI: 24.1 to 31.9) groups (chi-square test = 18.9, p = 0.00029). The 2-year incidence of ST in the EES group (1%; 95% CI: 0.4 to 2.2) was similar to that in the ZES-S group (1.4%; 95% CI: 0.7 to 2.8), whereas it was lower compared with the PES (4.6%, 95% CI: 3.1 to 6.8) and BMS (3.6%; 95% CI: 2.4 to 5.6) groups (chi-square = 16.9; p = 0.0001).. Our study shows that cumulative MACE rate, encompassing both safety and efficacy endpoints, was lowest for EES, highest for BMS, and intermediate for PES and ZES-S groups. EES outperformed BMS also with respect to the safety endpoints with regard to definite or probable and definite, probable, or possible ST. (PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY [PRODIGY]; NCT00611286).

Topics: Aged, 80 and over; Chi-Square Distribution; Clopidogrel; Coronary Restenosis; Coronary Thrombosis; Drug Administration Schedule; Drug Therapy, Combination; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Italy; Kaplan-Meier Estimate; Male; Metals; Middle Aged; Myocardial Infarction; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prosthesis Design; Risk Factors; Sirolimus; Stents; Ticlopidine; Time Factors; Treatment Outcome

Restenosis is a frequent complication of coronary stent implantation, especially bare metal stent (BMS) implantation. The everolimus-eluting stent (EES) has previously been shown to be efficacious in the treatment of de novo lesions. We performed this study to evaluate clinical, angiographic and IVUS results after EES implantation for the treatment of BMS ISR. XERES was a prospective, multicentre, nationwide study, enrolling 97 consecutive patients with in-stent restenosis (ISR) after BMS implantation across 20 centres in France. Suitable lesions had a reference vessel diameter between 2.5 mm and 4 mm, a length ≤22 mm and a diameter stenosis between 50 and 100%. The primary endpoint was angiographic in-stent late loss (LL) as determined by quantitative coronary angiography (QCA) at nine-month follow-up. QCA was required to be performed in each included patient and IVUS was performed in a subgroup of 27 patients. At nine-month follow-up, the in-stent late loss was 0.35±0.63 mm. The rate of in-stent binary restenosis was 12.22%, including two complete occlusions. The average volume of neointimal hyperplasia was 15.6±9.9 mm3. The in-stent percent volume obstruction was 8.5±5.2%. The in-segment percent area and diameter obstruction were 32±17% and 27±11%, respectively. Two initial malappositions were persistent and two other patients had late acquired stent malapposition. The cumulative incidence of major adverse cardiac events (MACE) was 10.1%. EES for the treatment of bare metal in-stent restenosis seemed safe and efficacious.

Topics: Adult; Aged; Aged, 80 and over; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; France; Humans; Hyperplasia; Male; Middle Aged; Myocardial Infarction; Neointima; Prospective Studies; Sirolimus; Stents; Thrombosis; Ultrasonography, Interventional

The INSPIRON-I trial is a first-in-man evaluation of the safety and efficacy of the Inspiron drug-eluting stent, a sirolimus-eluting stent with abluminal biodegradable polymer coating and thin cobalt-chromium alloy.. This is a randomised, multicentre comparison between Inspiron and a stent with the same metallic structure but without polymer coating or drug elution (Cronus). The primary objective was to evaluate the in-segment late loss (LLL) at six months. Secondary endpoints included percent in-stent obstruction as measured by intravascular ultrasound (IVUS) at six months and major adverse cardiac events (MACE). Fifty-eight patients were enrolled (60 lesions), 39 for Inspiron and 19 for Cronus. Baseline clinical and angiographic characteristics of both groups were similar. At six months, the in-segment LLL was reduced in the Inspiron group compared to the control group (0.19±0.16 mm vs. 0.58±0.4 mm, respectively; p<0.001), as well as the percent neointimal obstruction (7.8±7.1% vs. 26.5±11.4%; p<0.001). At two-year follow-up, incidence of MACE was similar between groups (7.9 vs. 21.1%, respectively; p=0.20), with lower target lesion revascularisation for Inspiron (0 vs. 21.1%, respectively; p=0.01) and no stent thrombosis.. Sirolimus eluted from an abluminal biodegradable polymer on a cobalt-chromium alloy proved effective in reducing restenosis at six months.

Topics: Absorbable Implants; Aged; Angioplasty, Balloon, Coronary; Brazil; Cardiovascular Agents; Chromium Alloys; Coronary Angiography; Coronary Artery Disease; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Prospective Studies; Prosthesis Design; Single-Blind Method; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Nobori is a novel biolimus A9-eluting stent (BES) coated with a biodegradable polymer only on the abluminal side, which degrades over 6-9 months post-stent deployment. The course of vessel reaction after deployment at these time points remains unclear.. We serially evaluated 28 BES implanted in de novo coronary lesions of 23 patients using optical coherence tomography (OCT) at 6 and 12 months post-stenting. Standard OCT variables, the percentage of stent with peri-strut low-intensity area (PLIA, a region around stent struts homogenously showing lesser intensity than the surrounding tissue, suggesting fibrin deposition or impaired neointima maturation) and that with in-stent thrombi were evaluated. There was a significant, but small increase in neointimal thickness (72 ± 23 to 82 ± 25 µm, P=0.006) from the 6- to the 12-month follow-up, without a significant decrease in minimum lumen area (P=0.30). The incidences of uncovered and malapposed struts were low at 6 months and reduced further at 12 months (3.96 ± 3.97% to 1.51 ± 1.63%, P=0.001, and 0.50 ± 1.84% to 0.06 ± 0.24%, P=0.20, respectively). The frequency of stent with PLIA decreased during the follow-up (57% to 32%, P=0.05) and that with in-stent thrombi also numerically decreased (7% to 0%, P=0.24).. Neointimal hyperplasia was persistently suppressed following BES implantation up to 12 months. Simultaneously, favorable vessel healing was achieved at 6 months without a delaying adverse reaction for up to 12 months.

Topics: Aged; Biodegradable Plastics; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Hyperplasia; Male; Middle Aged; Neointima; Regeneration; Sirolimus; Tomography, Optical Coherence

To our knowledge, no randomised study has compared rates of uncovered stent struts in everolimus (EES) vs. new-generation zotarolimus-eluting (ZES-R) stents in acute coronary syndrome (ACS). The aim of our study was to evaluate the completeness of neointimal coverage with optical coherence tomography (OCT) in ACS patients treated with drug-eluting stents (DES) comparing EES versus new-generation ZES-R.. All eligible ACS patients admitted to four Italian centres with a clinical indication for culprit lesion intervention were randomised 1:1 to EES or ZES-R. The primary study endpoint was the percentage of uncovered stent struts evaluated by optical coherence tomography (OCT) at six months. Secondary endpoints were the percentage of malapposed stent struts, percent neointimal hyperplasia cross-sectional area (CSA) and major adverse cardiac events (MACE) at six months. A total of 60 patients were randomised to EES (n=29) or ZES-R (n=31). No differences were observed in baseline characteristics between the two groups. Overall, 31.7% presented with STEMI, of which 68.4% were anterior. The other patients comprised 41.7% NSTEMI and 26.7% troponin-negative ACS. A mean of 1.3±0.6 lesions were treated per patient, with a mean of 1.3±0.5 stents per lesion. At 30 days there was one sudden death. Six-month OCT analysis was performed in 25 lesions in the EES group and in 24 lesions in the ZES-R group. There was no difference in the primary endpoint of uncovered stent struts between groups (EES 6.42% [3.27, 9.57] vs. ZES-R 7.07% [3.22, 10.92]; p=0.80). Furthermore, there were no differences between groups in the percentage of malapposed stent struts, either with (EES 1.19% [0.34, 2.04] vs. ZES-R 0.85% [0.40, 1.30]; p=0.49) or without coverage (EES 1.06% [0.12, 2.01] vs. ZES-R 0.24% [0.05, 0.44]; p=0.09). Percent neointima CSA was similar in both groups (EES 37.0% [18.6, 55.3] vs. ZES-R 26.6% [18.4, 34.8]; p=0.31). At six-month clinical follow-up, no additional patients died or suffered MI. There were four MACE in the EES group and one in the ZES-R group.. In our study, in patients presenting with ACS, both EES and ZES-R had low percentages of malapposed and uncovered stent struts at six-month OCT analysis.

Topics: Acute Coronary Syndrome; Aged; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Single-Blind Method; Sirolimus; Tomography, Optical Coherence

Previous reports have shown potential disadvantages of limus-derivative drugs for the stenting treatment of patients with diabetes mellitus (DM). METHODS AND RESULTS: We studied 159 coronary artery lesions (DM: n=72, non-DM: n=87) in 123 patients treated with everolimus-eluting stent (EES) and who underwent scheduled 9-month follow-up angiography with optical coherence tomography (OCT) regardless of symptoms. In addition to standard OCT variables, neointimal unevenness score (maximum/average neointimal thickness) and stent eccentricity index (minimum/maximum stent diameter) were calculated for each cross-section. To investigate a potential baseline difference between DM and non-DM lesions, pre- and post-interventional intravascular ultrasound (IVUS) images were also evaluated as an IVUS subgroup analysis. The average neointimal thickness and neointimal coverage did not differ between DM and non-DM patients. DM patients had, however, greater asymmetric stent expansion and variability of neointimal thickness than non-DM patients. There was a weak, but significant association between average stent eccentricity index and neointimal unevenness score. The IVUS substudy showed that the culprit plaque volume and plaque eccentricity in DM patients were significantly greater than in non-DM patients.. Although EES provided a similar level of average neointimal thickness and coverage both in the presence and absence of DM, uneven neointimal suppression occurred in DM patients. A larger plaque volume of the culprit lesion may hamper symmetric stent expansion, possibly explaining the non-uniform neointimal suppression in DM patients.

Topics: Aged; Coronary Artery Disease; Diabetes Mellitus; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Sirolimus; Tomography, Optical Coherence

The aim of the present study was to compare vascular healing response between everolimus-eluting stent (EES) and biolimus-eluting stent (BES) using optical coherence tomography (OCT).. In the NOBORI Biolimus-Eluting Versus XIENCE V/PROMUS Everolimus-Eluting Stent Trial (NEXT), a formal OCT substudy investigated 91 patients (55 EES-treated lesions in 48 patients and 51 BES-treated lesions in 43 patients) with 8-12 months follow-up imaging at 18 centers. A total of 980 frames with 8,996 struts in EES and 907 frames with 8,745 struts in BES were analyzed. Mean neointima thickness in EES and BES was 105±82μm and 91±80μm, respectively (P<0.001). With regard to stent-treated lesions, the percentage of struts not covered by neointima (3±7% vs. 9±10%, P<0.001) and the frequency of stent-treated lesions with any uncovered struts (n=28, 51% vs. n=42, 82%; P<0.001) were significantly lower in EES compared with BES. In addition, the percentage of malapposed struts (0.2±0.8% vs. 1.3±2.8%, P=0.006) and the frequency of stent-treated lesions with any malapposed struts (n=6, 11% vs. n=14, 27%; P=0.028) were significantly lower in EES compared with BES.. Incomplete vascular healing characterized by the presence of struts not covered by neointima and malapposed struts was less common in EES compared with BES.

Topics: Absorbable Implants; Aged; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Sirolimus

This study sought to assess in vivo sex differences in the pathophysiology of ST-segment elevation myocardial infarction (STEMI) and vascular response to primary percutaneous coronary intervention (PCI).. There is no consensus on whether differences in the pathophysiology of STEMI and response to primary PCI between women and men reflect biological factors as opposed to differences in age.. In this prospective, multicenter study, 140 age-matched men and women with STEMI undergoing primary PCI with everolimus-eluting stent were investigated with intravascular optical coherence tomography, histopathology-immunohistochemistry of thrombus aspirates, and serum biomarkers. Primary endpoints were the percentages of culprit plaque rupture at baseline and everolimus-eluting stent strut coverage at 9-month follow-up as determined by optical coherence tomography.. Men and women had similar rates of plaque rupture (50.0% vs. 48.4%; risk ratio [RR]: 1.03; 95% confidence interval [CI]: 0.73 to 1.47; p = 0.56). Nonruptured/eroded plaques comprised 25% of all cases (p = 0.86 in men vs. women). There were no sex differences in composition of aspirated thrombus and immune and inflammatory serum biomarkers. At 9 months, women had similar strut coverage (90.9% vs. 92.5%; difference in medians: RR: 0.2%; 95% CI: -0.4% to 1.3%; p = 0.89) and amount of in-stent neointimal obstruction (10.3% vs. 10.6%; p = 0.76) as men did. There were no sex differences in clinical outcome either at 30-day or 1-year follow-up.. In patients presenting with STEMI undergoing primary PCI, no differences in culprit plaque morphology and factors associated with coronary thrombosis were observed between age-matched men and women. Women also showed similar vascular healing response to everolimus-eluting stents as men did. (Optical Coherence Tomography Assessment of Gender Diversity In Primary Angioplasty: The OCTAVIA Trial [OCTAVIA]; NCT01377207).

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Female; Health Status Disparities; Humans; Male; Middle Aged; Myocardial Infarction; Neointima; Odds Ratio; Percutaneous Coronary Intervention; Prospective Studies; Risk Factors; Rupture, Spontaneous; Sex Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

In this randomized trial, strut coverage and neointimal proliferation of a therapy of bare metal stents (BMSs) postdilated with the paclitaxel drug-eluting balloon (DEB) was compared with everolimus drug-eluting stents (DESs) at 6-month follow-up using optical coherence tomography. We hypothesized sufficient stent coverage at follow-up.. A total of 105 lesions in 90 patients were treated with either XIENCE V DES (n=51) or BMS postdilated with the SeQuent Please DEB (n=54). At follow-up, comparable results on the primary optical coherence tomography end point (percentage uncovered struts 5.64±9.65% in BMS+DEB versus 4.93±9.29% in DES; P=0.366) were found. Thus, BMS+DEB achieved the prespecified noninferiority margin of 5% uncovered struts versus DES (difference between treatment means, 0.71%; one-sided upper 95% confidence interval, 4.14%; noninferiority P=0.04). Optical coherence tomography analysis showed significantly more global neointimal proliferation in the BMS+DEB group (15.7±7.8 versus 11.0±5.2 mm(3) proliferation volume/cm stent length; P=0.002). No significant focal in-stent stenosis analyzed with angiography (percentage diameter stenosis at follow-up, 22.8±11.9 versus 16.9±10.4; P=0.014) and optical coherence tomography (peak local area stenosis, 39.5±13.8% versus 36.8±15.6%; P=0.409) was found.. Good stent strut coverage of >94% was found in both therapy groups. Despite greater suppression of global neointimal growth in DES, both DES and BMS+DEB effectively prevented clinically relevant focal restenosis at 6-month follow-up.. http://www.clinicaltrials.gov. Unique identifier: NCT01056744.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cell Proliferation; Coated Materials, Biocompatible; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Germany; Humans; Male; Metals; Middle Aged; Neointima; Paclitaxel; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Single-Blind Method; Sirolimus; Stents; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Vascular Access Devices

to compare the vascular healing process between the sirolimus-eluting NEVO and the everolimus-eluting Xience stent by optical coherence tomography (OCT) at 1-year follow-up.. Presence of durable polymer on a drug-eluting metallic stent may be the basis of an inflammatory reaction with abnormal healing response. The NEVO stent, having a bioresorbable polymer eluted by reservoir technology, may overcome this problem.. All consecutive patients, who received NEVO or Xience stent implantation between September 2010 and October 2010 in our institution, were included. Vascular healing was assessed at 1-year as percentage of uncovered struts, neointimal thickness (NIT), in-stent/stent area obstruction and pattern of neointima.. A total 47 patients (2:1 randomization, n = 32 NEVO, n = 15 Xience) were included. Eighteen patients underwent angiographic follow-up (eight patients with nine lesions for NEVO vs. 10 patients with 11 lesions for Xience). The angiographic late loss was numerically higher but not statistically different in NEVO compared with Xience treated lesions (0.38 ± 0.47 mm vs. 0.18 ± 0.27 mm; P = 0.171). OCT analysis of 4,912 struts demonstrated similar rates of uncovered struts (0.5 vs. 0.7%, P = 0.462), higher mean NIT (177.76 ± 87.76 µm vs. 132.22 ± 30.91 µm; P = 0.170) and in stent/stent area obstruction (23.02 ± 14.74% vs. 14.17 ± 5.94%, P = 0.120) in the NEVO as compared with Xience.. The NEVO stent with a reservoir technology seems to exhibit more neointimal proliferation as compared to Xience stent. The findings of our study, which currently represent the unique data existing on this reservoir technology, would need to be confirmed in a large population.

Topics: Aged; Cardiovascular Agents; Cell Proliferation; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Europe; Everolimus; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

This study was designed to compare neointimal hyperplasia and peri-stent arterial remodeling after implantation of everolimus-eluting stent (EES) versus sirolimus-eluting stent (SES) using intravascular ultrasound (IVUS). The study population was a subgroup of 278 patients from the EXCELLENT trial, a randomized study comparing EES to SES in de novo coronary artery lesions (total n = 1,443, 3:1 randomization) who underwent post-PCI and 9-month follow-up IVUS evaluation. There were 209 patients in the EES group and 69 in the SES group. Baseline clinical and angiographic characteristics were similar between the two groups except for age and target lesion locations. At 9 months, percent neointimal volume obstruction did not differ between EES and SES (2.6 ± 4.0 % vs. 2.5 ± 4.8 %, p = 0.814). However, the relative change in the vessel (4.3 ± 13.7 % vs. 8.8 ± 18.6 %, p = 0.030) and plaque volume index (4.2 ± 17.4 % vs. 10.5 ± 22.3 %, p = 0.016) of the stented segment from post-intervention to follow-up was significantly less with EES than with SES. In addition, positive peri-stent vascular remodeling defined as an increase in vessel volume index >10 % (27.8 vs. 42.0 %, p = 0.027) and late acquired stent malapposition (LASM, 1.9 vs. 15.9 %, p < 0.001) were observed less frequently with EES than SES. EES and SES were similarly effective in reducing neointimal hyperplasia. However, positive peri-stent vascular remodeling and LASM occurred less frequently with EES than SES.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Logistic Models; Male; Middle Aged; Multivariate Analysis; Neointima; Odds Ratio; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Republic of Korea; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional

The ZOMAXX I trial tested the noninferiority of a zotarolimus-eluting coronary stent (ZoMaxx(™) ) when compared with a paclitaxel-eluting coronary stent (Taxus(™) Express(2™) ) in a randomized trial of percutaneous intervention for de novo coronary artery stenosis. Angiographic analysis at the primary endpoint of 9 months has been reported previously. The purpose of this follow-on analysis was to describe the clinical results of the ZoMaxx and Taxus cohorts of the ZOMAXX I trial after 5 years.. In the ZOMAXX I trial, 199 patients received a ZoMaxx stent and 197 patients received a Taxus stent at 29 investigative sites in Europe, Australia, and New Zealand. The two groups were generally well matched with respect to both clinical and lesional characteristics, including the incidence of diabetes (ZoMaxx 22% vs. Taxus 26%; P = 0.29), reference vessel diameter (ZoMaxx 2.79 ± 0.43 mm vs. Taxus 2.81 ± 0.46 mm; P = 0.65), and lesion length (ZoMaxx 14.9 ± 5.7 mm vs. Taxus 14.6 ± 5.5; P = 0.61). Through 5 years of follow-up, a total of 21 patients had died, six patients had withdrawn, nine had been lost to follow-up, and 13 missed their 5-year visit, leaving a total of 347 patients for analysis (169 ZoMaxx and 178 Taxus). At the 5-year time point, there were no significant differences in any clinical metric including ischemia-driven target lesion revascularization (TLR; ZoMaxx 10.6% vs. Taxus 7.1%; P = 0.29), Q-wave myocardial infarction (ZoMaxx 1.5% vs. Taxus 1.0%; P = 0.99), definite/probable stent thrombosis (ZoMaxx 1.5% vs. Taxus 3.0%; P = 0.34), and cardiac death (ZoMaxx 3.0% vs. Taxus 1.0%; P = 0.28).. After 5 years, the differences in clinical outcome between patients treated with ZoMaxx vs. Taxus stents did not reach statistical significance. However, the nominally higher rate of ischemia-driven TLR (10.6 vs. 7.1%) and the previously reported higher rate of restenosis after 9 months suggest that the ZoMaxx stent afforded less neointimal inhibition when compared with Taxus. © 2013 Wiley Periodicals, Inc.

Topics: Aged; Australia; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Drug-Eluting Stents; Europe; Female; Humans; Male; Middle Aged; Myocardial Infarction; Neointima; New Zealand; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Risk Factors; Severity of Illness Index; Sirolimus; Time Factors; Treatment Outcome

Everolimus-eluting stents (EES) have shown favorable clinical outcomes. However, there have been no studies evaluating early vascular response after EES implantation. We designed a prospective study to compare the neointimal response between zotarolimus-eluting stents (ZES) and EES at 3 and 12 months using serial optical coherence tomography examinations.. Sixty patients who underwent 3-month and 12-month follow-up optical coherence tomography (36 EES, 24 ZES) were included. Neointimal coverage and malapposition were evaluated using a strut-based analysis at both 3 and 12 months. Neointimal hyperplasia area and thrombus were assessed. ZES showed a higher incidence of covered struts (81.5 vs. 77.1%, P<0.0001) and lower incidence of malapposed struts (1.4 vs. 2.3%, P=0.001) than EES at 3 months. However, at 12 months, EES showed a slightly higher incidence of covered struts (96.4 vs. 93.6%, P<0.0001) and a lower incidence of malapposed struts (0.9 vs. 1.1%, P=0.03) than ZES. Neointimal hyperplasia area was greater in the ZES group than in the EES group at both 3 and 12 months (0.77 vs. 0.49 mm, P=0.03 and 1.50 vs. 0.97 mm, P=0.01, respectively). No significant difference in the incidence of thrombus was observed at both 3 and 12 months.. ZES showed rapid neointimal healing compared with EES at 3 months. However, at 12 months, EES had a slightly better vascular healing profile than ZES.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Male; Middle Aged; Neointima; Observer Variation; Odds Ratio; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Reproducibility of Results; Republic of Korea; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

Histologic experimental studies have reported incomplete neointimal healing in overlapping with respect to nonoverlapping segments in drug-eluting stents (DESs), but these observations have not been confirmed in human coronary arteries hitherto. On the contrary, angiographic and optical coherence tomography studies suggest that DES overlap elicits rather an exaggerated than an incomplete neointimal reaction.. Optical coherence tomography studies from 2 randomized trials including sirolimus-eluting, biolimus-eluting, everolimus-eluting, and zotarolimus-eluting stents were analyzed at 9- to 13-month follow-up. Coverage in overlapping segments was compared versus the corresponding nonoverlapping segments of the same stents, using statistical pooled analysis.. Forty-two overlaps were found in 31 patients: 11 in sirolimus-eluting stents, 3 in biolimus-eluting stents, 17 in everolimus-eluting stents, and 11 in zotarolimus-eluting stents. The risk ratio of incomplete coverage was 2.35 (95% CI 1.86-2.98) in overlapping versus nonoverlapping segments. Thickness of coverage in overlaps was only 85% (95% CI 81%-90%) of the thickness in nonoverlaps. Significant heterogeneity of the effect was observed, especially pronounced in the comparison of thickness of coverage (I(2) = 90.31).. The effect of overlapping DES on neointimal inhibition is markedly heterogeneous: on average, DES overlap is associated with more incomplete and thinner coverage, but in some cases, the overlap elicits an exaggerated neointimal reaction, thicker than in the corresponding nonoverlapping segments. These results might help to understand why overlapping DES is associated with worse clinical outcomes, both in terms of thrombotic phenomena and in terms of restenosis and revascularization.

Topics: Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Feasibility Studies; Female; Follow-Up Studies; Humans; Hyperplasia; Immunosuppressive Agents; Male; Middle Aged; Neointima; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Incomplete stent endothelialization is associated with late and very late stent thrombosis. In a post hoc analysis of the BASE-ACS trial, we sought to assess neointimal coverage and coronary flow reserve (CFR) 9 months after implantation of titanium-nitride-oxide-coated bioactive stents (BAS) versus everolimus-eluting stents (EES) in patients with acute coronary syndrome (ACS). In the BASE-ACS trial, 827 patients with ACS were randomized to receive either BAS or EES. In the current study, we examined neointimal growth and strut coverage by optical coherence tomography and CFR by trans-thoracic echocardiography in 28 consecutive non-diabetic patients with the culprit lesion in the left anterior descending coronary artery. The primary endpoints were binary stent strut coverage and CFR at 9-month follow-up. A total of 13 patients were included in the BAS group (2,033 struts); 15 in the EES group (2,898 struts). Binary stent strut coverage was higher and malapposed struts lower with BAS versus EES (99.4 vs 89.2, and 0.2 vs 4.6%, respectively, p < 0.001 for both). Neointimal hyperplasia thickness was greater with BAS versus EES (274.2 vs 100.1 μm, respectively, p < 0.001). CFR was lower with EES versus BAS (2.2 ± 0.8 vs. 3.0 ± 0.5, respectively, p = 0.001). Abnormal CFR (<2.5) were detected in 10 patients in the EES group versus one in the BAS group (p = 0.002). The current study demonstrated that in patients with ACS, BAS resulted in improved neointimal stent strut coverage and better coronary vasodilator function as compared with EES at 9-month follow-up.

Topics: Acute Coronary Syndrome; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Circulation; Coronary Vessels; Drug-Eluting Stents; Echocardiography, Doppler, Color; Echocardiography, Doppler, Pulsed; Everolimus; Humans; Hyperplasia; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Single-Blind Method; Sirolimus; Stents; Time Factors; Titanium; Tomography, Optical Coherence; Treatment Outcome; Vasodilation

This first-in-human multicenter study sought to examine prospectively the safety and efficacy of a new, cobalt chromium thin-strut, coronary absorbable polymer-coated, sirolimus-eluting stent.. Bioabsorbable polymers on drug-eluting stents may lower the long-term risks of inflammation, delayed healing, and adverse events.. We enrolled patients with symptomatic coronary artery disease with stable or unstable angina pectoris and >50% diameter stenosis, amenable to coverage with a ≤23-mm long stent in a vessel 2.5 to 3.5 mm in diameter. All patients received dual antiplatelet therapy after implantation. Patients, in groups of 10, underwent repeat angiography, intravascular ultrasound, and optical coherence tomography at 4, 6, or 8 months, and all patients were seen or contacted at 18 months of follow-up.. The median (range) in-stent late lumen loss (LLL) was 0.03 mm (-0.22 to 0.21 mm), 0.10 mm (-0.03 to 1.2 mm), and 0.08 mm (-0.01 to 0.28 mm), at 4, 6, and 8 months, respectively. At 18 months, the median in-stent LLL was 0.08 mm (-0.30 to 0.46 mm). On optical coherence tomography, the proportion of uncovered stent struts decreased from a median of 7.3% (range 0.4% to 46.3%) at 4 months to 0% (range: 0% to 3.4%) at 18 months. The percentage of neointimal volume obstruction by intravascular ultrasound increased from a median of 5.3% to 9.1% between 4 and 6 months and remained nearly unchanged thereafter through 18 months of follow-up. The only recorded major adverse cardiac event was a myocardial infarction.. At 18 months of follow-up, this absorbable polymer-coated, cobalt chromium sirolimus-eluting stent was associated with a low and stable in-stent LLL, complete strut coverage, and no stent thrombosis. (First-In-Human Trial of the MiStent Drug-Eluting Stent [DES] in Coronary Artery Disease [DESSOLVE-I]; NCT01247428).

Topics: Absorbable Implants; Adult; Aged; Aged, 80 and over; Angina, Stable; Angina, Unstable; Australia; Belgium; Cardiovascular Agents; Chromium Alloys; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug Therapy, Combination; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Neointima; New Zealand; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Polymers; Prospective Studies; Prosthesis Design; Severity of Illness Index; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

The drug-eluting absorbable metal scaffold has demonstrated feasibility, safety, and promising clinical and angiographic outcomes at 12 months in human coronary arteries. This study aimed to evaluate the degradation rate and long-term vascular responses to drug-eluting absorbable metal scaffold.. BIOSOLVE-I was a multicenter, single-arm, first-in-man trial assessing the safety and performance of drug-eluting absorbable metal scaffold in 46 patients with coronary artery disease. Patients who underwent serial invasive imaging, such as quantitative coronary angiography, intravascular ultrasound, and optical coherence tomography, at 6 and 12 months were included in this study. From postimplantation to follow-up, arterial curvature and angulation were significantly increased by the degradation process. The greatest increase was seen from postimplantation to 6 months. The systolic-diastolic changes of the curvature and angulation gradually improved throughout the follow-up period. At the site of implantation, vasoconstriction (-10% mean reduction) was observed during the acetylcholine test at 6 months. The average percent hyperechogenicity of the scaffolded segments showed a continuous decrease over time, with the most pronounced changes within the first 6 months (from 22.1±7.0% to 15.8±3.7%; P<0.001). Struts discernible on optical coherence tomography at 6 and 12 months showed full neointimal coverage, with stabilization of the mean scaffold area from 6 to 12 months. Furthermore, the mean neointimal area (1.55±0.51 versus 1.58±0.34 mm(2); P=0.794) remained unchanged from 6 to 12 months.. This serial analysis of drug-eluting absorbable metal scaffold confirmed the safety and efficacy of this new device, with vasomotion restoration and continued degradation over time demonstrated by multi-invasive imaging modalities.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01168830.

Topics: Absorbable Implants; Angioplasty; Coronary Angiography; Coronary Artery Disease; Everolimus; Follow-Up Studies; Humans; Incidence; Magnesium; Neointima; Sirolimus; Tissue Scaffolds; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

To evaluate long-term patterns of luminal changes after implantation of different types of drug-eluting stents (DES), we analyzed the serial angiographic outcomes of patients implanted with zotarolimus-eluting stents (ZES), sirolimus-eluting stents (SES), or paclitaxel-eluting stents (PES).. Little is known regarding long-term luminal changes after DES implantation.. As a subgroup analysis of the ZEST trial, we performed complete angiographic evaluation immediately after the procedure and at 9 months and 2 years in 111 patients with 165 lesions (36 patients with ZES, 40 with SES, and 35 with PES).. Baseline clinical, angiographic, and procedural characteristics were similar among the three groups. Quantitative angiographic analysis revealed significant decreases in minimal luminal diameter 9 months after stent implantation in the ZES (from 2.71 ± 0.49 to 2.21 ± 0.42 mm, P < 0.001), SES (from 2.79 ± 0.49 to 2.58 ± 0.57 mm, P < 0.001), and PES (from 2.66 ± 0.45 to 2.19 ± 0.52 mm, P < 0.001) groups. However, significant late improvements with different degree in luminal diameter were observed between 9 months and 2 years in the ZES (from 2.21 ± 0.42 to 2.39 ± 0.58 mm, P = 0.001), SES (from 2.58 ± 0.57 to 2.66 ± 0.60 mm, P = 0.039), and PES (from 2.19 ± 0.52 to 2.43 ± 0.52 mm, P < 0.001) groups.. Serial angiographic follow-up study revealed a biphasic luminal response after DES implantation, characterized by an early progression phase for the first 9 months and a late regression phase from 9 months to 2 years.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Linear Models; Male; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Republic of Korea; Single-Blind Method; Sirolimus; Time Factors; Treatment Outcome

There have been no optical coherence tomographic (OCT) data directly comparing the pattern of strut coverage between the 2 second-generation drug-eluting stents in the early period. The aim of this prospective study was to evaluate early strut coverage using optical coherence tomography 3 months after Resolute zotarolimus-eluting stent (ZES-R) or everolimus-eluting stent (EES) implantation in de novo coronary artery lesions. A total of 40 patients who were suitable for the OCT procedure and consented to the study protocol were randomized 1:1 to receive either ZES-R or EES. Among these patients, 35 stented lesions (18 ZES-R, 17 EES) in 34 patients were evaluated by optical coherence tomography immediately and 3 months after stent implantation. Neointimal hyperplasia thickness, percentage of uncovered struts, and the proportion of malapposed struts were measured at 1-mm intervals. An uncovered strut was defined as having a neointimal hyperplasia thickness of 0 μm. At the 3-month OCT evaluation, mean neointimal hyperplasia thickness (ZES-R vs EES 74 ± 41 vs 75 ± 35 μm, p = 0.89) and mean percentage of uncovered struts (ZES-R vs EES 6.2 ± 6.9 vs 4.7 ± 5.1%, p = 0.62) were not significantly different between the groups. The percentage of malapposed struts was also similar between the groups (0.7 ± 2.2% for ZES-R and 0.7 ± 1.7% for EES, p = 0.64). Thrombi were documented in 3 stents (1 [5.6%] in a ZES-R vs 2 [11.8%] in EES, p = 0.60). In conclusion, early stent strut coverage on the basis of serial OCT evaluation was comparable between ZES-R and EES 3 months after stent implantation.

Topics: Aged; Antineoplastic Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Prospective Studies; Sirolimus; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

To quantify the circumferential healing process at 6 and 12 months following scaffold implantation.. The healing process following stent implantation consists of tissue growing on the top of and in the space between each strut. With the ABSORB bioresorbable vascular scaffold (BVS), the outer circumference of the scaffold is detectable by optical coherence tomography (OCT), allowing a more accurate and complete evaluation of the intra-scaffold neointima.. A total of 58 patients (59 lesions), who received an ABSORB BVS 1.1 implantation and a subsequent OCT investigation at 6 (n=28 patients/lesions) or 12 (n=30 patients with 31 lesions) months follow-up were included in the analysis. The thickness of the neointima was calculated circumferentially in the area between the abluminal side of the scaffold and the lumen by means of an automated detection algorithm. The symmetry of the neointima thickness in each cross section was evaluated as the ratio between minimum and maximum thickness.. The neointima area was not different between 6 and 12 months follow-up (1.57±0.42 mm(2) vs. 1.64±0.77 mm(2); p=0.691). No difference was also found in the mean thickness of the neointima (median [IQR]) between the two follow-up time points (210 μm [180-260]) vs. 220 μm [150-260]; p=0.904). However, the symmetry of the neointima thickness was higher at 12 than at 6 months follow-up (0.23 [0.13-0.28] vs. 0.16 [0.08-0.21], p=0.019).. A circumferential evaluation of the healing process following ABSORB implantation is feasible, showing the formation of a neointima layer, that resembles a thick fibrous cap, known for its contribution to plaque stability.

Topics: Absorbable Implants; Algorithms; Cardiovascular Agents; Coronary Artery Disease; Coronary Vessels; Delayed-Action Preparations; Endovascular Procedures; Everolimus; Fibrosis; Humans; Image Processing, Computer-Assisted; Neointima; Polyesters; Predictive Value of Tests; Sirolimus; Time Factors; Tissue Scaffolds; Tomography, Optical Coherence; Treatment Outcome

Statins have anti-inflammatory and antiproliferative properties irrespective of their cholesterol-lowering effects. The aim of the present study was to evaluate a simvastatin-eluting stent (SimvES) in the treatment of de novo coronary lesions.. Forty-two patients with de novo coronary artery lesions were assigned to SimvES, bare-metal stent (BMS) or everolimus-eluting stent (EES) implantation followed by intravascular ultrasound (IVUS) for neointimal quantitative analysis. Six months later, quantitative coronary angiography (QCA) and IVUS were repeated. QCA showed no binary restenosis, a mean in-stent late loss of 1.05 ± 0.25 mm (BMS, 1.12 ± 0.48 mm; EES, 0.20 ± 0.16 mm) and a diameter stenosis of 33.5 ± 7.1% (BMS, 35.5 ± 15.30%; EES, 7.2 ± 3.12%). Control IVUS showed a mean in-stent obstruction of 18.3 ± 9.4% (BMS, 32.8 ± 19.1%; EES, 9.8 ± 2.4%) and a neointimal volume index of 1.58 ± 0.75 mm(3)/mm (BMS, 2.93 ± 1.76 mm(3)/mm; EES, 0.80 ± 0.16 mm(3)/mm). Thrombus, late incomplete apposition and major adverse cardiac events were not observed.. In this sample of patients with de novo coronary lesions, the use of a SimvES was not related to major adverse cardiac events, but it was associated with a higher level of neointimal proliferation than expected.

Topics: Aged; Anticholesteremic Agents; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Simvastatin; Sirolimus; Ultrasonography, Interventional

Restenosis after PCI and/or stent implantation is still one of the challenging problems in the field of interventional cardiology. Different approaches to prevent and to treat restenosis include the use of drug-eluting stents, which have shown to reduce restenosis. Another approach is the treatment with drug-coated balloons. This approach has been proven for different indications, e.g., in-stent restenosis and treatment of peripheral artery disease.. Patients from the PEPCAD III multicentre randomised trial in two study centres (Homburg and Hannover, Germany) were asked to participate in this intravascular ultrasound (IVUS) study at nine-month follow-up. At baseline (nine months before), patients were randomly assigned to receive either a paclitaxel-coated balloon (drug-coated balloon [DCB]) plus a premounted bare metal stent (DCB/BMS) or a sirolimus-eluting stent (drug-eluting stent [DES]) to treat de novo lesions. IVUS at follow-up was performed in order to analyse the restenosis for potential understanding of the mechanism leading to restenosis. IVUS data is available for 55 patients; 26 patients were treated with Cypher(®) DES (Cordis, Miami Lakes, FL, USA) and 29 patients with DCB/BMS. A focal malapposition of the stent was seen in six patients; four after DES and two after DCB/BMS. Stent expansion, calculated as symmetric expansion index, was equal for both groups (0.89 and 0.90). Mean stent area was also equal for both groups (6.25 ± 1.7 vs. 5.65 ± 1.5 mm(2), p=n.s.). The neointimal hyperplasia (calculated as stent area minus lumen area) was significantly different between both groups (0.69 ± 0.49 [DES] vs. 1.08 ± 0.53 mm(2) [DCB/BMS], p<0.01). This resulted in a significantly higher in-stent restenosis in the DCB/BMS group (19.7 vs. 11 %, p<0.01). There is no evidence of geographical mismatch.. First IVUS insights for the DCB/BMS showed a comparable, low incidence of malapposition for the combination of drug-coated balloon and premounted bare metal stent compared to the DES, and stent expansion was good and comparable to DES. However, at nine-month follow-up, the combination of drug-coated balloon and premounted bare metal stent showed higher in-stent restenosis compared to sirolimus DES. Geographical mismatch can be excluded as a reason for this result.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Equipment Failure; Follow-Up Studies; Foreign-Body Migration; Humans; Incidence; Middle Aged; Neointima; Paclitaxel; Sirolimus; Stents; Treatment Outcome; Ultrasonography, Interventional

This study sought to assess stent strut coverage, malapposition, protrusion, and coronary evaginations as markers of healing 5 years after implantation of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES), by optical coherence tomography (OCT).. Early-generation drug-eluting stents have been shown to delay vascular healing.. A total of 88 event-free patients with 1 randomly selected lesion were suitable for final OCT analysis 5 years after drug-eluting stent implantation. The analytical approach was based on a hierarchical Bayesian random-effects model.. OCT analysis was performed at 5 years in 41 SES lesions with 6,380 struts, and in 47 PES lesions with 6,782 struts. A total of 196 struts were uncovered in SES (1.5%) compared with 185 struts in PES lesions (1.0%, 95% credibility interval [CrI]: 0.5 to 1.6; p = 0.32). Malapposed struts were present in 1.2% of SES compared with 0.7% of PES struts (0.7%, 95% CrI: 0.03 to 1.6; p = 0.23). Protruding struts were more frequent among SES (n = 114; 0.8%) than PES lesions (n = 24; 0.1%, 95% CrI: 0.3 to 1.3; p < 0.01). Coronary evaginations were more common among SES- than PES-treated lesions (17 vs. 7 per 100 cross sections, p = 0.003). During extended clinical follow-up, 2 patients suffered from very late stent thrombosis showing a high degree of malapposition, protrusion, and coronary evaginations at the time of OCT investigation.. Early-generation drug-eluting stents show a similar degree of strut coverage and malapposition at 5 years of follow-up. Despite an overall low degree of uncovered and malapposed struts in event-free patients, some lesions show a clustering of these characteristics, indicating a heterogeneous healing response, which may be the source for very late adverse events.

