Implantation In Coronary Arteries Research Articles

Efficacy of intravascular lithotripsy (IVL) in coronary stenosis with severe calcification: A multicenter systematic review and meta-analysis.

With heavily calcified coronary and peripheral artery lesions, lesion preparation is crucial before stent placement to avoid underexpansion, associated with stent thrombosis or restenosis and patency failure in the long-term. Intravascular lithotripsy (IVL) technology disrupts superficial and deep calcium by using localized pulsative sonic pressure waves, making it to a promising tool for patients with severe calcification in coronary bed. The aim of the study is to systematically review and summarize available data regarding the safety and efficacy of IVL for lesion preparation in severely calcified coronary arteries before stenting. This study was conducted according to the PRISMA guidelines. We systematically searched PubMed, SCOPUS, and Cochrane databases from their inception to February 23, 2023, for studies assessing the characteristics and outcomes of patients undergoing IVL before stent implantation. The diameter of the vessel lumen before and after IVL, as well as stent implantation, were analyzed. The occurrence of major adverse cardiovascular events (MACE) was assessed using a random-effects model. This meta-analysis comprised 38 studies including 2977 patients with heavily calcified coronary lesions. The mean age was 72.2 ± 9.1 years, with an overall IVL clinical success of 93% (95% confidence interval [CI]: 91%-95%, I2 = 0%) and procedural success rate of 97% (95% CI: 95%-98%, I2 = 73.7%), while the in-hospital and 30-days incidence of MACE, myocardial infarction (MI), and death were 8% (95% CI: 6%-11%, I2 = 84.5%), 5% (95% CI: 2%-8%, I2 = 85.6%), and 2% (95% CI: 1%-3%, I2 = 69.3%), respectively. There was a significant increase in the vessel diameter (standardized mean difference [SMD]: 2.47, 95% CI: 1.77-3.17, I2 = 96%)and a decrease in diameter stenosis (SMD: -3.44, 95% CI: -4.36 to -2.52, I2 = 97.5%) immediately after IVL application, while it was observed further reduction in diameter stenosis (SMD: -6.57, 95% CI: -7.43 to -5.72, I2 = 95.8%) and increase in the vessel diameter (SMD: 4.37, 95% CI: 3.63-5.12, I2 = 96.7%) and the calculated lumen area (SMD: 3.23, 95% CI: 2.10-4.37, I2 = 98%), after stent implantation. The mean acute luminal gain following IVL and stent implantation was estimated to be 1.27 ± 0.6and 1.94 ± 1.1 mm, respectively. Periprocedural complications were rare, with just a few cases of perforations, dissection, or no-reflow phenomena recorded. IVL seems to be a safe and effective strategy for lesion preparation in severely calcified lesions before stent implantation in coronary arteries. Future prospective studies are now warranted to compare IVL to other lesion preparation strategies.

Efficacy of intravascular lithotripsy (IVL) in coronary stenosis with severe calcification: a systematic review and meta-analysis of 38 studies

Abstract Introduction Heavily calcified coronary lesions impede appropriate stent deployment and expansion, increasing the risk of complications. Intravascular Lithotripsy (IVL) technology disrupts subendothelial calcification by using localized pulsative sonic pressure waves and is a promising technique for patients with severe coronary calcification. Purpose Our aim was to systematically review and summarize available data regarding the safety and efficacy of IVL in preparing severely calcified plaques in coronary before stenting. Methods This study was conducted according to the PRISMA guidelines. We systematically searched PubMed, SCOPUS, and Cochrane databases from their inception to February 23, 2023, for studies assessing the characteristics and outcomes of patients undergoing IVL before stent implantation. The diameter of the vessel lumen before and after IVL as well as stent implantation were analyzed. The occurrence of peri-procedural complications and major adverse cardiovascular events (MACE) in a 30-day period were assessed using a random-effects model. Results This meta-analysis comprised 38 studies including 2,977 patients with heavily calcified coronary lesions. The mean age was 72.2 ± 9.1 years, with an overall IVL procedural success rate of 98% (95% CI: 96%-99%, I2=69.2%) and clinical success of 96% (95% CI: 93%-98%, I2=72.2%), while the in-hospital and 30-days incidence of MACE, myocardial infarction (MI) and death were 8% (95% CI: 6%-11%, I2=84.5%), 5% (95% CI: 2%-8%, I2=85.6%) and 2% (95% CI: 1%-3%, I2=69.3%), respectively. There was a significant increase in the vessel diameter (SMD: 2.47, 95% CI: 1.77-3.17, I2=96%) and a decrease in diameter stenosis (SMD: -3.44, 95% CI: -4.36 to -2.52, I2=97.5%) immediately after IVL application, while it was observed further reduction in diameter stenosis (SMD: -6.57, 95% CI: -7.43 to -5.72, I2=95.8%) and increase in the vessel diameter (SMD: 4.37, 95% CI: 3.63-5.12, I2=96.7%) and the calculated lumen area (SMD: 3.23, 95% CI: 2.10-4.37, I2=98%), after stent implantation. The mean acute luminal gain following IVL and stent implantation was estimated to be 1.27 ± 0.6 mm and 1.94 ± 1.1 mm, respectively. Peri-procedural complications were rare, with just a few cases of perforations, dissection, or no-reflow phenomena recorded. Conclusions The present meta-analysis shows that IVL constitutes an effective and safe technique for preparing severely calcified lesions before stent implantation in coronary arteries. These results support the use of IVL in the high procedural risk setting of severe coronary calcification.

Formation of Calcified Nodule as a Cause of Early In-Stent Restenosis in Patients Undergoing Dialysis.

BackgroundDialysis is an independent risk factor for in‐stent restenosis (ISR) after stent implantation in coronary arteries. However, the characteristics of ISR in patients undergoing dialysis remain unclear, as there are no histological studies evaluating the causes of this condition. The aim of the present study was to investigate the causes of ISR between patients who are undergoing dialysis and those who are not by evaluating tissues obtained from ISR lesions using directional coronary atherectomy.Methods and ResultsA total of 29 ISR lesions from 29 patients included in a multicenter directional coronary atherectomy registry of 128 patients were selected for analysis and divided into a dialysis group (n=8) and a nondialysis group (n=21). Histopathological evaluation demonstrated that an in‐stent calcified nodule was a major histological characteristic of ISR lesions in the dialysis group and the prevalence of an in‐stent calcified nodule was significantly higher in the dialysis group compared with the nondialysis group (75% versus 5%, respectively; P<0.01). On the other hand, the prevalence of an in‐stent lipid‐rich plaque was significantly lower in the dialysis group compared with the nondialysis group (0% versus 43%, respectively; P=0.03). In all cases with an in‐stent calcified nodule, the underlying calcification before stent implantation was moderate to severe. When tissue characteristics were stratified according to duration post–stent implantation, an in‐stent calcified nodule in the dialysis group was mainly observed within 1 year after stent implantation.ConclusionsIn‐stent calcified nodules are a common cause of ISR in patients undergoing dialysis and are observed within 1 year after stent implantation, suggesting different causes of ISR between patients undergoing dialysis and those who are not.

Reduced histologic neo in-stent restenosis after use of a paclitaxel-coated cutting balloon in porcine coronary arteries.