Topics: Angioplasty, Balloon, Coronary; Bayes Theorem; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Paclitaxel; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

The Sparrow stent system (Biosensors International) consists of a self-expanding, ultra-thin nitinol stent mounted within a 0.014″ guidewire designed for small or tortuous coronary lesions. We compared the intravascular ultrasound (IVUS) findings between the novel self-expanding sirolimus-eluting stent (Sparrow-SES) and a conventional balloon-expandable sirolimus-eluting stent (Cypher-SES) in patients with small coronary disease.. We examined 14 lesions treated with the Sparrow-SES from CARE II, compared with 22 small vessel lesions treated with Cypher-SES. IVUS examination was performed post-procedure and 8 months later. Volumetric data were standardized by length as volume index (VI; mm³/mm).. While baseline stent VI trended smaller in Sparrow-SES, follow-up stent VI became similar between the 2 groups due to a significant increase of stent VI in self-expanding Sparrow-SES during the follow-up period. At 8 months, Sparrow-SES showed greater neointima than Cypher-SES (0.8 ± 0.6 mm³/mm vs 0.2 ± 0.2 mm³/mm; P<.001). However, the decrease in lumen VI was only 0.3 ± 0.7 mm³/mm in Sparrow-SES, as compared to 0.1 ± 0.3 mm³/mm in Cypher-SES (P=.259), since the late loss due to neointimal hyperplasia was partly counterbalanced by the chronic stent expansion in Sparrow-SES.. While 8-month follow-up of Sparrow-SES revealed greater amounts of neointimal hyperplasia compared with conventional Cypher-SES, chronic stent expansion preserved the lumen by increasing stent volume. This novel, guidewire-based, self-expanding stent system designed to be delivered through complex anatomies may be useful to treat patients with small-caliber coronary lesions by offering sufficient lumen preservation at follow-up.

Topics: Aged; Coronary Disease; Coronary Vessels; Drug-Eluting Stents; Equipment Design; Female; Follow-Up Studies; Humans; Hyperplasia; Male; Middle Aged; Neointima; Prospective Studies; Retrospective Studies; Single-Blind Method; Sirolimus; Treatment Outcome; Ultrasonography, Interventional

Nonserial observations have shown this bioresorbable scaffold to have no signs of area reduction at 6 months and recovery of vasomotion at 1 year. Serial observations at 6 months and 2 years have to confirm the absence of late restenosis or unfavorable imaging outcomes.. The ABSORB trial is a multicenter single-arm trial assessing the safety and performance of an everolimus-eluting bioresorbable vascular scaffold. Forty-five patients underwent serial invasive imaging, such as quantitative coronary angiography, intravascular ultrasound, and optical coherence tomography at 6 and 24 months of follow-up. From 6 to 24 months, late luminal loss increased from 0.16±0.18 to 0.27±0.20 mm on quantitative coronary angiography, with an increase in neointima of 0.68±0.43 mm(2) on optical coherence tomography and 0.17±0.26 mm(2) on intravascular ultrasound. Struts still recognizable on optical coherence tomography at 2 years showed 99% of neointimal coverage with optical and ultrasonic signs of bioresorption accompanied by increase in mean scaffold area compared with baseline (0.54±1.09 mm(2) on intravascular ultrasound, P=0.003 and 0.77±1.33 m(2) on optical coherence tomography, P=0.016). Two-year major adverse cardiac event rate was 6.8% without any scaffold thrombosis.. This serial analysis of the second generation of the everolimus-eluting bioresorbable vascular scaffold confirmed, at medium term, the safety and efficacy of the new device.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00856856.

Topics: Absorbable Implants; Aged; Angioplasty, Balloon, Coronary; Australia; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Diagnostic Imaging; Drug-Eluting Stents; Europe; Everolimus; Female; Humans; Male; Middle Aged; Neointima; New Zealand; Predictive Value of Tests; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Tissue Scaffolds; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

The purpose of this study was to investigate the vascular response of the everolimus-eluting stent (EES) compared with the paclitaxel-eluting stent (PES) using serial intravascular ultrasound (IVUS).. Data were obtained from the SPIRIT III trial, a multicentre, 2:1 randomised, controlled study comparing EES and PES in de novo native coronary artery lesions. IVUS images were eligible for volumetric analysis at eight-month follow-up in 158 lesions (EES: 113, PES: 45). At eight months, EES had a smaller neointimal volume index (VI: mm3/mm) (EES: 0.4±0.4 vs. PES: 0.8±0.8 mm3/mm, p=0.002) and also a smaller % neointimal obstruction (EES: 7.1±6.7% vs. PES: 11.1±10.5%, p=0.005) compared with PES. While there was no significant change in vessel VI with EES, there was a significant increase in vessel VI in PES during eight-month follow-up (EES: 0.1±1.2 vs. PES: 1.2±0.8 mm3/mm, p=0.001). There were no statistical differences in the frequency of edge dissection or incomplete stent apposition between the two groups.. Detailed IVUS analysis confirmed significantly less neointimal hyperplasia with EES compared with PES. While there was no increase in vessel volume with EES during the eight-month follow-up period, vessel enlargement was seen at the stented segment in PES.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Japan; Male; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Registries; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional; United States

Percutaneous recanalization of total coronary occlusion (TCO) was historically hampered by high rates of restenosis and reocclusions. The PRISON II trial demonstrated a significant restenosis reduction in patients treated with sirolimus-eluting stents compared with bare metal stents for TCO. Similar reductions in restenosis were observed with the second-generation zotarolimus-eluting stent and everolimus-eluting stent. Despite favorable anti-restenotic efficacy, safety concerns evolved after identifying an increased rate of very late stent thrombosis (VLST) with drug-eluting stents (DES) for the treatment of TCO. Late malapposition caused by hypersensitivity reactions and chronic inflammation was suggested as a probable cause of these VLST. New DES with bioresorbable polymer coatings were developed to address these safety concerns. No randomized trials have evaluated the efficacy and safety of the new-generation DES with bioresorbable polymers in patients treated for TCO.. The prospective, randomized, single-blinded, multicenter, non-inferiority PRISON IV trial was designed to evaluate the safety, efficacy, and angiographic outcome of hybrid sirolimus-eluting stents with bioresorbable polymers (Orsiro; Biotronik, Berlin, Germany) compared with everolimus-eluting stents with durable polymers (Xience Prime/Xpedition; Abbott Vascular, Santa Clara, CA, USA) in patients with successfully recanalized TCOs. In total, 330 patients have been randomly allocated to each treatment arm. Patients are eligible with estimated duration of TCO ≥4 weeks with evidence of ischemia in the supply area of the TCO. The primary endpoint is in-segment late luminal loss at 9-month follow-up angiography. Secondary angiographic endpoints include in-stent late luminal loss, minimal luminal diameter, percentage of diameter stenosis, in-stent and in-segment binary restenosis and reocclusions at 9-month follow-up. Additionally, optical coherence tomography is performed in the first 60 randomized patients at 9 months to assess neointima thickness, percentage of neointima coverage, and stent strut malapposition and coverage. Personnel blinded to the allocated treatment will review all angiographic and optical coherence assessments. Secondary clinical endpoints include major adverse cardiac events, clinically driven target vessel revascularization, target vessel failure and stent thrombosis to 5-year clinical follow-up. An independent clinical event committee blinded to the allocated treatment will review all clinical events.. Clinical Trials.gov: NCT01516723. Patient recruitment started in February 2012.

Topics: Angioplasty, Balloon, Coronary; Belgium; Cardiovascular Agents; Clinical Protocols; Coronary Angiography; Coronary Occlusion; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Humans; Neointima; Netherlands; Polymers; Prospective Studies; Prosthesis Design; Research Design; Single-Blind Method; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

The NEVO sirolimus-eluting stent (NEVO SES) is a novel cobalt-chromium stent combining sirolimus release from reservoirs with bioabsorbable polymer to reduce spatial and temporal polymer exposure. The aim of this study was to assess the arterial response to the NEVO SES in a randomized, blinded comparison versus the surface-coated TAXUS Liberte paclitaxel-eluting stent (TAXUS Liberté PES) in human native coronary lesions using intravascular ultrasound (IVUS).. The NEVO ResElution-I IVUS substudy enrolled 100 patients (1:1 randomization). In addition to standard IVUS variables, uniformity of neointimal distribution within stents was evaluated in 3 dimensions by computing mean neointimal thickness within 12 equally spaced radial sectors on every 1-mm cross section along the stented segment. The NEVO SES showed significantly less neointimal proliferation (neointimal obstruction: 5.5±11.0% versus 11.5±9.7%, P=0.02), resulting in less late lumen area loss and smaller maximum cross-sectional narrowing at 6 months. The absolute variability of neointima distribution, assessed by the standard deviation of neointimal thickness within each stent, was significantly reduced with the NEVO SES compared with the TAXUS Liberté PES(0.04±0.04 mm versus 0.10±0.07 mm, P<0.0001). TAXUS Liberté PES showed significantly greater positive vessel remodeling than the NEVO SES (Δvessel volume index: 1.30±1.36 mm(3)/mm versus 0.36±0.63 mm(3)/mm, respectively, P=0.003).. The NEVO SES with focal release of sirolimus from reservoirs achieved significantly greater and more consistent suppression of neointimal hyperplasia than the surface-coated TAXUS Liberté PES. This was associated with less positive remodeling and no increased morphological or morphometric abnormalities surrounding the stent or at the stent margins.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00714883.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Artery Disease; Drug-Eluting Stents; Female; Humans; Hyperplasia; Male; Middle Aged; Neointima; Paclitaxel; Prospective Studies; Single-Blind Method; Sirolimus; Ultrasonography, Interventional

Polymer formulation may affect the efficacy of drug-eluting stents. Resolute, Endeavor, and ZoMaxx are zotarolimus-eluting stents with different stent platforms and different polymer coatings and have been tested in clinical trials. The aim of this analysis was to compare the efficacy of zotarolimus-eluting stents with different polymers.. Data were obtained from the first-in man trial or first randomized trials of each stent, The Clinical RESpOnse EvaLUation of the MedTronic Endeavor CR ABT-578 Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions (RESOLUTE), Randomized Controlled Trial to Evaluate the Safety and Efficacy of the Medtronic AVE ABT-578 Eluting Driver Coronary Stent in De Novo Native Coronary Artery Lesions (ENDEAVOR II), and ZoMaxx I trials. Follow-up intravascular ultrasound analyses (8 to 9 months of follow-up) were possible in 353 patients (Resolute: 88, Endeavor: 98, ZoMaxx: 82, Driver: 85). Volume index (volume/stent length) was obtained for vessel, stent, lumen, peristent plaque, and neointima. Cross-sectional narrowing was defined as neointimal area divided by stent area (%). Neointima-free frame ratio was calculated as the number of frames without intravascular ultrasound-detectable neointima divided by the total number of frames within the stent. At baseline, vessel, lumen, and peristent plaque volume index were not significantly different among the 4 stent groups. At follow-up, percent neointimal obstruction was significantly lower in Resolute compared with Endeavor, ZoMaxx, and Driver (Resolute: 3.7±4.0, Endeavor: 17.5±10.1, ZoMaxx: 14.6±8.1, Driver: 29.4±17.2%; P<0.001). Greater maximum cross-sectional narrowing and higher neointima-free frame ratio, suggesting less neointimal coverage, were observed in Resolute compared with other stent groups. Multiple regression analysis confirmed that the biodurable polymer used in Resolute independently correlated with neointimal suppression among 3 zotarolimus-eluting stents.. The different polymer formulations significantly affect the relative amount of neointima for zotarolimus-eluting stents.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00248079.

Topics: Aged; Angioplasty, Balloon, Coronary; Cell Proliferation; Coronary Angiography; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Polymers; Regression Analysis; Sirolimus; Ultrasonography, Interventional

Telmisartan is a peroxisome proliferator-activated receptor-γ activator with potent anti-inflammatory and antiatherogenic effects. The authors compared the effects of telmisartan and valsartan on neointima volume, atherosclerosis progression and brachial-ankle pulse wave velocity (baPWV) after stenting in hypertensive type 2 diabetes.. This was a prospective, randomised, 8-month follow-up study that included patients with significant coronary stenosis who received telmisartan (n=36) or valsartan (n=37).. University hospital.. Neointima volume and atherosclerosis progression 10 mm proximal and distal to the stented segment were analysed using repeat intravascular ultrasonography. baPWV and inflammatory markers such as interleukin 6, tumour necrosis factor α, C-reactive protein and adiponectin were compared.. Neointima volume at 8 months was significantly lower in the telmisartan group than the valsartan group (1.9±1.0 vs 2.6±1.4 mm(3)/1 mm, p=0.007, respectively). Total plaque volumes 10 mm proximal (7.1±1.5 vs 7.8±1.6 mm(3)/1 mm, p=0.032, respectively) and distal (3.5±1.4 vs 4.1±1.3 mm(3)/1 mm, p=0.028, respectively) to the stent were significantly lower in the telmisartan group than the valsartan group at 8 months. The decrease from baseline in baPWV was significantly greater in the telmisartan group than the valsartan group (-52±104 vs 30±113 cm/s, p=0.002, respectively). The increase from baseline in adiponectin levels and the decreases from baseline in interleukin 6 and tumour necrosis factor α levels were significantly greater in the telmisartan group at 8 months. Retinol-binding protein-4, homeostasis model of assessment index, hemoglobin A(1c) and low-density lipoprotein cholesterol levels decreased significantly in both groups without differences in changes from baseline between the two groups.. Telmisartan reduced neointima volume; atherosclerosis progression 10 mm proximal and distal to the stented segment and baPWV independent of blood pressure, glucose and lipid control in hypertensive type 2 diabetes. Clinical trial no NCT00599885 (clinicaltrials.gov.).

Topics: Adiponectin; Aged; Ankle Brachial Index; Anti-Inflammatory Agents; Benzimidazoles; Benzoates; C-Reactive Protein; Coronary Stenosis; Diabetes Mellitus, Type 2; Disease Progression; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Hypertension; Interleukin-6; Male; Middle Aged; Neointima; Prospective Studies; Single-Blind Method; Sirolimus; Telmisartan; Tetrazoles; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha; Ultrasonography, Interventional; Valine; Valsartan

Patients with diabetes mellitus have increased risk of in-stent restenosis after coronary stent implantation due to neointimal hyperplasia (NIH). The aim of this study was to use quantitative coronary angiography (QCA) and volumetric intravascular ultrasound (IVUS) to evaluate the effects of the sirolimus-eluting Cypher® stent (SES) and the zotarolimus-eluting Endeavor® stent (ZES) on angiographic late lumen loss and intima hyperplasia in diabetic patients.. In the DiabeDES III trial, 127 patients were randomised to SES or ZES stent implantation. Angiographic 10-month follow-up data were available in 105 patients, including 48 SES and 57 ZES treated patients. Angiographic endpoints were in-stent late lumen loss and minimal lumen diameter. IVUS endpoints included NIH volume and in-stent percent volume obstruction. Baseline clinical characteristics and lesion parameters were similar in the two groups. At 10-month follow-up, angiographic in-stent late lumen loss (0.14±0.37 mm vs. 0.74±0.45 mm, p<0.001) was reduced and minimum lumen diameter was higher (2.36±0.53 mm vs. 1.96±0.65, p<0.001) in the SES group as compared to the ZES group. As compared to the ZES group, NIH volume was significantly reduced in the SES group (median [interquartile range]: 0.0 mm3 [0.0 to 1.2] vs. 16.5 mm3 [6.2 to 31.1], p<0.001). In-stent% volume obstruction was significantly reduced in SES as compared to ZES (median [interquartile range]: 0.0% [0.0-0.7] vs. 13.0% [6.7-20.8], p<0.001).. In diabetic patients, the SES reduced angiographic late lumen loss and inhibited NIH more effectively than ZES.

Topics: Aged; Angioplasty, Balloon, Laser-Assisted; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Diabetes Complications; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Hyperplasia; Male; Middle Aged; Neointima; Risk Factors; Single-Blind Method; Sirolimus; Treatment Outcome; Ultrasonography, Interventional

Inconsistent results in outcomes have been observed between the genders after drug-eluting stent implantation. The aim of this study was to investigate gender differences in neointimal proliferation for the Endeavor zotarolimus-eluting stent (ZES) and the Driver bare-metal stent (BMS). A total of 476 (n = 391 ZES, n = 85 BMS) patients whose volumetric intravascular ultrasound analyses were available at 8-month follow-up were studied. At 8 months, neointimal obstruction and maximum cross-sectional narrowing (CSN) were significantly lower in women than in men receiving ZES (neointimal obstruction 15.5 ± 9.5% vs 18.2 ± 10.9%, p = 0.025; maximum CSN 30.3 ± 13.2% vs 34.8 ± 15.0%, p = 0.007). Conversely, these parameters tended to be higher in women than in men receiving BMS (neointimal obstruction 36.3 ± 15.9% vs 27.5 ± 17.2%, p = 0.053; maximum CSN 54.3 ± 18.6% vs 45.6 ± 18.3%, p = 0.080). There was a significant interaction between stent type and gender regarding neointimal obstruction (p = 0.001) and maximum CSN (p = 0.003). Multivariate linear regression analysis revealed that female gender was independently associated with lower neointimal obstruction (p = 0.027) and maximum CSN (p = 0.004) for ZES but not for BMS. Compared to BMS, ZES were independently associated with a reduced risk for binary restenosis in both genders (odds ratio for women 0.003, p = 0.001; odds ratio for men 0.191, p <0.001), but the magnitude of this risk reduction with ZES was significantly greater in women than men (p = 0.015). In conclusion, female gender is independently associated with decreased neointimal hyperplasia in patients treated with ZES. The magnitude of risk reduction for binary restenosis with ZES is significantly greater in women than in men.

Topics: Angioplasty, Balloon, Coronary; California; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Hyperplasia; Male; Middle Aged; Myocardial Infarction; Neointima; Prognosis; Prosthesis Design; Retrospective Studies; Risk Factors; Sex Distribution; Sex Factors; Sirolimus

This study sought to assess the temporal course of neointimal hyperplasia (NIH) formation following implantation of 2 different generations of drug-eluting stents (DES).. The amount of NIH following DES implantation correlates with the potency of the antiproliferative drug, its kinetic release, as well as some individual characteristics, as the presence of diabetes mellitus (DM). Recently, some publications have suggested a continuous growth of NIH following DES, which in some cases, might result in late "catch-up.". Twenty-five patients with single, de novo lesions were treated with sirolimus-eluting stents (SES) (n = 12) and biolimus-eluting stents (BES) (n = 13) and underwent intravascular ultrasound evaluation immediately after the procedure and at 9-month and 5-year follow-ups. The primary endpoint was the comparison of the percentage of NIH obstruction between mid- and long-term follow-up.. Mean age was 59 years and 28% of patients had DM. Overall, the percentage of NIH obstruction significantly increased from 9 months to 5 years (1.3% at first follow-up vs. 4.8% at second follow-up, p = 0.002). There was no significant difference in the variation of vessel volume (Δ = -0.70 mm(3)/mm BES vs. Δ = 0.18 mm(3)/mm SES, p = 0.56), lumen volume (Δ = 0.40 mm(3)/mm BES vs. Δ = -0.05 mm(3)/mm SES, p = 0.71), and percentage of NIH obstruction (Δ = 3.0% BES vs. Δ = 3.8% SES, p = 0.55) among DES. However, diabetic patients had a marked NIH increase along the years (NIH volume at second follow-up: 10.15 mm(3) DM vs. 5.11 mm(3) non-DM, p = 0.028).. The present serial intravascular ultrasound assessment supports the occurrence of continuous NIH growth following different generations of DES. These findings seem to be particularly more pronounced among patients with DM.

Topics: Clopidogrel; Coronary Angiography; Coronary Restenosis; Diabetes Mellitus; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Risk Factors; Sirolimus; Statistics as Topic; Statistics, Nonparametric; Ticlopidine; Time Factors; Ultrasonography, Interventional

The Resolute stent is a newly developed system with a bio-histocompatible polymer that allows programmed drug delivery up to 180 days. The aim of this intravascular ultrasound (IVUS) analysis was to evaluate the short- (4 months) and mid-term (9 months) efficacy using the Resolute stent.. Data were derived from the RESOLUTE trial, a prospective, multicenter, non-randomized, single-arm study to treat de novo native coronary artery lesions. This trial included 2 cohorts with different follow-up periods, and all enrollment patients in this trial received IVUS study. Follow-up IVUS was available in 24 patients (4-month group) and 88 patients (9-month group). Neointimal obstruction (%) was defined as neointimal volume divided by stent volume. Cross-sectional narrowing (CSN, %) was defined as neointimal area divided by stent area. No significant differences in vessel, lumen and stent volume at post-procedure were observed within stented segments between the 4- and 9-month follow-up groups. Although neointimal volume and % neointimal obstruction showed no significant difference between the 2 groups (% neointimal obstruction: 2.2 ± 2.5 vs 3.7 ± 4.0%, P=0.09), maximum CSN was significantly larger in the 9-month group. There were 7 cases of late incomplete stent apposition.. These IVUS results showed minimum growth of neointimal proliferation by the Resolute stent throughout the stented segment up to 9 months follow up. 

Topics: Aged; Coronary Vessels; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neointima; Polymers; Sirolimus; Time Factors; Ultrasonography, Interventional

Ultra-thin strut polymer-free sirolimus-eluting stent (UPF-SES) have two novel characteristics, ultra-thin strut and polymer-free coating, which have the potential to achieve early re-endotherialization. However, a little is known whether early vascular healing of UPF-SES can be achieved in patients with acute coronary syndrome (ACS). The aim of this study was to evaluate the vascular healing after an implantation of UPF-SES in patients with ACS using optical coherence tomography (OCT) at 3 months after the stent implantation. From September 2020 and January 2021, a total of 31 consecutive patients presenting with ACS who underwent OCT-guided percutaneous coronary intervention (PCI) and 3 month follow-up OCT examination were enrolled in the USUI-ACS study. The endpoints of this study were neointimal strut coverage, malapposition, and mean neointimal hyperplasia (NIH) thickness at 3 month follow-up. Over a mean follow-up of 91 days after the initial PCI, the follow-up OCT was examined. The median percentage of covered struts was 98.4% and malapposed struts 0%, and the mean NIH thickness was 80 μm. UPF-SES exhibited an excellent early vascular healing at 3 months in patients with ACS.

Topics: Acute Coronary Syndrome; Coronary Vessels; Drug-Eluting Stents; Humans; Neointima; Percutaneous Coronary Intervention; Polymers; Sirolimus; Stents; Tomography, Optical Coherence; Treatment Outcome

Topics: Angioscopy; Humans; Intracranial Aneurysm; Neointima; Sirolimus; Stents

Topics: Coronary Vessels; Drug-Eluting Stents; Everolimus; Fluorocarbon Polymers; Humans; Neointima; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Tomography, Optical Coherence; Treatment Outcome

We investigated the role of a sirolimus-embedded silk microneedle (MN) wrap as an external vascular device for drug delivery efficacy, inhibition of neointimal hyperplasia, and vascular remodeling. Using dogs, a vein graft model was developed to interpose the carotid or femoral artery with the jugular or femoral vein. The control group contained four dogs with only interposed grafts; the intervention group contained four dogs with vein grafts in which sirolimus-embedded silk-MN wraps were applied. After 12-weeks post-implantation, 15 vein grafts in each group were explanted and analyzed. Vein grafts applied with the rhodamine B-embedded silk-MN wrap showed far higher fluorescent signals than those without the wrap. The diameter of vein grafts in the intervention group decreased or remained stable without dilatation; however, it increased in the control group. The intervention group had femoral vein grafts with a significantly lower mean neointima-to-media ratio, and had vein grafts with an intima layer showing a significantly lower collagen density ratio than the control group. In conclusion, sirolimus-embedded silk-MN wrap in a vein graft model successfully delivered the drug to the intimal layer of the vein grafts. It prevented vein graft dilatation, avoiding shear stress and decreasing wall tension, and it inhibited neointimal hyperplasia.

Topics: Animals; Carotid Arteries; Dogs; Drug Delivery Systems; Hyperplasia; Neointima; Sirolimus

Genoss drug-eluting stent (DES) (Genoss Company Limited) is a new ultrathin sirolimus-eluting stent with an abluminal biodegradable polymer and a cobalt-chromium platform.. The aim of this study was to evaluate vascular healing and neointimal coverage after implantation of the Genoss DES using optical coherence tomography (OCT) 6 months postimplantation.. From August 22, 2019 to June 17, 2020, this multicenter, observational, investigator-initiated study enrolled 20 patients who underwent OCT examination 6 months after Genoss DES implantation and provided informed consent. An analyst, blinded to the patients' and procedural information analyzed OCT images at an independent core laboratory.. Of the 20 patients, 19 with 27 stents in 21 lesions from 21 vessels were included in the analysis, while one patient withdrew consent and was unwilling to undergo follow-up OCT. OCT analysis was performed 204.4 ± 31.9 days after Genoss DES implantation. A total of 4285 stent struts from 661 cross-sections were analyzed. Strut tissue coverage was observed in 98.7 ± 4.3% of struts, with 0.1 ± 1.2% malapposed struts per lesion. The mean thickness of neointimal hyperplasia (NIH) on the covered struts was 0.12 ± 0.04 mm.. Six months after stent implantation, most Genoss DES struts were covered with a thin layer of NIH that was evenly distributed along the stent length. This pilot study evaluated the outcomes of 6 months dual antiplatelet therapy in the context of ultrathin strut stents, providing insight into developing ethical standards and a scientific foundation for conducting an adequately designed clinical trial.

Topics: Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Humans; Neointima; Percutaneous Coronary Intervention; Pilot Projects; Polymers; Prosthesis Design; Sirolimus; Stents; Time Factors; Tomography, Optical Coherence; Treatment Outcome

The role of circulating progenitor cells (CPC) in vascular repair following everolimus-eluting stent (EES) implantation is largely unknown. The aim of the study was to investigate the relationship between temporal variation in CPC levels following EES implantation and the degree of peri-procedural vascular damage, and stent healing, as measured by optical coherence tomography (OCT).Methods and Results: CPC populations (CD133+/KDR+/CD45low) included patients with stable coronary artery disease undergoing stent implantation, and were evaluated using a flow cytometry technique both at baseline and at 1 week. OCT evaluation was performed immediately post-implantation to quantify the stent-related injury and at a 9-month follow up to assess the mid-term vascular response. Twenty patients (mean age 66±9 years; 80% male) with EES-treated stenoses (n=24) were included in this study. Vascular injury score was associated with the 1-week increase of CD133+/KDR+/CD45low (β 0.28 [95% CI 0.15; 0.41]; P<0.001) and with maximum neointimal thickness at a 9-month follow up (β 0.008 [95% CI 0.0004; 0.002]; P=0.04). Inverse relationships between numbers of uncoated and apposed struts for the 9-month and the 1-week delta values of CD133+/KDR+/CD45low (β -12.53 [95% CI -22.17; -2.90]; P=0.011), were also found.. The extent of vessel wall injury influences early changes in the levels of CPC and had an effect on mid-term vascular healing after EES implantation. Early CPC mobilisation was associated with mid-term strut coverage.

Topics: Aged; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Sirolimus; Tomography, Optical Coherence; Treatment Outcome; Vascular System Injuries

Neointimal hyperplasia is a persistent complication after vascular interventions, and it is also the leading cause of vascular graft restenosis and failure after arterial interventions, so novel treatment methods are needed to treat this complication. We hypothesized that adventitial injection of HA/SA hydrogel loaded with PLGA rapamycin nanoparticle (hydrogel-PLGA-rapamycin) could inhibit neointimal hyperplasia in a rat aortic wire injury model. The HA/SA hydrogel was fabricated by the interaction of hyaluronic acid (HA), sodium alginate (SA), and CaCO

Topics: Adventitia; Animals; Endothelial Cells; Hyaluronic Acid; Hydrogels; Hyperplasia; Nanoparticles; Neointima; Rats; Rats, Sprague-Dawley; Rhodamines; Sirolimus; Vascular System Injuries

Balloon angioplasty, stent implantation, and application of an arterial clamp during surgery can induce artery injury such as elastin breaks and endothelium injury, but there is little research focused on the injury induced by these therapeutic manipulations. We established a simple and reproducible small animal aortic injury model and examined intramural injection as a potential therapeutic method to alleviate injury.. The abdominal aorta of male Sprague Dawley (SD) rats or C57BL/6 J mice was clamped sequentially throughout its length. Transforming growth factor β1 (TGFβ1), SB431542, lipopolysaccharide (LPS), Necrostatin-1 (Nec-1), rapamycin, or MHY1485 contained in Pluronic gel was injected intramurally at day 0 or day 7. Animals were fed with chow containing 0.25% beta-aminopropionitrile (BAPN) to evaluate the influence of BAPN. All samples were harvested and examined by immunohistochemistry and immunofluorescence.. The clamped rat aorta showed luminal dilation, elastin fiber breaks, neointimal hyperplasia, and dissection (days 0-90). Intramural injection of TGFβ1, rapamycin and Nec-1 showed a protective effect on the injured aorta, whereas SB431542, MHY1485 and LPS showed more severe wall damage. The aortic lumen in rats fed with BAPN was significantly larger than in control rats (day 7). Mouse aorta showed similar injury with neointimal hyperplasia and elastin fiber breaks.. The rodent arterial injury model is reproducible and may mimic early changes of arterial injury. The model accommodates intramural injection of different drugs that may show mechanisms of arterial injury. Although this is a preliminary animal model, the intramural injection method may have potential clinical application in the future.

Topics: Aminopropionitrile; Animals; Aorta, Abdominal; Disease Models, Animal; Elastin; Hyperplasia; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Neointima; Poloxamer; Rats; Rats, Sprague-Dawley; Sirolimus

Neointimal hyperplasia is a complex process after vascular interventions, acute platelet deposition and smooth muscle cell proliferation both contributed to this process. There are still no perfect solutions to solve this problem. Rivaroxaban is a novel anticoagulant that has been widely used in clinic, it has a good pharmacological effects both in vivo and in vitro. Chitosan microparticle rapamycin (MP-rapa) was fabricated, interspaces of polyglycolic acid (PGA) scaffold were used as a reservoir of MP-rapa, and the scaffold was coated with hyaluronic acid rivaroxaban (MP-rapa-riva). Scanning electronic microscopy (SEM) photographs were taken and water contact angles were measured, rat inferior vena cava (IVC) patch venoplasty model was used; patches were harvested at day 14 and examined by immunohistochemistry and immunofluorescence. SEM photographs showed the microparticles rapamycin were inside the interspace of the scaffold, hyaluronic acid rivaroxaban was also successfully coated onto the surface of the scaffold. There was a thinner neointima, fewer proliferating cell nuclear antigen (PCNA) positive cells, fewer macrophages in the MP-rapa and MP-rapa-riva grafts compared to the control PGA graft. The result showed that this scaffold with dual anticoagulation and antiproliferation functions can effectively inhibit venous neointimal hyperplasia, although this is an animal experiment, it showed promising potential clinical application in the future.

Topics: Animals; Chitosan; Hyaluronic Acid; Hyperplasia; Neointima; Rats; Rivaroxaban; Sirolimus; Tunica Intima

To study the impact of diabetes mellitus (DM) on vascular healing process after implantation of everolimus-eluting stent (EES).. Data from 3 prospective studies (HEAL-EES, REVER, and RESERVOIR), including patients with EES implantation and OCT follow-up, were merged. Differences in vascular healing process assessed by OCT were compared between DM and non-DM using generalized estimating equations. Neointimal proliferation, neointimal signal pattern (high, low, and layered), and uncovered/malapposed struts were evaluated.. A total of 96 lesions (61 DM lesions and 35 non-DM lesions) were included. Mean OCT follow-up time was 8.9 ± 1.5 months and comparable between groups. DM were older, high frequently female and acute coronary syndrome, and received smaller stent than non-DM. No differences were observed in quantitative vascular healing process between groups. However, DM exhibited higher low and layered signal pattern neointima compared to non-DM at lesion level (p = 0.030) and cross-section level (p < 0.001). Uncovered/malapposed struts were comparable between groups.. Quantitative vascular healing process was comparable between groups. However, DM was significantly associated with low signal pattern, which is characteristic of focal inflammation, after EES implantation. Further study might be required to study relationship between neointimal signal pattern and clinical events.

Topics: Coronary Vessels; Diabetes Mellitus; Drug-Eluting Stents; Everolimus; Female; Humans; Neointima; Prospective Studies; Sirolimus; Stents; Time Factors; Tomography, Optical Coherence; Treatment Outcome

To evaluate healing response at strut-level and cross-section level after implanting an ultra-thin strut, everolimus-eluting stent with biodegradable polymer (Tetrilimus) using optical coherence tomography (OCT) at 3 and 6 months.. This was prospective, multi-centre, single-arm, and investigator-initiated study performed at seven Indian sites between January, 2017 and September, 2018. OCT evaluations were performed in 57 patients who underwent Tetrilimus stent implantation. Follow-up OCT was scheduled at 3 months for first 16 patients and at 6 months for 41 patients. Primary outcomes included degree of strut coverage, malapposition and thickness of neointimal hyperplasia (NIH) over covered struts.. Sixty one Tetrilimus stents were implanted to treat 59 lesions in 57 patients. Paired (baseline and follow-up) OCT data was available for 12 patients and 30 patients at 3 and 6 months, respectively. At 3 months, rapid early healing was indicated by 95.48% covered struts per lesion with very low (0.11 ± 0.06 mm) NIH. At 6 months, NIH accumulation was greater (0.21 ± 0.07 mm) as compared to 3 months. 99.77% of struts per lesion were covered at 6 months. There was a very symmetrical healing as shown by very low eccentricity index. There was no difference in vascular healing between stents with small to moderate size vessels (≤3.00 mm) and large size vessels (>3.00 mm).. Present study demonstrated nearly complete endothelization and low NIH accumulation at 3 and 6 months following implantation of ultra-thin strut everolimus-eluting biodegradable polymer-coated Tetrilimus stent. Moreover, though being an ultra-thin strut stent, there was no difference in vascular healing and eccentricity after implantation of the Tetrilimus stents with smaller and larger diameters.

Topics: Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Humans; Neointima; Percutaneous Coronary Intervention; Prospective Studies; Sirolimus; Stents; Tomography, Optical Coherence; Treatment Outcome

The TAXCO study was designed to compare the degree of neointimal coverage and the prevalence of malapposition at 6 months subsequent to implantation of ultrathin biodegradable polymer-coated sirolimus-eluting stents (SES) and durable polymer-coated everolimus-eluting stents (EES) of thin strut thickness using optical coherence tomography (OCT).. The TAXCO study included a total of 42 patients who gave consent and underwent OCT examination between August 2017 and September 2017. Of 42, five patients' OCT examinations were of insufficient quality for quantitative analysis. Thus, the OCT analysis group consisted of 37 patients. Among them, 16 patients were treated with Xience (Abbott Vascular) and 21 with Tetriflex (Sahajanand Medical Technologies Pvt. Ltd., Surat, India), 6 (±1) months earlier at our institution. The OCT was performed using a C7 Dragonfly™ imaging catheter (St. Jude Medical Inc.). All OCT images were analyzed at an independent core laboratory (Cardiovascular Research Center, São Paulo, Brazil) by analysts who were blinded to patient and procedural information.. A total of 763 crosssections (6,882 struts) were analyzed in Xience group, and 1,127 crosssections (9,968 struts) in Tetriflex group. At 6 months, on per-lesion basis, no significant differences were observed between Xience group and Tetriflex group in mean percentage of uncovered struts (1.87 ± 3.86 vs. 2.42 ± 3.46, p = .137) and malapposed struts (0.05 ± 0.2 vs. 0.21 ± 0.69, p = .302). Strut-level neointimal thickness also did not differ between Xience group and Tetriflex group (0.18 ± 0.12 vs. 0.14 ± 0.08 mm, p = .286).. This OCT study found no significant difference in strut coverage and neointimal thickness at 6 months after implantation of biodegradable polymer-coated Tetriflex, when compared with durable polymer-coated Xience.

Topics: Absorbable Implants; Animals; Drug-Eluting Stents; Everolimus; Follow-Up Studies; Humans; Neointima; Odonata; Percutaneous Coronary Intervention; Polymers; Sirolimus; Stents; Tomography, Optical Coherence; Treatment Outcome

Everolimus-eluting stents (EES) are established as latest generation drug eluting stents. However, optical coherence tomography (OCT) assessment of neointimal distribution after EES implantation is lacking. We aimed to assess the longitudinal neointimal distribution pattern after EES implantation using OCT.. Data from 3 prospective studies (HEAL-EES, REVER and RESERVOIR), including patients with EES implantation and OCT follow-up study, were merged. Analyzed stents were divided into 3 segments of equal length (distal, medial, proximal). Longitudinal neointimal distribution patterns were compared between the 3 segments using generalized estimating equation. Neointimal thickness (NIT), neointimal area obstruction, and uncovered or malapposed struts were analyzed.. In total, 86 patients (92 lesions) were analyzed. Time of OCT follow-up was 9.0 ± 1.5 months. NIT was 101.7 ± 65.4 μm and neointimal obstruction area was 12.2 ± 7.6%. The number of assessed struts was the same in all three segments. NIT tended to be higher at the medial segment (108.8 ± 71.1 μm) compared to distal (103.0 ± 63.4 μm) and proximal (93.3 ± 61.1 μm) (p = 0.076). Neointimal area obstruction was significantly different between the 3 segments (12.4 ± 7.5% [distal], 13.1 ± 7.7% [medial], 11.1 ± 7.5% [proximal]; p = 0.037). In the proximal segment, there was a significantly higher frequency of uncovered struts compared to medial and distal segments (3.9% vs. 2.1% vs. 2.5%, p = 0.009). The distribution of malapposed struts was not significantly different.. Distribution of neointimal hyperplasia seems to be different between stent segments, being higher in the medial segment as compared to proximal and distal. Whether this may reflect a response to local pre-interventional plaque burden centrally covered by the stent should be confirmed in a future study.. As optical coherence tomography based assessment of neointimal distribution after everolimus-eluting stent implantation is lacking, we analyzed data of 86 patients (92 lesions) from 3 prospective trials to evaluate neointimal distribution in distal, medial and proximal stent segments. Neointimal hyperplasia seemed to be different between the three segments, with a higher burden in the medial stent segment. Whether this reflects a response to local pre-interventional plaque burden centrally covered by the stent should be confirmed in a future study.

Topics: Coronary Vessels; Drug-Eluting Stents; Everolimus; Follow-Up Studies; Humans; Neointima; Prospective Studies; Sirolimus; Stents; Time Factors; Tomography, Optical Coherence; Treatment Outcome

The aim of SiBi study was to evaluate the early vascular healing and neointimal coverage after implantation of ultrathin (60 μm) biodegradable polymer-coated Tetriflex (Sahajanand Medical Technologies Pvt. Ltd., Surat, India) sirolimus-eluting stent (SES) using optical coherence tomography (OCT) at 4 to 6 weeks after implantation.. SiBi was a single-center, observational, investigator-initiated study. From January 15, 2018 to April 15, 2018, total 29 consecutive patients who had consented and underwent OCT examination at 4-6 weeks after Tetriflex SES implantation were enrolled. All OCT images were analyzed at an independent core laboratory by analysts who were blinded to patient and procedural information.. Of 29 patients, four patients were excluded, as those OCT images were technically inadequate for analysis. Therefore, 25 patients were included in final OCT analysis. Average OCT analysis was performed after 35.3 ± 5 days of Tetriflex implantation. Total 14,024 stent struts in 1,520 cross sections were analyzed. Strut tissue coverage was observed in 91.26 ± 5.53% of struts and malapposed struts were seen in 0.89 ± 1.67%. The mean neointimal hyperplasia (NIH) thickness on the covered struts was 50 ± 30 μm.. A large percentage of struts were found to be covered with thin layer of NIH evenly distributed along the stent length at around 1 month from stent implantation. The results of this pilot study serve as ethical and scientific backbone to conduct an adequately powered clinical trial to evaluate outcomes of short dual-antiplatelet therapy in context of ultrathin strut stent.

Topics: Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Humans; Neointima; Percutaneous Coronary Intervention; Pilot Projects; Polymers; Sirolimus; Stents; Tomography, Optical Coherence; Treatment Outcome

We sought to investigate stent healing and neointimal hyperplasia with ihtDEStiny drug-eluting stent (DES) by optical coherence tomography (OCT) examination conducted 9 months after implantation.. The currently used DES present certain features that have been linked separately to their better performance in terms of efficacy and safety.. First-in-man, prospective and multicenter study including patients treated with ihtDEStiny stent undergoing OCT examination at 9 months follow up. The ihtDEStiny stent is a sirolimus eluting stent with an oval shape ultrathin struts (68 μm) and an abluminal coating of a fluoropolymer containing the antiplatelet agent triflusal. Primary endpoint was the percentage of obstruction of the in-stent volume by the neointima.. In 58 patients (63 lesions) in-stent late lumen loss was 0.11 ± 0.23 mm (95% CI 0.05-0.16) with only in 6% of stents being > 0.5 mm and in-segment binary stenosis was 1.6%. In OCT mean neointima volume obstruction was 10.5 ± 6.9% with a mean neointima thickness of 110.9 ± 89.8 μm. The proportion of uncovered struts was 2.5%, malapposed struts 1.1% and malapposed/uncovered struts 0.7% and no subclinical thrombi detected. Mean incomplete stent apposition area was 0.1 ± 0.1 mm. In this study the ihtDEStiny stent has shown a very low degree of neointimal proliferation associated with a low rate of uncovered/malapposed struts and total absence of subclinical thrombi at 9 months follow up.

Topics: Coronary Vessels; Drug-Eluting Stents; Humans; Neointima; Percutaneous Coronary Intervention; Prospective Studies; Salicylates; Sirolimus; Stents; Tomography, Optical Coherence; Treatment Outcome

The DESSOLVE III OCT substudy aimed to compare serially neointimal hyperplasia volume obstruction (%VO) between the thin-strut MiStent with early polymer elimination and nine-month sustained drug release from microcrystalline sirolimus and the durable polymer-coated everolimus-eluting XIENCE stent at six and 24 months after implantation.. The efficacy endpoint was %VO, calculated as abluminal neointimal volume/stent volume. Thirty-six patients (MiStent 16 patients, 16 lesions; XIENCE 20 patients, 22 lesions) underwent serial OCT evaluation at both six and 24 months. At six months, mean abluminal %VO was significantly lower in the MiStent group than in the XIENCE group (14.54±3.70% vs 19.11±6.70%; p=0.011), whereas the difference in %VO between the two groups decreased at 24 months (20.88±5.72% vs 23.50±7.33%; p=0.24). There was no significant difference in percentage malapposed struts and percentage uncovered struts between the two groups at both time points.. In the serial comparative OCT analysis of the MiStent versus the XIENCE, the MiStent showed a more favourable efficacy for preventing neointimal formation with comparable strut tissue coverage, as compared with the XIENCE at six months, but this difference in %VO decreased at 24 months so that the difference in neointima at 24 months was no longer significant.

Topics: Coronary Artery Disease; Drug-Eluting Stents; Everolimus; Humans; Hyperplasia; Neointima; Percutaneous Coronary Intervention; Polymers; Prosthesis Design; Sirolimus; Stents; Tomography, Optical Coherence; Treatment Outcome

Endovascular therapy in peripheral intervention has grown exponentially in the past decade, but the issue of high restenosis rates in lower extremity arteries still persist. While drug-coated balloons (DCB) have been the device of choice, recent controversary regarding the long-term safety of paclitaxel have raised concern over current DCBs. In our study, we proposed that the direct injection of a sirolimus nanoliposomal formulation (Nanolimus) using a infusion catheter can attenuate inflammation response in injured vessels. In vitro characterization showed retention of the nanoliposomes size and detectable drug amount up to 336 days in storage. For in vivo study, four female, mixed breed swines were subjected to balloon injury of the femoral arteries before treatment with either injection of saline (n = 4) or Nanolimus (n = 12) using the Bullfrog catheter. Pharmacokinetic analysis demonstrated sustained sirolimus release in the arteries and undetectable systemic drug level at 28 days. Arteries treated with Nanolimus showed significant reduction in neointima area (0.2 ± 0.3 mm

Topics: Animals; Constriction, Pathologic; Female; Femoral Artery; Lower Extremity; Neointima; Paclitaxel; Sirolimus; Swine

Pulmonary vein obstruction (PVO) frequently occurs after repair of total anomalous pulmonary vein connection with progression of intimal hyperplasia from the anastomotic site toward upstream pulmonary veins (PVs). However, the understanding of mechanism in PVO progression is constrained by lack of data derived from a physiological model of the disease, and no prophylaxis has been established. We developed a new PVO animal model, investigated the mechanisms of PVO progression, and examined a new prophylactic strategy.. We developed a chronic PVO model using infant domestic pigs by cutting and resuturing the left lower PV followed by weekly hemodynamic parameter measurement and angiographic assessment of the anastomosed PV. Subsequently, we tested a novel therapeutic strategy with external application of rapamycin-eluting film to the anastomotic site.. We found the pig PVO model mimicked human PVO hemodynamically and histopathologically. This model exhibited increased expression levels of Ki-67 and phospho-mammalian target of rapamycin in smooth muscle-like cells at the anastomotic neointima. In addition, contractile to synthetic phenotypic transition; that is, dedifferentiation of smooth muscle cells and mammalian target of rapamycin pathway activation in the neointima of upstream PVs were observed. Rapamycin-eluting films externally applied around the anastomotic site inhibited the activation of mammalian target of rapamycin in the smooth muscle-like cells of neointima, and delayed PV anastomotic stenosis.. We demonstrate the evidence on dedifferentiation of smooth muscle-like cells and mammalian target of rapamycin pathway activation in the pathogenesis of PVO progression. Delivery of rapamycin to the anastomotic site from the external side delayed PV anastomotic stenosis, implicating a new therapeutic strategy to prevent PVO progression.

Topics: Angiography; Animals; Biomarkers; Disease Models, Animal; Disease Progression; Muscle, Smooth; Neointima; Pulmonary Veins; Pulmonary Veno-Occlusive Disease; Sirolimus; Swine; TOR Serine-Threonine Kinases; Vascular Remodeling

Topics: Angioplasty, Balloon; Angioplasty, Balloon, Coronary; Animals; Coronary Restenosis; Heparin; Neointima; Rats; Sirolimus; Stents; Swine

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.. 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.. 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.. 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.

Topics: Absorbable Implants; Animals; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Vessels; Materials Testing; Models, Animal; Neointima; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Swine; Swine, Miniature; Time Factors; Tomography, Optical Coherence

Peri-strut low-intensity area (PLIA) assessed by optical coherence tomography (OCT) has been reported as a potential marker of abnormal neointimal healing. We aimed to evaluate the impact of PLIA on clinical events and its risk factors.. We enrolled 264 consecutive patients treated with an everolimus-eluting stent (EES) who underwent follow-up OCT six to 12 months after stenting. Target lesion revascularisation (TLR) was evaluated at a mean 42.6 months after stenting. PLIA was identified in 102 patients; 162 patients did not exhibit PLIA. Multivariate Cox hazard regression analysis indicated that the presence of PLIA (PLIA+) was an independent risk factor for an increased incidence of TLR (hazard ratio [HR]: 4.608, p=0.003). In both the early (<1 year) and late (>1 year) phases, the incidence of TLR was significantly higher in the PLIA+ group (p<0.001 and p<0.001, respectively). In the Cox hazard regression analysis, current smoking and increased C-reactive protein level were independently associated with PLIA+ (HR: 1.737, p=0.009; HR: 2.435, p=0.008, respectively).. The presence of PLIA on midterm OCT was associated with TLR after EES implantation. Detailed stent assessment by midterm OCT may help to predict stent failure in patients treated with EES.

Topics: Coronary Vessels; Drug-Eluting Stents; Everolimus; Follow-Up Studies; Humans; Neointima; Sirolimus; Tomography, Optical Coherence; Treatment Outcome

Early-generation drug-eluting stents (DES) have been demonstrated to delay vascular healing. Limited optical coherence tomography (OCT) data on the very long-term neointimal response after DES implantation are available. The aim of this study was a serial OCT assessment of neointimal thickness, stent strut coverage, malapposition, and protrusion as markers of neointimal response at 3 and 9 years after implantation of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). In this single-centre, longitudinal study consecutive patients undergoing elective PCI with SES or PES were included. OCT analysis was performed after 3 and 9 years by the independent core laboratory. A total of 22 subjects (8 SES and 14 PES) underwent an OCT assessment at 3 and 9 years post index procedure. The lumen, neointimal and malapposition area and the neointimal thickness (SES ∆50 µm, p = 0.195, PES ∆10 µm, p = 0.951) did not change significantly over the 6 year follow-up. No differences in the incidence of uncovered, malapposed or protruding struts were found in each type of stent. At 3 and 9 years after PCI, implantation of early-generation SES and PES may be associated with similar neointimal thickness, strut coverage, malapposition and protrusion, as assessed by serial OCT examination among patients with uneventful follow-up at 3 years post procedure. The small size of the study warrants judicious interpretation of our results and confirmation in larger multimodality imaging studies, including patients treated with contemporary stent platforms.

Topics: Aged; Cardiovascular Agents; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Longitudinal Studies; Male; Middle Aged; Neointima; Observer Variation; Paclitaxel; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Reproducibility of Results; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

Topics: Absorbable Implants; Drug-Eluting Stents; Humans; Magnesium; Neointima; Sirolimus

Normalized optical density (NOD) measured by optical coherence tomography represents neointimal maturity after coronary stent implantation and is correlated with morphologic information provided by both light and electron microscopy. We aimed to test the hypothesis that even second generation drug-eluting stents (DESs) are problematic in terms of neointimal maturity. We implanted bare-metal stents (BMS: n = 14), everolimus-eluting stents (EESs: n = 15) or zotarolimus-eluting stents (ZESs: n = 12) at 41 sites in 32 patients with stable coronary artery disease. OCT was performed at up to 12 months of follow-up, and the average optical density of neointima covering struts was evaluated. NOD was calculated as the optical density of stent-strut covering tissue divided by the optical density of the struts. We also measured circulating CD34+ /CD133+ /CD45low cells, and serum levels of stromal cell-derived factor (SDF)-1, interleukin (IL)-8 and matrix metalloproteinase (MMP)-9 at baseline and follow-up. NOD was lower in the EES (0.70 ± 0.06) group than in the BMS (0.76 ± 0.07, P < 0.05) and ZES (0.76 ± 0.06, P < 0.05) groups. The mean neointimal area (R = 0.33, P < 0.05) and mean neointimal thickness (R = 0.37, P < 0.05) were correlated with NOD. Although NOD was not correlated with percent changes in circulating endothelial progenitor cells, and the levels of SDF-1 and IL-8, it was negatively correlated with the change in MMP-9 level (R = - 0.51, P < 0.01). Neointimal maturity might be lower at EES sites than BMS or ZES sites. This might lead to impaired neointimal tissue growth and matrix degradation. These results suggest a specific pathophysiology after DES implantation.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Chemokine CXCL12; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Endothelial Progenitor Cells; Everolimus; Female; Humans; Interleukin-8; Male; Matrix Metalloproteinase 9; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Vascular Remodeling

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.. 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.. 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.

Topics: Absorbable Implants; Animals; Coronary Stenosis; Disease Models, Animal; Drug-Eluting Stents; Everolimus; Inflammation; Neointima; Percutaneous Coronary Intervention; Polymers; Sirolimus; Swine; Wound Healing

The aim of this study was to compare neointima proliferation in three drug-eluting stents (DES) produced by the same company (Balton, Poland) which are covered with a biodegradable polymer and elute sirolimus (concentration: 1.0 and 1.2 µg/mm

Topics: Absorbable Implants; Aged; Cardiovascular Agents; Cell Proliferation; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Hyperplasia; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Polymers; Predictive Value of Tests; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

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).. Optical coherence tomography (OCT) suggests that in-stent neointimal morphology influences clinical outcomes after DES implantation.. 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.. 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.. 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.

Topics: Absorbable Implants; Aged; Cardiovascular Agents; Chromium Alloys; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Poland; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Little is known regarding the association between chronological out-stent vessel remodeling and in-stent tissue characteristics of drug-eluting stent (DES) failure. We aimed to evaluate the relationship between serial vessel remodeling after DES implantation and neoatherosclerosis (NA) assessed by optical coherence tomography (OCT) in patients with DES failure.. Forty-eight patients with late and very late stent failure after DES implantation, who underwent intravascular ultrasound (IVUS) at both the initial percutaneous coronary intervention and the time of stent failure and OCT imaging at the time of stent failure, were retrospectively investigated. NA on OCT was defined as neointimal formation with the presence of lipids or calcification inside the stents. Lesions were divided into two groups: those with NA and those without NA (NA: n=21; non-NA: n=27). From the serial IVUS examinations, external elastic membrane (EEM) volume and out-stent plaque volume were normalized by stent length and their changes were compared between the two groups.. The NA group showed older stent age [median, 5.1 years (IQR, 4.8-8.3) vs 1.4 years (IQR, 0.8-4.5); p<0.01] and more prevalent sirolimus-eluting stents (SES; 81.0% vs. 29.6%; p<0.01). IVUS findings of the NA group showed a greater serial increase in both normalized EEM volume and normalized out-stent plaque volume (OSPVI) [1.05 (0.41-1.90) vs. 0.11 (-0.64 to 0.80) mm. NA in late and very late DES failure was associated with out-stent positive vessel remodeling. In addition to SES, out-stent progressive positive remodeling may help predict NA in late and very late DES failure.

Topics: Aged; Drug-Eluting Stents; Equipment Failure Analysis; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Prosthesis Failure; Retrospective Studies; Sirolimus; Time Factors; Tomography, Optical Coherence; Ultrasonography; Vascular Remodeling

The clinical benefit of second-generation drug-eluting stents (2nd DES) has been established, compared to first-generation drug-eluting stents (1st DES). However, pathological response after 2nd DES implantation remains unclear, particularly in the Japanese population.. Using specimens obtained by autopsy, we compared the histology between 2nd DES (41 sections) and 1st DES (38 sections) lesions within 1 year after stent implantation to evaluate early tissue reaction in Japanese patients. Stent segments were fixed with 10% buffered formalin and embedded in plastic, followed by hematoxylin-eosin and Masson's trichrome staining. Ratio of covered stent struts was calculated, and the area of fibrin deposition was morphometrically evaluated. The degree of inflammation around struts was examined semi-quantitatively (score 0-3).. The ratio of covered struts and mean fibrin area of 2nd DES were 0.69±0.05 and 658.0±173.4μm. Histopathological analysis showed advanced healing process in 2nd DES compared with 1st DES lesions. These results are consistent with clinical beneficial outcome of 2nd DES implantation.

Topics: Aged; Aneurysm, Ruptured; Colitis, Ischemic; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Fibrin; Heart Failure; Humans; Inflammation; Japan; Male; Middle Aged; Neointima; Pancreatitis; Pneumonia; Renal Insufficiency; Risk Factors; Sepsis; Sirolimus; Treatment Outcome

The objectives of this study are to assess the healing score (HS) and neointimal thickness of the Xinsorb scaffold, and explore the relationships between the implanted patterns, neointimal thickness, and HS. The Xinsorb bioresorbable sirolimus-eluting scaffold is the first domestically designed and fabricated bioresorbable scaffold in China. The 6-month follow-up found it to be safe and effective in the treatment of single de novo coronary lesions. The Xinsorb scaffolds were implanted in 30 patients with symptomatic ischemic coronary disease. A 6-month follow-up was performed in a subset of 19 patients; the HS and neointimal thickness were evaluated by optical coherence tomography. Struts were classified as ApposedCovered, ApposedUncovered, MalapposedCovered, MalapposedUncovered, jailing and presence of intraluminal masses. The implanted pressure, implanted duration, and post-expansion pressure were recorded during the operation. We evaluated the relationship between the HS or neointimal thickness and the implanted pressure, holding time, and post-expansion pressure. The device and procedure success rates were both 100%. No major adverse cardiac or scaffold-thrombus related events occurred. At 6 months, 12,295 struts were analyzed to determine the HS (6.23) and neointimal thickness (0.1021 ± 0.05718 mm) in the Xinsorb scaffolds. There was a strong negative relationship between the HS and the implantation duration (Pearson r = - 0.518, p = 0.023). A significant negative relationship also existed between the HS and post-dilatation (Pearson r = - 0.631, p = 0.004). The Xinsorb scaffold HS appears negative correlated with the implanted duration and post-dilatation. We will further evaluate the HS of randomized controlled trial of the Xissorb scaffold.

Topics: Absorbable Implants; Adult; Aged; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Coronary Angiography; Coronary Disease; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Prospective Studies; Severity of Illness Index; Sirolimus; Tissue Scaffolds; Tomography, Optical Coherence

We aimed to assess early neointimal healing by optical coherence tomography (OCT) 3 months after implantation of the ultrathin Orsiro® sirolimus-eluting stent with biodegradable polymer.. New generations of drug-eluting stents with biodegradable polymer have been developed to avoid the continued vascular irritation of durable polymers.. In this prospective, open-label study, 34 patients received an Orsiro® sirolimus-eluting stent with biodegradable polymer. In a subgroup of patients (n = 15), the intervention was performed under OCT guidance. All patients underwent OCT-examination at three months. The primary endpoint was 3-month neointimal healing (NIH) score, calculated by weighing the presence of filling defects, malapposed and uncovered struts. Secondary endpoint was maturity of tissue coverage at 3 months.. At 3 months, NIH score was 13.7 (5.4-22), covered struts per lesion were 90% (84-97%), malapposed struts were 2.7% (0.8-5.4%) and rate of mature tissue coverage was 47% (42-53%). No target lesion failure occurred up to 12 months. Patients with OCT-guided stent implantation demonstrated a trend toward earlier stent healing as demonstrated by superior NIH scores (angio guided: 17.6% [8.8-26.4]; OCT-guided: 9.8% [4.0-15.5]; mean difference -8, [95%CI: -18.7-2.9], P = 0.123). This group had significantly more covered struts per lesion (angio-guided: 86% [82-90]; 95% [92-99]; mean difference 9% [95%CI: 3-15], P = 0.001).. The Orsiro® sirolimus-eluting stent with biodegradable polymer shows early vascular healing with a high rate of strut coverage at 3-month follow-up. OCT guided stent implantation had a positive impact on early vascular healing.

Topics: Aged; Biodegradable Plastics; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Prospective Studies; Sirolimus; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

Delayed healing and endothelial dysfunction may occur with drug-eluting stents (DES), promoting accelerated infiltration of lipids in the neointima and development of neoatherosclerosis (NA). Pathology data suggest durable polymer (DP) of DES to play a major role in this process. Whether biodegradable polymer (BP) may address these issues is uncertain. We compared in vivo vessel healing and NA of current generation BP- or DP-DES using serial optical coherence tomography (OCT) assessments.. Ninety patients with multivessel coronary artery disease were randomized 1:1 to BP everolimus-eluting stents (EES, Synergy) or DP zotarolimus-eluting stents (ZES, Resolute Integrity). Co-primary endpoints were the maximum length of uncovered struts at 3 months (powered for non-inferiority) and the percentage of patients presenting with frames of NA at 18 months (powered for superiority) as measured by OCT. The maximum length of uncovered struts at 3 months was 10 ± 8 mm in the BP-EES group and 11 ± 7 mm in the DP-ZES group (mean difference -1 mm; upper 97.5% confidence interval +2 mm; P = 0.05 for non-inferiority; P = 0.45 for superiority). The percentage of patients presenting with frames of NA at 18 months was low and similar between BP-EES and DP-ZES groups (11.6% vs. 15.9%; P = 0.56). There was no stent thrombosis in both groups at 24 months.. BP-EES and DP-ZES showed a similar healing response at 3 months and a low incidence of NA at 18 months. Biocompatible polymers, regardless of whether they are durable or biodegradable, may favourably impact the long-term vascular response to current-generation DES.

Topics: Absorbable Implants; Aged; Atherosclerosis; Biocompatible Materials; Coronary Artery Disease; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Sirolimus; Time Factors; Tomography, Optical Coherence; Wound Healing

Drug-eluting stents are the most commonly employed method to control post-angioplasty restenosis. Unfortunately, they exacerbate life-threatening stent thrombosis because of endothelium damage caused by both drug and stenting. To solve this major medical problem, an endothelium-protective and stent-free anti-restenotic method is highly desirable. Here we have generated a biomimetic intravenous delivery system using dendritic polymer-based nanoclusters, which were coated with platelet membranes for targeting to the injured arterial wall where restenosis occurs. These nanoclusters were loaded with an endothelium-protective epigenetic inhibitor (JQ1) or an endothelium-toxic status quo drug (rapamycin), and compared for their ability to mitigate restenosis without hindering the process of re-endothelialization. Fluorescence imaging of Cy5-tagged biomimetic nanoclusters indicated their robust homing to injured, but not uninjured arteries. Two weeks after angioplasty, compared to no-drug control, both rapamycin- and JQ1-loaded biomimetic nanoclusters substantially reduced (by >60%) neointimal hyperplasia, the primary cause of restenosis. However, whereas the rapamycin formulation impaired the endothelial re-coverage of the denuded inner arterial wall, the JQ1 formulation preserved endothelial recovery. In summary, we have created an endothelium-protective anti-restenotic system with biomimetic nanoclusters containing an epigenetic inhibitor. This system warrants further development for a non-thrombogenic and stent-free method for clinical applications.

Topics: Animals; Azepines; Biomimetic Materials; Carotid Arteries; Carotid Artery Injuries; Coronary Restenosis; Drug-Eluting Stents; Endothelium, Vascular; Humans; Male; Nanoparticles; Neointima; Rats, Sprague-Dawley; Sirolimus; Triazoles

The aim of this study was to investigate whether the underlying plaque type affects the neointimal coverage after drug-eluting stent implantation.. A total of 1793 struts in 22 zotarolimus-eluting stents were assessed using optical coherence tomography imaging within 3 months of implantation. Neointimal coverage was evaluated within 5 mm from each stent edge on cross-sectional optical coherence tomography images at every 1-mm interval. The percentage of struts covered by neointima was compared among the normal segment group, the fibrous plaque group, and the lipid plaque group on the basis of the underlying plaque type.. The percentage of covered strut was significantly lower in the normal segment group than in the fibrous plaque group (35.9±30.2 vs. 57.1±31.0%, P<0.05) and the lipid plaque group (vs. 64.7±23.5%, P<0.01). The neointima was significantly thinner in the normal segment group than in the lipid plaque group (19.0±22.3 vs. 32.0±18.8 μm, P<0.01). The percentage of struts on the normal segment was significantly higher in cross-sections with a ratio of uncovered to total struts per section more than 0.3 than in cross-sections with a ratio up to 0.3 (32.4±31.7 vs. 19.5±33.8%, P<0.01).. Struts on the normal segment were less covered and had thinner neointima than struts on the lipid plaque at the stent edge within 3 months after zotarolimus-eluting stent implantation. Caution should be exercised when implanting longer drug-eluting stents to achieve uniform strut coverage in the early phase.

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Fibrosis; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Prosthesis Design; Retrospective Studies; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

We sought to investigate subclinical neoatherosclerotic changes and the healing response to sirolimus-eluting stents (SES) to clarify the clinical safety and the neointimal pathology of SES more than 10 years after implantation.. We investigated a total of 180 SES without stent failure in 103 patients who underwent optical coherence tomography (OCT) examination of stented vessels more than five years after implantation. We assessed the presence or absence of neoatherosclerosis and the healing process using OCT and compared the results between stents at five to 10 years after implantation (Group A, 114 stents with 19,873 struts) and stents more than 10 years after implantation (Group B, 66 stents with 10,937 struts). The median stent age of the whole cohort was 9.4 (7.8-10.9) years. In the OCT analysis, Group B was associated with higher frequencies of neoatherosclerosis than Group A. However, the prevalence of uncovered stents and stent malapposition was not significantly different between the two groups.. SES of more than 10 years of age are associated with a higher frequency of OCT-defined neoatherosclerosis than SES of five to 10 years of age, indicating continuous development of neoatherosclerosis beyond 10 years after implantation.

Topics: Coronary Vessels; Drug-Eluting Stents; Humans; Neointima; Prevalence; Sirolimus; Stents; Tomography, Optical Coherence; Treatment Outcome

Coronary angioscopy (CAS) is used to comprehensively evaluate vascular responses after drug-eluting stent (DES) implantation. This study sought to evaluate the capability of CAS for evaluating DES strut coverage grade and color grade of the intima compared with histological images in coronary autopsy specimens. Methods and Results: A total of 23 DES extracted from 11 autopsy hearts were imaged by CAS. All stent segments were graded as white or yellow according to the luminal surface color, and thrombus was evaluated according to a previous report. Neointimal coverage over the DES was graded as 0 (stent struts fully visible) to grade 3 (stent struts fully embedded and invisible). Of 76 segments, neointimal coverage was graded as 0 in 35 (46%), 1 in 22 (29%), 2 in 8 (11%), and 3 in 11 (14%). The neointimal thickness increased significantly with increasing neointimal coverage grade on angioscopy. Neointimal color was graded as white in 40 (53%) and yellow in 36 segments (47%). Histological analysis revealed that yellow neointima contained fibroatheroma, foam cells accumulation or superficial calcium deposition. A thrombus was identified in 13 segments. Thrombi adherent around the stent strut were partly intimal erythrocyte accumulation around the strut.. In-stent yellow segment had atherosclerotic components. CAS could evaluate vascular status comprehensively after DES implantation.

Topics: Aged; Coronary Artery Disease; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Plaque, Atherosclerotic; Sirolimus

To compare vascular healing after drug-eluting stent (DES) implantation between plaque rupture (PR) and plaque erosion (PE).. Vascular response after stent implantation in patients with PR has been extensively studied. Little is known about vascular healing after stent implantation in PE.. Sixty-five ACS patients who received optical coherence tomography (OCT) imaging of the culprit lesions both before and after stent implantation at baseline as well as at 6 months were included in this study. Patients were divided into two groups: PR (n = 19) and PE (n = 24). Prestent thrombus burden and poststent intrastent structure (ISS) volume were analyzed during the index procedure. The ratio of uncovered to total stent struts per cross-section score (RUTTS) and neointimal thickness and area were measured at follow-up.. OCT imaging showed that compared with PR, PE showed a significantly lower prestent thrombus score (34.2 ± 19.2 vs. 68.6 ± 44.2, P = 0.009) at baseline and a smaller poststent ISS volume (0.7 ± 0.9 mm. PE was associated with less favorable healing following DES implantation when compared to PR at 6 months, indicating longer dual-antiplatelet therapy may be necessary for patients with PE. © 2017 Wiley Periodicals, Inc.

Topics: Aged; Cardiovascular Agents; Chronic Disease; Coronary Occlusion; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Predictive Value of Tests; Prosthesis Design; Rupture, Spontaneous; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

Systemic treatment with sirolimus, as used for immunosuppression in transplant patients, results in markedly low rates of in-stent restenosis. Since the underlying mechanisms remain obscure, we aimed to determine the molecular and cellular effects of systemic sirolimus treatment on vascular remodeling processes.. Systemic sirolimus treatment significantly reduced smooth muscle cell (SMC) proliferation 14days after wire-induced injury and neointima formation 28days after injury in C57BL/6 mice, while simultaneously impairing re-endothelialization. Interestingly, in vitro, sirolimus had no direct effect on the proliferation of SMC or endothelial cells (EC) at serum concentrations observed after systemic application. In contrast, sirolimus reduced the adhesion of leukocytes (CD45. Our findings show that systemic sirolimus treatment effectively prevents SMC and EC proliferation in vivo without directly affecting these cells. Instead, sirolimus prevents neointima formation and re-endothelialization by attenuating the inflammatory response after injury with secondary effects on SMC and EC proliferation. Thus, despite a similar net effect, the mechanisms of systemic sirolimus treatment are largely different from the local effects achieved after application of sirolimus-eluting stents.

Topics: Animals; Anti-Inflammatory Agents; Cell Proliferation; Cells, Cultured; Dose-Response Relationship, Drug; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neointima; Random Allocation; Sirolimus; Treatment Outcome

At present, there are no clinical options for preventing neointima-caused (re)stenosis after open surgery such as bypass surgery for treating flow-limiting vascular disease. Perivascular drug delivery is a promising strategy, but in translational research, it remains a major challenge to achieve long-term (e.g., > 3 months) anti(re)stenotic efficacy. In this study, we engineered a unique drug delivery system consisting of durable unimolecular micelles, formed by single multiarm star amphiphilic block copolymers with only covalent bonds, and a thermosensitive hydrogel formed by a poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide) triblock copolymer (abbreviated as triblock gel) that is stable for about 4 weeks in vitro. The drug-containing unimolecular micelles (UMs) suspended in Triblock gel were able to sustain rapamycin release for over 4 months. Remarkably, even 3 months after perivascular application of the rapamycin-loaded micelles in Triblock gel in the rat model, the intimal/medial area ratio (a restenosis measure) was still 80% inhibited compared to the control treated with empty micelle/gel (no drug). This could not be achieved by applying rapamycin in Triblock gel alone, which reduced the intimal/medial ratio only by 27%. In summary, we created a new UM/Triblock gel hybrid system for perivascular drug delivery, which produced a rare feat of 3-month restenosis inhibition in animal tests. This system exhibits a real potential for further translation into an anti(re)stenotic application with open surgery.

Topics: Animals; Drug Delivery Systems; Hydrogels; Male; Micelles; Neointima; Rats; Rats, Sprague-Dawley; Sirolimus

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.

Topics: Animals; Cardiac Catheterization; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Vessels; Drug-Eluting Stents; Hyperplasia; Metals; Microscopy, Electron, Scanning; Models, Animal; Neointima; Percutaneous Coronary Intervention; Prosthesis Design; Prosthesis Failure; Sirolimus; Swine; Swine, Miniature; Time Factors; Tomography, Optical Coherence

New drug-eluting stents (DES) designed to overcome the limitations of existing devices should initially be tested in preclinical studies. Our objective was to analyze the safety and efficacy of new biodegradable polymer-based DES compared with bare-metal stents (BMS) and commercially available DES in a model of normal porcine coronary arteries.. We randomly implanted 101 stents (BMS and biodegradable polymer-based sirolimus-eluting stents: 3 test stent iterations [BD1, BD2, and BD3], Orsiro, Biomime and Biomatrix) in the coronary arteries of 34 domestic pigs. Angiographic and histomorphometric studies were conducted 1 month (n = 83) and 3 months (n = 18) later.. The stents were implanted at a stent/artery ratio of 1.31 ± 0.21, with no significant differences between groups. At 1 month, the new test stents (BD1, BD2 and BD3) showed less late loss and angiographic restenosis, as well as lower histologic restenosis and neointimal area (P < .0005), than the BMS. There were no differences in endothelialization, vascular injury, or inflammation between the new test stents and BMS, although the new stents showed higher fibrin deposition (P = .0006). At 3 months, all these differences disappeared, except for a lower neointimal area with the new BD1 stent (P = .027). No differences at any time point were observed between the new test stents and commercially available controls.. In this preclinical model, the new biodegradable polymer-based DES studied showed less restenosis than BMS and no significant differences in safety or efficacy vs commercially available DES.

Topics: Absorbable Implants; Animals; Antibiotics, Antineoplastic; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Metals; Neointima; Polymers; Prosthesis Design; Random Allocation; Sirolimus; Stents; Sus scrofa; Swine; Treatment Outcome

There is debate regarding whether smoking results in microstructural changes after stenting. The aim of this study was to evaluate the microstructural changes after stenting in patients with different smoking statuses. We retrospectively identified 220 sirolimus-eluting stents in 179 patients who underwent follow-up optical coherence tomography examination 12 months after sirolimus stenting. Subjects were classified as current smokers (CS, n = 31), smoking cessation ≤1 year (n = 36), smoking cessation >1 year (SC > 1Y, n = 27), and never smokers (NS, n = 85). The neointimal hyperplasia (NIH) area was larger in CS than in NS (1.04 ± 0.72 mm

Topics: Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Postoperative Period; Prosthesis Design; Retrospective Studies; Sirolimus; Smoking; Smoking Cessation; Tomography, Optical Coherence

Drug-eluting stent delivery of mTORC1 (mechanistic target of rapamycin complex 1) inhibitors is highly effective in preventing intimal hyperplasia after coronary revascularization, but adverse effects limit their use for systemic vascular disease. Understanding the mechanism of action may lead to new treatment strategies. We have shown that rapamycin promotes vascular smooth muscle cell differentiation in an AKT2-dependent manner in vitro. Here, we investigate the roles of AKT (protein kinase B) isoforms in intimal hyperplasia.. We found that germ-line-specific or smooth muscle-specific deletion of. Our data reveal opposing roles for AKT isoforms in smooth muscle cell remodeling. AKT2 is required for rapamycin's therapeutic inhibition of intimal hyperplasia, likely mediated in part through AKT2-specific regulation of MYOCD via FOXO4. Because AKT2 signaling is impaired in diabetes mellitus, this work has important implications for rapamycin therapy, particularly in diabetic patients.

Topics: Animals; Binding Sites; Cell Cycle Proteins; Cell Differentiation; Cell Movement; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Forkhead Transcription Factors; Gene Expression Regulation; Genetic Predisposition to Disease; Humans; Mice, Knockout; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Neointima; Nuclear Proteins; Phenotype; Promoter Regions, Genetic; Proto-Oncogene Proteins c-akt; RNA Interference; RNA, Messenger; Signal Transduction; Sirolimus; Time Factors; Trans-Activators; Transcription Factors; Transfection; Vascular System Injuries

Six-month PCI follow-up results of left anterior descending (LAD) and circumflex (CX) drug-eluting stent implantation are presented. Angiography showed patent LAD and CX stents. However, OCT revealed almost all abluminal cavities were completely filled, which the authors surmise was due to a neointimal healing process.

Topics: Coronary Angiography; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; ST Elevation Myocardial Infarction; Tomography, Optical Coherence

This study sought to investigate endothelial coverage and barrier protein expression following stent implantation.. Biodegradable polymer drug-eluting stents (BP-DES) have been purported to have biological advantages in vessel healing versus durable polymer DES (DP-DES), although clinical trial data suggest equipoise.. Biodegradable polymer-sirolimus-eluting stents (BP-SES), durable polymer-everolimus-eluting stents (DP-EES), and bare-metal stents (BMS) were compared. In the rabbit model (28, 45, and 120 days), stented arteries underwent light microscopic analysis and immunostaining for the presence of vascular endothelium (VE)-cadherin, an endothelial barrier protein, and were subjected to confocal microscopy and scanning electron microscopy. A cell culture study in stented silicone tubes was performed to assess cell proliferation.. Light microscopic assessments were similar between BP-SES and DP-EES. BMS showed nearly complete expression of VE-cadherin at 28 days, whereas both DES showed significantly less with results favoring BP-SES versus DP-EES (39% coverage in BP-SES, 22% in DP-EES, 95% in BMS). Endothelial cell morphologic patterns differed according to stent type with BMS showing a spindle-like shape, DP-EES a cobblestone pattern, and BP-SES a shape in between. VE-cadherin-negative areas showed greater surface monocytes regardless of type of stent. Cell proliferation was suppressed in both DES with numerically less suppression in BP-SES versus DP-EES.. This is the first study to examine VE-cadherin expression after DES. All DES demonstrated deficient barrier expression relative to BMS with results favoring BP-SES versus DP-EES. These findings may have important implications for the development of neoatherosclerosis in different stent types.

Topics: Absorbable Implants; Animals; Antigens, CD; Cadherins; Cardiovascular Agents; Cell Proliferation; Cells, Cultured; Drug-Eluting Stents; Endothelial Cells; Endovascular Procedures; Everolimus; Iliac Artery; Intercellular Junctions; Male; Metals; Models, Animal; Neointima; Polymers; Prosthesis Design; Rabbits; Sirolimus; Time Factors

Stent implantation often creates local vessel wall injuries which can be characterized in detail by optical coherence tomography (OCT). Little is known about the neointimal coverage at these areas. We aimed to evaluate neointimal coverage of vessel wall injuries area associated with stent implantation.. We retrospectively selected patients implanted with sirolimus-eluting stents (SES) having excellent OCT images immediately after stent implantation and at the 6-month follow-up. All OCT cross-sectional images were divided into three groups: intra-stent tissue prolapse (ISTP) areas, intra-stent dissection flaps (ISDF) areas, and non-injuried areas. The neointimal coverage in included sections was evaluated at 6 months follow-up.. Finally, 1690 cross-sectional images in 74 stents were analyzed totally. Among which, 240 images (14.20%) involved ISTP areas, 124 images (7.34%) at ISDF areas, and 1326 images (78.46%) at non-injuried areas. All ISTP and ISDF were disappeared at six months follow-up, Neointimal thickness at ISTP and ISDF areas increased significantly compared to the one in non-injuried areas (97.4±40.3μm vs. 68.4±47.6μm, P<0.001; 92.7±49.8μm vs. 68.4±47.6μm, P<0.001). Mean neointimal area of ISTP and ISDF areas was almost the same (0.8±0.3 mm2), which both had a significant difference compared to mean neointimal area (0.6±0.4mm2) at non-injuried areas (p1<0.001, p2=0.006).. Intra-stent tissue prolapse and intra-stent dissection flaps have benign clinical course up to 6 months. The areas with these local complications, however, have greater neointimal hyperplasia compared to the non-injuried areas.

Topics: Blood Vessels; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Retrospective Studies; Sirolimus; Surgical Flaps; Tomography, Optical Coherence

The aim of this study was to evaluate neointimal coverage in the very early phase after second-generation drug-eluting stent (DES) implantation using optical coherence tomography (OCT). Patients who underwent staged percutaneous coronary intervention within 30 days after DES implantation were enrolled. OCT was performed to observe DES previously implanted. The median time interval from implantation to OCT examination was 21.5 days. A total of 10,625 struts of 54 stents (52 everolimus-eluting stents and 2 zotarolimus-eluting stents) in 42 lesions were analyzed. Strut tissue coverage was observed in 71.1 ± 19.2 % of the struts, malapposed struts in 2.56 ± 3.37 %, strut tissue coverage at the side branch orifice in 10.6 ± 17.2 %, and struts with protrusion in 0.95 ± 3.46 %. Mean tissue thickness on the covered struts was 39.8 ± 14.2 µm. The percentage of stent coverage was significantly lower in the overlapping segments than in the non-overlapping segments (48.4 ± 17.5 % vs. 74.4 ± 20.2 %, P < 0.05). Most of the stent struts were covered by tissue within 30 days after second-generation DES implantation. However, the percentage of strut coverage was lower in the overlapping segments than in the non-overlapping segments, suggesting that very early interruption of dual antiplatelet therapy might result in increased risk of stent thrombosis, even in second-generation DES.

Topics: Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Japan; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Few studies have directly compared vascular responses to second-generation drug-eluting stents (DESs). We performed optical coherence tomography examinations in 56 consecutive patients with implanted single stent [19 cobalt-chromium everolimus-eluting stents (CoCr-EES), 22 platinum-chromium EES (PtCr-EES), and 15 resolute zotarolimus-eluting stents (R-ZES)] for de novo lesions, and who did not have restenosis at their 9-month follow-up. Neointimal thickness (NIT), stent apposition, and neointimal coverage were assessed in every strut. A neointimal unevenness score [(NUS), maximum NIT/average NIT in the same cross-section] was determined for every 1-mm cross-section (CS). A total of 8350 struts and 1159 CSs were analyzed. The CoCr- and PtCr-EES had significantly fewer malapposed struts compared to the R-ZES (CoCr-EES: 0.19 % vs. PtCr-EES: 0.19 % vs.. 0.61 %, p = 0.007). Furthermore, the PtCr-EES had a lower frequency of uncovered struts compared to the others (CoCr-EES: 2.0 % vs. PtCr-EES: 1.4 % vs.. 2.3 %, p = 0.047). The NUS correlated with the frequency of uncovered struts (p < 0.001, r = 0.54). The EESs demonstrated more homogenous neointimal growth, as shown in the NUS, compared to the R-ZES [CoCr-EES: 1.66 (1.38-1.97) vs. PtCr-EES: 1.67 (1.41-2.00) vs.. 1.94 (1.56-2.28), p < 0.001]. Our results demonstrate that unevenness neointimal growth may relate with strut coverage after second-generation DES implantation. The PtCr-EES had a high frequency of strut coverage with a homogeneous neointima, suggesting fewer risks for stent thrombosis.

Topics: Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Metals; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Retrospective Studies; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

To develop an ameliorated sirolimus (SIR) liposome for intramural delivery, the effects of various carrier physicochemical parameters on the antirestenosis efficacy were evaluated.. Different liposomes were prepared, characterized and administered to balloon injured rats (12 animal groups). Their efficacies were investigated using morphometric, immunohistochemical and in vivo computed tomography imaging analyses.. The antirestenosis efficacy of SIR liposomes decreased in the following order: cationic 100 nm vesicles ≥ cationic 60 nm vesicles > neutral 100 nm vesicles ≥ stealth 100 nm vesicles > anionic 100 nm vesicles. The 100 µg SIR loaded in cationic liposomes showed almost no artery stenosis.. Appropriate modulation of physicochemical characteristics makes it possible to optimize the liposomes for local delivery.