The incidence of in-stent restenosis (ISR) has declined dramatically, but once it develops, no current treatment option, such as drug-eluting stents, drug-coated balloons, or cutting balloons (CBs), prevents re-narrowing of the stented atherosclerotic artery. In this preclinical study, we aimed to improve the efficacy of ISR treatment by coating CBs with paclitaxel (paclitaxel-eluting cutting balloon; PECB) and to characterize the histological features of neo-ISRs that arise after ISR treatment. ISR was induced by bare metal stent (BMS) implantation in coronary arteries in pigs. After one month of follow-up, the BMS-induced ISR was treated with either CB or PECB. After another month, we performed quantitative coronary angiography, explanted the treated arteries and assessed histopathological and histomorphometric parameters. In addition, we compared the histological features of neo-ISRs with pre-treatment ISRs. Injury, inflammation, fibrin deposition, and endothelialization scores were similar between the CB and PECB groups at one month after ISR treatment. Neointimal area (0.87±0.61 vs. 1.95±1.14 mm², p=0.02), mean neointimal thickness (0.40±0.39 vs. 0.99±0.56 mm, p=0.01), and percent area stenosis (27.3±20.4 vs. 48.3±22.9%, p=0.04) were decreased in PECB-treated coronary arteries compared to CB-treated arteries, respectively. Density of cells (predominantly smooth muscle cells; SMCs) was increased in neo-ISRs (3.51±3.05×10³ vs. 6.35±2.57×10³ cells/mm², p<0.01), but significantly more CD68⁺ and CD20⁺ cells were found in the pre-treatment ISRs. In conclusion, PECB treatment of ISRs led to better results in terms of smaller neointimal area and %area stenosis of the neo-ISR. SMC density was increased in neo-ISRs in contrast with higher percentage of CD68⁺ and CD20⁺ cells in pre-treatment ISRs.

P4143IL-6 production in the vascular adventitia and adventitia-media-crosstalk in neointima formation

Abstract Background The aim of this study was to analyze the impact of the adventitial layer on vascular remodeling processes and to define the underlying cellular mechanisms. Methods and results Morphometric analysis of human coronary arteries and of murine femoral arteries at several times following vascular intervention revealed a significant correlation of neointimal and adventitial thickening (R2=0.6845, P&lt;0.001 for human samples; R2=0.6845, P&lt;0.001 for human samples. Immunohistochemical staining for the proliferation marker Ki-67 was performed 7, 14, and 21 days following injury of the murine femoral artery. Formation of a neointimal lesion at 21 days was preceded by high adventitial proliferation rates at 7 and 14 days (85.00±6.041 Ki67+adventitial cells vs. 5.118±0.633 Ki-67+neointimal cells at 7d, P&lt;0.0014; 28.80±5.240 Ki-67+adv. cells vs. 19.40±2.468 Ki-67+neoint. cells at 14d, P&lt;0.006, n=17). Complete removal of the adventitial layer prevented neointima formation, attributing pivotal importance to the adventitial layer (luminal stenosis: 71.73±3.77% vs. 7.44±1.71%, n=5, P&lt;0.0001). Re-transplantation of the aortic adventitia of ubiquitously GFP expressing C57BL/6-Tg (CAG-EGFP)1Osb/Jmice around the medial vascular layer of the femoral artery where the native adventitia has been removed completely restored neointima formation. Importantly, only very view GFP+cells were present in the neointimal layer, indicating that a direct contribution of adventitial cells to the neointimal lesion represents an extremely rare event. To investigate a potential paracrine effect of the activated adventitial layer, we explanted adventitial transplants 14 days following injury and transplantation and incubated the respective samples in serum-free media for 24 hours. BrdU incorporation assays and scratch wound assays revealed significantly increased proliferation and migration rates of human coronary artery SMCs in response to the supernatant of adventitial transplants compared to the supernatant of control samples. Further secretome analyses of the same adventitial supernatants identified predominantly interleukin (IL)-6 to trigger SMC proliferation and migration. Accordingly, serum-free media incubated with adventitial grafts of IL-6−/− mice prevented SMC proliferation and migration. Transplantation of the adventitia of IL-6−/− mice into C57BL/6J wild type mice was not sufficient to trigger neointima formation. Plain old balloon angioplasty, bare metal stent implantation, or drug-eluting stent implantation in swine coronary arteries and analysis for Ki-67+ cell counts supported the hypothesis in the large animal model and a more clinical setting. Conclusion Acute vascular injury is followed by an expansion of cytokine-producing adventitial cells, whose paracrine function and especially whose release of IL-6 is essential for the subsequent induction of the proliferation and migration of local SMC and thus for neointima formation.

In vivo and in vitro analyses of the effects of a novel high-nitrogen low-nickel coronary stent on reducing in-stent restenosis.

Currently, percutaneous coronary intervention is an important treatment for coronary heart disease. However, the in-stent restenosis rate is still approximately 10-30% after stenting. Nickel ions from the stent are considered to be associated with in-stent restenosis. Therefore, in the present study, we quantitatively evaluated in-stent restenosis after implanting the novel high-nitrogen low-nickel coronary stent (HNS) and studied the mechanism underlying the reduction in in-stent restenosis by using ELISA and Western blot. The in vivo results showed that the HNS could significantly reduce neointima formation and inflammation as compared to SUS316L stents (316L) at 180 days after implantation in porcine coronary arteries and that vascular endothelial growth factor-A expression in porcine coronary arteries after HNS implantation also decreased. The in vitro results showed that, in the case of the HNS, human umbilical vein endothelial cell (HUVEC) proliferation was lower and lesser IL-6 release was noted from HUVECs at one and three days after culture than in the 316L group. Furthermore, p-STAT3 expression in HUVECs on the HNS surface was downregulated after culture for seven days. Thus, we conclude that the HNS could be a promising alternative coronary stent for percutaneous coronary intervention.

Initial pathological responses of second-generation everolimus-eluting stents implantation in Japanese coronary arteries: Comparison with first-generation sirolimus-eluting stents

BackgroundThe 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. MethodsUsing 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). ResultsThe ratio of covered struts and mean fibrin area of 2nd DES were 0.69±0.05 and 658.0±173.4μm2. Those of 1st DES were 0.44±0.12 and 3107.5±1405.9μm2. In the 2nd DES, there was significantly less fibrin deposition and a higher covered struts ratio. The inflammation score was significantly lower in 2nd DESs compared to 1st DESs (1.02±0.16 vs. 1.19±0.54, p<0.05). ConclusionsHistopathological 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.

Bioresorbable vascular scaffolds for small vessels coronary disease: The BVS-save registry.

In this study, we investigated long-term results following bioresorbable vascular scaffold (BVS) implantation in small coronary arteries. Management of small coronary vessel disease with percutaneous coronary interventions (PCI) is often associated with high recurrencies and an increased risk of late or very late adverse events. Currently, little is known about BVS behavior in this setting. A retrospective cohort analysis in a consecutive all-comer population was performed in patients that had a BVS implanted for coronary artery disease (CAD) in vessels with reference diameter <2.75 mm. Primary end-point was the occurrence of BVS failure (any event between target lesion revascularization (TLR) and definite/probable thrombosis) at the longest available follow-up. Secondary end-points were device-oriented clinical outcome (DOCE, a composite of cardiac death, target-vessel non-fatal myocardial infarction (MI) and TLR) and its single components at 12-month follow-up. A total of 121 patients (133 lesions) were treated between March 2013 and December 2014 at three high volume Italian centers. From baseline clinical and angiographic characteristics emerges a highly complex patient population. Procedural success was obtained in 120 (99.2%) patients. In-hospital events included one cardiac death. At the longest available clinical follow-up (average 12 ± 6, median 11.4 months, interquartile ranges (IQR) 8, primary end-point occurred in 12 patients (9.0%), including 12 (9.0%) TLR and 2 (1.5%) BVS thrombosis. DOCE occurred in 9.0% of cases. The use of overlapping BVS in this setting did not increase the risk of adverse events. BVS implantation in a highly complex clinical and angiographic setting of small coronary vessels was technically feasible and effective in maintaining vessel patency after 12 months. © 2016 Wiley Periodicals, Inc.