Topics: Animals; Cardiovascular Agents; Carotid Arteries; Carotid Artery Injuries; Coronary Restenosis; Ki-67 Antigen; Liposomes; Male; Neointima; Plasma; Polysorbates; Rats; Rats, Sprague-Dawley; Sirolimus

First-generation drug-eluting stents (DES) have reduced short-term stent failure as compared to bare-metal stents due to the inhibition of neointima hyperplasia, but instead increased the risk of very-late stent failure. Although better outcomes have been reported for second-generation DES than for first-generation DES, the difference in the angioscopic findings at 1-year follow-up has not been adequately elucidated among second-generation DES.. Consecutive 161 patients who received angioscopic examination at 1 year after implantation of second-generation DES, i.e. Nobori biolimus-eluting stents (Terumo, Tokyo, Japan) (N-BES, n=25), Xience everolimus-eluting stents (Abbot Vascular, Santa Clara, CA, USA; X-EES, n=95), or Resolute zotarolimus-eluting stents (Resolute Integrity; Medtronic, Minneapolis, MN, USA; R-ZES, n=41), in de novo native coronary lesions were analyzed.. Maximum neointima coverage grade (N-BES, 0.9±0.3; X-EES, 1.2±0.4; R-ZES, 1.5±0.5; p<0.001) was the highest in R-ZES and lowest in N-BES. Heterogeneity score was higher in R-ZES than in N-BES (N-BES, 0.8±0.4; X-EES, 0.9±0.4; R-ZES, 1.1±0.5; p=0.007). Maximum yellow color grade and prevalence of thrombus were not different. Multivariate analysis demonstrated that only stent type was associated with maximum neointima coverage grade; stent type and total stent length were associated with heterogeneity score; and stenting for acute coronary syndrome (ACS) and total stent length were associated with maximum yellow color grade.. Neointima coverage and heterogeneity were mainly determined by stent type even among second-generation DES, while yellow color was determined mainly by whether target lesion was of ACS.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Angioscopy; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neointima; Sirolimus; Thrombosis; Treatment Outcome

Prosthetic grafts and patches are commonly used in cardiovascular surgery, however neointimal hyperplasia remains a significant concern, especially under low flow conditions. We hypothesized that delivery of rapamycin from nanoparticles (NP) covalently attached to patches allows sustained site-specific delivery of therapeutic agents targeted to inhibit localized neointimal hyperplasia. NP were covalently linked to pericardial patches using EDC/NHS chemistry and could deliver at least 360 ng rapamycin per patch without detectable rapamycin in serum; nanoparticles were detectable in the liver, kidney and spleen but no other sites within 24 hours. In a rat venous patch angioplasty model, control patches developed robust neointimal hyperplasia on the patch luminal surface characterized by Eph-B4-positive endothelium and underlying SMC and infiltrating cells such as macrophages and leukocytes. Patches delivering rapamycin developed less neointimal hyperplasia, less smooth muscle cell proliferation, and had fewer infiltrating cells but retained endothelialization. NP covalently linked to pericardial patches are a novel composite delivery system that allows sustained site-specific delivery of therapeutics; NP delivering rapamycin inhibit patch neointimal hyperplasia. NP linked to patches may represent a next generation of tissue engineered cardiovascular implants.

Topics: Angioplasty; Animals; Drug Carriers; Growth Inhibitors; Histocytochemistry; Hyperplasia; Nanoparticles; Neointima; Rats; Sirolimus; Transplants; Treatment Outcome

A recent OCT study revealed that the lack of stent strut endothelial coverage is associated with late stent thrombosis after drug-eluting stent implantation. However, the sequential changes of stent strut endothelial coverage in the extremely early period have never been reported. Serial OCTs were performed in 35 patients with 35 EES (everolimus-eluting stent)-treated de novo lesions at 0, 2, 4, and 12 weeks after EES implantation. Serial changes in quantitative parameters of the neointima (neointimal thickness, stent strut coverage, and apposition of each strut) were analyzed. Mean neointimal thickness significantly increased from 35.9 to 51.8 and 108.2 μm at 2, 4, and 12 weeks, respectively (p < 0.001 for all), and the percentage of uncovered stent struts significantly decreased from 74.7 to 19.5% and 0.4% (p < 0.001, respectively). There was no stent malapposition at 4 weeks compared with immediate post-intervention (0 vs. 5.4 %, p = 0.031). This OCT study demonstrates that neointimal coverage of stent struts progresses to about 80 % and malapposition of stent struts completely disappears at 4 weeks after EES implantation. In addition, neointimal coverage of stent struts was almost complete within 12 weeks.

Topics: Aged; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Japan; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Thrombosis; Tomography, Optical Coherence

The external lumen of a stent [defined as extra-stent lumen (ESL)] assessed by optical coherence tomography (OCT) may be related to the risk of thrombus formation after sirolimus-eluting stent (SES) implantation. An everolimus-eluting stent (EES) might provide relatively minimal inflammatory reaction and appropriate neointimal coverage. The purpose of this study was to compare the neointimal thickness and ESL between SES and EES. Patients who underwent OCT examination more than 7 months after either SES or EES implantation were enrolled. Stent area (SA), lumen area (LA), neointimal area (NIA) and neointimal thickness (NIT) of each strut were measured at 1-mm intervals between stented segments. The area, angle (summation per cross-section) and depth (maximum distance from adjacent vessel surface to the outline of stent) of ESL were analyzed. A total of 49 lesions were included (SES n = 20, EES n = 29). Mean follow-up period was 11 months. A total of 998 cross-sections and 9874 struts were analyzed. There were no differences in stent area, lumen area and neointimal area (SA: 6.01 ± 1.60 vs. 6.02 ± 1.40 mm(2), p = 0.572, LA: 5.37 ± 1.52 vs. 5.29 ± 1.34 mm(2), p = 0.692, NIA: 0.64 ± 0.49 vs. 0.72 ± 0.37 mm(2), p = 0.493). Mean NIT of SES and EES were 0.11 ± 0.05 and 0.10 ± 0.05 mm, respectively (p = 0.367). Conversely, area, angle and depth of ESL in SES group were significantly greater than those in EES group (0.20 ± 0.39 vs. 0.03 ± 0.09 mm(2), p < 0.001, 56.2 ± 59.1° vs. 20.1 ± 41.9°, p < 0.001, 0.10 ± 0.09 vs. 0.03 ± 0.03 mm, p < 0.001). OCT showed that the efficacy of neointimal growth suppression is similar between SES and EES, whereas the adverse vascular response after EES implantation is smaller than that after SES implantation.

Topics: Adult; Aged; Aged, 80 and over; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Sirolimus; Time Factors; Tomography, Optical Coherence

A 70-year-old man underwent stent implantation for right coronary artery (RCA) lesions with a bare metal stent (BMS) and two sirolimus-eluting stents (SES). However, as both the BMS and SES stented sites developed restenosis after 13 months, he underwent target lesion revascularization using directional coronary atherectomy (DCA). On histopathology, the restenosis lesion at the SES-deployed site showed greater inflammation and less re-endothelialization than that at the BMS-deployed site. Three months later, the SES-deployed site developed a second restenosis, in which paclitaxel-eluting stents (PES) were implanted (PES-in-SES), while the BMS-deployed site was restenosis free. Five years later, restenosis was absent in these RCA lesions. However, by optical coherence tomography and/or coronary angioscopy, the PES-in-SES site in the RCA showed poor neointimal coverage over the stent struts and yellowish neointima, suggesting lipid-rich neoatheroma formation, whereas at the BMS site appropriate white neointima formation was observed. Drug-eluting stents still have problems of persistent inflammation, inappropriate neointima formation, and neoatherosclerosis. Although we are now in the era of second generation DESs in which better stent performance would be promising, we should remember that we are obliged to continue to follow-up all patients in whom first generation DESs such as SES or PES have been placed.

Topics: Aged; Angioscopy; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Humans; Immunohistochemistry; Male; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Retreatment; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

Very late stent thrombosis (VLST) is a serious complication after percutaneous coronary intervention. However, the best therapy for VLST with late-acquired incomplete stent apposition and incomplete neointimal coverage remains unknown. In these cases, neointimal coverage was nearly complete and no late-acquired malapposition was detected at 18 months after Endeavor zotarolimus-eluting stent (ZES) implantation for the treatment of VLST with late-acquired incomplete stent apposition after sirolimus-eluting stent implantation. We presented that Endeavor ZES implantation may become an attractive therapeutic strategy for the treatment of VLST with late-acquired incomplete stent apposition and incomplete neointimal coverage.

Topics: Aged; Angioplasty, Balloon; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Thrombosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Thrombectomy; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

Overall stent performance should be characterized by geometric luminal gain acquisition, neointimal coverage of the stent struts, and stabilization of the underlying inflammatory neoatheroma. The aim of this study was to compare the performance of zotarolimus-eluting stent (ZES), everolimus-eluting stent (EES) and bare metal stent (BMS) using optical coherence tomography (OCT) and coronary angioscopy. For 36 stented coronary lesions (BMS, 12 lesions; ZES, 11 lesions; EES, 13 lesions) in 27 patients, we calculated neointimal area and uncovered stent strut rate based on OCT findings at 10 months after stent placement. The grades of neointimal coverage and yellow color, both of which were classified from 0 to 3, were also assessed by coronary angioscopy. The plaque area of the ZES lesions was larger than that of the EES lesions (P < 0.05) but smaller than that of the BMS lesions (P < 0.05). The OCT-based uncovered rate of the ZES lesions was less than that of the EES lesions (P < 0.01), but similar to that of the BMS lesions. The stent coverage grade by angioscopy was higher in the ZES lesions than in the EES lesions (P < 0.05), but similar to the BMS lesions. The yellow grade was less in the ZES lesions than in the EES lesions (P < 0.01), but similar to the BMS lesions. ZES might be better than BMS in terms of neointimal thickening, and better than EES in terms of neointimal coverage as well as prevention of neoatheroma formation. ZES may have superior performance compared with EES.

Topics: Aged; Angioscopy; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Sirolimus; Tomography, Optical Coherence

Little is known about the very late-phase morphological vessel characteristics within the sirolimus-eluting stent (SES).. We assessed a total of 12 patients with 15 SES implantations who underwent repeat angiographic and angioscopic procedures after 5 and 7 years. The degree of neointimal stent coverage (NSC) was classified as follows: grade 0, uncovered struts; grade 1, visible struts through a thin neointima; or grade 2, invisible struts with complete neointimal coverage. The maximum and minimum NSC grades were evaluated and the existence of in-stent thrombus was also recorded for all patients. The prevalence of a maximum NSC grade of 2 increased and that of a minimum NSC grade of 0 decreased, although there was no significant difference in prevalence between 5 and 7 years. One of four in-stent thrombus identified at 5 years had disappeared from 5 to 7 years and a new thrombus was found in another patient at 7 years. Thus, the incidence of in-stent thrombus did not change from 5 to 7 years. In one case, a thrombus was observed inside the angiographic aneurysmal change, but none of the thrombi were related to adverse events.. This angioscopic study reported gradual arterial repair and continuous delayed healing associated with subclinical thrombus formation 7 years after SES deployment.

Topics: Aged; Angioscopy; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Male; Neointima; Reproducibility of Results; Retrospective Studies; Sirolimus; Time Factors; Tunica Intima

Drug-eluting stents (DES) have reduced late loss and target lesion revascularization through the inhibition of neointimal hyperplasia, but instead increased the risk of very late stent failure due to incomplete neointimal coverage and neoatherosclerosis. Although newer DES are more effective and safer than the first-generation DES, the difference in the condition of the stented lesions between Resolute zotarolimus-eluting stents (R-ZES) and Endeavor zotarolimus-eluting stents (E-ZES) on angioscopy has not been reported.. Consecutive patients who received R-ZES (n=46) or E-ZES (n=46) for de novo lesion of native coronary artery and had 1-year follow-up angioscopy were examined. Yellow color (grade 0-3), neointimal coverage (grade 0-2), heterogeneity score (maximum-minimum neointimal coverage grade) and thrombus (presence or absence) at stented lesion were evaluated. The maximum yellow color grade (1.2±0.9 vs. 0.7±1.0, P=0.005) was higher in R-ZES than in E-ZES. The maximum (1.9±0.3 vs. 1.5±0.5, P<0.001) and minimum (1.1±0.7 vs. 0.4±0.5, P<0.001) coverage grade was higher in E-ZES than in R-ZES. The heterogeneity score was higher in R-ZES than in E-ZES (1.0±0.5 vs. 0.7±0.7, P=0.007). Prevalence of thrombus was not different between the 2 stents (6.5% vs. 2.2%, P=0.4).. E-ZES had better neointimal coverage with less yellow plaque and lower heterogeneity score than R-ZES. The lesions with E-ZES appeared more stable than those with R-ZES. (Circ J 2016; 80: 650-656).

Topics: Aged; Angioscopy; Atherosclerosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neointima; Plaque, Atherosclerotic; Sirolimus

We aimed to investigate short-term outcomes of the XINSORB bioresorbable sirolimus-eluting scaffold in human coronary artery.. Bioresorbable scaffolds are considered to be the fourth milestone in percutaneous coronary intervention.. 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.. 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.. This first-in-human study demonstrates the effectiveness and safety of the XINSORB scaffold in treating single de novo coronary lesions.

Topics: Absorbable Implants; Adult; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Artery Disease; Coronary Stenosis; Coronary Vessels; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

To evaluate, in the FLEX Registry, clinical outcomes of an ultrathin (60 µm) biodegradable polymer-coated Supraflex sirolimus-eluting stent (SES) for the treatment of coronary artery disease. Additionally, to determine the vascular response to the Supraflex SES through optical coherence tomography (OCT) analysis.. Multicentre, single-arm, all-comers, observational registry of patients who were treated with the Supraflex SES, between July 2013 and May 2014, at nine different centres in India.. 995 patients (1242 lesions) who were treated with the Supraflex SES, between July 2013 and May 2014, at nine different centres in India. A total of 47 participants underwent OCT analysis at 6 months' follow-up.. Percutaneous coronary intervention with Supraflex SES, PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint-the rate of major adverse cardiac events (defined as a composite of cardiac death, myocardial infarction (MI), target lesion revascularisation (TLR))-was analysed during 12 months.. At 12 months, the primary endpoint occurred in 36 (3.7%) of 980 patients, consisting of 18 (1.8%) cardiac deaths, 16 (1.6%) MI, 7 (0.7%) TLR and 2 (0.2%) cases of non-target lesion target vessel revascularization. In a subset of 47 patients, 1227 cross-sections (9309 struts) were analysed at 6 months by OCT. Overall, a high percentage of struts was covered (98.1%), with a mean neointimal thickness of 0.13 ± 0.06 µm.. The FLEX Registry evaluated clinical outcomes in real-world and more complex cohorts and thus provides evidence that the Supraflex SEX can be used safely and routinely in a broader percutaneous coronary intervention population. Also, the Supraflex SES showed high percentage of stent strut coverage and good stent apposition during OCT follow-up.

Topics: Absorbable Implants; Aged; Antibiotics, Antineoplastic; Cardiovascular Diseases; Coronary Artery Disease; Drug-Eluting Stents; Female; Humans; India; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Neointima; Percutaneous Coronary Intervention; Polymers; Registries; Sirolimus; Tomography, Optical Coherence

Limus-eluting stents are dominating coronary interventions, although paclitaxel is the only drug on balloon catheters with proven inhibition of restenosis. Neointimal inhibition by limus-coated balloons has been shown in few animal studies, but data from randomized clinical trials are not available. The aim of the present preclinical studies was to achieve high and persistent sirolimus levels in the vessel wall after administration by a coated balloon.. Different coating formulations and doses were studied in the porcine coronary model to investigate sirolimus tissue levels at different time points as well as efficacy at 1 month using quantitative coronary angiography and histomorphometry. Loss of the selected coating in the valve, guiding catheter, and blood was low (2±14% of dose). Acute drug transfer to the vessel wall was 14.4±4.6% with the crystalline coating, whereas the amorphous coatings were less effective in this respect. Persistence of sirolimus in the vessel wall until 1 month was 40% to 50% of the transferred drug. At 1-month follow-up, a modest but significant reduction of neointimal growth was demonstrated in a dose range from 4 μg/mm(2) to 2×7 μg/mm(2), for example, maximum neointimal thickness of 0.38±0.13 versus 0.65±0.21 mm in the uncoated control group.. Various sirolimus-coated balloons effectively reduce neointimal proliferation in the porcine coronary model but differ considerably in retention time in the vessel wall. It has to be determined if such a formulation with persistent high vessel concentration will result in a relevant clinical effect.

Topics: Animals; Cardiac Catheters; Cardiovascular Agents; Cell Proliferation; Coated Materials, Biocompatible; Coronary Angiography; Coronary Vessels; Drug-Eluting Stents; Equipment Design; Male; Models, Animal; Neointima; Percutaneous Coronary Intervention; Sirolimus; Swine; Time Factors

Our aim was to assess vascular response after polymer-free sirolimus-eluting stent (SES) implantation by using an optical coherence tomography (OCT)-derived vascular healing score (HS), quantifying the deficiency of healing.. In a prospective, multicentre, single-arm, open-label study, OCT examinations were performed at three months in 45 patients (47 lesions). Per protocol, 24 lesions which had not reached adequate vascular healing according to study criteria were scheduled for OCT examination at six months. The HS was calculated at two time points. Serial OCT imaging demonstrated that the proportion of covered stent struts increased from a median of 87.1% at three months to 98.6% at six months (p<0.001). The neointimal thickness increased from a median of 82.8 µm to 112.2 µm (p<0.001), whereas the median percentages of malapposed struts were 0.2% and 0.0% at the two respective time points. Neointimal volume obstruction increased from 6.3% to 12.8%, and the HS decreased from a median of 28.1 at three months to 2.4 at six months.. In patients who had inadequate vascular healing three months after polymer-free SES implantation, serial OCT showed almost complete vascular healing at six months.

Topics: Absorbable Implants; Adult; Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Artery Disease; Coronary Stenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Polymers; Sirolimus; Tomography, Optical Coherence

Previous studies have associated issues such as incomplete stent apposition with delayed healing and adverse events (stent thrombosis). The aim of this study was to evaluate the impact of strut apposition and stent type on the progression of stent strut coverage.. We evaluated in vivo in porcine models the follow-up response and coverage characteristics of well-apposed and malapposed segments of drug-eluting stents (DES) (CYPHER, PROMUS Element and Orsiro) and the Absorb bioresorbable vascular scaffold (BVS) by optical coherence tomography (OCT) sequentially, at baseline, and at one week and four weeks of follow-up. Supporting results were provided by histological analysis performed at four-week follow-up and computer simulation describing the shear characteristics around apposed and non-apposed struts. A total of 325 cross-sections containing 3,166 struts were analysed. The extent of malapposition decreased over time as a result of neointimal healing (from 7.1% at baseline to 0% at four weeks; p=0.03). At one week, 13.6% of struts in well-apposed segments were still uncovered versus 19.2% of struts in malapposed cross-sections and 77.8% of NASB struts (p<0.01). At four-week follow-up, 3.1% of struts were uncovered in well-apposed cross-sections vs. 1.6% in malapposed cross-sections and 35.7% of NASB struts (p<0.01). A comparison of the apposed segments revealed that the thin-strut Orsiro had only 1.3% of uncovered struts at one week while PROMUS Element, CYPHER and BVS had 6.6%, 48.4% and 16.2% of struts still uncovered, respectively.. This study shows that early coverage is influenced by stent apposition as well as platform strut characteristics (stent type). At four weeks, NASB struts remained a focus of delayed endothelialisation.

Topics: Angioplasty, Balloon, Coronary; Animals; Computer Simulation; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Humans; Models, Animal; Neointima; Prosthesis Design; Sirolimus; Swine; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

Topics: Angioscopy; Antineoplastic Agents, Phytogenic; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Neointima; Paclitaxel; Prosthesis Design; Sirolimus

In-stent hyperplasia (ISH) may develop in regions of low endothelial shear stress (ESS), but the relationship between the magnitude of low ESS, the extent of ISH, and subsequent clinical events has not been investigated.. We assessed the association of poststent ESS with neointimal ISH and clinical outcomes in patients treated with percutaneous coronary interventions (PCI). Three-dimensional coronary reconstruction was performed in 374 post-PCI patients at baseline and 6 to 10 months follow-up as part of the PREDICTION Study. Each vessel was divided into 1.5-mm-long segments, and we calculated the local ESS within each stented segment at baseline. At follow-up, we assessed ISH and the occurrence of a clinically indicated repeat PCI for in-stent restenosis. In 246 total stents (54 overlapping), 100 (40.7%) were bare-metal stents (BMS), 104 (42.3%) sirolimus-eluting stents, and 42 (17.1%) paclitaxel-eluting stents. In BMS, low ESS post-PCI at baseline was independently associated with ISH (β=1.47 mm(2) per 1-Pa decrease; 95% CI, 0.38-2.56; P<0.01). ISH was minimal in drug-eluting stents. During follow-up, repeat PCI in BMS was performed in 21 stents (8.5%). There was no significant association between post-PCI ESS and in-stent restenosis requiring PCI.. Low ESS after BMS implantation is associated with subsequent ISH. ISH is strongly inhibited by drug-eluting stents. Post-PCI ESS is not associated with in-stent restenosis requiring repeat PCI. ESS is an important determinant of ISH in BMS, but ISH of large magnitude to require PCI for in-stent restenosis is likely attributed to factors other than ESS within the stent.

Topics: Aged; Coronary Restenosis; Drug-Eluting Stents; Early Diagnosis; Female; Follow-Up Studies; Hemodynamics; Humans; Hyperplasia; Immunosuppressive Agents; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Sirolimus; Stents; Stress, Mechanical; Treatment Outcome

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).. 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.. 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.

Topics: Absorbable Implants; Animals; Biopsy; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Vessels; Materials Testing; Models, Animal; Molecular Weight; Neointima; Percutaneous Coronary Intervention; Polyesters; Prosthesis Failure; Sirolimus; Swine; Swine, Miniature; Tomography, Optical Coherence; Wound Healing

Although previous optical coherence tomography (OCT) studies reported that restenosis tissue after implantation of a drug-eluting stent (DES) was composed of a variety of cells, the clinical significance of morphologic characteristics for in-stent neointimal tissue as assessed by OCT has not been clarified. We experienced a patient with stable angina who underwent percutaneous coronary intervention with a 2.5 × 18-mm DES implantation 6 months before the OCT examination. OCT imaging showed a mild intimal hyperplasia (39 % neointimal hyperplasia) with eccentric, heterogeneous tissue, predominantly of low signal intensity. Seventeen months after the initial procedure, OCT revealed a significant increase in percent neointimal hyperplasia of 58 %, with morphologically different intimal tissue of concentric homogeneous high intensity in the stented segments. This finding suggests that low-intensity intimal tissue morphology detected by OCT could be a morphometric predictor of late neointimal tissue growth after DES implantation.

Topics: Aged; Chest Pain; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Humans; Hyperplasia; Male; Neointima; Percutaneous Coronary Intervention; Sirolimus; Tomography, Optical Coherence

To investigate the extent and the circumferential distribution of the neointima tissue developed following an Absorb bioresorbable vascular scaffold (BVS) implantation.. Twenty-three patients who were treated with the Absorb BVS and had optical coherence tomographic examination after scaffold implantation, at six-month and at two-year follow-up, were included in the current analysis. The lumen and the scaffold borders were detected and the circumferential thickness of the neointima was measured at one degree intervals. The symmetry of the neointima was defined as: minimum/maximum thickness. The lumen area was decreased at six months compared to baseline but it did not change between six-month and two-year follow-up (baseline: 7.49 [6.13-8.00] mm², six months: 6.31 (4.75-7.06) mm², two years: 6.01 [4.67-7.11] mm², p=0.373). However, the mean neointima thickness (six months: 189 [173-229] m, two years: 258 [222-283] m, p<0.0001) and the symmetry index of the neointima (six months: 0.06 [0.02-0.09], two years: 0.27 [0.24-0.36], p<0.0001) were increased at two years. Full circumferential coverage of the vessel wall by neointima tissue was seen in 91% of the studied frames at two years.. This study demonstrates that after an Absorb BVS implantation neointima tissue develops that covers almost the whole circumference of the vessel wall. In contrast to the metallic stents, the neointima tissue does not compromise the luminal dimensions. Further research is required to evaluate the neointimal characteristics and assess the potential value of the device in passivating high-risk plaques.

Topics: Absorbable Implants; Adult; Aged; Antineoplastic Agents; Cohort Studies; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Prospective Studies; Sirolimus; Tissue Scaffolds; Tomography, Optical Coherence

Previous reports have suggested the importance of delayed arterial healing and the development of neoatherosclerosis as major contributors to stent thrombosis and delayed restenosis. The difference of in vivo assessment of long-term vessel healing between first-generation drug-eluting stents and current generation everolimus-eluting stents (EESs) is limited. The aim of this study was to evaluate long-term arterial healing in EES in comparison with the first generation sirolimus-eluting stents (SES).. We evaluated 31 EES (23 patients) and 8 SES (7 patients) by serial optical coherence tomography at 12 months (mid-phase) and 24 months (late-phase) after stenting and evaluated the change in neointimal thickness (NIT), the percentages of uncovered struts, peri-strut low intensity area (PLIA; region around stent struts homogenously lower-intensity appearance than surrounding tissue), and thrombus.. Although the average NIT showed no significant changes from the mid- to the late-phase follow-up in both EES and SES groups, the change in NIT and minimum lumen area was significantly larger in SES than EES (5.2±29.4 vs. 37.2±48.9; p=0.02, -0.06±0.36 vs. -0.45±0.74; p=0.04, respectively). The incidence of uncovered struts and struts with PLIA of EES was lower than those of SES, at both phases. Stents with in-stent thrombus of EES tended to be lower than that of SES at both phase follow-ups.. Although both SES and EES showed progressive luminal narrowing from the mid- to the late-phase follow-up, the extent of delayed lumen narrowing and delayed neointimal proliferation was significantly less in the second generation EES than the first generation SES. EESs seem to offer sustained stability in efficacy, without sacrificing safety, up to 2 years after implantation.

Topics: Aged; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Sirolimus; Time Factors; Tomography, Optical Coherence

To report the six-month angiographic and two-year clinical outcome data from the first-in-man study with the Ultimaster DES, a thin-strut cobalt-chromium sirolimus-eluting stent (SES) with an innovative abluminal-gradient-coated bioresorbable polymer.. CENTURY is a multicentre, single-arm, prospective study that enrolled 105 patients (113 lesions) with coronary artery disease. All patients were scheduled to have an angiographic follow-up at six months, while 45 and 20 patients respectively had IVUS and OCT assessments. The primary endpoint was six-month in-stent late lumen loss. Secondary endpoints included clinical, IVUS and OCT outcomes. Clinical follow-up is available up to two years and will continue up to five years. Procedural success was 97.1% and device success was 100%. Angiographic late loss at six months was 0.04±0.35 mm, also reflected in a low binary restenosis rate of 0.9% and confirmed by IVUS-assessed neointimal volume obstruction of 1.02±1.62%. The mean strut coverage assessed by OCT was 96.2% with 1.66±4.02 malapposed stent struts. There were no deaths in the study, three (2.9%) periprocedural and one (0.9%) spontaneous myocardial infarction, not related to the target vessel. At one and two years, the target lesion failure rate was 3.8% and 5.7%, while the TLR rate was 1.9% and 2.8%, respectively. There was one acute definite stent thrombosis.. The Ultimaster™ novel bioresorbable polymer sirolimus-eluting stent demonstrated good performance, including high procedural success and strong suppression of neointimal proliferation at six months. Good safety and effectiveness were shown up to two years in the studied population.

Topics: Absorbable Implants; Aged; Antibiotics, Antineoplastic; Chromium Alloys; Coronary Angiography; Coronary Artery Disease; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Neointima; Percutaneous Coronary Intervention; Polymers; Prospective Studies; Sirolimus; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

This study evaluated the safety and efficacy of the RESOLUTE(TM)zotarolimus-eluting stent (R-ZES; Medtronic, Inc, Santa Rosa, CA, USA) in Japanese patients for the treatment of de novo native coronary lesions.. Both RESOLUTE Japan (R-Japan) and RESOLUTE Japan Small Vessel Study (R-Japan SVS) were prospective, multicenter, single-arm observational studies. R-Japan enrolled 100 patients (reference vessel diameter, 2.5-3.5 mm) and R-Japan SVS enrolled 65 patients (at least 1 lesion suitable for 2.25-mm stent) treated with R-ZES. In R-Japan, in-stent late lumen loss (LLL; the primary endpoint) at 8 months was 0.12 ± 0.22 mm and volume obstruction on intravascular ultrasound was 2.33 ± 3.51%. At 4 years, there were no cases of clinically driven target lesion revascularization (TLR); the target lesion failure (TLF; composite of cardiac death, target vessel myocardial infarction, and clinically driven TLR) was 5.6% (5/90). In R-Japan SVS, in-stent LLL at 9 months was 0.27 ± 0.33 mm, TLF (primary endpoint) was 4.6% (3/65), without incidence of TLR. At 3 years, TLF was 7.9% (5/63) and clinically driven TLR, 3.2% (2/63).. R-Japan and R-Japan SVS demonstrate substantial suppression of neointimal hyperplasia, low LLL, and excellent and sustained long-term clinical outcome with R-ZES in Japanese patients.

Topics: Combined Modality Therapy; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Heart Diseases; Humans; Incidence; Japan; Myocardial Infarction; Myocardial Revascularization; Neointima; Platelet Aggregation Inhibitors; Postoperative Complications; Prospective Studies; Risk Factors; Sirolimus; Treatment Outcome; Ultrasonography, Interventional

Cigarette smoking is known to be deleterious to patients with coronary artery disease; however, the effect of smoking on vascular responses after coronary drug-eluting stent implantation is unknown. We sought to examine vascular response after sirolimus-eluting stent implantation in patients with ongoing smoking using optical coherence tomography, compared with former smokers and nonsmokers. We identified 181 sirolimus-eluting stents in 140 subjects who underwent follow-up optical coherence tomography imaging. Subjects were divided into 3 groups: current smokers (n = 28), former smokers (n = 35), and nonsmokers (n = 77). Stent strut coverage, neointimal characteristics, and strut malapposition were evaluated. The incidence of uncovered stent struts was significantly higher in nonsmokers compared with current smokers (13.3 ± 13.3% vs 6.7 ± 8.3%; p = 0.001). On qualitative evaluation of neointimal morphology, the prevalence of heterogeneous neointima was higher in current smokers (71.9%) than in former smokers (36.0%) or nonsmokers (10.1%) (p = 0.004 and p <0.001, respectively). There was no difference in the incidence of malapposition among the 3 groups. Multivariate modeling showed that current smoking was negatively associated with the presence of uncovered struts (odds ratio 0.33; 95% confidence interval 0.14 to 0.79; p = 0.013) and positively associated with the presence of heterogeneous neointima (odds ratio 9.47; 95% confidence interval 3.79 to 23.72; p <0.001). In conclusion, the incidence of strut coverage was higher in current smokers compared with nonsmokers. However, the pattern of neointima was more heterogeneous in current smokers.

Topics: Adult; Anti-Bacterial Agents; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Follow-Up Studies; Hospitals, General; Humans; Immunosuppressive Agents; Male; Medical Records Systems, Computerized; Middle Aged; Neointima; Predictive Value of Tests; Prosthesis Design; Risk Factors; Sensitivity and Specificity; Sirolimus; Smoking; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

Coronary adventitia harbors a wide variety of components, such as inflammatory cells and vasa vasorum (VV). Adventitial VV initiates the development of coronary artery diseases as an outside-in supply route of inflammation. We have recently demonstrated that drug-eluting stent implantation causes the enhancement of VV formation, with extending to the stent edges in the porcine coronary arteries, and also that optical frequency domain imaging (OFDI) is capable of visualizing VV in humans in vivo. However, it remains to be fully validated whether OFDI enables the precise measurement of VV formation in pigs and humans.. In the pig protocol, a total of 6 bare-metal stents and 12 drug-eluting stents were implanted into the coronary arteries, and at 1 month, the stented coronary arteries were imaged by OFDI ex vivo. OFDI data including the measurement of VV area at the stent edge portions were compared with histological data. There was a significant positive correlation between VV area on OFDI and that on histology (R=0.91, P<0.01). In the human protocol, OFDI enabled the measurement of the VV area at the stent edges after coronary stent implantation in vivo.. These results provide the first direct evidence that OFDI enables the precise measurement of the VV area in coronary arteries after stent implantation in pigs and humans.

Topics: Adventitia; Aged; Aged, 80 and over; Animals; Aspirin; Clopidogrel; Coronary Stenosis; Coronary Vessels; Disease Progression; Drug-Eluting Stents; Everolimus; Female; Humans; Interferometry; Male; Middle Aged; Neointima; Neovascularization, Physiologic; Platelet Aggregation Inhibitors; Postoperative Period; Prosthesis Implantation; Sirolimus; Stents; Swine; Swine, Miniature; Ticlopidine; Tomography, Optical Coherence; Vasa Vasorum; Vasculitis

Potent therapeutic compounds with dose dependent side effects require more efficient and selective drug delivery to reduce systemic drug doses. Here, we demonstrate a new platform that combines intravascular ultrasound (IVUS) and drug-loaded microbubbles to enhance and localize drug delivery, while enabling versatility of drug type and dosing. Localization and degree of delivery with IVUS and microbubbles was assessed using fluorophore-loaded microbubbles and different IVUS parameters in ex vivo swine arteries. Using a swine model of neointimal hyperplasia, reduction of neointima formation following balloon injury was evaluated when using the combination of IVUS and sirolimus-loaded microbubbles. IVUS and microbubble enhanced fluorophore delivery was greatest when applying low amplitude pulses in the ex vivo model. In the in vivo model, neointima formation was reduced by 50% after treatment with IVUS and the sirolimus-loaded microbubbles. This reduction was achieved with a sirolimus whole blood concentration comparable to a commercial drug-eluting stent (0.999 ng/mL). We anticipate this therapy will find clinical use localizing drug delivery for numerous other diseases in addition to serving as an adjunct to stents in treating atherosclerosis.

Topics: Angioplasty, Balloon, Coronary; Animals; Coronary Vessels; Drug Delivery Systems; Immunosuppressive Agents; Microbubbles; Neointima; Sirolimus; Swine; Ultrasonography, Interventional

We investigated whether the combination coating of a novel "prohealing coating" hyaluronan-chitosan (HC) and anti-CD34 antibody applied on an SES (HCASES) can reduce neointimal formation while promoting endothelialization compared to either agent alone.. Drug-eluting stents have considerably reduced the incidence of in-stent restenosis compared with bare metal stents. However, the beneficial effect of drug elution is overshadowed by delayed re-endothelialization as well as later "catch-up" proliferation related to the drug.. Three different stents: Sirolimus-eluting stents (SES), Genous anti-CD34 antibody stents (GS), and the combination of HC-anti-CD34 antibody with sirolimus-eluting stents (HCASES) were deployed in 54 normal porcine coronary arteries and harvested for scanning electron microscopy (SEM) and histological analysis at 60, 90, and 120 days.. At 60 and 90 days, SEM analysis showed stent surface endothelial coverage was nearly completed in the HCASES (87 ± 3%, 95 ± 3%) compared with that in the SES (68 ± 6%, 77 ± 8%, P = 0.03). Histological examination at 90 days showed that the HCASES group had less percentage of stenosis than the GS group (P < 0.05). At 120 days, SEM showed a significantly higher extent of endothelial coverage above struts in the HCASES (96 ± 2%) and the GS (95 ± 3%) as compared with the SES group (66 ± 3%; P = 0.02). The HCASES group showed less stenosis than that in the GS group (P < 0.05), but it was not significantly different from the SES group (P = 0.063).. Histological and SEM analyses demonstrate that the HCASES can reduce neointimal formation and inflammation while promoting endothelialization in the long term.

Topics: Animals; Antibodies; Antigens, CD34; Drug-Eluting Stents; Endothelial Cells; Microscopy, Electron, Scanning; Neointima; Sirolimus; Swine

Topics: Absorbable Implants; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Middle Aged; Neointima; Percutaneous Coronary Intervention; Prosthesis Design; Prosthesis Failure; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

The Nobori (Terumo Corporation, Tokyo, Japan) is a biolimus A9-eluting stent (BES) featured with a biodegradable polymer coated on the abluminal side only. We previously reported that favourable vessel healing was achieved at 6-12 months after BES implantation. However, detailed long-term vessel reaction after BES deployment is unclear.. Twenty-two BESs were serially evaluated using optical coherence tomography (OCT) at 6, 12, and 24 months after stenting. Average neointimal thickness, uncovered struts, and neointimal unevenness score (each cross-section as maximum neointimal thickness in 1 cross section divided by the average neointimal thickness of the same cross-section) were manually measured. In addition, we evaluated the percentage of struts with peri-strut low-intensity area (a region around stent struts that homogenously showed less intensity than the surrounding tissue, which suggests fibrin deposition or impaired neointima maturation), thrombi, and atherogenic neointimas (neointimas containing a diffuse border and poor-signal region with invisible struts due to marked signal attenuation).. Serial OCT observation revealed a small gradual increase in neointimal thickness from 6 to 24 months (73 ± 24 μm; 81 ± 26 μm; and 108 ± 35 μm, respectively, P = 0.001) with a nonsignificant decrease in the lumen area (6.36 ± 1.98 mm(2); 6.18 ± 2.04 mm(2); and 5.87 ± 2.06 mm(2); P = 0.72). Frequency of uncovered struts (3.89 ± 3.91%; 1.55 ± 1.63%; and 0.23 ± 0.67%; P = 0.001), neointimal unevenness score (1.95 ± 0.18% to 1.86 ± 0.19% to 1.78 ± 0.17; P = 0.012), percentage of thrombi (5%, 0%, and 0%; P = 0.37) and peri-strut low-intensity area (6.8%, 5.1%, and 1.6%; P = 0.017) decreased from 6 to 12 and 24 months. Atherogenic neointima was not observed in the event-free OCT cohort.. The Nobori stent achieved acceptable long-term vessel healing, mostly without adverse vessel reactions.

Topics: Aged; Coated Materials, Biocompatible; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Neointima; Polymers; Prospective Studies; Prosthesis Design; Reproducibility of Results; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

To compare the effects of sirolimus, paclitaxel, and combretastatin A4 (CA4) on regulatory proteins of the cell cycle in proliferating smooth muscle cells (SMCs).. Human aortic SMCs were treated with sirolimus, paclitaxel, and CA4 at 5 × 10(-9) mol/L. After 1 day, half of the cells were harvested (DAY1 group). The treatment medium of the other half was replaced with culture medium on day 4, and those cells were harvested on day 5 (DAY5 group). Cyclins D1, D2, E, and A and cyclin-dependent kinase (CDK) inhibitors p16, p21, and p27 were detected by Western blot technique. Quantification was performed by scanning densitometry of the specific bands.. In the DAY1 group, treatment with sirolimus resulted in decreased intracellular levels of cyclins D2 and A (P < .05). Increased D cyclins and reduced levels of cyclins E and A (P < .05) in the DAY5 group indicated a permanent G1/S block by sirolimus. Paclitaxel led to only slight alterations of cyclin and CDK inhibitor expression (P > .05). In the DAY1 group, CA4 decreased intracellular levels of cyclins D2, E, and A (P < .05). Despite recovery effects in the DAY5 group (increase of cyclins D1, D2, and A compared with DAY1 group; P < .05), the upregulation of the CDK inhibitor p21, increased D cyclins, and decreased cyclins E and A (P < .05) are compatible with a G1 arrest.. CA4 is a stronger inhibitor of the SMC cycle than sirolimus or paclitaxel and may represent an alternative for drug-eluting stents in atherosclerotic luminal stenosis. The effect of CA4 on neointima formation should be evaluated further.

Topics: Cell Cycle; Cell Proliferation; Cells, Cultured; Humans; Myocytes, Smooth Muscle; Neointima; Paclitaxel; Sirolimus; Stilbenes; Treatment Outcome; Tubulin Modulators

The most common causes of in-stent restenosis (ISR) are intimal hyperplasia and stent under expansion. The purpose of this study was to use intravascular ultrasound (IVUS) to compare the ISR mechanisms of bare metal stents (BMS), first-generation drug-eluting stents (DES), and second-generation DES. There were 298 ISR lesions including 52 BMS, 73 sirolimus-eluting stents, 52 paclitaxel-eluting stents, 16 zotarolimus-eluting stents, and 105 everolimus-eluting stent. Mean patient age was 66.6 ± 1.1 years, 74.2% were men, and 48.3% had diabetes mellitus. BMS restenosis presented later (70.0 ± 66.7 months) with more intimal hyperplasia compared with DES (BMS 58.6 ± 15.5%, first-generation DES 52.6 ± 20.9%, second-generation DES 48.2 ± 22.2%, p = 0.02). Although reference lumen areas were similar in BMS and first- and second-generation DES, restenotic DES were longer (BMS 21.8 ± 13.5 mm, first-generation DES 29.4 ± 16.1 mm, second-generation DES 32.1 ± 18.7 mm, p = 0.003), and stent areas were smaller (BMS 7.2 ± 2.4 mm(2), first-generation DES 6.1 ± 2.1 mm(2), second-generation DES 5.7 ± 2.0 mm(2), p <0.001). Stent fracture was seen only in DES (first-generation DES 7 [5.0%], second-generation DES 8 [7.4%], p = 0.13). In conclusion, restenotic first- and second-generation DES were characterized by less neointimal hyperplasia, smaller stent areas, longer stent lengths, and more stent fractures than restenotic BMS.