TCT-63 One Year Results Of The REMEDEE Registry: Clinical Outcomes After Deployment Of The Abluminal Sirolimus Coated Bio-Engineerd Stent In A Multicenter, Prospective Post Market Registry

Drug-eluting stents (DES) reduce angiographic restenosis and enhance event-free survival compared with bare-metal stents after implantation in coronary arteries. Limitations of current DES remain stent thrombosis and neo-atherosclerosis related to impaired healing, and repeat revascularization due

Long-term clinical efficacy and safety of adding cilostazol to dual antiplatelet therapy after drug-eluting stent implantation in coronary arteries: A meta-analysis of randomized controlled trials

ObjectiveTo assess the long-term clinical efficacy and safety of adding cilostazol (TAT) to conventional dual antiplatelet therapy (DAT) for patients undergoing drug-eluting stent (DES) implantation in coronary arteries. MethodsWe performed PUBMED, MEDLINE, EMBASE, and Cochrane CENTRAL searches for randomized clinical trials of TAT versus DAT in patients after DES implantation with criteria to include trials with a follow-up of more than 6months. ResultsSeven RCTs with a total of 3487 patients were included in this review. The meta-analysis showed that TAT was associated with a significant reduction in major adverse cardiac events (MACEs) (relative risk (RR)=0.66; 95% CI=0.50–0.88), target lesion revascularization (TLR) (RR=0.61, 95% CI=0.43–0.84), target vessel revascularization (TVR) (RR=0.53, 95% CI=0.37–0.75), in-stent restenosis (RR=0.64, 95% CI=0.44–0.85), in-segment restenosis (RR=0.58, 95% CI=0.43–0.79, P<.01), in-stent late loss (LL) (standardized mean difference (SMD)=−0.21, 95% CI=0.32–0.17), and in-segment LL (SMD=−0.27, 95% CI=−0.38–0.16). TAT also did not appear to significantly alter any of the other meta-analysis secondary efficacy outcomes and had similar rates of bleeding, but TAT had significantly higher rates of rash, gastrointestinal side-effects, headache and drug discontinuation. ConclusionsCompared with standard DAT, the long-term use of TAT in patients after DES implantation gave more benefits in reducing the incidence of MACEs, TLR, TVR, in-stent and in-segment LL and restenosis without increasing bleeding but was associated with an increase in minor adverse events.

Preclinical Study of a Biodegradable Polymer-based Stent with Abluminal Sirolimus Release

BackgroundBioabsorbable polymer stents with drug elution only on the abluminal surface may be safer than durable polymer drug-eluting stents.ObjectiveTo report the experimental findings with the InspironTM stent - a bioabsorbable polymer-coated stent with sirolimus release from the abluminal surface only, recently approved for clinical use.Methods45 stents were implanted in the coronary arteries of 15 pigs. On day 28 after implantation, angiographic, intracoronary ultrasonographic and histomorphological data were collected. Five groups were analyzed: Group I (nine bare-metal stents); Group II (nine coated with bioabsorbable polymer on the luminal and abluminal surfaces); Group III (eight stents coated with bioabsorbable polymer on the abluminal surface); Group IV (nine stents with bioabsorbable polymer and sirolimus on the luminal and abluminal surfaces); and Group V (ten stents with bioabsorbable polymer and sirolimus only on the abluminal surface).ResultsThe following results were observed for Groups I, II, III, IV and V, respectively: percentage stenosis of 29 ± 20; 36 ± 14; 33 ± 19; 22 ± 13 and 26 ± 15 (p = 0.443); late lumen loss (in mm) of 1.02 ± 0.60; 1.24 ± 0.48; 1.11 ± 0.54; 0.72 ± 0.44 and 0.78 ± 0.39 (p = 0.253); neointimal area (in mm2) of 2.60 ± 1.99; 2.74 ± 1.51; 2.74 ± 1.30; 1.30 ± 1.14 and 0.97 ± 0.84 (p = 0.001; Groups IV and V versus Groups I, II and III); and percentage neointimal area of 35 ± 25; 38 ± 18; 39 ± 19; 19 ± 18 and 15 ± 12 (p = 0.001; Groups IV and V versus Groups I, II and III). Injury and inflammation scores were low and with no differences between the groups.ConclusionThe InspironTM stent proved to be safe and was able to significantly inhibit the neointimal hyperplasia observed on day 28 after implantation in porcine coronary arteries.