Topics: Aged; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Metals; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Retrospective Studies; Risk Factors; Sirolimus; Stents; Time Factors; Treatment Outcome; Ultrasonography, Interventional

The drug-eluting stent still has limitations such as thrombosis and inflammation. These limitations often occur in the absence of endothelialization. This study investigated the effects of WKYMVm- and sirolimus-coated stents on re-endothelialization and anti-restenosis. The WKYMVm peptide, specially synthesized for homing endothelial colony-forming cells, was coated onto a bare-metal stent with hyaluronic acid through a simple dip-coating method (designated HA-Pep). Thereafter, sirolimus was consecutively coated to onto the HA-Pep (designated Pep/SRL). The cellular response to stents by human umbilical-vein endothelial cells and vascular smooth-muscle cells was examined by XTT assay. Stents were implanted into rabbit iliac arteries, isolated 6 weeks post-implantation, and then subjected to histological analysis. The peptide was well attached to the surface of the stents and the sirolimus coating made the surface smooth. The release pattern for sirolimus was similar to that of commercial sirolimus-coated stents (57.2% within 7 days, with further release for up to 28 days). Endothelial-cell proliferation was enhanced in the HA-Pep group after 7 days of culture (38.2 ± 7.62%, compared with controls). On the other hand, the proliferation of smooth-muscle cells was inhibited in the Pep/SRL group after 7 days of culture (40.7 ± 6.71%, compared with controls). In an animal study, the restenosis rates for the Pep/SRL group (13.5 ± 4.50%) and commercial drug-eluting stents (Xience Prime™; 9.2 ± 7.20%) were lower than those for bare-metal stents (25.2 ± 4.52%) and HA-Pep stents (26.9 ± 3.88%). CD31 staining was incomplete for the bare-metal and Xience Prime™ groups. On the other hand, CD31 staining showed a consecutive linear pattern in the HA-Pep and Pep/SRL groups, suggesting that WKYMVm promotes endothelialization. These results indicate that the WKYMVm coating could promote endothelial healing, and consecutive coatings of WKYMVm and sirolimus onto bare-metal stents have a potential role in re-endothelialization and neointimal suppression.

Topics: Animals; Biocompatible Materials; Cell Proliferation; Cells, Cultured; Coronary Restenosis; Drug-Eluting Stents; Endothelium, Vascular; Human Umbilical Vein Endothelial Cells; Humans; Iliac Artery; Male; Materials Testing; Myocytes, Smooth Muscle; Neointima; Oligopeptides; Rabbits; Rats; Sirolimus

Novel polymer-free drug-eluting stents have been developed to reduce polymer-related adverse events. However, neointimal coverage after polymer-free DES implantation is unclear and validation between optical coherence tomography (OCT) and histology is required. Sixteen polymer-free sirolimus-eluting stents were randomly implanted into coronary arteries of 8 normal swine. OCT and histological measurement were conducted at 3 or 6 months after stent placement. For quantitative measures, lumen area, stent area, neointimal area and neointimal thickness were validated in every single OCT and histology matched cross-section. Moreover, for qualitative analysis, OCT signal patterns of neointimal tissue were classified as homogeneous, layered and heterogeneous patterns based on optical intensity and backscatter pattern and peri-strut inflammation was also determined by histology. In total, 70 OCT and histology matched cross-sections were analyzed. At quantitative analysis, good correlations and agreements were found in the measurement of lumen area (ICC = 0.67, P<0.001), neointimal area (ICC = 0.89, P<0.001) and neointimal thickness (ICC = 0.94, P<0.001) except for stent area (ICC 0.19, P = 0.13) between OCT and histology. At qualitative analysis, lymphocyte infiltrations of peri-strut were more frequently seen in heterogeneous sections than in homogeneous sections (10/14 sections, 71.4% vs. 12/50 sections, 24%; P = 0.003). In conclusion, OCT has proper correlation and agreement with histology in assessment of neointimal formation and heterogeneous neointima assessed by OCT may also be associated with peri-strut inflammation detected in histology after polymer-free sirolimus-eluting stents implantation, supporting the use of OCT to evaluate neointimal coverage after polymer-free stent implantation in clinical practice.

Topics: Animals; Cardiovascular Agents; Coronary Vessels; Drug-Eluting Stents; Models, Animal; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Reproducibility of Results; Sirolimus; Swine; Time Factors; Tomography, Optical Coherence

While older age associates with adverse percutaneous coronary intervention (PCI) outcomes, detailed information relating age to stent strut coverage and neointimal characteristics is lacking. One hundred nineteen patients with 123 sirolimus-eluting stents (SESs) were divided into 3 groups: group A (≤55 years), group B (56-65 years), and group C (>65 years). At 6 and 12 months of follow-up, optical coherence tomography was performed to assess strut coverage and neointimal remodeling. At 6 months, the proportion of uncovered struts increased with age: 6.1% in group A versus 7.3% in group B versus 11.7% in group C (P < 0.001) while the proportion of embedded struts decreased: 72.1% versus 57.0% vs. 55.0%, respectively (P < 0.001). Mean neointimal thicknesses were 90  μm versus 60  μm versus 60  μm, respectively (P < 0.001), and neointimal areas were 0.82  mm2 versus 0.52  mm2 versus 0.57  mm2 (P < 0.001). At 12 months, the proportion of uncovered struts increased with age (3.9% vs. 3.3% vs. 4.9 %; P < 0.001), while mean neointimal thicknesses were 100 versus 70 versus 80  μm (P < 0.001) and neointimal areas were 0.87 versus 0.60 versus 0.67  mm2 (P < 0.001). Patients ≤55 years receiving SES showed highest strut coverage and neointimal repair rate compared with the other 2 groups. A "catch-up phenomenon" appeared to occur in the oldest patients, as in the first 6 months the neointima showed lowest endothelial cell coverage and lowest neointimal proliferation rate, whereas from 6 to 12 months, the highest neointimal proliferation rate was seen in the oldest patients.

Topics: Age Factors; Aged; Coronary Artery Disease; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Retrospective Studies; Sirolimus; Tomography, Optical Coherence; Treatment Outcome; Vascular Remodeling

Compared with the bare metal stent (BMS), suppression of neointimal growth in the sirolimus-eluting stent (SES) reduced restenosis at the cost of more exposed struts that could impose the risk of stent thrombosis. The present study was conducted to analyze neointimal coverage patterns of stents at a strut-level after implantation of BMS or SES with the use of optical coherence tomography (OCT). We enrolled 35 patients and analyzed neointimal coverage of every strut from 41 stents (BMS: n = 8, SES: n = 33) by using OCT at follow-up of the stent implantation. All of the 371 struts from eight BMSs were covered with ≥100 μm of neointima, while 19.8 and 3.5% of 3,478 struts from 33 SESs were uncovered (neointimal thickness of <10 μm) and malapposed, respectively. The histogram of neointimal thickness showed basically normal distribution in BMS but skewed in SES. No regional difference in neointimal thickness was observed in BMS (proximal, 535.7 ± 25.2 μm; body, 532.4 ± 17.0 μm; distal, 485.8 ± 27.0 μm). In SES, however, the body segment showed thinner neointima [median 40 μm (interquartile range (IQR) 10-90 μm)] than proximal [60 μm (IQR 10-140 μm), p < 0.001] or distal [50 μm (IQR 10-110 μm), p < 0.001] segment, while uncovered and malapposed struts were more frequent in the proximal and body segments. In conclusion, SES, compared with BMS, showed more suppressed neointimal growth with regional variation: neointimal thickness was the least in the body part while the ratio of exposed and malapposed struts was minimal in the distal segment. OCT was useful for a strut-level analysis of neointimal coverage over the whole stent.

Topics: Aged; Cardiovascular Agents; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Metals; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Stents; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Several studies have reported re-endothelialization and endothelial function after drug-eluting stent (DES) implantation; however, the relationship between re-endothelialization and endothelial function after DES implantation has not been investigated yet.. A total of 14 patients underwent evaluation of re-endothelialization by optical coherence tomography (OCT) and endothelial function by incremental Ach infusion at 9 months after DES implantation (ZES: N = 7, PES: N = 7). The neointimal thickness (NIT) inside each strut, strut coverage, and malapposition at every 1 mm cross-section were evaluated by OCT and the endothelial function was estimated by measuring the coronary vaso-reactivity in response to acetylcholine (Ach) infusion into coronary arteries.. Zotarolims eluting stent (ZES), compared with paclitaxcel eluting stent (PES), showed more homogeneous neointimal coverage of stent struts and low rate of malapposition. Vasoconstriction in response to Ach in the peri-stent region was also less pronounced in ZES than PES. In particular, vasoconstriction was more often observed in cases with inhomogeneous neointimal coverage of stent struts in the PES group.. Our findings suggest that endothelial function seems to be better preserved with ZES than PES, and homogeneous neointimal coverage of stent struts seem to be associated with the preserved endothelial function.

Topics: Acetylcholine; Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Endothelial Cells; Female; Humans; Infusions, Intra-Arterial; Male; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Re-Epithelialization; Retrospective Studies; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Vasoconstriction; Vasoconstrictor Agents

Clinical trials have demonstrated that the second-generation cobalt-chromium everolimus-eluting stent (CoCr-EES) is superior to the first-generation paclitaxel-eluting stent (PES) and is noninferior or superior to the sirolimus-eluting stent (SES) in terms of safety and efficacy. It remains unclear whether vascular responses to CoCr-EES are different from those to SES and PES because the pathology of CoCr-EES has not been described in humans.. A total of 204 lesions (SES=73; PES=85; CoCr-EES=46) from 149 autopsy cases with duration of implantation >30 days and ≤3 years were pathologically analyzed, and comparison of vascular responses was corrected for duration of implantation. The observed frequency of late and very late stent thrombosis was less in CoCr-EES (4%) versus SES (21%; P=0.029) and PES (26%; P=0.008). Neointimal thickness was comparable among the groups, whereas the percentage of uncovered struts was strikingly lower in CoCr-EES (median=2.6%) versus SES (18.0%; P<0.0005) and PES (18.7%; P<0.0005). CoCr-EES showed a lower inflammation score (with no hypersensitivity) and less fibrin deposition versus SES and PES. The observed frequency of neoatherosclerosis, however, did not differ significantly among the groups (CoCr-EES=29%; SES=35%; PES=19%). CoCr-EES had the least frequency of stent fracture (CoCr-EES=13%; SES=40%; PES=19%; P=0.007 for CoCr-EES versus SES), whereas fracture-related restenosis or thrombosis was comparable among the groups (CoCr-EES=6.5%; SES=5.5%; PES=1.2%).. CoCr-EES demonstrated greater strut coverage with less inflammation, less fibrin deposition, and less late and very late stent thrombosis compared with SES and PES in human autopsy analysis. Nevertheless, the observed frequencies of neoatherosclerosis and fracture-related adverse pathological events were comparable in these devices, indicating that careful long-term follow-up remains important even after CoCr-EES placement.

Topics: Aged; Aged, 80 and over; Autopsy; Biocompatible Materials; Chromium Alloys; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Paclitaxel; Prevalence; Registries; Retrospective Studies; Sirolimus

Impaired re-endothelialization and stent thrombosis are a safety concern associated with drug-eluting stents (DES). PI3K/p110α controls cellular wound healing pathways, thereby representing an emerging drug target to modulate vascular homoeostasis after injury.. PI3K/p110α was inhibited by treatment with the small molecule inhibitor PIK75 or a specific siRNA. Arterial thrombosis, neointima formation, and re-endothelialization were studied in a murine carotid artery injury model. Proliferation and migration of human vascular smooth muscle cell (VSMC) and endothelial cell (EC) were assessed by cell number and Boyden chamber, respectively. Endothelial senescence was evaluated by the β-galactosidase assay, endothelial dysfunction by organ chambers for isometric tension. Arterial thrombus formation was delayed in mice treated with PIK75 when compared with controls. PIK75 impaired arterial expression and activity of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1); in contrast, plasma clotting and platelet aggregation did not differ. In VSMC and EC, PIK75 inhibited expression and activity of TF and PAI-1. These effects occurred at the transcriptional level via the RhoA signalling cascade and the transcription factor NFkB. Furthermore, inhibition of PI3K/p110α with PIK75 or a specific siRNA selectively impaired proliferation and migration of VSMC while sparing EC completely. Treatment with PIK75 did not induce endothelial senescence nor inhibit endothelium-dependent relaxations. In line with this observation, treatment with PIK75 selectively inhibited neointima formation without affecting re-endothelialization following vascular injury.. Following vascular injury, PI3K/p110α inhibition selectively interferes with arterial thrombosis and neointima formation, but not re-endothelialization. Hence, PI3K/p110α represents an attractive new target in DES design.

Topics: Animals; Cell Proliferation; Cells, Cultured; Chemotaxis; Drug-Eluting Stents; Endothelium, Vascular; GTP Phosphohydrolases; Hydrazones; Immunosuppressive Agents; Leukocytes, Mononuclear; Male; Mice, Inbred C57BL; Muscle, Smooth, Vascular; Neointima; NF-kappaB-Inducing Kinase; Nitric Oxide; Paclitaxel; Phosphoinositide-3 Kinase Inhibitors; Plasminogen Activator Inhibitor 1; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; RNA Interference; RNA, Small Interfering; Sirolimus; Sulfonamides; Thrombosis; Tumor Necrosis Factor-alpha

The differences in lesion morphology between ST-segment elevation myocardial infarction (STEMI) and stable angina (SAP) significantly influence chronic intra-stent conditions after first-generation drug-eluting stent implantation. The study aimed to compare the intra-stent conditions 12 months after implantation of a second-generation everolimus-eluting stent (EES) in patients with STEMI or SAP.. We examined the lesion morphology before EES implantation in 53 patients (23 STEMI, 30 SAP) using virtual histology intravascular ultrasound. We maintained dual anti-platelet therapy for 12 months and subsequently analyzed intra-stent conditions using optical coherence tomography and angioscopy. Pre-intervention plaque and necrotic core volume/length, remodeling index, and the incidence of thin-cap fibroatheroma and thrombus were significantly greater in STEMI than in SAP. After 12 months, the median neointimal thickness (117.6 μm vs. 126.0 μm), frequency of uncovered struts (1.2% ± 2.3% vs. 1.0% ± 2.3%), and percentage of stents fully covered with neointima (60.9% vs. 61.1%) were similar between the 2 groups. Meanwhile, the frequency of malapposed struts (0.4% ± 0.6% vs. 0.1% ± 0.4%, p=0.04) and neointimal unevenness score (1.74 ± 0.21 vs. 1.64 ± 0.16, p=0.04) were significantly higher in STEMI than in SAP. The neointimal color grade was more xanthochromatic in STEMI than in SAP. However, the differences were not associated with the incidence of clinical events and intra-stent thrombus (21.7% vs. 16.7%, p=0.89).. Although a small degree of delayed healing still persists with second-generation EES, EES promotes a favorable arterial healing response in patients with STEMI, as well as those with SAP.

Topics: Aged; Aged, 80 and over; Angina, Stable; Angioplasty, Balloon, Coronary; Coronary Vessels; Drug-Eluting Stents; Electrocardiography; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Neointima; Prosthesis Design; Retrospective Studies; Sirolimus; Thrombosis; Tomography, Optical Coherence; Ultrasonography, Interventional; Wound Healing

We aimed to compare the vascular effects exclusive to antiproliferative agents by using identical stent and biodegradable polymeric matrices eluting everolimus (BP-EES) (Carlo; Balton) and paclitaxel (BP-PES) (Luc-Chopin2; Balton) in the porcine model of coronary injury. A total of 37 stents were implanted with 110% overstretch in the coronary arteries of 14 domestic pigs: 13 BP-PES, 16 BP-EES and eight bare metal stents (BMS) (Chopin2; Balton). Coronary angiography was performed after 28 and 90 days, the animals were sacrificed and the stented segments harvested for histopathological evaluation. At 28 days, BP-PES most effectively limited angiographic late loss (LL PES: 0.15±0.1 vs. EES: 0.40±0.3 vs. BMS: 0.5±0.2 mm; p=0.04) and neointimal thickness (NT) in histology (PES: 0.12 [0.1-0.2] vs. EES: 0.38 [0.3-0.4] vs. BMS: 0.35 [0.3-0.4] mm; p<0.01). The BP-PES had lower endothelialisation (EES: 100% vs. PES: 40±4% vs. BMS: 97.5±5%; p<0.01) and slightly higher inflammation scores (EES: 1 vs. PES: 2.1±0.3 vs. BMS: 1; p<0.01). At three months, LL remained unchanged in the EES and BMS groups in contrast to an increase in the PES group (EES: 0.38±0.3 vs. PES: 0.52±0.4 vs. BMS: 0.51±0.3 mm; p=0.69). NT stabilised at 90 days in the EES group in comparison to a fourfold increase in the PES group and a 30% increase in the BMS group (EES: 0.35 [0.3-0.5] vs. PES: 0.53 [0.5-0.8] vs. BMS: 0.46 [0.4-0.5] mm: p=0.07). Stent endothelialisation and inflammation were comparable at 90 days in all groups. Temporal differences in vascular response were seen by the delivery of different antiproliferative agents. In contrast to everolimus, paclitaxel seems to induce a slightly higher degree of inflammation in the short term, potentially leading to further neointimal hyperplasia in the long term.

Topics: Absorbable Implants; Animals; Coated Materials, Biocompatible; Coronary Angiography; Coronary Vessels; Drug-Eluting Stents; Endothelium, Vascular; Everolimus; Hyperplasia; Inflammation; Models, Animal; Neointima; Paclitaxel; Polymers; Sirolimus; Stents; Swine

Topics: Adult; Drug-Eluting Stents; Female; Humans; Neointima; Saphenous Vein; Sirolimus; Tomography, Optical Coherence; Ultrasonography, Interventional

Neointimal proliferation of bifurcation lesions after implantation of drug-eluting stents (DES) has not been well evaluated. Thus, we compared neointimal proliferation of bifurcation lesions among four DES using optical coherence tomography (OCT).. 8-month follow-up OCT was performed in 68 bifurcation lesions treated by 15 sirolimus-eluting stents (SES) and 17 paclitaxel-eluting stents (PES) as first-generation DES, and by 17 zotarolimus-eluting stents (ZES) and 19 everolimus-eluting stents (EES) as second-generation DES. Cross-sectional images of the bifurcation lesion using OCT were analyzed every 450 µm. All images were divided into three areas: inner wall of the bifurcation (IB), outer wall of the bifurcation (OB), and ostium of the side branch (SB). We compared the incidence of uncovered struts (IUS) among three areas and the averaged neointimal thickness (NIH) between IB and OB in each stent and also compared these OCT parameters among all DES.. There were no significant differences of IUS between IB and OB in second-generation DES, while in first-generation DES, IUS of IB and OB showed significant differences. The IUS of SES in both areas was significantly higher than in the other DES (all P < 0.001). PES had a significantly higher IUS in SB than the others (all P < 0.001). NIH of OB was significantly higher than that of IB in PES, ZES, and EES, but in SES the NIH was similar in the two areas.. OCT revealed different neointimal growth patterns among SES, PES, ZES, and EES in bifurcation lesions.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Stenosis; Cross-Sectional Studies; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neointima; Paclitaxel; Prosthesis Failure; Retrospective Studies; Risk Assessment; Severity of Illness Index; Sirolimus; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

Detailed long-term changes of the neointima in sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) are still unclear.. We consecutively enrolled 14 patients (18 SES) and 12 patients (13 PES) who underwent optical coherence tomography (OCT) serially at eight months and 18 months after stent implantation. For 18 SES and 13 PES, OCT was used to visualise 2,486 and 1,361 stent struts at the eight-month and 2,199 and 1,309 stent struts at the 18-month follow-up, respectively. The OCT parameters, including incidence of uncovered and malapposed struts (uncovered and malapposed percentage), average neointimal hyperplasia thickness (NIH thickness) and %NIH volume obstruction, which was defined as ([mean NIH area*stent length]/[mean stent area*stent length])100, and qualitative analysis of the neointima were compared between SES and PES and also compared between the eight- and 18-month follow-up for SES and PES, respectively. The uncovered and malapposed percentage was significantly higher in SES than PES at the eight- and 18-month follow-up, and the NIH thickness and %NIH volume obstruction were lower in SES than PES at both follow-ups. The uncovered and malapposed percentage decreased in both SES and PES between the eight- and 18-month follow-up. Percent NIH volume obstruction and NIH thickness in SES significantly increased from the eight- to 18-month follow-up; however, those parameters significantly decreased in PES. The incidence of high signal with peri-strut low-intensity areas increased in SES but decreased in PES from the eight- to 18-month follow-up.. Uncovered and malapposed struts were reduced in both SES and PES, while the neointimal hyperplasia and qualitative changes showed different patterns.

Topics: Acute Coronary Syndrome; Aged; Antineoplastic Agents; Cohort Studies; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Disease Progression; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Retrospective Studies; Sirolimus; Tomography, Optical Coherence

The utility of animal models for the prediction of drug-eluting stent (DES) efficacy in human clinical trials is still unclear. The familial hypercholesterolemic swine (FHS) model has been shown to induce a human-like neointimal response to bare metal stent (BMS) implantation. However, its utility to discriminate efficacy signals following DES implantation is unknown. In this study, we aimed to test the efficacy and healing response of several everolimus-eluting stent (EES) platforms in the coronary territory of the FHS.. A total of 19 EES platforms (SYNERGY=6, SYNERGY½-dose=7, and PROMUS Element=6) and an identical BMS control (Element=6) were implanted into the coronary arteries of nine FHS. All implants were performed under intravascular ultrasound guidance using a 1.2 : 1 overstretch ratio. At 30 days, the vascular response to the implant was evaluated by quantitative coronary angiography, optical coherence tomography, and histology.. At 28 days, all EES platforms showed a significant decrease in angiographic late lumen loss (between 27 and 37%) compared with the BMS control group. This finding was confirmed both by optical coherence tomography (mean neointimal thickness=28-42% reduction) and by histology (mean neointimal thickness=44-55% reduction). All EES platforms showed similar degrees of neointimal inhibition. The presence of moderate to severe para-strut inflammation was observed in 83% of the stent sections in the BMS group compared with 28.6% in the SYNERGY½-dose group and 0% in the SYNERGY and PROMUS groups (P=0.0002). There was a 68-95% reduction in MMP9 expression in the media in all EES platforms compared with the BMS controls. The presence of mild to moderate para-strut fibrin deposits ranged from 66.7 to 83.4% in all EES platforms compared with 16.7% in the EBMS group.. The FHS coronary injury model showed the efficacy of several EES platforms compared with an identical BMS control. Everolimus eluted from different polymeric platforms showed lower levels of inflammation and slightly higher fibrin deposits compared with BMS controls.

Topics: Animals; Blood Vessel Prosthesis Implantation; Coronary Angiography; Coronary Vessels; Disease Models, Animal; Drug-Eluting Stents; Everolimus; Humans; Hyperlipoproteinemia Type II; Immunosuppressive Agents; Male; Models, Cardiovascular; Neointima; Polymers; Sirolimus; Swine; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

Topics: Angioscopy; Autopsy; Biopsy; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Fatal Outcome; Fibrosis; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Tomography, Optical Coherence

Topics: Animals; Coronary Vessels; Disease Models, Animal; Drug-Eluting Stents; Everolimus; Humans; Hyperlipoproteinemia Type II; Male; Neointima; Sirolimus

To assess the late postinterventional response to iliac stenting in atheromatous rabbits using the Xience V everolimus-eluting stent (Xience V EES; Abbott Vascular) and the Resolute zotarolimus-eluting stent (Resolute ZES; Medtronic Vascular) with the MultiLink Vision bare metal stent (BMS; Abbott Vascular) as a reference.. Xience V EES and Resolute ZES were developed to overcome shortcomings of first-generation DES.. Functional and microscopic changes were assessed by organ bath experiments and histopathologic examination. Gene expression was investigated using RT-PCR.. After 91 days, re-endothelialization was nearly complete (BMS: 93 ± 3%; Resolute ZES: 92 ± 2%; Xience V EES: 94 ± 3%; P = 0.10). Neointima thickness was similar in Resolute ZES (0.17 ± 0.08 mm) and BMS (0.17 ± 0.09 mm), and reduced in Xience V EES (0.03 ± 0.01 mm; P < 0.0001). Xience V EES had less peri-strut inflammation compared with BMS (P = 0.001) and Resolute ZES (P = 0.0001), while arterial segments distal to Xience V EES were more sensitive to acetylcholine than those distal to BMS and Resolute ZES (P = 0.02). Lectin-like oxidized receptor-1 was overexpressed in stented arteries (P < 0.001), whereas thrombomodulin was downregulated in Resolute ZES (P = 0.01) and BMS (P = 0.02) compared to unstented arteries of rabbits on regular chow. No significant changes were seen for vascular cell adhesion molecule-1, nitric oxide synthase 3, or endothelin-1.. At 3-month follow-up, nearly complete re-endothelialization was achieved for all stent groups. Xience V EES induced greater suppression of neointimal growth and peri-strut inflammation, higher vasorelaxation to acetylcholine, and expression of thrombomodulin at the level of unstented controls.

Topics: Acetylcholine; Angioplasty, Balloon; Animals; Atherosclerosis; Disease Models, Animal; Down-Regulation; Drug-Eluting Stents; Endothelium, Vascular; Everolimus; Iliac Artery; Inflammation; Neointima; Rabbits; Scavenger Receptors, Class E; Sirolimus; Thrombomodulin; Vasodilator Agents

Intimal hyperplasia produces restenosis (re-narrowing) of the vessel lumen following vascular intervention. Drugs that inhibit intimal hyperplasia have been developed, however there is currently no clinical method of perivascular drug-delivery to prevent restenosis following open surgical procedures. Here we report a poly(ε-caprolactone) (PCL) sheath that is highly effective in preventing intimal hyperplasia through perivascular delivery of rapamycin. We first screened a series of bioresorbable polymers, i.e., poly(lactide-co-glycolide) (PLGA), poly(lactic acid) (PLLA), PCL, and their blends, to identify desired release kinetics and sheath physical properties. Both PLGA and PLLA sheaths produced minimal (<30%) rapamycin release within 50days in PBS buffer. In contrast, PCL sheaths exhibited more rapid and near-linear release kinetics, as well as durable integrity (>90days) as evidenced in both scanning electron microscopy and subcutaneous embedding experiments. Moreover, a PCL sheath deployed around balloon-injured rat carotid arteries was associated with a minimum rate of thrombosis compared to PLGA and PLLA. Morphometric analysis and immunohistochemistry revealed that rapamycin-loaded perivascular PCL sheaths produced pronounced (85%) inhibition of intimal hyperplasia (0.15±0.05 vs 1.01±0.16), without impairment of the luminal endothelium, the vessel's anti-thrombotic layer. Our data collectively show that a rapamycin-loaded PCL delivery system produces substantial mitigation of neointima, likely due to its favorable physical properties leading to a stable yet flexible perivascular sheath and steady and prolonged release kinetics. Thus, a PCL sheath may provide useful scaffolding for devising effective perivascular drug delivery particularly suited for preventing restenosis following open vascular surgery.

Topics: Animals; Cardiovascular Agents; Carotid Artery Injuries; Carotid Stenosis; Cell Proliferation; Chemistry, Pharmaceutical; Delayed-Action Preparations; Disease Models, Animal; Drug Carriers; Hyperplasia; Kinetics; Linear Models; Male; Neointima; Polyesters; Rats; Rats, Sprague-Dawley; Sirolimus; Solubility; Technology, Pharmaceutical

Topics: Cardiovascular Agents; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Neointima; Paclitaxel; Sirolimus

Although drug-eluting stents have significantly reduced the midterm incidence of target lesion revascularization (TLR), in vivo studies on long-term vessel healing of sirolimus-eluting stents (SESs) and paclitaxel-eluting stents (PESs) are limited. The aim of this study was to compare long-term arterial healing with SESs and PESs.. We evaluated 27 SESs (23 patients) and 21 PESs (20 patients) by serial optical coherence tomography at 6 months (midphase) and ≥ 3 years (late phase) after stenting and evaluated the change of neointimal thickness (NIT), the percentages of uncovered and malapposed struts, peristrut low-intensity area (region around stent struts with a homogeneously lower intensity appearance than surrounding tissue), thrombus, and atherogenic neointima.. At follow-up, most SESs showed a progressive increase in the average NIT, whereas PESs showed variable changes. Between midphase and late phase, NIT increased significantly in SESs (midphase, 94.1 ± 49.3; late phase, 130.2 ± 78.7; P = 0.001) but decreased significantly in PESs (midphase, 167.4 ± 122.9; late phase, 136.0 ± 77.7; P = 0.04). The percentages of uncovered struts decreased significantly in SESs; conversely, variable changes were observed in PESs. Peristrut low-intensity area and thrombus formation decreased in SESs but remained largely unchanged in PESs. The prevalence of atherogenic neointima was greater in the late phase than in the midphase in both groups but was similar for both stents.. Long-term vessel healing was different for SESs and PESs. Progressive vessel healing was consistently observed in SESs, whereas a heterogeneous process of delayed vessel healing was noted for PESs.

Topics: Aged; Cardiovascular Agents; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Sirolimus; Tomography, Optical Coherence

Development of neoatherosclerosis (NA) has been reported to be a potential cause of late stent failure. However, the distribution of NA and its relationship with neovascularization (NV) and adjacent plaque characteristics remain unclear.. We investigated 167 stents (40 bare-metal stents, 84 sirolimus-eluting stents, and 43 everolimus-eluting stents) with optical coherence tomography. Each stent was divided into the proximal section (PS), mid section (MS) and distal section (DS). Neoatherosclerosis was defined as lipid-laden neointima or calcification inside stent. Adjacent plaque characteristics were evaluated within 5 mm proximal and distal reference segments.. Neoatherosclerosis was more frequent in PS and DS than in MS (PS 19.8% vs. MS 3.6% vs. DS 21%: PS vs. MS, P < .001: MS vs. DS, P < .001). Neovascularization in PS and DS was also more prevalent compared with that in MS (PS 15% vs. MS 5.4% vs. DS 13.8%: PS vs. MS, P = .001: MS vs. DS, P = .001). Neoatherosclerosis was more frequently observed in stents with intraintima NV (68.6% vs. 20.5%, P < .001). The incidence of NA was higher, when adjacent plaque was lipid (43.2% with lipid plaque vs. 12.2% without lipid plaque, P < .001).. Neoatherosclerosis occurs more frequently at PS and DS. Neoatherosclerosis was associated with NV and adjacent lipid plaque, suggesting potential interrelationship between development of NA and NV and adjacent plaque characteristics.

Topics: Aged; Cohort Studies; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Neovascularization, Pathologic; Plaque, Atherosclerotic; Prosthesis Failure; Sirolimus; Stents; Tomography, Optical Coherence

The Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb) has shown promising clinical results; however, only limited preclinical data have been published. We sought to investigate detailed pathological responses to the Absorb versus XIENCE V (XV) in a porcine coronary model with duration of implant extending from 1 to 42 months.. A total of 335 devices (263 Absorb and 72 XV) were implanted in 2 or 3 main coronary arteries of 136 nonatherosclerotic swine and examined by light microscopy, scanning electron microscopy, pharmacokinetics, and gel permeation chromatography analyses at various time points. Vascular responses to Absorb and XV were largely comparable at all time points, with struts being sequestered within the neointima. Inflammation was mild to moderate (with absence of inflammation at 1 month) for both devices, although the scores were greater in Absorb at 6 to 36 months. Percent area stenosis was significantly greater in Absorb than XV at all time points except at 3 months. The extent of fibrin deposition was similar between Absorb and XV, which peaked at 1 month and decreased rapidly thereafter. Histomorphometry showed expansile remodeling of Absorb-implanted arteries starting after 12 months, and lumen area was significantly greater in Absorb than XV at 36 and 42 months. These changes correlated with dismantling of Absorb seen after 12 months. Gel permeation chromatography analysis confirmed that degradation of Absorb was complete by 36 months.. Absorb demonstrates comparable long-term safety to XV in porcine coronary arteries with mild to moderate inflammation. Although Absorb was associated with greater percent stenosis relative to XV, expansile remodeling was observed after 12 months in Absorb with significantly greater lumen area at ≥ 36 months. Resorption is considered complete at 36 months.

Topics: Absorbable Implants; Animals; Chromium Alloys; Coronary Angiography; Coronary Vessels; Drug-Eluting Stents; Everolimus; Incidence; Microscopy, Electron, Scanning; Models, Animal; Neointima; Sirolimus; Stents; Swine; Swine, Miniature; Time Factors; Tissue Scaffolds; Vasculitis

Preclinical evaluation of the vascular response of drug-eluting stents is limited especially in the setting of diabetes mellitus preventing the evaluation of changes in drug-eluting stent design and eluted drugs after clinical use.. Cultured human aortic endothelial cells were used to assess the differences between sirolimus and its analog, everolimus, in the setting of hyperglycemia on various cellular functions necessary for endothelial recovery. A diabetic rabbit model of iliac artery stenting was used to compare histological and morphometric characteristics of the vascular response to everolimus-eluting, sirolimus-eluting, and bare metal stent placement. Under hyperglycemic conditions, sirolimus impaired human aortic endothelial cell barrier function, migration, and proliferation to a greater degree compared with everolimus. In our in vivo model of diabetes mellitus, endothelialization at 28 days was significantly lower and endothelial integrity was impaired in sirolimus-eluting stent compared with both everolimus-eluting and bare metal stents. Neointimal area, uncovered struts, and fibrin deposition were significantly higher in sirolimus-eluting compared with everolimus-eluting and bare metal stents.. Use of everolimus-eluting stent results in improved vascular response in our preclinical models of diabetes mellitus.

Topics: Animals; Aorta; Cell Movement; Cells, Cultured; Diabetes Mellitus; Disease Models, Animal; Drug-Eluting Stents; Endothelial Cells; Everolimus; Fibrin; Humans; Hyperglycemia; Iliac Artery; Male; Neointima; Rabbits; Sirolimus

Topics: Algorithms; Angina, Unstable; Automation; Cardiovascular Agents; Coronary Vessels; Drug-Eluting Stents; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

Topics: Coronary Artery Disease; Drug-Eluting Stents; Everolimus; Female; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Male; Neointima; Sirolimus; Tomography, Optical Coherence

Topics: Absorbable Implants; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Neointima; Percutaneous Coronary Intervention; Sirolimus

The long-term coronary arterial response of biodegradable polymer biolimus-eluting stents (BES) remains unclear. We sought to evaluate the coronary arterial response of biodegradable polymer BES at 5 years after stent implantation using optical coherence tomography (OCT) as compared with that of durable polymer sirolimus-eluting stents (SES) and bare-metal stents (BMS).. Five-year follow-up OCT was performed in 30 patients with 33 stents (10 with 12 BES; 10 with 11 SES; 10 with 10 BMS). Quantitative parameters and qualitative characteristics of the neointima were evaluated. A total of 5178 struts (BES, n = 2056; SES, n = 1410; BMS, n = 1712) were analyzed.. Uncovered struts were found in 15 out of 2055 struts in the BES (weighted estimate 0.01%, 95% confidence intervals [CI]: 0.00-0.33%) and 54 out of 1410 struts in the SES (0.11%, 95% CI: 0.00-3.33%) (odds ratio [OR] 0.12, 95% CI: 0.01-1.95, p = 0.13). None of 1712 struts were uncovered in the BMS. Cross-sectional qualitative analysis of neointimal tissue showed that the frequency of lipid-laden neointima tended to be lower in the BES (2.26%, 95% CI: 0.38-12.3%) compared with the SES (9.90%, 95% CI: 4.37-20.9%; OR 0.21, 95% CI 0.03-1.16, p = 0.07), and was similar to the BMS (2.23%, 95% CI: 0.54-8.74%; OR 0.98, 95% CI 0.13-7.14, p = 0.98).. Biodegradable polymer BES shows a favorable coronary arterial response compared with SES, but different response with BMS at 5 years follow-up. The observed frequency of in-stent neoatherosclerosis within BES was similar to BMS and tended to be lower than SES.

Topics: Absorbable Implants; Aged; Aged, 80 and over; Atherosclerosis; Coronary Angiography; Coronary Vessels; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Lipids; Male; Metals; Neointima; Polymers; Sirolimus; Stents; Ticlopidine; Time Factors; Tomography, Optical Coherence

The serial changes in neointimal tissues were compared between everolimus-eluting stent (EES) and bare-metal stent (BMS) in the porcine coronary artery using optical coherence tomography (OCT).. Serial (1, 3, and 6 month follow-up after stent implantation) OCT examinations were performed in 15 swine with 15 BMS- and 15 EES-treated lesions in porcine coronary arteries.. In BMS-implanted lesions, neointimal volume decreased from 7.3 mm(3) to 6.9 mm(3) and 6.4 mm(3) at 1, 3, and 6 months follow-up without statistical significance (P = 0.369). At the time points of 1, 3, and 6 months, neointimal tissue appearance was mainly a homogeneous pattern (80.0%, 93.3%, and 100%, resp.), while the other pattern was layered. In contrast, in EES-implanted lesions, neointimal volume significantly increased from 4.8 mm(3) to 9.8 mm(3) between 1 and 3 months but significantly decreased to 8.6 mm(3) between 3 and 6 months (P < 0.001). Between 1 and 3 months, the layered pattern of neointimal tissue increased from 26.7% to 66.7% but decreased to 20.0% between 3 and 6 months.. EES had a biphasic pattern of neointimal amounts that correlated with changes in neointimal morphology.

Topics: Animals; Blood Vessel Prosthesis; Coronary Angiography; Coronary Vessels; Drug-Eluting Stents; Everolimus; Hyperplasia; Neointima; Sirolimus; Sus scrofa; Tomography, Optical Coherence

Biodegradable polymer-based drug-eluting stents are thought to be safer than durable polymer-based stents. However, the long-term vascular response remains unclear. The aim of this study was to compare the biocompatibility of durable polymer-based sirolimus-eluting (SES) and everolimus-eluting (EES) stents with biodegradable polymer-based biolimus-eluting (BES) stents in a porcine coronary model. Stents were implanted in porcine coronaries. Acetylcholine challenge tests and optical coherence tomography (OCT) examination were performed at one month. Animals were sacrificed at three and six months (n=6 each), and the stents were analysed histologically. At one month, acetylcholine challenge tests revealed a trend towards greatest vasoconstriction in SES, less in BES, and least in EES, but the differences were not significant. OCT analysis demonstrated the highest incidence of uncovered struts in SES, followed by BES, while EES showed almost complete strut coverage (41.7±27.0%, 24.5±23.8%, 0.4±0.8%, respectively; p=0.004). Upon histological analysis at three months, SES showed a significantly higher inflammatory score than BES and EES (2.9±1.4, 0.8±0.9, 0.5±0.4, respectively; p=0.001), and this was maintained at six months (1.6±1.5, 0.3±0.3, 0.4±0.6, respectively; p=0.049). While SES showed an increased inflammatory reaction, EES and BES showed minimal inflammation. These results indicate that the late inflammatory reaction does not necessarily depend on degradability of the polymer, if the combination of the drug, metal, and polymer is biocompatible.

Topics: Absorbable Implants; Acetylcholine; Animals; Coated Materials, Biocompatible; Coronary Angiography; Coronary Vessels; Drug-Eluting Stents; Everolimus; Inflammation; Materials Testing; Models, Animal; Neointima; Polymers; Sirolimus; Swine; Tomography, Optical Coherence; Vasodilator Agents

Topics: Aged; Angioplasty, Balloon, Coronary; Angioscopy; Biopsy; Cardiovascular Agents; Coronary Aneurysm; Coronary Angiography; Coronary Artery Disease; Coronary Thrombosis; Drug-Eluting Stents; Female; Humans; Myocardial Infarction; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Risk Factors; Sirolimus; Syndrome; Thrombectomy; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

Arterial repair in the early phase following implantation of a zotarolimus-eluting stent (ZES) remains unknown.. Following implantation of 49 Endeavor ZES in 33 patients, follow-up angioscopy was performed in 13 patients (26 ZES) in the early phase (EP; 123±24 days) and in 20 patients (23 ZES) in the middle phase (MP; 247±17 days). Neointimal coverage (NIC) was graded as follows: grade 0, stent struts exposed; grade 1, struts bulging into the lumen, although covered; grade 2, struts were embedded by the neointima but were seen translucently; grade 3, struts fully embedded and invisible. NIC was defined as heterogeneous for NIC grade variation≥1. The presence of thrombus and yellow plaque was also investigated. Although NIC heterogeneity tended to be more frequent in EP than in MP (50% vs. 22%, P=0.070), and yellow plaque significantly more frequent (58% vs. 13%, P=0.0025), the majority of stents were dominant NIC grade 3 at both follow-up periods (73% in EP vs. 78% in MP, P=0.75). There was no significant difference in thrombus (23% in EP vs. 4% in MP, P=0.10) between the follow-ups.. Sufficient arterial repair may have occurred by 4 months after ZES implantation. 