Nickel-free stainless steel avoids neointima formation following coronary stent implantation

SUS316L stainless steel and cobalt–chromium and platinum–chromium alloys are widely used platforms for coronary stents. These alloys also contain nickel (Ni), which reportedly induces allergic reactions in some subjects and is known to have various cellular effects. The effects of Ni on neointima formation after stent implantation remain unknown, however. We developed coronary stents made of Ni-free high-nitrogen austenitic stainless steel prepared using a N2-gas pressurized electroslag remelting (P-ESR) process. Neointima formation and inflammatory responses following stent implantation in porcine coronary arteries were then compared between the Ni-free and SUS316L stainless steel stents. We found significantly less neointima formation and inflammation in arteries implanted with Ni-free stents, as compared to SUS316L stents. Notably, Ni2+ was eluted into the medium from SUS316L but not from Ni-free stainless steel. Mechanistically, Ni2+ increased levels of hypoxia inducible factor protein-1α (HIF-1α) and its target genes in cultured smooth muscle cells. HIF-1α and their target gene levels were also increased in the vascular wall at SUS316L stent sites but not at Ni-free stent sites. The Ni-free stainless steel coronary stent reduces neointima formation, in part by avoiding activation of inflammatory processes via the Ni-HIF pathway. The Ni-free-stainless steel stent is a promising new coronary stent platform.

Characteristics of patients and types of lesions in patients with drug-eluting or bare-metal stent implantation in small coronary arteries: From the FU-Registry

Although the use of drug-eluting stents (DES) has reduced the rate of restenosis, some problems remain regarding the usefulness of DES in small coronary arteries in addition to late thrombosis and a longer duration of dual-antiplatelet therapy. We considered 335 patients with 698 lesions who underwent DES or bare-metal stent (BMS) implantation, and randomly selected 172 DES and 124 BMS lesions that had undergone a complete data analysis and evaluation. Patients had a history of stable angina with at least 1 lesion with 50% diameter stenosis in a vessel and with a successfully minimum stent implantation (stent diameter=2.5mm). The baseline characteristics including the clinical presentation and cardiovascular risk factors were similar between the DES and BMS groups, except for the percentage of dyslipidemia (DL). Pre-procedure reference vessel diameter (RVD pre) in the DES group was significantly smaller than that in the BMS group (p<0.01), and stent length in the DES group was significantly longer (p<0.01). There was no significant difference in the cumulative incidence of major adverse cardiac events including the target lesion revascularization rate, whereas in-stent restenosis (ISR) in the DES group was significantly lower than that in the BMS group. In a multivariate analysis of ISR, diabetes mellitus, prior percutaneous coronary intervention, and DES use in clinical background were identified as independent predictors of ISR. In addition, RVD pre, stent length, and DES use in angiographical background were also identified. In conclusion, DES use is an independent predictor of ISR, although the DES group included more severely diseased small coronary arteries.

Angiographic and histological results following implantation of a novel stent-on-a-wire in the animal model

The Svelte Stent-On-A-Wire (SOAW) is a thin strut novel device consisting of a balloon-expandable cobalt-chromium stent premounted onto a single lumen fixed-wire delivery catheter platform. We evaluated the performance of the novel Svelte SOAW in comparison with the MultiLink Vision (ML Vision) balloon-expandable stent, in porcine coronary arteries. Eight Yorkshire swine (30-day follow-up cohort) and eight Yucatan mini-swine (90-day follow-up cohort) were implanted with either Svelte or control ML Vision. Acute performance characteristics were graded by interventionalists during implantation. Angiographic assessments were performed at the index procedure and at 30 or at 90 days post implantation. Scanning electron microscopy (SEM), histological and histomorphometric analysis of stented segments were performed after angiographic follow-up. Acute implantation performance was similar between the two stents; however, deflation time was significantly lower in the Svelte stent group (Svelte 4.70±0.93 s vs. ML Vision 9.56±0.96 s, p <0.05). Angiographic late loss was similar for both stents at 30 (Svelte 0.83±0.59 mm vs. ML Vision 0.88±0.71 mm, p=0.969) and at 90 days (Svelte 0.76±0.35 mm vs. ML Vision 0.83±0.35 mm, p=0.679). SEM analysis showed complete endothelialisation at 30 days in both stent types. Histopathological assessment demonstrated minimal injury and inflammation at 30 and 90 days with Svelte and ML Vision stents as well as similar endothelialisation, neointimal maturation, adventitial fibrosis and neointimal fibrin. No evidence of in-stent thrombus was reported in either stent group. Histomorphometric analysis showed no differences between the two groups in lumen, stent, media or neointimal areas at either 30 or 90 days post implantation. At 30 and 90 days after implantation in porcine coronary arteries, the Svelte Stent-On- A-Wire showed vascular healing and tissue response equivalent to that observed with ML Vision stent.

Inhibition of neointimal proliferation after bare metal stent implantation with low-pressure drug delivery using a paclitaxel-coated balloon in porcine coronary arteries

A variety of mechanical and laser-based methods remove or shift atherosclerotic plaques and reopen the artery to its original lumen. Subsequent treatment with drug-coated balloons (DCB) may smooth the vessel wall but does not require high-pressure inflation. We investigated the efficacy of paclitaxel-coated balloons inflated with only 2atm after bare metal stent implantation in coronary arteries of 24 pigs. Angiography and histomorphometry was performed on day 28. DCB inflated with 2atm caused similar reduction of late lumen loss (LLL) as high-pressure inflation with 12atm (0.89±0.58 vs. 0.72±0.39mm, p=0.34). Both DCB treatments significantly (p<0.01) reduced LLL versus uncoated balloons (1.50±0.51mm). Treatment with low-pressure DCB resulted in less maximal intimal thickness (0.45±0.15 vs. 0.67±0.25mm) and neointimal area (2.93±0.73 vs. 3.82±1.27mm(2)) than treatment with uncoated balloons (p<0.05). In conclusion, low-pressure treatment with DCB was similarly effective as high-pressure treatment justifying clinical trials in vessels which will benefit from inhibition of neointimal proliferation but may not tolerate high inflation pressure.

Comparative vascular responses three months after paclitaxel and everolimus-eluting stent implantation in streptozotocin-induced diabetic porcine coronary arteries

BackgroundDiabetes 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.MethodTwelve 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.ResultsAfter 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.ConclusionAfter 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.

TCT-458: Which Genes of the Nitric Oxide Pathway Contribute to Vascular Dysfunction Following DES Implantation in Swine Coronary Arteries?

TCT-458: Which Genes of the Nitric Oxide Pathway Contribute to Vascular Dysfunction Following DES Implantation in Swine Coronary Arteries?

Expression and function of calcium-activated potassium channels following in-stent restenosis in a porcine coronary artery model

In-stent restenosis (ISR) occurs due to proliferation and migration of smooth muscle cells from media to intima resulting in re-narrowing of the vessel lumen. This study aims to investigate changes in the three main KCa channels in response to stent implantation in porcine coronary arteries as their expression and function in ISR is yet to be defined. Twenty-eight days after stent implantation, immunofluorescent labelling with anti-desmin and anti-vWF confirm the presence of both endothelial and smooth muscle cells within the neointimal layer. Using real-time PCR, significant increase in the SK3 and IKCa and BKCa channel mRNA was observed within this layer alone. Western blot analysis confirms the expression of KCa channels in neointima. Although expression of BKCa was increased in the neointima in comparison with medial region of the artery, microelectrode recordings showed that the function of this channel was unchanged. However, the presence of functional BKCa in both medial and intimal cells suggests that smooth muscle cells migration may contribute to neointimal hyperplasia.Functional analysis using 1-EBIO and Bradykinin produced hyperpolarization of neointimal but not medial myocytes, which indicated the expression of functional endothelial SK3 and IKCa in the former and not in the latter. The expression of IKCa and SK3 within the neointimal layer suggested that some degree of recovery of both endothelial as well as smooth muscle regeneration had occurred. Future development of selective modulators of IKCa and SK3 channels may decrease the progression of ISR and improve coronary vascular function after stent placement, and is an area for future investigation.