Topics: Aged; Aged, 80 and over; Angioscopy; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Previous intravascular ultrasound studies have shown that echolucent neointimal hyperplasia occasionally appears after bare-metal stent (BMS) or sirolimus-eluting stent (SES) implantation. Optical coherence tomography (OCT) studies have also demonstrated that paclitaxel-eluting stent (PES) restenosis exhibited similar images showing low signal intensity areas (LSIA) surrounding stent struts and three-layer appearance (TLA). The aim of the present study was to investigate the clinical significance of LSIA on OCT images in various types of stents. Fifty nine consecutive patients who underwent scheduled follow-up coronary angiography and OCT were enrolled. There was no significant difference in the prevalence of LSIA among the 3 stent groups (BMS 30%, SES 19%, PES 28%, P = 0.70). LSIA thickness was larger in the PES group than in the other stent groups (BMS 0.51 ± 0.21 mm, SES 0.35 ± 0.06 mm, PES 0.87 ± 0.19 mm, P < 0.01). The ratio of LSIA thickness to the neointimal thickness was also larger in PES compared with other stents (BMS 53 ± 9 %, SES 57 ± 8 %, PES 77 ± 5 %, P < 0.01). Also, LSIA thickness in patients with in-stent restenosis (ISR) was significantly larger than in those without ISR (0.37 ± 0.37 mm versus 0.12 ± 0.26 mm, P = 0.048). Our results suggest that LSIA might be involved in excessive neointimal formation, and that the healing response after PES implantation might be different from BMS or SES.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Disease; Coronary Restenosis; Female; Humans; Hyperplasia; Immunosuppressive Agents; Japan; Male; Middle Aged; Neointima; Outcome Assessment, Health Care; Paclitaxel; Postoperative Complications; Prospective Studies; Sirolimus; Stents; Tomography, Optical Coherence; Tubulin Modulators

Two patients who underwent simultaneous kissing stenting with sirolimus-eluting stents in the left main coronary artery were investigated with optical coherence tomography (OCT) at just more than 1 year postoperatively. In both cases, follow-up angiogram indicated complete coverage of the new metal carina with a membranous diaphragm, yet OCT showed varying tissue-coverage patterns transitioning from stent inflow to stent outflow. These patterns included single-strut coverage, bridge-like membrane formation between more than 1 strut, and end-to-end coverage of the carina; no uncovered stent struts were detected. OCT also demonstrated mixed patterns of tissue characteristics on the metal carina, ranging from poor endothelialization to modest neointima formation. These varying tissue characteristics suggest that the process of tissue coverage in the metal carina is different from that occurring on the vessel wall; this may indicate delayed healing in the carina.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Endothelium, Vascular; Female; Humans; Hyperplasia; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

First generation drug-eluting stents (DES) are associated with reduced in-stent restenosis but significant increased risk of very late stent thrombosis (VLST). The absence of polymer in DES systems may reduce the occurrence of VLST. Optic coherence tomography (OCT) has been used for stent analysis as a surrogate safety endpoint. This study aimed to assess the long-term follow up of strut apposition and tissue coverage of BioMatrix DES by OCT. 20 patients undergoing BioMatrix DES (n = 15) or S-Stent BMS (n = 5) implantation were followed for at least 5 years and evaluated by quantitative coronary angiography, intravascular ultrasound, and OCT. The difference between the stent types was evaluated by nonparametric Mann-Whitney U test while categorical variables were evaluated by Fisher exact test. Rates of in-stent late loss were similar between groups [0.40 (0.21;0.77) vs. 0.68 (0.66; 0.82) mm, p = 0.205, for BioMatrix and S-Stent, respectively]. The vessel, stent and lumen volumes did not differ between groups. Patients treated with BioMatrix had significantly less stent obstruction [5.6 (4.4;9.7) vs. 28.6 (24.7;29.0) %, p = 0.001]. OCT analysis of 12 stents (Biomatrix = 9 and S-Stent = 3) demonstrated 126 (8.7 %) uncovered struts in the BioMatrix group compared to 23 (4.0 %) in the S-Stent group (p = 0.297), being the majority of them well apposed (117/126 and 21/23, respectively, p = 0.292). Only 9 (0.6 %) struts in the DES and 2 (0.4 %) struts in the BMS groups were simultaneously uncovered and malapposed (p = 0.924). BioMatrix DES was associated with lower rates of in-stent obstruction, and similar percentage of neointimal coverage on struts and of complete strut apposition.

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

To validate optical coherence tomography (OCT) imaging for assessment of vascular healing in a preclinical animal model and human autopsy cases and to translate the findings to the assessment of vascular healing after drug-eluting stent implantation in clinical practice.. Drug-eluting and bare metal stents were imaged 28 and 42 days after implantation in atherosclerotic rabbits using OCT and simultaneously evaluated by histology. After coregistration with histology, gray-scale signal intensity (GSI) was measured for identified mature or immature neointimal tissue. Autopsy specimens were imaged with OCT and GSI values correlated with histology. Finally, prospective OCT imaging and GSI measurements were acquired in 10 patients undergoing follow-up 6 months after stenting with drug-eluting stents. Histopathologic and OCT morphometric analysis of implanted stents showed excellent correlation. Neointimal growth and vessel healing at 28 days in the animal model best correlated with human stented arteries at 6 months. In animal and human autopsy specimens, mature neointimal tissue consistently showed higher GSI values. Receiver operating characteristic curve analysis displayed high sensitivity and specificity for detection of mature neointima in animal (96% and 79%, respectively) and human autopsy (89% and 71%, respectively) data. In patients undergoing OCT follow-up 6 months after drug-eluting stent implantation, prospective GSI analysis revealed that a minimum of 27.7% of areas above stent struts represented mature neointima.. Novel GSI analysis of OCT imaging data allows distinction between mature and immature neointimal tissue in animal models, autopsy specimens, and patients undergoing invasive surveillance in simple atherosclerotic lesions.

Topics: Aged; Angioplasty, Balloon, Coronary; Animals; Autopsy; Coronary Artery Disease; Disease Models, Animal; Drug-Eluting Stents; Female; Humans; Male; Metals; Middle Aged; Neointima; Neovascularization, Physiologic; Prospective Studies; Prosthesis Failure; Rabbits; Reproducibility of Results; ROC Curve; Sirolimus; Species Specificity; Tomography, Optical Coherence

The effectiveness of angioplasty and stenting in intracranial atherosclerotic diseases is controversial due to high rates of delayed restenosis and hemorrhage compared with extracranial arteries. However, the mechanisms underlying these differences are still unclear, because their pathophysiology is yet to be examined. To address this issue, we established a novel vascular injury model in the intracranial internal carotid arteries (IICAs) in mice, and analyzed the remodeling process in comparison to that of the femoral arteries (FAs). In IICAs, neointimal hyperplasia was observed from day 14 and grew until day 56. Although smooth muscle cells (SMCs) emerged in the neointima from day 28, SMCs in the injured media were continuously lost with eventual extinction of the media. Re-endothelialization was started from day 7 and completed on day 28. Accumulation of macrophages was continued in the adventitia until day 56. Compared with FAs, the following points are unique in IICAs: (1) delayed continuous formation of neointima; (2) accumulation of macrophages in the media on day 14; (3) continuous loss of SMCs in the media followed by extinction of the media itself; and (4) continuously growing adventitia. These pathophysiologic differences might be associated with unfavorable outcomes in percutaneous transluminal angioplasty and stenting in intracranial arteries.

Topics: Animals; Anti-Bacterial Agents; Carotid Artery, Internal; Cerebral Arteries; Cerebrovascular Circulation; Cerebrovascular Disorders; Cytokines; Femoral Artery; In Situ Nick-End Labeling; Laser-Doppler Flowmetry; Macrophages; Male; Mice; Neointima; Sirolimus; Tissue Fixation

The goal of this study was to evaluate the efficacy of a nanoporous CREG-eluting stent (CREGES) in inhibiting neointimal formation in a porcine coronary model.. In vitro proliferation assays were performed using isolated human endothelial and smooth muscle cells to investigate the cell-specific pharmacokinetic effects of CREG and sirolimus. We implanted CREGES, control sirolimus-eluting stents (SES) or bare metal stents (BMS) into pig coronary arteries. Histology and immunohistochemistry were performed to assess the efficacy of CREGES in inhibiting neointimal formation.. CREG and sirolimus inhibited in vitro vascular smooth muscle cell proliferation to a similar degree. Interestingly, human endothelial cell proliferation was only significantly inhibited by sirolimus and was increased by CREG. CREGES attenuated neointimal formation after 4 weeks in porcine coronary model compared with BMS. No differences were found in the injury and inflammation scores among the groups. Scanning electron microscopy and CD31 staining by immunohistochemistry demonstrated an accelerated reendothelialization in the CREGES group compared with the SES or BMS control groups.. The current study suggests that CREGES reduces neointimal formation, promotes reendothelialization in porcine coronary stent model.

Topics: Adsorption; Animals; Cell Proliferation; Cells, Cultured; Coronary Vessels; Drug-Eluting Stents; Female; Human Umbilical Vein Endothelial Cells; Humans; Myocytes, Smooth Muscle; Neointima; Platelet-Derived Growth Factor; Repressor Proteins; Sirolimus; Sus scrofa

Everolimus, a derivative of sirolimus, is a potent immunosuppressant that has important anti-proliferative properties. In the present study, we demonstrated the inhibiting neointimal hyperplasia in injured carotid arteries in rats by using two different doses of everolimus administrated via the oral route for a long time.. A rat model of carotid artery injury was established by balloon inflation. Eighty rats were randomly divided into the sham-operated group (n = 20), injury group (n = 20), low dosage of everolimus group (n = 20), and high dosage of everolimus group (n = 20). The low dose of everolimus (1.5 mg/kg) was given one day before injuring the carotid artery by balloon, followed by 0.75 mg/kg per day for 28 days via intragastric gavage. High dose everolimus (2.5 mg/kg) was given one day before injuring the carotid artery by balloon, followed by 1 mg/kg per day for 28 days. Expression of eukaryotic translation initiation factor 4E (eIF-4E) and phosphorylation of ribosomal protein S6 kinase 1 (P70S6K) were determined by reverse transcription-polymerase chain reaction and Western blotting analysis.. In the injured carotid artery, neointimal hyperplasia was normally observed four weeks after injury. Everolimus inhibited neointimal hyperplasia after balloon injury in a dose dependent manner. At the same time, the study demonstrated that everolimus reduced the expression of P-P70S6K, eIF-4E, transforming growth factor (TGF)-β1 and of proliferating cell nuclear antigen (PCNA).. Everolimus significantly inhibited neointimal hyperplasia of the injured carotid artery. The effect depended on dosage and was associated with the reduction of phosphorylation of P70S6K and the eIF-4E expression level.

Topics: Animals; Carotid Arteries; Carotid Artery Injuries; Carrier Proteins; Everolimus; Intracellular Signaling Peptides and Proteins; Male; Neointima; Phosphoproteins; Phosphorylation; Rats; Rats, Sprague-Dawley; Ribosomal Protein S6 Kinases, 70-kDa; Sirolimus

Implantation of drug eluting stents (DES) has become a standard treatment of patients undergoing percutaneous coronary intervention (PCI). Incomplete strut coverage is a potential risk factor for late stent thrombosis. Optical coherence tomography (OCT) enables in vivo identification of incomplete neointimal coverage.. Study included 62 patients after sirolimus eluting stents (SES) or paclitaxel eluting stents (PES) implantation. OCT examination was performed at least 24 months after the initial procedure (35.4± 9.4 months). In cross-sectional still frames selected from each 1 mm of analyzed stents a total number of visible struts and number of struts with or without complete neointimal coverage was assessed. Measurements of neointimal coverage, presented as a mean thickness of tissue, were performed. Patients were followed up for 3 years and the frequency ofmajor adverse cardiac events was recorded.. In the analyzed 28 SES and 37 PES 9998 struts were identified. Complete neointimalcoverage was observed in 83.5% and 79.2% of SES and PES struts respectively (p = 0.48).There was no difference in incidence of not covered or malapposed struts between SES and PES groups. Mean thickness of the tissue covering SES struts was 0.165 ± 0.095 mm, and 0.157 ± 0.121 mm for PES. The mean neointimal thickness difference (SES vs. PES) was notstatistically significant. In a 36 months follow-up 1 death was observed - potentially attributed to stent thrombosis.. A long term OCT follow-up after DES implantation shows high incidence ofuncovered struts regardless of the stent type. Clinical significance of this finding remains questionable and requires further large scale trials.

Topics: Aged; Cardiovascular Agents; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Predictive Value of Tests; Registries; Retrospective Studies; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

The presence of uncovered struts overlying side branch is considered to be a potential risk of stent thrombosis. The accuracy in detection of neointimal strut coverage at branch point by optical coherence tomography (OCT) has not been validated in comparison with histology.. A total of 5 stents (3 drug-eluting stents and 2 bare-metal stents) were implanted in the bifurcation segment of normal coronary arteries in 4 domestic swine (weight, 25-40 kg). The animals underwent follow-up OCT at 30 days after stent implantation and were then sacrificed for histologic evaluation. The neointimal coverage of the non-apposed struts over the side branch was assessed by light microscopy. Every millimeter of the stent was specified by the OCT frame rate, and comparisons between OCT and pathologic findings were performed through precise histological-OCT frame matching.. OCT images at the side branch corresponded well with histological cross-sections. The tissues covering struts as assessed by OCT contained smooth muscle cells with proteoglycan-collagen matrix, but platelets are attached above the neointima in one of them on histologic examination, suggesting that most of the struts were well healed, with normal neointimal coverage.. This study demonstrated the accuracy of OCT for the detection of neointimal coverage of non-apposed struts over the side branch.

Topics: Animals; Coronary Vessels; Drug-Eluting Stents; Incidence; Metals; Models, Animal; Muscle, Smooth, Vascular; Neointima; Risk Factors; Sirolimus; Stents; Sus scrofa; Tomography, Optical Coherence

Restenosis after angioplasty remains a serious complication in clinical cardiology. This study aims to investigate the stealth colloidal systems for local intra-arterial drug delivery. Micelles from polyethylene glycol conjugated with phosphatidylethanolamine and PEGylated liposomes loaded with sirolimus were prepared and characterized with regard to their loading efficiency, particle size distribution, zeta potential, morphology, nuclear magnetic resonance spectroscopy, drug release profile and stability. The antirestenotic effects of the sirolimus-loaded micelles (14 nm) and liposomes (90 nm) were evaluated and compared in the rat carotid injury model following local intravascular delivery. In comparison to control groups, treatment of balloon injured rats with drug loaded micelles and nanoliposomes significantly reduced vascular stenosis by 42% and 19%, respectively (P<0.05). In addition, the luminal area was significantly enlarged by 39% and 60% following treatment with sirolimus-loaded liposomes and micelles, respectively (P<0.05). Immunohistochemistry revealed that sirolimus-loaded nanocarriers suppressed cell proliferation (Ki67-positive cells) as compared to control groups without affecting the density of smooth muscle actin staining. These results suggest that both colloidal nanocarriers could serve as effective intramural drug delivery systems for the treatment of restenosis; however, phospholipid based micelles provided better antirestenotic effects than PEGylated liposomes.

Topics: Angioplasty, Balloon, Coronary; Animals; Carotid Artery Injuries; Hyperplasia; Lipids; Liposomes; Male; Micelles; Neointima; Polyethylene Glycols; Rats; Rats, Sprague-Dawley; Sirolimus

To obtain imaging evidence by 2-week optical coherence tomography (OCT) on the completion of neointimal coverage (NIC; the percentage of stent strut coverage and thickness of the formed neointima) completion after implantation of the Endeavor zotarolimus-eluting stent (E-ZES).. Despite the fact that NIC is a cardinal process in the pathomechanism of late stent thrombosis, little imaging information is available on morphological changes thereof on a short-time interval basis.. 27 Japanese patients with stable angina pectoris and de novo native coronary artery lesions were enrolled, and 27 lesions (30 implantations) were examined. OCT was performed at weeks 2, 4, 6, 8, and 10 after E-ZES implantation. NIC was examined using cross-sectional OCT images obtained at the 1.0-mm intervals.. In total, 621 cross-sectional OCT images, which depicted 7,747 stent struts, were analyzed. The mean percentages of stent strut coverage at weeks 2, 4, 6, 8, and 10 after E-ZES implantation were 12.3, 70.4, 67.9, 86.0, and 99.2%, respectively; a marked increase was found between weeks 2 and 4. The mean thicknesses of the formed neointima were 40.2, 52.1, 48.1, 86.5, and 146.2 μm at respective weeks, with the high-signal and thick neointima (146 µm) at week 10. An intracoronary thrombus was detected in only one stent at week 4.. The full circumferential coverage of the vessel wall by the high-signal neointima was found at as early as week 10 after E-ZES implantation, imparting a surrogate index for vascular healing by NIC.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Artery Disease; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Japan; Male; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

Topics: Coronary Restenosis; Drug-Eluting Stents; Humans; Immunosuppressive Agents; Neointima; Sirolimus; Tomography, Optical Coherence

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

This study sought to assess stent-vessel interactions after drug-eluting stent (DES) implantation in unprotected left main coronary artery (ULM) by frequency-domain optical coherence tomography (FD-OCT).. Percutaneous coronary intervention using DES in ULM has been increasingly performed in routine practice. Recently, FD-OCT assessments of DES-vessel interactions have been used as surrogates for DES safety; however, there are no FD-OCT studies in ULM.. We prospectively enrolled 33 consecutive patients with ULM disease treated with sirolimus- (n = 11) and everolimus-eluting stents (n = 22). FD-OCT assessments were performed post-percutaneous coronary intervention and at 9-month follow-up. Three different segments of ULM were compared: distal (DIS), bifurcation (BIF), and ostial-body (BODY). The primary endpoints were percentages of uncovered and malapposed struts at 9-month follow-up, and the secondary endpoint was neointimal hyperplasia area.. We analyzed 25,873 stent struts. Significant differences were demonstrated for percentage of uncovered struts (3.4%, 11.7%, and 18.7%, respectively for DIS, BIF, and BODY; p < 0.05 for all the comparisons). Malapposition was also more common in BODY (5.3%) than in DIS (0.6%) and BIF (2.0%) segments (p < 0.05 for BODY vs. DIS, and BODY vs. BIF). Equivalent neointimal hyperplasia areas were demonstrated in all segments. Acute malapposition rates led to different patterns of DES-vessel interactions at 9-month follow-up.. Distinct patterns of DES-vessel interactions were demonstrated in different segments of ULM. Acute stent strut malapposition affects these findings.

Topics: Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Drug-eluting stents represent a major advance in interventional cardiology. However, the current drug-eluting stents have significant limitations. One of the major problems is very late stent thrombosis, which is likely caused by inflammation and a hypersensitivity reaction related to a polymer on the stent. A polymer-free sirolimus-eluting stent with a unique nano-porous surface has been developed. This study aimed to evaluate this novel polymer-free sirolimus-eluting stent for its efficacy and safety in a pig model.. Stents were directly coated with sirolimus (a drug concentration of 2.2 µg/mm(2) on the stent surface). The polymer-free sirolimus-eluting stents (PFSES) were compared to standard polymer-coated sirolimus-eluting stents (PCSES) and bare-metal stents (BMS) in 18 pigs.. At one month the degree of neointimal hyperplasia was similar between the two sirolimus-eluting stent groups and was significantly less compared to BMS ((1.93 ± 0.51) mm(2), (1.57 ± 0.69) mm(2) vs. (4.45 ± 1.05) mm(2), P < 0.05) At three months, PFSES maintained the low level of neointima ((2.41 ± 0.99) mm(2) vs. (4.32 ± 1.16) mm(2), P < 0.05), whereas PCSES had developed significant neointimal proliferation similar to BMS. The inflammation level was significantly higher in PCSES when compared with BMS three months post-implantation (2.50 ± 0.55 vs. 0.83 ± 0.75, P < 0.05) whereas PFSES showed a low level of inflammation comparable to PCSES (1.33 ± 0.52 vs. 2.50 ± 0.55, P < 0.05).. The PFSES is effective and safe, and appears to be superior to standard PCSEs.

Topics: Animals; Drug-Eluting Stents; Neointima; Polymers; Sirolimus; Swine

We investigate the influence of stent design on stent coverage at 6-9 months after sirolimus eluting stent (SES) implantation using optical coherence tomography (OCT).. Although some reports suggest that stent design may correlate with stent coverage of stent struts, there were few detailed data whether stent design impact on stent coverage in the same drug-eluting stent.. A total of 21 SESs (15 patients), who had implanted 2.5, 2.75, and 3.0 mm stents, underwent OCT at 6-9 months after stent implantation. SES is constructed by two different strut width-components; narrow strut width parts (59 μm) and wide strut width parts (115 μm). Thus, we divided stent struts of SESs into two groups: narrow strut width parts (narrow group) and wide ones (wide group). We compared the incidence of incomplete apposed struts, uncovered struts, and neointimal hyperplasia (NIH) thickness between the two groups.. We could detect 2,948 struts (narrow group consisted of 1,132 struts and wide group consisted of 1,816 struts). Incidence of uncovered struts in the narrow group was significantly lower than in the wide group (30.2% vs. 40.8%, P < 0.001), and NIH thickness in the narrow group was significantly greater than in the wide group (127.5 ± 93.4 μm vs. 118.6 ± 81.4 μm, P = 0.03).. Stent design, especially strut width, affects stent coverage of SES. The narrow strut may avoid the absence of stent coverage in SES, which correlates with stent thrombosis.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Chi-Square Distribution; Coronary Artery Disease; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

To test the local delivery of sirolimus nanoparticles following percutaneous transluminal coronary angioplasty (PTCA) to treat in-stent restenosis (ISR) in a swine model.. Coronary bare-metal stent (BMS) implantation reduces major adverse cardiac events when compared with PTCA; however, ISR rates remain high.. Eighteen swine underwent BMS deployment guided by intravascular ultrasound (IVUS). Of these, 16 developed ISR (1 stent/swine) and underwent angioplasty with a noncompliant balloon (PTCA-NC). The animals were then randomized into four groups for local infusion of sirolimus nanoparticles through a porous balloon catheter, as follows: (1) PTCA-NC alone (control); (2) PTCA-NC + (polylactic acid)-based nanoparticle formulation (anionic 1); (3) PTCA-NC + (polylactic-co-glycolic acid)-based nanoparticle formulation (anionic 2); and (4) PTCA-NC + Eudragit RS nanoparticle formulation (cationic). Coronary angiography and IVUS follow-up were performed 28 days after ISR treatment.. There was one episode of acute coronary occlusion with the cationic formulation. Late area loss was similar in all groups at 28 days according to IVUS. However, luminal volume loss (control = 20.7%, anionic 1 = 4.0%, anionic 2 = 6.7%, cationic = 9.6%; P = 0.01) and neointimal volume gain (control = 68.7%, anionic 1 = 17.4%, anionic 2 = 29.5%, cationic = 31.2%; P = 0.019) were significantly reduced in all treatment groups, especially in anionic 1.. PTCA-NC followed by local infusion of sirolimus nanoparticles was safe and efficacious to reduce neointima in this model, and this strategy may be a promising treatment for BMS ISR. Further studies are required to validate this method in humans.

Topics: Acrylic Resins; Animals; Cardiac Catheters; Cardiovascular Agents; Chemistry, Pharmaceutical; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Disease Models, Animal; Drug Carriers; Drug Delivery Systems; Equipment Design; Infusions, Parenteral; Lactic Acid; Nanoparticles; Neointima; Percutaneous Coronary Intervention; Polyesters; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Porosity; Sirolimus; Swine; Time Factors; Ultrasonography, Interventional

The aim of this study was to assess the efficacy of stent-based delivery of succinobucol alone and in combination with rapamycin in a porcine coronary model.. Current drugs and polymers used to coat coronary stents remain suboptimal in terms of long term efficacy and safety. Succinobucol is a novel derivative of probucol with improved antioxidant and anti-inflammatory properties.. Polymer-free Yukon stents were coated with 1% succinobucol (SucES), 2% rapamycin (RES), or 1% succinobucol plus 2% rapamycin solutions (SucRES) and compared with a bare metal stent (BMS).. The in vivo release profile of SucES indicated drug release up to 28 days (60% drug released at 7 days); 41 stents (BMS, n = 11; SucES, n =10; RES, n = 10; SucRES, n = 10) were implanted in the coronary arteries of 17 pigs. After 28 days, mean neointimal thickness was 0.31 ± 0.14 mm for BMS, 0.51 ± 0.14 mm for SucES, 0.19 ± 0.11 mm for RES, and 0.36 ± 0.17 mm for SucRES (P < 0.05 for SucES vs. BMS). SucES increased inflammation and fibrin deposition compared with BMS (P < 0.05), whereas RES reduced inflammation compared with BMS (P < 0.05).. In this model, stent-based delivery of 1% succinobucol using a polymer-free stent platform increased neointimal formation and inflammation following coronary stenting.

Topics: Animals; Cardiovascular Agents; Cattle; Cell Survival; Cells, Cultured; Coronary Vessels; Dose-Response Relationship, Drug; Drug Therapy, Combination; Drug-Eluting Stents; Endothelial Cells; Fibrin; Inflammation; Male; Metals; Models, Animal; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Neointima; Percutaneous Coronary Intervention; Probucol; Prosthesis Design; Sirolimus; Swine

Late stent thrombosis related to delayed endothelialization is a major concern after drug-eluting stent (DES) implantation. The long-term vascular response towards DES implantation remains unclear. Optical coherence tomography (OCT) is a high-resolution imaging modality which provides new opportunities for evaluating neointimal coverage and stent strut apposition after stent implantation.. Fifty two patients who accepted 64 sirolimus-eluting stents (SESs, Cypher Select) were enrolled in the study. The OCT procedure was performed in 20 patients at 12 months (group 1), 17 patients at 24 months (group 2), and 15 patients at 48 months (group 3) after SESs implantation, respectively. The neointimal hyperplasia (NIH) thickness and stent strut apposition were assessed at 1-mm interval, and the presence of thrombus was observed in each stent.. The NIH thickness was significantly higher at 48 months than that of 12 months (0.1694 ± 0.1455 mm in G3 vs. 0.1455 ± 0.1373 mm in G1, P < 0.01) and 24 months (0.1514 ± 0.1296 mm in G2, P <0.01) after SESs implantation, but no significant difference existed between that of 12 months and 24 months (P > 0.05). Longer follow-up time was associated with significant decrease in the prevalence of uncovered struts (17.3% in group 1 vs. 8.8% in group 2 vs. 2.6% in group 3, P < 0.01) and malapposed struts (14.2% in group 1 vs. 10.3% in group 2 vs. 4.7% in group 3, P < 0.01). The incidence of intracoronary thrombus steadily decreased from 3.6% at 12 months to 2.4% at 24 months, and to 0.8% at 48 months (P < 0.01).. Neointimal growth continued for as long as 48 months after SES implantation. NIH thickness increased insignificantly from 12 to 24 months, but markedly increased at 48 months after stent implantation. Late neointimal growth was accompanied by a higher rate of covered struts and lower rate of malapposed stent struts.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Artery Disease; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Multivariate Analysis; Neointima; Odds Ratio; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

To evaluate differences in strut coverage, inflammation and endothelialization between two second-generation polymer-based drug-eluting stents (DES) in an atherosclerotic rabbit double-injury iliac artery model at 28 days follow-up.. Rabbits with induced atheroma received bilateral iliac artery stents: everolimus-eluting stent (Xience V EES; Abbott Vascular), zotarolimus-eluting stent (Resolute ZES; Medtronic CardioVascular), or bare-metal stent (BMS; MultiLink Vision; Abbott Vascular). After 28 days, total neointimal coverage examined by scanning electron microscopy was >98% for all three stent types. Neointimal thickness above stent struts was decreased by 50% in Xience V EES (0.06 ± 0.01 mm; P = 0.00001) compared with BMS (0.15 ± 0.03 mm) and Resolute ZES (0.12 ± 0.04 mm). Luminal area was largest for Xience V EES (3.79 ± 0.33 mm(2) ; P = 0.0003 for Xience V EES vs. BMS), followed by Resolute ZES (3.46 ± 0.45 mm(2) ; P = 0.083 for Resolute ZES vs. BMS) and BMS (3.07 ± 0.53 mm(2) ). Percentage area stenosis was smallest for Xience V EES (17.23 ± 3.64%; P = 0.00001), while BMS (30.25 ± 7.48%) and Resolute ZES (30.79 ± 7.15%) did not differ. Endothelial monolayer regrowth was significantly lower in Resolute ZES (65 ± 13%) versus BMS (79 ± 11%; P = 0.004). There was no difference between Xience V EES (74 ± 10%) and BMS. Xience V EES was further associated with a lower number of inflammatory cells surrounding the stent struts (7 ± 2 per strut) in comparison to Resolute ZES (15 ± 6; P = 0.0001) and BMS (17 ± 9; P = 0.0005).. In this atherosclerotic rabbit model, Xience V EES suppressed neointimal thickening better, with normal endothelial regrowth as compared with BMS, and less strut-induced inflammation.

Topics: Angioplasty, Balloon; Animals; Atherosclerosis; Cardiovascular Agents; Cell Proliferation; Disease Models, Animal; Drug-Eluting Stents; Endothelial Cells; Everolimus; Iliac Artery; Inflammation; Male; Neointima; Prosthesis Design; Rabbits; Radiography; Sirolimus; Time Factors; Vascular System Injuries

We hypothesized that the tissue components of in-stent restenosis (ISR) might differ between drug-eluting stents (DES) and bare-metal stents (BMS) and that these differences could be distinguished by qualitative and quantitative optical coherence tomography (OCT) analyses.. One-hundred and twenty-two initial ISR lesions (sirolimus-eluting stents: n=28; paclitaxel-eluting stents: n=51; BMS: n=43) were evaluated with OCT. Based on their OCT appearance, the lesions were classified as homogeneous, layered or heterogeneous. The optical properties of backscatter, attenuation and signal intensity of the neointimal tissue (NIT) were quantified. To evaluate the vascular response after balloon angioplasty (BA), the rate of reduction of the NIT area (NITA) was calculated (NITA before - after BA/NITA before BA at the minimum lumen cross-sectional area). Among the morphologic OCT patterns, the layered type was predominant with DES, whereas lesions were homogeneous with BMS (P<0.001). Backscatter and signal intensity were significantly higher with BMS (P<0.05 and P<0.001 respectively). The NITA reduction rate was significantly greater in the layered and heterogeneous groups than in the homogeneous group (P<0.01).. The morphologic OCT patterns of the NIT in ISR differed significantly between DES and BMS, probably reflecting pathologic differences. Layered and heterogeneous tissues might respond better than homogeneous tissue to simple balloon dilatation, suggesting a possible direction for OCT-based ISR treatment strategies. 

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Incidence; Male; Metals; Middle Aged; Neointima; Paclitaxel; Retrospective Studies; Sirolimus; Stents; Tomography, Optical Coherence; Treatment Outcome

To report the four-month and nine-month angiographic results as well as one-year clinical follow-up from the first-in-man study with the silicon carbide and sirolimus-eluting bioabsorbable polymer (poly-L-lactic acid (PLLA) polymer) -coated cobalt-chromium Orsiro stent.. A group of 30 patients with documented myocardial ischaemia related to a single de novo coronary stenosis up to 22 mm in length, in vessels with a 2.5 to 3.5 mm reference diameter, and between >50% and <90% diameter stenosis were enrolled at two sites. The primary endpoint of the study was in-stent late lumen loss at nine months. The secondary endpoints included major adverse cardiac events (MACE) at one year defined as the composite of cardiac death, ischaemia-driven target lesion revascularisation (TLR) and target vessel myocardial infarction (MI). Procedural success was 100%. Angiographic late lumen loss was 0.12±0.19 mm and 0.05±0.22 mm at four and nine months respectively. At one-year clinical follow-up, the composite MACE was 10% with one patient who died from cardiac death and two patients who had ischaemia-driven target lesion revascularisation. There was no report of MI or stent thrombosis.. The Orsiro drug-eluting stent demonstrated potency with low rates of in-stent neointimal hyperplasia and cardiovascular events but warrants further evaluation in a larger population cohort with longer follow-up time points.

Topics: Aged; Carbon Compounds, Inorganic; Chromium Alloys; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Hyperplasia; Incidence; Male; Middle Aged; Myocardial Infarction; Neointima; Percutaneous Coronary Intervention; Prospective Studies; Silicon Compounds; Sirolimus; Treatment Outcome

The pathogenesis of in-stent restenosis (ISR) after drug-eluting stent (DES) implantation remains unclear. The purpose of this study is to analyse tissue characterizations of neointima in restenosis lesions after sirolimus-eluting stent (SES), comparing with those after bare metal stent (BMS) using integrated backscatter intravascular ultrasound (IB-IVUS).. A total of 54 consecutive patients who had ISR lesions after SES (n = 20) or BMS (n = 34) implantation were enrolled. For tissue characterization of neointima, IB-IVUS was performed by cross-sectional (at the minimum lumen area) and volumetric (within the stented segment) analyses. In addition, angiographic patterns of restenosis were evaluated with division into focal and diffuse. The focal angiographic pattern of restenosis was predominantly observed in the SES group (SES vs. BMS; 80.0 vs. 26.5%; P = 0.0001), whereas the diffuse pattern was more common in the BMS group (SES vs. BMS; 20.0 vs. 73.5%; P = 0.0001). On both cross-sectional and volumetric IB-IVUS analyses, the neointimal tissue in restenosis lesions after SES implantation had a significantly larger percentage of lipid tissue (cross-sectional: 23.3 ± 12.7 vs. 15.7 ± 11.9%; P = 0.033; volumetric: 22.8 ± 10.4 vs. 16.3 ± 7.0%; P = 0.008) and a significantly smaller percentage of fibrous tissue compared with that after BMS implantation (cross-sectional: 73.6 ± 11.6 vs. 82.0 ± 11.2%; P = 0.011, volumetric: 73.8 ± 9.5 vs. 80.5 ± 6.7%; P = 0.004).. This IB-IVUS study indicates that larger amounts of lipid tissue are present in neointima of SES when compared with BMS, suggesting that neoatherosclerosis may in part be responsible for ISR after SES implantation.

Topics: Aged; Angioplasty, Balloon, Coronary; Cohort Studies; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Metals; Middle Aged; Neointima; Prospective Studies; Prosthesis Design; Prosthesis Failure; Retreatment; Sirolimus; Stents; Ultrasonography, Interventional

The aim of this study was to evaluate neointimal coverage obtained using a new method of polytetrafluoroethylene-covered stent (PCS) implantation combined with underlying longer sirolimus-eluting stent (SES) implantation using optical coherence tomography. Nine patients were enrolled in this study, including patients with coronary artery perforations, original coronary aneurysms, and acquired coronary aneurysms after drug-eluting stent implantation. All patients were first treated with long SES implantation and then with focal PCS implantation. Postprocedural and follow-up angiographic and optical coherence tomographic examinations were performed in all patients, and intravascular ultrasound was performed in 5 patients. All patients were asymptomatic during follow-up, without recurrent angina. There was no stent-edge or stent-segment binary restenosis. Values of late loss for proximal SES segments, PCS segments, and distal SES segments were similar (0.09, 0.07, and 0.04 mm, respectively, p = 0.8113). The mean neointimal thickness of PCS was less than that of proximal and distal SES. However, no malapposed cross sections or uncovered cross sections were found in PCS segments compared with SES segments (p = 0.0011). In conclusion, the combination of PCS and underlying longer SES implantation can offer better angiographic follow-up results. High-resolution optical coherence tomography provided convincing proof of full neointimal coverage of PCS. This new method of combined PCS and SES implantation may be a better choice compared with direct PCS implantation in certain clinical settings.

Topics: Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Drug-Eluting Stents; Humans; Neointima; Polytetrafluoroethylene; Radiographic Image Interpretation, Computer-Assisted; Sirolimus; Statistics, Nonparametric; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

Late in-stent restenosis (ISR) is an important clinical issue in the drug-eluting stent era. Autopsy studies have reported different underlying mechanisms between early ISR and late ISR. The aim of the present study was to compare the neointimal tissue appearance between early ISR (<1 year) and late ISR (>1 year) after sirolimus-eluting stent (SES) implantation using optical coherence tomography (OCT).. We examined the neointimal tissue appearance in 48 ISR lesions after SES implantation [30 early ISR lesions (8±1 months after stenting) and 18 late ISR lesions (34±14 months after stenting)] by OCT. ISR was defined as percent diameter stenosis more than 50% within the stented segment in angiography. Lipid-rich neointima was characterized by signal-poor regions with diffuse borders. Thin-cap fibroatheroma (TCFA)-like neointima was defined by lipid-rich neointima with cap thickness 65 μm or less.. In the OCT findings, heterogeneous neointima was more often observed in the late ISR group compared with the early ISR group (89 vs. 43%, P=0.002). Although the frequency of intraluminal thrombus was not different between the two groups (P=0.085), the frequency of lipid-rich neointima (83 vs. 27%, P<0.001), TCFA-like neointima (39 vs. 10%, P=0.028), microchannels within neointima (67 vs. 27%, P=0.007), and neointimal disruption (33 vs. 3%, P=0.008) was significantly higher in the late ISR group.. In the present OCT study, it was found that atherosclerotic progression of neointima, such as lipid-rich neointima, TCFA-like neointima, microchannels, and neointimal disruption, was more often observed in late ISR lesions after SES implantation compared with early ISR ones.

Topics: Aged; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Disease Progression; Drug-Eluting Stents; Female; Humans; Lipids; Male; Neointima; Sirolimus; Time Factors; Tomography, Optical Coherence

We aimed to uncover the protein changes of coronary artery in-stent restenosis (ISR) tissue in minipigs with and without streptozotocin-induced diabetes mellitus by quantitative 2-dimensional fluorescence in-gel electrophoresis (2D-DIGE), and to investigate the influences of crucial proteins identified, particularly adipocyte fatty acid binding protein (AFABP), in human arterial smooth muscle cells.. Sirolimus-eluting stents were implanted in the coronary arteries of 15 diabetic and 26 nondiabetic minipigs, and angiography was repeated after 6 months. The intima tissue of significant ISR and non-ISR segments in both diabetic and nondiabetic minipigs was analyzed by 2D-DIGE and MALDI-TOF/TOF mass spectrometry. AFABP level was significantly increased in ISR tissue than in non-ISR tissue in both diabetic and nondiabetic minipigs, with level being higher in diabetic ISR than in nondiabetic ISR tissue. In human arterial smooth muscle cells, overexpression of AFABP significantly altered phenotype and promoted growth and migration, with effects more prominent in high-glucose than in low-glucose medium, whereas AFABP knockdown inhibited these effects. AFABP overexpression increased reactive oxygen species production by upregulating the expression of NADPH oxidase subunits Nox1, Nox4, and P22 through multiple pathways, with elevation of downstream gene cyclin D1, matrix metalloproteinase-2, and monocyte chemoattractant protein-1. However, AFABP-induced effects were inhibited by diphenyleneiodonium, pathway inhibitors, and small interfering RNA. In addition, the supernatant from AFABP-expressing human arterial smooth muscle cells and recombinant AFABP also promoted cellular growth and migration.. This study has demonstrated that AFABP is significantly increased in coronary artery ISR segments of both diabetic and nondiabetic minipigs. Increased AFABP expression and secretory AFABP of human arterial smooth muscle cells promote growth and migration via reactive oxygen species-mediated activation.

Topics: Animals; Cardiovascular Agents; Cell Movement; Cell Proliferation; Cells, Cultured; Coronary Restenosis; Coronary Vessels; Diabetes Mellitus, Experimental; Drug-Eluting Stents; Electrophoresis, Gel, Two-Dimensional; Enzyme Inhibitors; Fatty Acid-Binding Proteins; Fluorescence; Glucose; Humans; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; NADPH Oxidases; Neointima; NF-kappa B; Oxidative Stress; Percutaneous Coronary Intervention; Phenotype; Reactive Oxygen Species; RNA Interference; RNA, Messenger; Signal Transduction; Sirolimus; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; STAT3 Transcription Factor; Swine; Swine, Miniature; Time Factors; Transcription Factor AP-1; Transfection; Up-Regulation

This study examined whether sirolimus-eluting stent (SES) implantation exerts an antiproliferative action on a bare metal stent (BMS) placed distally in the same coronary artery.. Diffusion of sirolimus into flowing coronary blood may cause accumulation of this drug in the coronary bed beyond the distal edge of an SES.. We analyzed data from 115 consecutive patients with ischemic heart disease who were treated with two overlapping stents without a gap in the same coronary artery for a long de novo lesion. The distal stent was a 2.25 mm BMS in all patients, and the proximal stent was an SES in 73 patients (SES-BMS group) and a BMS in 42 patients (BMS-BMS group). Quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) were performed at stent implantation and 8 months later.. Clinical and procedural variables were comparable between the two groups. QCA and IVUS showed that the SES-BMS group had less luminal late loss and a lower percent of in-stent volume obstruction in the distal BMS compared with the BMS-BMS group. Furthermore, compared with the BMS-BMS group, the SES-BMS group had less in-stent restenosis (23.3 vs. 54.8%, P < 0.0005) and target lesion revascularization (21.9 vs. 50.0%, P < 0.005).. SES implantation just proximal to a BMS inhibits neointimal proliferation in the BMS, when both stents are implanted in the same coronary artery to treat a de novo lesion.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Cell Proliferation; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Metals; Neointima; Percutaneous Coronary Intervention; Prospective Studies; Prosthesis Design; Severity of Illness Index; Sirolimus; Stents; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Recent pathological studies have demonstrated that peri-strut low intensity area (PLIA) seen on optical coherence tomography (OCT) imaging represents the presence of fibrinogen and/or extracellular matrix. We sought to assess the clinical prevalence of PLIA and its relation to neointimal proliferation after the implantation of sirolimus- (SES) and paclitaxel-eluting stents (PES) in humans.. Seventy patients underwent 6-months follow-up OCT after SES (43 stents) or PES (37 stents) implantation. PLIA was defined as a region around stent struts with homogenous lower intensity than surrounding tissue on OCT images without signal attenuation. The incidence of stent struts with PLIA (+PLIA struts) was calculated as the number of +PLIA struts/number of all struts (%).. PES showed a higher incidence of stents with PLIA than SES (86% vs. 58%; p=0.005) with a higher prevalence of +PLIA struts (27.8±21.9% vs. 10.9±11.0%; p=0.0008). SES with PLIA showed a significantly greater neointimal thickness (NIT) than SES without PLIA (p=0.02), while PES showed a similar tendency (p=0.19). In a detailed strut basis analysis, average NIT on +PLIA struts were significantly greater than that on -PLIA struts in both SES and PES. In addition, average NIT was positively correlated with the prevalence of +PLIA struts (SES: Rho=0.73; p<0.0001, PES: Rho=0.58, p=0.0005) in both stents.. The prevalence of PLIA was significantly higher in PES than in SES. The presence and extent of PLIA might be associated with intimal thickening after 1st-generation DES implantation.