The genous™ endothelial progenitor cell capture stent accelerates stent re‐endothelialization but does not affect intimal hyperplasia in porcine coronary arteries

To study the effect of endothelial progenitor cell (EPC) capture on the vascular response to coronary stenting. The introduction of drug-eluting stents has reduced the need for target lesion revascularization, but their effect on delayed healing, inflammation, and vascular dysfunction has emphasized the need to design strategies that improve current DES. One such strategy is to improve endothelialization by capturing CD34-positive cells (EPC) by the stent surface. The first human clinical trial using coronary EPC capture stents showed stent safety but neointimal thickness (NIT) was not reduced compared to bare metal stents (BMS). To understand these responses we studied the coronary response to the EPC capture stent in swine. The stent, coated with murine antihuman monoclonal CD34 antibodies, was assessed with QCA guided stent implantation in normal swine coronary arteries for early endothelialization at 2 and 5 days, and NIT at 28 and 90 days in comparison to control stents carrying a non-specific murine antibody or to BMS. The main finding was that while the EPC capture stent significantly improved early endothelialization it did not reduce NIT at 28 and 90 days. The EPC capture stent improves early endothelialization in swine but this does not affect neointimal thickness as compared to control stents at 28 and 90 days.

Avaliação pela tomografia de coerência óptica de stent nacional recoberto com polímero biodegradável eluidor de sirolimus vs. stent eluidor de biolimus A9 em artérias coronárias porcinas

INTRODUÇÃO: Está em desenvolvimento em nosso meio o stent InspironTM, um stent nacional metálico de cobalto-cromo recoberto com uma mistura de polímeros bioabsorvíveis exclusivamente em sua face abluminal e com liberação de sirolimus. O objetivo deste estudo foi comparar, em um modelo experimental, os achados da tomografia de coerência óptica dos stents InspironTM e BioMatrixTM. MÉTODOS: Os stents foram implantados em artérias coronárias porcinas. Cada indivíduo recebeu os dois tipos de stent, um em cada artéria (artérias descendente anterior e circunflexa), e após 28 dias foi realizado novo estudo angiográfico e empregada a tomografia de coerência óptica para avaliação da hiperplasia neointimal. RESULTADOS: Sete porcos receberam 7 stents InspironTM e 7 stents BioMatrixTM. O diâmetro de referência dos vasos tratados foi de 2,16 ± 0,37 mm e a relação balão de implante do stent/artéria foi de 1,17 ± 0,16 atm, sem diferença entre os grupos. A perda tardia intrastent foi de 0,53 ± 0,56 mm e de 0,32 ± 0,37 mm (P = 0,43) para os stents InspironTM e BioMatrixTM, respectivamente. Ocorreu um caso de reestenose angiográfica no grupo stent InspironTM (14% vs. 0; P = 0,2). A tomografia de coerência óptica evidenciou área neointimal intrastent no stent InspironTM de 1,61 ± 0,57 mm² e no stent BioMatrixTM de 1,36 ± 0,66 mm² (P = 0,47). A área neointimal porcentual foi de 31% no stent InspironTM vs. 23% no stent BioMatrixTM (P = 0,21). CONCLUSÕES: Após 28 dias de implante em artérias coronárias porcinas o stent InspironTM apresentou grau de hiperplasia neointimal intrastent semelhante ao do stent BioMatrixTM.