Topics: Aged; Coronary Artery Disease; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neointima; Paclitaxel; Radiography; Retrospective Studies; Sirolimus; Tomography, Optical Coherence; Treatment Outcome

Recent studies reported favorable angiographic and clinical outcomes after everolimus-eluting stent (EES) implantation. However, there were no studies to assess vascular responses after EES implantation using optical coherence tomography (OCT). Therefore, the OCT findings in EES were investigated and compared with those in sirolimus-eluting stent (SES). Follow-up OCT studies were performed in 110 lesions (40 EES and 70 SES) of 104 patients at 9 months after stent implantation. The strut apposition, neointimal hyperplasia (NIH) thickness and stent coverage on each stent struts were evaluated. The mean NIH thickness was significantly greater in EES-treated lesions than in SES-treated lesions (115 ± 52 μm vs. 89 ± 58 μm, P = 0.001, respectively). The percentage of uncovered strut was significantly smaller in EES-treated lesions than in SES-treated lesions (4.4 ± 4.7% vs. 10.5 ± 12.7%, P = 0.016, respectively). There was no significant difference in the percentage of malapposed strut between the two groups (0.4 ± 0.8% in EES vs. 1.7 ± 4.5% in SES, P = 0.344). The incidence of intracoronary thrombus was significantly lower in EES-treated lesions than in SES-treated lesions (5.0% vs. 34.3%, P < 0.001, respectively). EES showed a significantly lower incidence of uncovered stent struts and intracoronary thrombus than SES in 9-month follow-up OCT examination. Compared to SES, EES might have more favorable vascular responses after stent implantation.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Male; Middle Aged; Neointima; Predictive Value of Tests; Registries; Republic of Korea; Retrospective Studies; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

To quantify with in vivo OCT and histology, the device/vessel interaction after implantation of the bioresorbable vascular scaffold (BVS). We evaluated the area and thickness of the strut voids previously occupied by the polymeric struts, and the neointimal hyperplasia (NIH) area covering the endoluminal surface of the strut voids (NIH(EV)), as well as the NIH area occupying the space between the strut voids (NIH(BV)), in healthy porcine coronary arteries at 2, 3 and 4 years after implantation of the device. Twenty-two polymeric BVS were implanted in the coronary arteries of 11 healthy Yucatan minipigs that underwent OCT at 2, 3 and 4 years after implantation, immediately followed by euthanasia. The areas and thicknesses of 60 corresponding strut voids previously occupied by the polymeric struts and the size of 60 corresponding NIH(EV) and 49 NIH(BV) were evaluated with both OCT and histology by 2 independent observers, using a single quantitative analysis software for both techniques. At 3 and 4 years after implantation, the strut voids were no longer detectable by OCT or histology due to complete polymer resorption. However, analysis performed at 2 years still provided clear delineation of these structures, by both techniques. The median [ranges] areas of these strut voids were 0.04 [0.03-0.16] and 0.02 [0.01-0.07] mm(2) by histology and OCT, respectively. The mean (±SD) thickness by histology and OCT was 220 ± 40 and 120 ± 20 μm, respectively. The median [ranges] NIH(EV) by histology and OCT was 0.07 [0.04-0.20] and 0.03 [0.01-0.08] mm(2), while the mean (±SD) NIH(BV) by histology and OCT was 0.13 ± 0.07 and 0.10 ± 0.06 mm(2). Our study indicates that in vivo OCT of the BVS provides correlated measurements of the same order of magnitude as histomorphometry, and is reproducible for the evaluation of certain vascular and device-related characteristics. However, histology systematically gives larger values for all the measured structures compared to OCT, at 2 years post implantation.

Topics: Absorbable Implants; Angioplasty, Balloon, Coronary; Animals; Cardiovascular Agents; Coronary Vessels; Everolimus; Feasibility Studies; Hyperplasia; Models, Animal; Neointima; Pilot Projects; Sirolimus; Swine; Swine, Miniature; Time Factors; Tissue Scaffolds; Tomography, Optical Coherence

Previous optical coherence tomography (OCT) studies in patients with drug-eluting stents (DESs)-related very late stent thrombosis (VLST) were scarce. Therefore, we investigated OCT findings of VLST after implantation of DESs. Using OCT, we analyzed the status of stent struts and neointimal characteristics in 18 patients who developed VLST after DES implantation. These results were compared to those in 57 patients with neointimal hyperplasia causing >40% diameter stenosis. Lipid-laden neointima was defined as a region with marked signal attenuation and a diffuse border. Four (22.2%) of 18 patients with VLST had ruptured and lipid-laden neointima inside DESs without uncovered or malapposed stent struts. In the remaining 14 patients who developed VLST without neointimal rupture, uncovered and malapposed struts were observed in nine and seven patients, respectively, and lipid-laden neointima in four patients. Lipid-laden neointima was more frequently observed in four patients with neointimal rupture than in 14 patients without neointimal rupture (100% vs. 28.6%, respectively, P = 0.023). Of 57 patients with neointimal hyperplasia, eight (14.0%) had lipid-laden neointima. Time to OCT study after DES implantation was significantly longer in the eight patients with lipid-laden neointima than in 49 patients without lipid-laden neointima (45.5 ± 17.7 months vs. 11.7 ± 7.2 months, respectively, P < 0.001). Lipid-laden neointima was detected in some patients with neointimal hyperplasia > 1 year after DES implantation. In addition to uncovered or malapposed struts, rupture of lipid-laden neointima inside DESs was identified in some patients with DES-related VLST.

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Lipid Metabolism; Male; Middle Aged; Neointima; Paclitaxel; Predictive Value of Tests; Prosthesis Design; Republic of Korea; Risk Assessment; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

The time course of complete arterial healing after drug eluting stent implantation is unknown. We present a case of incomplete endothelialization and late stent malapposition identified by optical coherence tomography 8 years after a sirolimus-eluting stent implantation, which was not related with any adverse clinical event.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Humans; Male; Neointima; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

The Resolute zotarolimus-eluting stent (ZES-R) has a thinner stent strut with biocompatible polymer than first generation drug-eluting stents. However, minimal optical coherence tomography (OCT) data exists about vascular responses after ZES-R implantation. This study investigated OCT findings in ZES-R implantation and compared them to those in sirolimus-eluting stent (SES) implantation. A total of 123 lesions (43 ZES-R and 80 SES) in 111 patients were evaluated with OCT at 9 months after stent implantation. Strut apposition, neointimal hyperplasia (NIH) thickness, and stent coverage on each stent strut were evaluated. Mean NIH thickness was significantly greater in ZES-R-treated lesions than in SES-treated lesions (166 ± 73 μm vs. 96 ± 63 μm, respectively, P < 0.001). The percentage of uncovered strut was significantly lower in ZES-R-treated lesions than in SES-treated lesions (4.4 ± 4.8% vs. 10.3 ± 13.2%, respectively, P = 0.05). The percentage of malapposed struts was also significantly lower in ZES-R-treated than in SES-treated lesions (0.1 ± 0.4% vs. 1.5 ± 4.2%, respectively, P = 0.002). Intracoronary thrombus was less frequently detected in ZES-R-treated lesions (4.7% vs. 30.0%, respectively, P = 0.001). ZES-R showed a lower incidence of uncovered or malapposed stent struts and intracoronary thrombus than SES at 9-month follow-up OCT examination. Compared with SES, ZES-R may elicit more favorable vascular responses at the expense of an increased neointimal proliferation.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Linear Models; Male; Middle Aged; Multivariate Analysis; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Registries; Retrospective Studies; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

This study aimed to compare the neointimal coverage (NIC), subclinical thrombus, color of plaque underneath the stent at 9-month after implantation of sirolimus-eluting stent (SES) either with durable or with biodegradable polymer (BDPM).. A total of 175 patients were assigned as Cypher (n = 81, 97 stents with durable polymer) and Excel (n = 94, 112 stents with BDPM) stent at 9-month after indexed procedure. NIC was classified from grade 0-3. Color of plaque was divided into white, light-yellow, yellow, and dark yellow. Thrombus was diagnosed as white or red material with cotton-like or ragged appearance. Incomplete NIC (grade 0/1) circled by a blush was termed by "inflaming.". There were significant differences in unstable angina (90.5 vs. 52.4%, P = 0.015), previous myocardial infarction (33.3 vs. 4.0%, P = 0.045) and left ventricular eject fraction (55.2 ± 7.8 vs. 62.6 ± 6.3%, P = 0.021) between the Excel and Cypher groups. The minimal- and maximal-NIC grades in the Cypher group were 0.67 ± 0.58 and 2.29 ± 0.46, respectively, when compared with 1.45 ± 0.67 (P < 0.001) and 2.64 ± 0.49 (P = 0.023) in the Excel group. The percentage of yellow plaque, thrombus, "inflaming" and NIC grade of 0 in the Excel and Cypher groups, respectively, were as follows: 8.0 vs. 26.8% (P = 0.031), 9.8 vs. 32.9% (P = 0.024), 8.0 vs. 38.1% (P = 0.017), and 38.1 vs. 0% (P < 0.001). Of the stents with "inflaming," 63.6% had thrombus when compared with 20.1% of the non-erosion stents (P < 0.001). Overlapping segments had the lowest NIC grades and more "inflaming" demonstrating a significant difference between Cypher vs. Excel stents. NIC grade was positively correlated with thrombus.. SES with BDPM has improved NIC resulting in less yellow plaque, thrombus, and "inflaming." Overlapping segments had the lowest NIC grade and more "inflaming."

Topics: Absorbable Implants; Aged; Angioscopy; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Polymers; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Treatment Outcome

The transcription factor, Krüppel-like factor 4 (KLF4), plays an important role in regulating the proliferation of vascular smooth muscle cells. This study aimed to examine the effect of rapamycin on the expression of KLF4 and the role of KLF4 in arterial neointimal formation.. Expression of KLF4 was monitored using real-time PCR and immunoblotting in cultured vascular smooth muscle cells. and in rat carotid arteries in vivo after balloon injury. Adenovirus-mediated overexpression and siRNA-mediated knockdown of KLF4 were used to examine the role of KLF4 in mediating the anti-proliferative role of rapamycin . KLF4-regulated genes were identified using cDNA microarray.. Rapamycin induced the expression of KLF4 in vitro and in vivo. Overexpression of KLF4 inhibited cell proliferation and the activity of mammalian target of rapamycin (mTOR) and its downstream pathways, including 4EBP-1 and p70S6K in vascular smooth muscle cells and prevented the neointimal formation in the balloon-injured arteries. KLF4 up-regulated the expression of GADD45β, p57(kip2) and p27(kip1) . Furthermore, knockdown of KLF4 attenuated the anti-proliferative effect of rapamycin both in vitro and in vivo.. KLF4 plays an important role in mediating the anti-proliferative effect of rapamycin in VSMCs and balloon-injured arteries. Thus, it is a potential target for the treatment of proliferative vascular disorders such as restenosis after angioplasty.

Topics: Angioplasty, Balloon; Animals; Base Sequence; Carotid Artery Injuries; Cell Proliferation; Cells, Cultured; Cyclin-Dependent Kinase Inhibitor p27; Gene Knockdown Techniques; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Male; Myocytes, Smooth Muscle; Neointima; Rats; Rats, Sprague-Dawley; RNA, Small Interfering; Sirolimus; TOR Serine-Threonine Kinases

Topics: Cardiovascular Agents; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Neointima; Percutaneous Coronary Intervention; Sirolimus; Tomography, Optical Coherence

Haemodialysis vascular access dysfunction caused by aggressive venous neointimal hyperplasia is a major problem for haemodialysis patients with synthetic arteriovenous (AV) grafts. Several different strategies to prevent venous stenosis by inhibiting smooth muscle cell proliferation and migration using local delivery of potent antiproliferative agents are currently under investigation. We performed this study to evaluate the efficacy of sirolimus-eluting vascular grafts in preventing stenosis and to compare the effectiveness of sirolimus-coated grafts with that of paclitaxel-coated vascular grafts that we characterized in a previous study.. AV grafts were implanted laterally between the common carotid artery and external jugular vein of 14 female Landrace pigs. Three types of grafts were implanted: grafts coated with 1.08 μg/mm(2) sirolimus (low dose, n = 6), grafts coated with 2.41 μg/mm(2) sirolimus (high dose, n = 2) and uncoated control grafts (n = 6). Animals were sacrificed 6 weeks after surgery. Cross-sections of the venous anastomoses were analysed to determine the percentage of luminal stenosis in each group, and immunohistochemistry was performed to identify the cellular phenotypes of the neointimal hyperplasia and tissues adjacent to the implanted grafts.. Compared with the control group, neointimal hyperplasia in the venous anastomoses of the groups implanted with sirolimus-coated vascular grafts was significantly suppressed without infection. The mean ± standard error values for the percentage of luminal stenosis were 75.7 ± 12.7% in the control group and 22.2 ± 1.41% in the low-dose sirolimus-coated group. Myofibroblasts and fibroblasts were the major cell types found in the neointimal hyperplasia.. Neointimal hyperplasia was effectively suppressed by sirolimus-eluting grafts. However, the inhibitory effects of sirolimus-eluting grafts were weaker than those observed for paclitaxel-coated grafts in our previous study.

Topics: Animals; Arteriovenous Shunt, Surgical; Carotid Arteries; Cell Proliferation; Constriction, Pathologic; Female; Graft Occlusion, Vascular; Hyperplasia; Jugular Veins; Models, Animal; Neointima; Paclitaxel; Polytetrafluoroethylene; Renal Dialysis; Sirolimus; Swine; Vascular Grafting

To evaluate the effect of a polymer-free Biolimus A9-eluting stent [BioFreedom (BF)], compared with that of a biodegradable polymer-based Biolimus A9-eluting stent [BioMatrix Flex (BMF)] and a bare metal stent (BMS) in balloon denuded and radiated hypercholesterolemic rabbit iliac arteries.. Rabbits were fed with 1% cholesterol diet (n = 14) for 14 days, both iliac arteries were balloon denuded and radiated, and then rabbits were switched to 0.15% cholesterol diet. After 4 weeks, BF (n = 8), BMF (n = 8), and BMS (n = 8) were deployed in denuded and radiated areas. Four weeks later animals were euthanized, arterial segments were processed for morphometry.. The neointimal area in vessels implanted with BF stents was significantly less than that seen in vessels implanted with BMS (0.90 mm(2) ± 0.14 vs. 1.29 mm(2) ± 0.23, P <0.01). Percent fibrin and fibrin score were higher with BMF stents compared to BMS (P <0.03 and <0.04) and giant cell number was significantly higher with both BMF and BF stents (P < 0.01 for both). Percent endothelialization was significantly higher and % uncovered struts were lower with BMS compared to either BMF or BF stents (P < 0.05 for both).. This study demonstrates that compared to BMS, BF stents significantly decreased neointimal hyperplasia.

Topics: Absorbable Implants; Angioplasty, Balloon; Animals; Atherosclerosis; Cardiovascular Agents; Constriction, Pathologic; Disease Models, Animal; Drug-Eluting Stents; Fibrin; Hypercholesterolemia; Hyperplasia; Iliac Artery; Inflammation; Male; Metals; Neointima; Plaque, Atherosclerotic; Polymers; Prosthesis Design; Rabbits; Sirolimus; Stents; Time Factors

This new generation of DES has attempted to improve clinical safety by avoiding the presence of polymers. The present preclinical in vivo study was designed to investigate the safety profile of Cre8™ stent. This is a new coronary stent based on Amphilimus™, a sirolimus formulated with a polymer-free amphiphilic carrier released from reservoirs machined onto the abluminal stent surface.. Cre8™ stents were compared with two controls: R3 (the same platform only loaded with an amphiphilic carrier) and the Cypher Select Plus® stent (Cordis, Johnson & Johnson, Warren, NJ, USA). All devices (48 stents) were implanted in porcine coronary arteries with subsequent histological and morphometric evaluations at seven, 30 and 90 days. Early endothelisation at seven days was almost complete in all stents. Vessel wall histology at 30 days demonstrated a mild inflammation score in all groups (an inflammation score lower than 1 was observed in 100% of Cre8 stent, 71.5% for R3 and 66.7% for Cypher; p=n.s.) while morphometry showed a significantly smaller neointimal area in Cre8™ (Cre8 0.93±0.43 mm2; R3 1.49±0.67 mm2; Cypher 1.81±0.94 mm2; Cre8 vs. Cypher p<0.05); this difference was maintained after 90 days (inflammation score lower than 1 in 100% of Cre8 stent, 100% for R3 and 66.7% for Cypher; p=n.s. Neointimal area was 1.27±0.56 mm2 for Cre8, 1.74±0.60 mm2 for R3 and 2.79±1.14 mm2 for Cypher; Cre8 and R3 vs. Cypher p<0.05 while neointimal thickness was 0.15±0.07 mm for Cre8, 0.21±0.12 mm for R3 and 0.31±0.15 mm for Cypher; Cre8 vs. Cypher p<0.05).. The most significant experimental evidence appears to be the absence of chronic inflammatory response in Cre8™ stent. This is expressed by a reduced neointimal thickness and inflammatory score at all follow-ups. Such an outcome positively compares with the other DES where a trend to neointimal growth and increased cell infiltration was observed.

Topics: Animals; Coronary Angiography; Coronary Vessels; Drug-Eluting Stents; Incidence; Inflammation; Models, Animal; Neointima; Polymers; Sirolimus; Swine; Time Factors

Autopsy findings have suggested delayed arterial healing as a primary cause of very late stent thrombosis (VLST) after drug-eluting stent (DES) implantation.. Optical coherence tomography of DES-treated lesions that developed VLST (n = 6) was compared with that of DES-treated lesions that developed late in-stent restenosis (L-ISR: n = 32) among patients with recurrent ischemia >1 year after DES implantation (mean, 37 ± 17 months), and with the stented segment without any evidence of VLST or L-ISR (no-event: n = 20; mean, 38 ± 19 months). The proportion of uncovered and malapposed struts in each stented segment was evaluated. A total of 961 frames, 9,763 struts were analyzed. The proportion of uncovered struts was higher in the VLST group than in the L-ISR group and the no-event group (29.2 ± 22.8%, 7.9 ± 9.7%, and 7.6 ± 8.0%, respectively; P = 0.0002). The proportion of malapposed struts was higher in the VLST group than in the no-event group (7.3 ± 8.7% vs 1.1 ± 2.4%, P = 0.01). Two patients in the VLST group had lower rates of uncovered and malapposed struts, but this involved lipid-laden-like neointima with disruptions.. Delayed neointimal coverage and incomplete stent apposition were frequently observed in the DES-treated lesions that developed very late thrombosis. Lipid-laden-like neointima with disruption within the DES may be another possible mechanism for very late thrombosis.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Ischemia; Neointima; Sirolimus; Time Factors; Tomography, Optical Coherence

The differences in the vascular response to stent implantation or in the incidence of late acquired stent malapposition among different types of drug-eluting stents are not well known in patients with acute myocardial infarction (MI).. The pattern of vascular remodeling and degree of neointimal proliferation were different depending on the different types of drug-eluting stents.. This study used intravascular ultrasound (IVUS) to investigate vascular remodeling in patients treated with implantation of sirolimus-eluting stents (SESs) vs zotarolimus-eluting stents (ZESs) following acute MI. The study population consisted of 100 patients with acute MI who were treated either with SES (n = 41) or ZES (n = 59) and underwent both poststenting and 9-month follow-up IVUS examination. Serial vascular changes surrounding stented segments were compared between SES- and ZES-treated lesions.. Percentage of neointimal volume obstruction at follow-up was significantly smaller in SES-treated compared to ZES-treated lesions (2.8 ± 7.1% vs 18.1 ± 15.7%, respectively; P < 0.001). However, positive vascular remodeling, which was defined as greater than 10% increase in external elastic membrane volume index (31.7% vs 10.2%, respectively, P = 0.007), and late acquired stent malapposition (12.0% vs 0%, respectively, P = 0.006 ) occurred more frequently in SES-treated than in ZES-treated lesions.. The pattern of vascular remodeling, including positive remodeling, late acquired stent malapposition, and degree of neointimal proliferation might be different depending on the different types of drug-eluting stents in patients with acute MI.

Topics: Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Vessels; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Myocardial Infarction; Neointima; Sirolimus; Treatment Outcome; Ultrasonography, Interventional

The authors investigate whether the combination of anti-CD34 antibody with DES is win-win cooperation.. DES may reduce the risk of restenosis compared to bare-metal stents (BMS), but they were found to inhibit the healing process of intima.. Fifteen BMS, 17 DES, and 16 combined anti-CD34 antibody and DES were randomly implanted in the coronary arteries of 22 minipigs. Ten minipigs were followed up to 2 weeks. The stenting coronary segments were examined by histological examination and scanning electron microscopy after in vivo coronary angiography and intracoronary optical coherence tomography (OCT) examinations. The other 12 minipigs were followed up to 3 months. Coronary angiography and intracoronary OCT examination were performed in vivo and histological examination was performed on the stenting coronary segments.. After 2 weeks, the neointimal covering level of the DES was lower than that in BMS, but the covering level of the combined stents was even better than the BMS. After 3 months, neointimal hyperplasia was significant in the BMS, but not in the other two types of stents. The in-stent late lumen loss of the combined stents even showed a decreasing tendency when compared with the DES.. The combination of anti-CD34 antibody and DES can not only well offset the short-term inhibitory effect on re-endothelialization but also slightly enhance the long-term antiproliferative effect.

Topics: Angioplasty, Balloon, Coronary; Animals; Antibodies; Antigens, CD34; Cardiovascular Agents; Cell Proliferation; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Hyperplasia; Metals; Microscopy, Electron, Scanning; Neointima; Prosthesis Design; Sirolimus; Stents; Swine; Swine, Miniature; Time Factors; Tomography, Optical Coherence

Topics: Animals; Coronary Vessels; Drug-Eluting Stents; Neointima; Polymers; Sirolimus

Impaired endothelial recovery after the implantation of drug-eluting stents is a major concern because of the increased risk for late stent thrombosis. The disruption of the chemokine axis CXCL12/CXCR4 inhibits neointima formation by blocking the recruitment of smooth muscle progenitor cells. To directly compare a CXCR4-targeting treatment strategy with drugs that are currently used for stent coating, we studied the effects of the CXCR4 antagonist POL5551 and the drug sirolimus on neointima formation. Apolipoprotein E-deficient mice were treated with POL5551 or sirolimus continuously for 28 days after a carotid wire injury. POL5551 inhibited neointima formation by 63% (for a dosage of 2 mg/kg/day) and by 70% (for a dosage of 20 mg/kg/day). In comparison, sirolimus reduced the neointimal area by 69%. In contrast to treatment with POL5551 during the first three days after injury, injection of POL5551 (20 mg/kg) once per day for 28 days diminished neointimal hyperplasia by 53%. An analysis of the cellular composition of the neointima showed a reduction in the relative smooth muscle cell (SMC) and macrophage content in mice that had been treated with a high dose of POL5551. In contrast, the diminished SMC content after sirolimus treatment was associated with a neointimal enrichment of macrophages. Furthermore, endothelial recovery was impaired by sirolimus, but not by POL5551. Therefore, the inhibition of CXCR4 by POL5551 is equally effective in preventing neointima formation as sirolimus, but POL5551 might be more beneficial because treatment with it results in a more stable lesion phenotype and because it does not impair re-endothelialisation.

Topics: Angioplasty; Animals; Apolipoproteins E; Blood Vessel Prosthesis Implantation; Carotid Arteries; Cell Movement; Coronary Restenosis; Disease Models, Animal; Drug-Eluting Stents; Endothelium, Vascular; Humans; Lysophospholipids; Macrophages; Mice; Mice, Knockout; Myocytes, Smooth Muscle; Neointima; Postoperative Complications; Proteins; Receptors, CXCR4; Sirolimus

Non stent based delivery of antiproliferative agents using drug coated balloon catheters may offer additional flexibility and efficacy in a broad range of applications. The lipophilic antiproliferative drug zotarolimus makes it a potential candidate for balloon delivery. The aim of the present study was to evaluate the safety and efficacy of a prototype zotarolimus coated balloon (ZCB) catheter in comparison to a zotarolimus eluting stent (ZES) in the porcine coronary overstretch model.. Eighty-four stents (diameters 3.0 and 3.5 mm; length 15 mm) were implanted in LAD and Cx of 42 domestic pigs: control (TriMaxx, Abbott, polymer coated stent without drug, implanted with uncoated PCI catheter, n = 56); ZES (ZoMaxx, Abbott, stent coated with zotarolimus in polymer, implanted with uncoated PCI catheter, n = 14); ZCB (TriMaxx, Abbott, polymer coated stent without drug, implanted with zotarolimus coated PCI catheter, n = 14). Drug content of the vessel wall (n = 9) was measured about 10-30 min post intervention with ZCB in additional pigs.. Immediately after ZCB treatment 101 ± 31 μg of zotarolimus was detected in the coronary arteries. After 28 days ZES led to a reduction of neointimal area from 4.32 ± 1.45 to 3.32 ± 1.11 mm2 (P = 0.019 vs. control). The effect of neointimal inhibition was more pronounced with the novel ZCB (2.79 ± 1.43 mm², P = 0.001 vs. control). Inflammation score was significantly reduced in vessels treated with the ZCB (0.75 ± 0.86 compared to control (1.45 ± 0.94, P = 0.013) and ZES (1.65 ± 0.90, P = 0.012).. Zotarolimus coated balloons and stents were found to effectively reduce neointimal proliferation in the porcine coronary model. Inflammation scores were significantly reduced after treatment with the coated balloon. Zotarolimus balloon coating might be a novel option in preventing and treating restenosis.

Topics: Angioplasty, Balloon, Coronary; Animals; Coronary Restenosis; Coronary Vessels; Disease Models, Animal; Drug-Eluting Stents; Hyperplasia; Neointima; Sirolimus; Swine

Topics: Coronary Angiography; Coronary Vessels; Drug-Eluting Stents; Equipment Failure; Humans; Hyperplasia; Neointima; Sirolimus; Tomography, Optical Coherence

The neointimal tissue characteristics inside sirolimus-eluting stent (SES) were evaluated by optical coherence tomography (OCT) according to follow-up duration. One hundred and thirty-three Optical coherence tomography was performed in 96 patients with 143 SES which were retrospectively included and divided into 2 groups according to follow-up duration: Group 1, <24 months (98 stents in 71 patients); Group 2, >24 months (35 stents in 25 patients). The neointimal tissue coverage pattern and characteristics were studied using a new OCT analysis system which can quantitatively analyze tissue property by measuring attenuation, backscatter and signal intensity in the region of interest. Using these parameters, a multivariable logistic regression model was constructed to divide neointima into homogenous or heterogeneous type. We defined homogeneous nointima as neointimal tissue having uniform optical properties and does not showing focal variations in backscattering pattern and heterogeneous neointima as neointimal tissue with focally changing optical properties and showing various backscattering patterns. The average time between stent implantation and follow-up OCT imaging was 1.2 years in Group 1 and 3.2 years in Group 2. The number of neointima covered cross-sections, neointimal thickness, and neointimal area increased significantly with the length of follow-up duration after SES implantation (P < 0.01). The incidence of heterogeneous neointima was higher in Group 2 than in Group 1 (P < 0.01). Heterogeneous neointima was associated with higher incidence of microvessels (P = 0.0023) and lipid rich plaque (P = 0.0015) compared with homogeneous neointima. The neointimal tissue characteristics may change over time after SES implantation. The incidence of heterogeneous pattern was higher in the SES group with longer follow-up duration. Microvessels and lipid rich plaques were more frequently observed in neointima with heterogeneous pattern. Neointimal heterogeneity could be an important factor for the late stability of SES.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Image Interpretation, Computer-Assisted; Logistic Models; Male; Microvessels; Middle Aged; Multivariate Analysis; Neointima; Odds Ratio; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Predictive Value of Tests; Prosthesis Design; Retrospective Studies; Sirolimus; Software; Time Factors; Tomography, Optical Coherence; Treatment Outcome

A 52-year-old woman with Takayasu arteritis developed acute coronary syndrome and received percutaneous coronary intervention (PCI). The patient experienced restenosis three times even with drug-eluting stent (DES) implantation. We started steroid administration after the fourth PCI to reduce inflammation due to autoimmunity. With DES and a steroid combination, the patient remained free of chest pain, and a follow-up angiography demonstrated good patency of the stent site. Since in-stent restenosis may result from a complicated combination of neointimal proliferation and autoimmune mechanisms, physicians should consider a combination of DES and a steroid for the treatment of coronary artery disease in Takayasu arteritis.

Topics: Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Middle Aged; Neointima; Sirolimus; Steroids; Takayasu Arteritis; Tomography, X-Ray Computed

The goal of this study was to describe the neointimal healing on the abluminal side (ABL) of malapposed (ISA) struts and nonapposed side-branch (NASB) struts in terms of coverage by optical coherence tomography (OCT) and in comparison with the adluminal side (ADL).. The neointimal healing on the ABL of ISA and NASB struts has never to our knowledge been explored in vivo and could be involved in the correction of acute malapposition. The bioresorbable vascular scaffold (BVS) is made of a translucent polymer that enables imaging of the ABL with OCT.. Patients enrolled in the ABSORB B (ABSORB Clinical Investigation Cohort B) study were treated with implantation of a BVS and imaged with OCT at 6 months. Thickness of coverage on the ADL and ABL of ISA and NASB struts was measured by OCT.. Twenty-eight patients were analyzed; 114 (2.4%) struts were malapposed or at side branches. In 76 ISA struts (89.4%) and 29 NASB struts (100%), the thickness of ABL coverage was >30 μm. Coverage was thicker on the ABL than on the ADL side (101 vs. 71 μm; 95% confidence interval [CI] of the difference: 20 to 40 μm). In 70 struts (60.7%, 95% CI: 50.6% to 70.0%), the neointimal coverage was thicker on the ABL, versus only 20 struts (18.5%, 95% CI: 11.6% to 28.1%) with thicker neointimal coverage on the ADL side (odds ratio: 3.35, 95% CI: 2.22 to 5.07).. Most of the malapposed and side-branch struts are covered on the ABL side 6 months after BVS implantation, with thicker neointimal coverage than on the ADL side. The physiological correction of acute malapposition involves neointimal growth from the strut to the vessel wall or bidirectional. (ABSORB Clinical Investigation, Cohort B [ABSORB B]; NCT00856856).

Topics: Absorbable Implants; Aged; Angioplasty, Balloon, Coronary; Australia; Cardiovascular Agents; Cell Proliferation; Coated Materials, Biocompatible; Coronary Artery Disease; Coronary Vessels; Europe; Everolimus; Female; Humans; Lactic Acid; Male; Middle Aged; Neointima; New Zealand; Polyesters; Polymers; Predictive Value of Tests; Prosthesis Design; Registries; Sirolimus; Time Factors; Tissue Scaffolds; Tomography, Optical Coherence; Treatment Outcome

Biodegradable stent coatings were recently introduced as a potential solution to overcome sustained inflammatory responses observed with permanent polymer-based drug-eluting stents. In a preliminary study, selected biodegradable or permanent polymer-based sirolimus-eluting stent (SES) formulations were screened for effectiveness in comparison to bare metal stents (BMS) at 28 days. Subsequently, the most favourable SES formulation was compared to commercially available SES (Cypher™) at 28, 90 and 180 days to investigate the histopathologic response as well as tissue, blood and organ pharmacokinetics. Overlapping SES implantation was conducted to evaluate vascular healing at 28 days in this particular setting. SES with biodegradable poly (L-lactide) polymer (PLLA) or poly(lactide-co-glycolide) showed the most favourable outcome with regards to reductions in neointimal area in comparison to BMS at 28 days. The PLLA SES showed a similar reduction in neointimal area compared to Cypher™ at 28 days, with significant greater reductions at 90 and 180 days (1.7 ± 0.7 mm² vs. 3.1 ± 1.5 mm², p=0.03 and 1.8 ± 1.2 mm² vs. 3.0 ± 1.5 mm², p=0.01, respectively). Sirolimus vascular tissue concentrations were detectable up to 90 days following implantation. Overlapping stented segments showed favourable histopathologic results with respect to fibrin deposition and endothelialisation at 28 days. In conclusion, the use of PLLA as drug-eluting matrix resulted in mild inflammatory responses in the presence of effective sirolimus tissue concentrations. The greater efficacy observed at long-term follow-up in PLLA SES compared to Cypher™ may be a multifactorial result of stent design, polymer biocompatibility and improved release kinetics.

Topics: Absorbable Implants; Angioplasty, Balloon, Coronary; Animals; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Lactic Acid; Models, Animal; Neointima; Polyesters; Polyglactin 910; Polymers; Prosthesis Design; Sirolimus; Sus scrofa; Time Factors; Tissue Distribution

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.. 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.. 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.. 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.

Topics: Acetylcholine; Animals; Cardiovascular Agents; Chitosan; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Disease Models, Animal; Drug-Eluting Stents; Endothelial Cells; Heparin; Hyperplasia; Metals; Microscopy, Electron, Scanning; Neointima; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Swine; Swine, Miniature; Time Factors; Ultrasonography, Interventional; Vasoconstriction

Diabetes remains a significant risk factor for restenosis/thrombosis following stenting. Although vascular healing responses following drug-eluting stent (DES) treatment have been characterized previously in healthy animals, comparative assessments of different DES in a large animal model with isolated features of diabetes remains limited. We aimed to comparatively assess the vascular response to paclitaxel-eluting (PES) and everolimus-eluting (EES) stents in a porcine coronary model of streptozotocin (STZ)-induced type I diabetes.. Twelve Yucatan swine were induced hyperglycemic with a single STZ dose intravenously to ablate pancreatic β-cells. After two months, each animal received one XIENCE V® (EES) and one Taxus Liberte (PES) stent, respectively, in each coronary artery. After three months, vascular healing was assessed by angiography and histomorphometry. Comparative in vitro effects of everolimus and paclitaxel (10-5 M-10-12 M) after 24 hours on carotid endothelial (EC) and smooth muscle (SMC) cell viability under hyperglycemic (42 mM) conditions were assayed by ELISA. Caspase-3 fluorescent assay was used to quantify caspase-3 activity of EC treated with everolimus or paclitaxel (10-5 M, 10-7 M) for 24 hours.. After 3 months, EES reduced neointimal area (1.60 ± 0.41 mm, p < 0.001) with trends toward reduced % diameter stenosis (11.2 ± 9.8%, p = 0.12) and angiographic late-loss (0.28 ± 0.30 mm, p = 0.058) compared to PES (neointimal area: 2.74 ± 0.58 mm, % diameter stenosis: 19.3 ± 14.7%, late loss: 0.55 ± 0.53 mm). Histopathology revealed increased inflammation scores (0.54 ± 0.21 vs. 0.08 ± 0.05), greater medial necrosis grade (0.52 ± 0.26 vs. 0.0 ± 0.0), and persistently elevated fibrin scores (1.60 ± 0.60 vs. 0.63 ± 0.41) with PES compared to EES (p < 0.05). In vitro, paclitaxel significantly increased (p < 0.05) EC/SMC apoptosis/necrosis at high concentrations (≥ 10-7 M), while everolimus did not affect EC/SMC apoptosis/necrosis within the dose range tested. In ECs, paclitaxel (10-5 M) significantly increased caspase-3 activity (p < 0.05) while everolimus had no effect.. After 3 months, both DES exhibited signs of delayed healing in a STZ-induced diabetic swine model. PES exhibited greater neointimal area, increased inflammation, greater medial necrosis, and persistent fibrin compared to EES. Differential effects of everolimus and paclitaxel on vascular cell viability may potentially be a factor in regulating delayed healing observed with PES. Further investigation of molecular mechanisms may aid future development of stent-based therapies in treating coronary artery disease in diabetic patients.

Topics: Animals; Apoptosis; Cardiovascular Agents; Cells, Cultured; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Disease Models, Animal; Dose-Response Relationship, Drug; Drug-Eluting Stents; Endothelial Cells; Everolimus; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Necrosis; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Swine; Time Factors; Wound Healing

This study evaluated vascular compatibility of the novel platinum chromium alloy Element stent platform delivering abluminal everolimus from a poly-lactide-co-glycolide bioabsorbable polymer (SYNERGY stent), currently undergoing clinical trial, compared with the PROMUS (XIENCE V) and bare metal and polymer-only Element stents.. Stents (n=161) were implanted one per coronary artery in 72 swine at a stent-to-artery ratio of 1.1:1. Similar numbers of each device group were explanted at each of 30, 90, 180, and 360 days (except no PROMUS (XIENCE V) stent at 360 days) for pathological analysis. There was no stent thrombosis, myocardial infarction, or strut fractures in any group. Vascular response was similar between the SYNERGY and PROMUS (XIENCE V) stents, with no thrombi and complete endothelialisation on both scanning electron microscopy and histology at 30, 90 and 180 days. There were no significant differences for the morphologic parameters of luminal thrombus, endothelial cell coverage, strut tissue coverage, inflammation, internal elastic lamina (IEL) disruption, external elastic lamina (EEL) disruption and medial smooth muscle cell loss across device groups or between time points, but there was mild but greater (p<0.0001) para-strut fibrin at 30 days for both drug-eluting stents (DES) compared with the bare and polymer-only controls; this difference completely dissipated by 90 days. Inflammation was predominantly minimal to mild for all device types. No morphometric parameters, including intimal thickness, stent profile-based area stenosis, and EEL area were significantly different when comparing the SYNERGY stent with the bare metal Element and polymer-only Element control stents at 90, 180 and 360 days.. In this non-injured porcine coronary artery model, the bioabsorbable polymer SYNERGY stent demonstrated vascular compatibility equivalent to the PROMUS (XIENCE V) stent and to the bare metal and polymer-only Element stents.

Topics: Angioplasty, Balloon, Coronary; Animals; Everolimus; Metals; Microscopy, Electron, Scanning; Neointima; Polymers; Sirolimus; Stents; Swine

Recent studies have reported the development of neoatherosclerosis inside stents and subsequent acute coronary syndrome secondary to disruption of neointimal hyperplasia. The aim of the study was to compare the characteristics of neointimal hyperplasia and its time course between bare metal stents (BMSs) and drug-eluting stents (DESs) using optical coherence tomography. A total of 138 stents were divided into 3 groups according to the follow-up period: early phase, <9 months (25 BMSs and 27 DESs); intermediate phase, ≥9 and <48 months (18 BMSs and 43 DESs); and delayed phase, ≥48 months (13 BMSs and 12 DESs). Optical coherence tomographic analysis included the presence of lipid-laden intima, percentage of lipid-rich plaque, and signal attenuation. The optical coherence tomographic findings were compared between the BMSs and DESs in each period, and the difference between the periods was also determined. In the early phase, a greater incidence of lipid-laden plaque (37% vs 8%, p = 0.02) and a greater percentage of lipid-rich plaque (12.9 ± 25.1% vs 1.2 ± 4.3%, p = 0.01) were found in the DESs than in the BMSs. In the intermediate phase, the DES group continuously showed a significantly greater incidence of lipid-laden plaque (63% vs 28%, p = 0.03) and greater percentage of lipid-rich plaque (24.8 ± 28.1% vs 4.1 ± 7.3%, p <0.01). In addition, signal attenuation was greater in the DES group, suggesting early changes in neointimal hyperplasia properties. In the delayed phase, lipid-laden plaque was the predominant type in both groups. In conclusion, lipid-rich neoatherosclerosis develops inside stents earlier in DESs than in BMSs. After 48 months, most restenotic stents will have developed lipid-laden neointima in both groups.

Topics: Acute Coronary Syndrome; Atherosclerosis; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Hyperplasia; Immunosuppressive Agents; Incidence; Male; Massachusetts; Middle Aged; Myocardial Ischemia; Myocardial Revascularization; Neointima; Sirolimus; Time Factors; Tomography, Optical Coherence

Current drug eluting stent (DES) technology is not optimized with regard to the pharmacokinetics of drug delivery. A novel, absorbable-coating sirolimus-eluting stent (AC-SES) was evaluated for its capacity to deliver drug more evenly within the intimal area rather than concentrating drug around the stent struts and for its ability to match coating erosion with drug release. The coating consisted of absorbable poly-lactide-co-glycolic acid (PLGA) and crystalline sirolimus deposited by a dry-powder electrostatic process. The AC-SES demonstrated enhanced drug stability under simulated use conditions and consistent drug delivery balanced with coating erosion in a porcine coronary implant model. The initial drug burst was eliminated and drug release was sustained after implantation. The coating was absorbed within 90 days. Following implantation into porcine coronary arteries the AC-SES coating is distributed in the surrounding intimal tissue over the course of several weeks. Computational modeling of drug delivery characteristics demonstrates how distributed coating optimizes the load of drug immediately around each stent strut and extends drug delivery between stent struts. The result was a highly efficient arterial uptake of drug with superior performance to a clinical bare metal stent (BMS). Neointimal thickness (0.17±0.07 mm vs. 0.28±0.11 mm) and area percent stenosis (22±9% vs. 35±12%) were significantly reduced (p<0.05) by the AC-SES compared to the BMS 30 days after stent implantation in an overlap configuration in porcine coronary arteries. Inflammation was significantly reduced in the AC-SES compared to the BMS at both 30 and 90 days after implantation. Biocompatible, rapidly absorbable stent coatings enable the matching of drug release with coating erosion and provide for the controlled migration of coating material into tissue to reduce vicissitudes in drug tissue levels, optimizing efficacy and reducing potential toxicity.

Topics: Animals; Anti-Inflammatory Agents; Constriction, Pathologic; Coronary Vessels; Crystallization; Drug Delivery Systems; Drug-Eluting Stents; Lactic Acid; Models, Biological; Neointima; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Sirolimus; Swine; Tunica Media

A novel self-expanding, drug-eluting stent (DES) was designed to slowly release everolimus in order to prevent restenosis after percutaneous peripheral intervention. The purpose of this experimental animal study was to test the hypothesis that long-term local, stent-mediated delivery of everolimus would reduce neointimal hyperplasia in porcine iliac arteries.. The iliac arteries of 24 Yucatan mini-swine were percutaneously treated with overlapping 8- × 28-mm self-expanding nitinol stents loaded with everolimus (225 μg/cm2 stent surface area) formulated in a poly(ethylene-co-vinyl alcohol) copolymer intended to deliver the drug in a sustained fashion over about 6 months (DES). Bare nitinol self-expanding stents (bare metal stent [BMS]) were implanted in an identical fashion on the contralateral side to serve as controls. After 3, 6, or 12 months, the animals were sacrificed and the stented arteries perfusion-fixed for histomorphometric analysis.. The chronic presence of everolimus in arterial tissue reduced stent-induced inflammation after 3 months (inflammation score: BMS 2.29±0.44 vs DES 0.17±0.17; P=.001) and 6 months (BMS 2.06±0.43 vs DES 0.50±0.5; P=.007), although some late inflammation was observed after drug exhaustion (BMS 1.00±0.25 vs DES 2.56±0.62 after 12 months; P=not significant [NS]). Treatment with locally delivered everolimus significantly reduced neointimal hyperplasia after 3 months (neointimal thickness: BMS 0.79±0.20 vs DES 0.37±0.04 mm; P=.03) and 6 months (BMS 0.73±0.14 vs DES 0.41±0.08 mm; P=.05), although the effect had dissipated after 12 months (BMS 0.68±0.11 vs DES 0.67±0.11 mm; P=NS). Remarkably, stent-induced neoatherosclerosis, characterized by the histologic presence of foamy macrophages and cholesterol clefts, was significantly attenuated by treatment with everolimus (atherogenic change scores at 3 months: BMS 0.56±0.15 vs DES 0.04±0.04; P=.003; 6 months: BMS 0.84±0.23 vs DES 0.00±0.00; P=.004; and 12 months: BMS 0.09±0.10 vs DES 0.19±0.19; P=NS).. In this experimental animal model, local arterial stent-mediated delivery of everolimus inhibited the formation of neointimal hyperplasia and neoatherosclerosis during the first 6 months. The effect was transient, however, as arterial morphology and histology appeared similar to control stented arteries after 12 months.

Topics: Animals; Atherosclerosis; Disease Models, Animal; Drug-Eluting Stents; Endovascular Procedures; Everolimus; Graft Occlusion, Vascular; Hyperplasia; Iliac Artery; Immunosuppressive Agents; Neointima; Sirolimus; Swine; Swine, Miniature

The Stenting of Saphenous Grafts-Xience V (SOS-Xience V) trial prospectively examined the frequency of angiographic in-stent restenosis in saphenous vein graft (SVG) lesions 12 months after implantation of a Xience V everolimus-eluting stent (EES; Abbott Vascular). Optical coherence tomography (OCT) during follow-up angiography was added to the protocol after OCT was approved for clinical use in the United States.. Forty patients with 40 SVG lesions were enrolled in the study, of whom 27 underwent 12-month coronary angiography and 12 (only 1 of whom had in-stent restenosis) also had follow-up OCT evaluation. OCT strut-level analysis was performed to determine the percentage of strut coverage, malapposition, strut protrusion, neointimal thickness, and the existence of thrombus.. Mean patient age was 67 ± 7 years, and 95% were men. A total of 2584 struts were evaluated by OCT. The percentages for uncovered, malapposed, and protruding struts were 4%, 9%, and 15%, respectively. The mean strut neointimal thickness was 0.094 ± 0.094 mm. Of the 12 stents analyzed, 4 (33%) showed full neointimal coverage, 2 (17%) had all the struts embedded, 7 (58%) had at least 1 malapposed strut, and 10 (83%) had at least 1 protruding strut. The mean difference between the stent area and the lumen area was 0.36 ± 1.6 mm². No thrombus was detected in the stented areas.. Use of EES in SVGs is associated with high rates of stent strut coverage and high malapposition rates at 12 months post implantation.

Topics: Aged; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Graft Occlusion, Vascular; Humans; Immunosuppressive Agents; Male; Middle Aged; Monitoring, Physiologic; Myocardial Revascularization; Neointima; Percutaneous Coronary Intervention; Prospective Studies; Risk Assessment; Saphenous Vein; Sirolimus; Tomography, Optical Coherence; Treatment Outcome; Vascular Patency

Topics: Angina, Unstable; Cardiovascular Agents; Coronary Angiography; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Humans; Hyperplasia; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Thrombectomy; Time Factors; Tomography, Optical Coherence; Treatment Outcome

In-stent restenosis (ISR), especially focal ISR, after percutaneous coronary intervention (PCI) remains one of the major clinical problems in the drug-eluting stent (DES) era. Several reports have revealed that excimer laser coronary angioplasty (ELCA) is useful for ISR; however, detailed findings after ELCA are unknown. Therefore, we investigated the condition of the neointima after ELCA for ISR with optical coherence tomography (OCT) and compared the OCT findings and clinical outcome between ELCA and cutting-balloon angioplasty (CBA).. Twenty-one consecutive patients with focal ISR who underwent ELCA or CBA were enrolled. All patients underwent 12- to 15-month follow-up coronary angiography. OCT was performed immediately after successful PCI to evaluate the neointimal condition in the ISR lesion. We compared the following OCT parameters between ELCA and CBA groups: maximal thickness of remaining in-stent neointima (MTN), number of tears, minimum lumen dimension (MLD), and minimum lumen area (MLA). We also evaluated clinical outcomes, including target vessel revascularization, acute myocardial infarction, death, and stent thrombosis.. MLA in the ELCA group (n = 10) was significantly larger than in the CBA group, and number of tears in the ELCA group was significantly lower than in the CBA group. A trend was shown toward lower TLR with ELCA versus CBA (10.0% vs 45.5%).. OCT immediately after ELCA for ISR lesions revealed larger lumen area and smaller number of tears compared with CBA, which may support favorable effects of ELCA for focal ISR.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Incidence; Lasers, Excimer; Male; Middle Aged; Neointima; Paclitaxel; Retrospective Studies; Sirolimus; Tomography, Optical Coherence; Treatment Outcome

We aimed to assess the influence of different sirolimus analogues released from a uniform stent platform on re-endothelialisation and vascular healing responses.. Bare metal stents (BMS) were coated with a fluoropolymer containing everolimus (EES), sirolimus (SES) or zotarolimus (ZES) to generate drug-eluting stents (DES) with identical stent backbones, drug loads and release kinetics. DES constructs and control BMS were implanted into the iliac arteries of rabbits and were analysed at 14 days by scanning electron microscopy (SEM) and confocal microscopy for en face evaluation of endothelialisation (n=6 for each stent), or at 28 days to determine histomorphometric characteristics (n=11 for each stent). SEM analysis revealed low degrees of strut re-endothelialisation within the DES without differences among groups, while the BMS control showed almost complete endothelialisation. Percent stenosis was significantly reduced in all DES compared to BMS. Strut-based fibrin analysis revealed significantly greater deposition in the DES compared to BMS, with EES showing maximum fibrin deposition among the DES groups.. Sirolimus and its derivatives have similar effects on endothelial regrowth and neointimal thickening. The observation of greatest fibrin deposition in the experimental EES group indicates that everolimus may affect vascular healing differently.

Topics: Angioplasty, Balloon; Animals; Biomarkers; Cardiovascular Agents; Drug-Eluting Stents; Endothelial Cells; Everolimus; Fibrin; Iliac Artery; Immunohistochemistry; Male; Metals; Microscopy, Confocal; Microscopy, Electron, Scanning; Models, Animal; Neointima; Platelet Endothelial Cell Adhesion Molecule-1; Prosthesis Design; Rabbits; Sirolimus; Time Factors; Wound Healing

Circulating endothelial progenitor cells (EPCs) capture technology improves endothelialization rates of sirolimus-eluting stents (SES), but the problem of delayed re-endothelialization, as well as endothelial dysfunction, has still not been overcome. Therefore, we investigated whether the combination coating of hyaluronan-chitosan (HC) and anti-CD34 antibody applied on an SES (HCASES) can promote endothelialization, while reducing neointimal formation and inflammation.. Sirolimus-eluting stents(SES), anti-CD34 antibody stents (GS) and HC-anti-CD34 antibody combined with sirolimus-eluting stents (HCASES) were deployed in 54 normal porcine arteries and harvested for scanning electron microscopy (SEM) and histological analysis. The ratio of endothelial coverage above the stents was evaluated by SEM analysis at 7, 14 and 28 days. The percentage of in-stent stenosis was histologically analyzed at 14 and 28 days.. SEM analysis at 7 days showed that endothelial strut coverage was increased in the HCASES group (68±7%) compared with that in the SES group (31±4%, p=0.02). At 14 days, stent surface endothelialization, evaluated by SEM, showed a significantly higher extent of endothelial coverage above struts in the GS (95 ± 2%) and the HCASES groups (87±4%) compared with that in the SES group (51±6%, p=0.02). Histological examination showed that the percentage of stenosis in the HCASES group was not significantly different to that of the SES and GS groups (both p> 0.05). At 28 days, there was no difference in the rates of endothelial coverage between the HCASES and GS groups. The HCASES group showed less stenosis than that in the GS group (P < 0.05), but it was not significantly different from the SES group (P=0.068).. SEM and histology demonstrated that HCASESs can promote re-endothelialization while enhancing antiproliferative effects.

Topics: Angioplasty, Balloon, Coronary; Animals; Antigens, CD34; Chitosan; Drug-Eluting Stents; Endothelial Cells; Microscopy, Electron, Scanning; Neointima; Sirolimus; Swine

Serial changes in strut coverage of drug-eluting stents (DESs), which are placed across side-branch vessels, remain unclear.. The changes in strut coverage of DESs crossing side-branch vessels (size ≥2.0 mm) were serially evaluated by optical coherence tomography (OCT) in 30 patients at 9 months and 2 years after the index DES implantation. DESs were paclitaxel-eluting stents (PESs), sirolimus-eluting stents (SESs), and zotarolimus-eluting stents (ZESs), each in 10 patients. Measured neointimal hyperplasia (NIH) thickness of 0 μm on OCT was defined as an uncovered strut.. The percentage of uncovered side-branch struts significantly decreased from 55.7 ± 39.9% to 36.6 ± 32.0% (P<.0001) on serial follow-up: PES, 93.4 ± 10.5% to 67.6 ± 24.2%, P=.018; SES, 47.5 ± 34.4% to 29.6 ± 24.1%, P=.036; and ZES, 26.2 ± 34.8% to 12.4 ± 19.0%, P=.028. Among covered side-branch struts, the overall percentage of struts with NIH thickness more than 30 μm significantly increased from 36.3 ± 37.4% to 51.0 ± 36.0% (P<.0001). However, compared to other DES types, a significant increase in relatively thin NIH (0 to 30 μm) was observed in PESs (1.6 ± 3.4% to 17.4 ± 16.0%; P=.018).. Serial follow-up OCT examination showed a significant decrease in the percentage of uncovered side-branch struts, and the coverage pattern differed with DES type.

Topics: Aged; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Retrospective Studies; Sirolimus; Time Factors; Tomography, Optical Coherence

Novel vascular scaffolds aim at equipoise between safety and efficacy. Intravascular optical coherence tomography (OCT) allows in-vivo serial assessment of stent-vessel interactions with high resolution and frequent sampling and may complement histology assessment. We investigated the vascular response to a novel absorbable coating sirolimus-eluting stent (AC-SES) by means of serial OCT and histology evaluation in a porcine model.. One AC-SES and one bare-metal stent (BMS) were implanted in separate coronary arteries of three Yucatan mini-swine. Serial OCT was performed post procedure and at 3-, 28-, 90-, and 180-day follow-up. Normalized optical density (NOD) was used for the assessment of tissue response over time. Histological evaluation was performed at day 180.. A total of 6408 stent struts were analyzed. OCT revealed 100% of struts covered at 28 days, and a significant difference in NOD from 3 to 28 days (0.64 ± 0.07 vs 0.71 ± 0.05, respectively; P<.001) in the AC-SES group. Neointimal thickness was 0.14 ± 0.08 mm, 0.17 ± 0.11 mm, and 0.16 ± 0.09 mm in the AC-SES group and 0.18 ± 0.10 mm, 0.14 ± 0.09 mm, and 0.10 ± 0.08 mm in the BMS group, while rates of uncovered struts were 0%, 0%, and 3.1% and 1.4%, 7.8%, and 21.5%, respectively, at 28, 90, and 180 days. Minimal inflammation and a mature endothelialization were demonstrated in both groups by histology.. OCT serial assessment of vascular response suggested NIH maturation 28 days following AC-SES implantation in pigs. These findings, coupled with histological demonstration of low inflammation scores and complete endothelial coverage as measured at 180 days, suggest a satisfactory healing response to AC-SES.

Topics: Absorbable Implants; Animals; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Disease Models, Animal; Drug-Eluting Stents; Endothelium, Vascular; Follow-Up Studies; Neointima; Percutaneous Coronary Intervention; Sirolimus; Swine; Swine, Miniature; Time Factors; Tomography, Optical Coherence

The study evaluated serial quantitative and qualitative changes in vascular responses to drug-eluting stents (DES) using optical coherence tomography (OCT).. Serial changes in stent strut coverage and neointima characteristics in DES-treated lesions have not been sufficiently investigated using OCT.. Serial OCT was performed in 72 patients with 76 DES-treated lesions at 9 months and 2 years after DES implantation (sirolimus-eluting stent, n = 23; paclitaxel-eluting stent, n = 20; zotarolimus-eluting stent, n = 25; everolimus-eluting stent, n = 8). Serial changes in quantitative parameters (neointimal thickness, stent strut coverage, and apposition at each strut) and qualitative characteristics of the neointima were evaluated.. Mean neointimal thickness significantly increased from 164 μm to 214 μm between 9 months and 2 years (p < 0.001), and the percentage of uncovered stent struts significantly decreased (from 4.4% to 2.3%, p < 0.001). Completely covered lesions were more frequently observed at 2 years (44.7% vs. 59.2%, p = 0.07). However, the percentage of malapposed struts (0.6% vs. 0.9%, p = 0.24) and incidence of intracoronary thrombi (10.5% vs. 9.2%, p > 0.99) were similar. On qualitative evaluation of neointimal morphology, lipid-laden neointima (27.6% vs. 14.5%, p = 0.009) and thin-cap neoatheroma (13.2% vs. 3.9%, p = 0.07) were more frequently detected at 2-year follow-up compared with 9 months. In matched cross-sectional evaluation, the change of neointimal morphology from homogeneous to heterogeneous or lipid-laden pattern was observed in 23 (30.3%) of 76 lesions. There was a significant increase in percent neointimal hyperplasia cross-sectional area in those lesions.. This OCT study suggested that neointimal coverage improved from 9 months to 2 years without significant changes in the incidence of malapposed struts and intracoronary thrombus. Additionally, in-stent neoatherosclerosis including transformation to lipid-laden neointima might progress during extended follow-up periods after DES implantation.

Topics: Aged; Cardiovascular Agents; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Predictive Value of Tests; Registries; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Stent-based delivery of sirolimus has been shown to reduce neointimal hyperplasia significantly. However, the long-term effect of the polymer is thought to initiate and sustain an inflammatory response and contribute to the occurrence of late complications. Our study aimed to evaluate the efficacy and safety of the BuMA biodegradable drug-coated sirolimus-eluting stent (BSES) for inhibiting neointimal hyperplasia in a porcine coronary model.. Four types of stents were implanted at random in different coronary arteries of the same pig: BSES (n = 24), bare metal stent (BMS) (n = 24), biodegradable polymer coated stent without drug (PCS) (n = 24) and only poly (n-butyl methacrylate) base layer coated stent (EGS) (n = 23). In total, 26 animals underwent successful random placement of 95 oversized stents in the coronary arteries. Coronary angiography was performed after 28 days, 90 days and 240 days of stent implantation. After 14 days, 28 days, 90 days and 240 days, 6 animals at each timepoint were sacrificed for histomorphologic analysis.. The 28-day, 90-day and 240-day results of quantitative coronary angiography (QCA) showed reduction in luminal loss (LL) in the BSES group when compared with the BMS group; (0.20 ± 0.35) mm vs. (0.82 ± 0.51) mm (P = 0.035), (0.20 ± 0.30) mm vs. (0.93 ± 0.51) mm (P = 0.013), and (0.18 ± 0.16) mm vs. (0.19 ± 0.24) mm (P = 0.889), respectively. By 28-day, 90-day and 240-day histomorphomeric analysis results, there was also a corresponding significant reduction in neointimal tissue proliferation with similar injury scores of BSES compared with the BMS control; average neointimal area (0.90 ± 0.49) mm(2) vs. (2.16 ± 1.29) mm(2) (P = 0.049), (1.53 ± 0.84) mm(2) vs. (3.41 ± 1.55) mm(2) (P = 0.026), and (2.43 ± 0.95) mm(2) vs. (3.12 ± 1.16) mm(2) (P = 0.228), respectively. High magnification histomorphologic examination revealed similar inflammation scores and endothelialization scores in both the BSES and BMS groups.. The BuMA biodegradable drug-coated sirolimus-eluting stents can significantly reduce neointimal hyperplasia and in-stent restenosis. Re-endothelialization of the BuMA stent is as good as that of the BMS in the porcine coronary model due to the reduced inflammation response to the BuMA stent.

Topics: Absorbable Implants; Animals; Coronary Angiography; Drug-Eluting Stents; Female; Hyperplasia; Neointima; Polymers; Sirolimus; Swine

The aim of this study was to evaluate detailed vessel response after everolimus-eluting stents (EES) implantation in human de novo coronary lesions by optical coherence tomography (OCT).. Between November 2008 and October 2009, 25 patients (14 men, 65.5±8.6 years) with de novo native coronary artery lesions were implanted with 30 EES, and OCT was performed at 8 months post-implantation.. Neointimal thickness (NIT) on each strut, strut apposition to the vessel wall, the frequency of struts surrounded by low intensity area and the incidence of intra-stent thrombus were analysed. To evaluate the radial unevenness of NIT, the difference between the maximum and minimum NIT (dNT) was calculated for each cross-section.. At 236±39 days after implantation, there were no major adverse cardiac events, nor target vessel revascularisation. A total of 5,931 struts was evaluated by OCT. The median NIT was 80 μm (25th and 75th percentile 50 μm and 140 μm) and average NIT was 100±74 μm. The number of neointima-covered struts was 5,834 (98.4%), and 31 (0.52%) struts showed malapposition without neointimal coverage. The number of struts surrounded by low intensity area was 452 (7.62%). Eleven EES (37%) showed full neointimal coverage. No intra-stent thrombus was detected. The average dNT was 108±77 μm.. Most EES struts were covered with uniform and thin neointima. The frequency of low-intensity neointima was very low, which may be a result of promoted vessel healing. These results may support improved clinical outcomes with EES in clinical trials.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Sirolimus; Time Factors; Tomography, Optical Coherence

Zotarolimus-eluting stents (ZES) have a higher rate of neointimal coverage than the first-generation drug-eluting stents on optical coherence tomography (OCT).. To determine whether neointimal coverage of stent struts detected by OCT can be used as a surrogate for endothelial function after ZES implantation.. Cross-sectional observational study.. Three months after ZES implantation.. OCT was performed in 20 patients with a ZES at 3 months after stent implantation to evaluate strut coverage. Endothelium-dependent coronary vasomotion was estimated by infusing incremental doses of acetylcholine into the coronary ostium. The vascular response was measured in the 10 mm segments proximal and distal to the stent.. Of 20 ZES, 15 (75%) were covered completely with neointima, but the remaining 5 ZES had exposed struts. The high-dose acetylcholine infusion produced significant vasoconstriction in the proximal (-9.8±10.1%) and the distal stent segment (-29.7±22.7%). However, the degree of vasoconstriction to acetylcholine varied between individuals (from -0.6% to -77%). Although no relationship was observed between coronary vasomotor response (percentage change in diameter after acetylcholine administration) and average neointimal thickness, the number of cross-sections with uncovered struts showed an inverse correlation with coronary vasomotor response in proximal and distal stent segments (r=-0.57, p=0.007 and r=-0.83, p<0.001, respectively).. The existence of exposed struts was associated with abnormal vasoconstriction to acetylcholine at 3 months after ZES implantation. The findings suggest that complete neointimal coverage of stent struts assessed by OCT could be used as a surrogate for vasomotion impairment at 3 months after ZES implantation.

Topics: Acetylcholine; Aged; Aged, 80 and over; Angina Pectoris; Coronary Vessels; Drug-Eluting Stents; Endothelium, Vascular; Female; Humans; Immunosuppressive Agents; Male; Neointima; Prospective Studies; Sirolimus; Tomography, Optical Coherence; Vasoconstrictor Agents; Vasodilator Agents; Vasomotor System; Wound Healing

Nanoparticles possess several advantages as a carrier system for intracellular delivery of therapeutic agents. Rapamycin is an immunosuppressive agent which also exhibits marked antiproliferative properties. We investigated whether rapamycin-loaded nanoparticles(NPs) can reduce neointima formation in a rat model of vein graft disease.. Poly(lactic-co-glycolic acid) (PLGA) NPs containing rapamycin was prepared using an oil/water solvent evaporation technique. Nanoparticle size and morphology were determined by dynamic light scattering methodology and electron microscopy. In vitro cytotoxicity of blank, rapamycin-loaded PLGA (RPLGA) NPs was studied using MTT Assay. Excised rat jugular vein was treated ex vivo with blank-NPs, or rapamycin-loaded NPs, then interposed back into the carotid artery position using a cuff technique. Grafts were harvested at 21 days and underwent morphometric analysis as well as immunohistochemical analysis.. Rapamycin was efficiently loaded in PLGA nanoparticles with an encapsulation efficiency was 87.6%. The average diameter of NPs was 180.3 nm. The NPs-containing rapamycin at 1 ng/ml significantly inhibited vascular smooth muscular cells proliferation. Measurement of rapamycin levels in vein grafts shown that the concentration of rapamycin in vein grafts at 3 weeks after grafting were 0.9 ± 0.1 μg/g. In grafted veins without treatment intima-media thickness was 300.4 ± 181.5 μm after grafting 21 days. Whereas, Veins treated with rapamycin-loaded NPs showed a reduction of intimal-media thickness of 150.2 ± 62.5 μm (p = 0.001). CD-31 staining was used to measure luminal endothelial coverage in grafts and indicated a high level of endothelialization in 21 days vein grafts with no significant effect of blank or rapamycin-loaded NPs group.. We conclude that sustained-release rapamycin from rapymycin loaded NPs inhibits vein graft thickening without affecting the reendothelialization in rat carotid vein-to-artery interposition grafts and this may be a promising therapy for the treatment of vein graft disease.

Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Endothelium, Vascular; Graft Survival; Hyperplasia; Jugular Veins; Male; Microscopy, Electron, Transmission; Muscle, Smooth, Vascular; Nanoparticles; Neointima; Rats; Rats, Sprague-Dawley; Sirolimus

It has been suggested that sirolimus-eluting stents (SES) provoke a more sustained inflammatory response (IR) in neointimal hyperplasia (NIH). The purpose of this study was to compare morphological vessel characteristics, including post-stent IR in NIH, between patients with SES and bare metal stents (BMS) using optical coherence tomography (OCT).. Thirty-seven patients underwent OCT at their post-stent follow-up. OCT signal-intensity deviation (normalized standard-deviation; OCT-NSD) values in NIH were compared between the 2 groups. In addition, the serum concentration of high-sensitivity C-reactive protein (hs-CRP) was measured. Stent-malapposition rate (1.78% vs. 0.7%; P = 0.016), uncovered stent-strut rate (16% vs. 3.7%; P = 0.0002), peri-stent ulcer like appearance (PSUA; 50% vs. 0%; P = 0.006) were all significantly higher in the SES group than in the BMS group, respectively. The OCT-NSD value was also significantly higher in the SES group than in the BMS group (0.213 ± 0.005 vs. 0.198 ± 0.005; P < 0.001), as was the hs-CRP level (2.54 ± 1.89 vs. 0.64 ± 0.3 mg/L; P = 0.0006). In addition, a significant positive correlation was found between hs-CRP and OCT-NSD (r = 0.471; P = 0.0025).. PSUA-morphology was specific in the SES group, and higher levels of OCT-NSD and hs-CRP after SES implantation suggest sustained IR in NIH compared with following BMS implantation. These different characteristics may be some of the background that promotes thrombus formation as a late-stage post-stent complication of SES.

Topics: Aged; Angioplasty, Balloon, Coronary; Biomarkers; C-Reactive Protein; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Hyperplasia; Inflammation; Male; Metals; Middle Aged; Neointima; Sirolimus; Stents; Tomography, Optical Coherence; Ultrasonography, Interventional

Although very late stent thrombosis occurs several years after implantation of sirolimus-eluting stent (SES), the morphologic changes of the stent beyond 2 years have not yet been systematically studied in living patients. The late vascular response to SES was therefore evaluated by serial angioscopic studies at 2 and 5 years after stent implantation.. A total of 17 patients with 17 SES underwent a repeated angioscopy procedure at 2 and 5 years. Neointimal stent coverage (NSC) was classified as follows: grade 0, presence of uncovered struts; grade 1, visible struts through a thin neointima; or grade 2, complete neointimal coverage without visible struts. For each patient, the minimum and maximum NSC grade and the existence of in-stent thrombus were recorded.. The minimum and maximum NSC grade did not increase between the 2 and 5 years (0.59 ± 0.51 vs 0.88 ± 0.70, P = .17, and 1.82 ± 0.39 vs 1.94 ± 0.24, P = .30, respectively). The prevalence of patients with uncovered struts did not significantly decrease from 2 to 5 years (41% vs 29%, P = .49). During the follow-up period, 3 of 6 thrombi disappeared, whereas new thrombus formation was found in 3 patients without any clinical symptoms. In-stent thrombus did not decrease (35% vs 35%, P > .99).. The current serial angioscopic study suggests that incomplete NSC and the prevalence of latent thrombus within the SES segments did not decrease from 2 to 5 years. The risk of stent thrombosis related to incomplete healing of SES may continue for an extended period.

Topics: Aged; Angioplasty, Balloon, Coronary; Angioscopy; Coronary Angiography; Coronary Artery Disease; Coronary Thrombosis; Coronary Vessels; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Radiography, Interventional; Sirolimus; Stents; Time Factors

Topics: Coronary Artery Disease; Diabetes Complications; Drug-Eluting Stents; Female; Humans; Male; Neointima; Radiography; Sirolimus; Ultrasonography

The safety of sirolimus-eluting stents (SESs) in acute myocardial infarction (AMI) remains controversial. We compared long-term neointimal coverage after stent implantation for AMI evaluated by coronary angioscopy and 3-year clinical events between SESs and bare-metal stents (BMSs). Eighty-seven consecutive patients who received SESs or BMSs for AMI were enrolled. At 8 months after AMI coronary angiography with angioscopy was performed. Using angioscopy we evaluated maximum and minimum grades of neointimal coverage using an angioscopic score (0 to 3). We calculated the heterogeneity score as the maximum grade minus the minimum grade. We compared angioscopic parameters including minimum grade and heterogeneity score of neointimal coverage, thrombi and plaque color, serum parameters, and major adverse cardiac events for 3 years between the 2 groups. The restenosis rate of the SES group (n = 56) was significantly lower than that of the BMS group (n = 31, 9% vs 31%, p = 0.015). The SES group had a lower minimum grade of neointimal coverage and higher heterogeneity score and prevalence of thrombi than the BMS group, but from 8 months to 3 years after stent implantation there were no significant differences in major adverse cardiac events between the 2 groups. In conclusion, a lower minimum grade and greater heterogeneity of neointimal coverage and thrombi were shown for SESs compared to BMSs at 8 months after AMI. However, these findings did not correlate with cardiac events over a period of 3 years in our patients.

Topics: Aged; Angioscopy; Coronary Angiography; Coronary Restenosis; Coronary Thrombosis; Female; Follow-Up Studies; Humans; Male; Myocardial Infarction; Neointima; Sirolimus; Stents

Drug-coated balloons are rapidly emerging as a therapeutic alternative for the interventional treatment of peripheral vascular disease. The purpose of this study was to test the hypothesis that an angioplasty balloon coated with the mTOR inhibitor zotarolimus (ZCB) would inhibit neointimal hyperplasia in a novel injury-based superficial femoral artery model in the familial hypercholesterolemic swine.. A total of 44 familial hypercholesterolemic swine were included (12 designated to study tissue pharmacokinetics and 32 to study safety and efficacy). Fogarty balloon denudation was performed in all superficial femoral artery segments, followed by balloon angioplasty. In the pharmacokinetic study, a total of 24 ZCBs (300 μg/cm(2)) were used. Zotarolimus was detected in arterial tissue at 5 minutes (162 ng/mg of tissue), 24 hours (5.9 ng/mg of tissue), and 28 days (0.007 ng/mg of tissue) after ZCB inflation. In the safety and efficacy study, superficial femoral artery segments were randomized to either high-dose (600 μg/cm(2), n=16), low-dose (300 μg/cm(2), n=16), or paired uncoated balloons (high-dose ZCB control, n=16; low-dose ZCB control, n=16). At 28 days, the percentage of angiographic stenosis was similar among all tested groups. Histological analysis demonstrated a reduction in neointimal formation in both ZCB groups compared with controls (high-dose ZCB 44% reduction, P=0.007; low-dose ZCB 22% reduction, P=0.08). There was no evidence of delayed arterial healing or vascular toxicity in any of the ZCB groups.. The single delivery of zotarolimus via coated balloon is feasible, and therapeutic levels are maintained up to 28 days. The ZCB technology appears to be effective in the reduction of neointimal proliferation in the superficial femoral artery of the familial hypercholesterolemic swine.

Topics: Angioplasty, Balloon; Animals; Catheterization; Clinical Protocols; Femoral Artery; Humans; Hyperlipoproteinemia Type II; Infusion Pumps, Implantable; Models, Animal; Neointima; Postoperative Complications; Radiography; Sirolimus; Swine; TOR Serine-Threonine Kinases

We hypothesized that (1) neointima formation in a rat carotid balloon injury model could be reduced in vivo following targeted ultrasound delivery of rapamycin microbubbles (RMBs), and (2) the addition of dual-mode ultrasound decreases the total amount of drug needed to reduce neointima formation.. Balloon injury was performed in rat carotids to induce neointima formation. High or low doses of RMBs were injected intravenously and ruptured at the site of injury with ultrasound. Compared with nontreated injured arteries, neointima formation was reduced by 0% and 35.9% with 10(8) RMBs and by 28.7% and 34.9% in arteries treated with 10(9) RMBs with and without ultrasound, respectively.. Without ultrasound, 10-fold higher concentrations of RMBs were needed to reduce neointima formation by at least 28%, whereas 10(8) RMBs combined with ultrasound were sufficient to achieve the same therapeutic effect, demonstrating that this technology may have promise for localized potent drug therapy.

Topics: Animals; Carotid Arteries; Carotid Artery Injuries; Catheterization; Cell Division; Dose-Response Relationship, Drug; Drug Delivery Systems; Microbubbles; Models, Animal; Neointima; Rats; Rats, Sprague-Dawley; Sirolimus; Ultrasonics

Although the use of drug-eluting stents (DES) has been shown to limit neointimal hyperplasia in clinical coronary artery disease treatment, currently available DES may adversely affect re-endothelialization (RE) and thus increase fateful stent thrombosis. As stromal cell derived factor 1a (SDF-1a) plays an essential role in the regulation of endothelial progenitor cells (EPCs) mobilization, homing, and differentiation in response to vascular injury, we assumed that SDF-1a may enhance EPCs adhesion and attenuate delayed RE associated with DES.. Biologically active recombinant human SDF-1a (rhSDF-1a) was first produced using an Escherichia coli expression system. Twenty-four male rabbits were then underwent sirolimus-eluting stents implantation in aorta abdominalis. After operation, they were randomly divided into two groups and subcutaneously injected daily with 50 μg/kg rhSDF-1a or the same volume of saline for 7 days.. With the application of scanning electron microscopy (SEM) and histological analysis, we found that rhSDF-1a significantly promoted RE on days 7, 14, 28 and inhibited neointimal hyperplasia on day 28 after stent implantation.. Our results revealed a potential role of rhSDF-1a in facilitating RE and inhibiting neointimal proliferation after DES implantation, leading to a conclusion that this protein may be a potential candidate agent for the treatment of in-stent restenosis and stent thrombosis.

Topics: Animals; Aorta, Abdominal; Chemokine CXCL12; Drug-Eluting Stents; Endothelium, Vascular; Humans; Hyperplasia; Male; Microscopy, Electron, Scanning; Neointima; Rabbits; Recombinant Proteins; Sirolimus; Time Factors

Topics: Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Immunosuppressive Agents; Male; Neointima; Sirolimus

Late vascular responses after implantation of drug-eluting stents may play a key role in steadily increasing occurrence of very late stent thrombosis have not yet been fully investigated in human beings.. Serial optical coherence tomography observations at 2 and 4 years were collected for 17 patients treated with 21 sirolimus-eluting stents. Corresponding 376 cross sections within single-stent segments at intervals of 1 mm were selected for analyses, and neointimal thickness on each strut was measured. Extrastent lumen (ESL) was defined as an external lumen of the stent. Area and angle of ESL were measured. A total of 3369 and 3221 struts were identified at 2 and 4 years, respectively. From 2 to 4 years, mean neointimal thickness increased (76.8±75.6 μm versus 123.0±102.5 μm; P<0.0001), whereas frequency of patients with uncovered struts decreased (88% versus 29%; P=0.002). Although prevalence of patients that had ESL was similar (59% of 2 years versus 65% of 4 years; P=1.0), the cross sections with ESL increased (9.6% versus 15.2%; P=0.02). Moreover, area and angle of ESL increased from 2 to 4 years (0.28±0.27 mm(2) versus 0.62±0.68 mm(2) and 16.6±5.4° versus 65.1±38.4°; P<0.01, respectively). The incidence of subclinical thrombus did not decrease (24% at 2 years versus 29% at 4 years; P=1.0). All thrombi were identified in patients who had cross sections with ESL.. The current serial optical coherence tomography study showed an augmentation of neointimal growth at the late phase of sirolimus-eluting stent implantation. ESL may contribute to thrombus formation and ESL of sirolimus-eluting stents expanded from 2 to 4 years.

Topics: Aged; Blood Vessel Prosthesis Implantation; Coronary Angiography; Coronary Vessels; Drug-Eluting Stents; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Myocardial Ischemia; Neointima; Prevalence; Sirolimus; Thrombosis; Time Factors; Tomography, Optical Coherence

Poly lactic-co-glycolic acid nanoparticles (PLGA-NP) are widely used as a biodegradable biomaterial in medicine. Rapamycin-eluting stents have been used for prevention of restenosis during surgery. This study investigated the effect of pretreatment with intraluminal perfusion of carbopol-encapsulated rapamycin-loaded PLGA nanoparticles (RAP-PLGA-NP) on neointimal hyperplasia in a rabbit vein graft model.. A segment of common carotid artery was replaced with a segment of external jugular vein in 60 rabbits which were then separated into four treatment groups, ie, Group 1, in which vein grafts were pretreated with intraluminal RAP-PLGA-NP perfusion, Group 2 in which vein grafts underwent equivalent empty vehicle (PLGA-NP) perfusion, Group 3, in which vein grafts received no treatment, and Group 4, which served as a sham operation group receiving normal vein contrast. On postoperative day 28, the grafts and normal veins were harvested for histologic examination, flow cytometry analysis, and high-performance liquid chromatography measurement.. Compared with Group 1, the intima of the grafts were thickened, the ratio of intimal area to vessel area increased, and the collagen volume index of the vein grafts increased significantly in Groups 2 and 3. The cell proliferation index in Group 1 (21.11 ± 3.15%) was much lower than that in Group 2 (30.35 ± 2.69%) and in Group 3 (33.86 ± 8.72%). By high-performance liquid chromatography measurement, retention of rapamycin was detected in Group 1 (11.2 ± 0.37 μg/10 mg) 28 days after single drug perfusion.. Pretreatment with intraluminal RAP-PLGA-NP perfusion may inhibit neointimal hyperplasia in vein grafts by penetrating into local tissue and limiting cell proliferation.

Topics: Animals; Graft Occlusion, Vascular; In Vitro Techniques; Jugular Veins; Lactic Acid; Models, Animal; Nanomedicine; Nanoparticles; Neointima; Perfusion; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rabbits; Sirolimus; Transplantation, Autologous

Neointimal proliferation after sirolimus-eluting stent (SES) implantation is generally inhibited by the pharmacological effects of sirolimus in comparison to bare metal stent (BMS). Neointimal hyperplasia after BMS implantation is mainly composed of vascular smooth muscle cells, and is usually observed as a white mass by angioscopy and as a layer of uniform signal intensity without attenuation on optical coherence tomography (OCT). In this case, angioscopic color of the neointima covering the SES was obviously yellow and OCT signal patterns of the neointima showed rapid attenuation similar to lipid tissues in atherosclerotic lesions. These findings suggest that neointima within the SES is quite different from that of the BMS and may contain atherosclerotic components.

Topics: Angioscopy; Coronary Vessels; Drug-Eluting Stents; Humans; Male; Middle Aged; Neointima; Sirolimus; Tomography, Optical Coherence

Coronary angioscopy is a useful tool for understanding plaque characteristics through the plaque color and surface thrombus formation. We experienced an interesting case of a newly developed yellow neointima 400 days after a sirolimus-eluting stent implantation. A 72-year-old woman suffering from angina pectoris was admitted to our hospital. Coronary angiography revealed severe stenosis at the proximal left descending artery and she was implanted with a sirolimus-eluting stent. Coronary angioscopic observation immediately after stent implantation revealed the presence of yellow plaque only at the most severe stenosis lesion in the stent placement site. We performed a coronary angiography 400 days after the sirolimus-eluting stent implantation and did not find an in-stent restenosis. An intravascular ultrasound indicated minimum neointimal formation. By coronary angioscopy, we could clearly observe that the neointima had covered the surface of the stent struts; the stent struts were barely visible under the neointima. Surprisingly, neointima formed in response to the sirolimus-eluting stent was entirely yellow. Precise mechanisms of producing yellow neointima was unknown, we may observe a pathologic neointima induced by sirolimus-eluting stent.

Topics: Aged; Angioscopy; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Neointima; Sirolimus