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Marta Francesca Brancati, 1 Francesco Burzotta, 2 Carlo Trani, 2 Ornella Leonzi, 1 Claudio Cuccia, 1 Filippo Crea2 1 Department of Cardiology, Poliambulanza Foundation Hospital, Brescia, 2 Department of Cardiology, Catholic University of the Sacred Heart of Rome, Italy Summary : Drug Stents coated (DES) minimize the limitations of using bare metal stents (BMS) after percutaneous coronary intervention. However, while the introduction of second-generation DES appears to have reduced this phenomenon compared to first-generation DES, significant concerns remain about possible late complications of stent implantation such as stent thrombosis (ST) and stent resection, stenosis (SSI). ST is a potentially catastrophic event that has been greatly reduced by optimized stent implantation, novel stent designs, and dual antiplatelet therapy. The exact mechanism that explains its occurrence is under investigation, and indeed several factors are responsible. ISR in BMS was previously considered a steady state with an early peak of intimal hyperplasia (at 6 months) followed by a regression period of more than 1 year. In contrast, both clinical and histological studies of DES have demonstrated evidence of persistent neointimal growth over a long follow-up period, a phenomenon known as the “late catch-up” phenomenon. The notion that ISR is a relatively benign clinical condition has recently been refuted by evidence that patients with ISR may develop acute coronary syndromes. Intracoronary imaging is an invasive technique to identify stented atherosclerotic plaques and signs of vessel healing after stenting, and is often used to complete diagnostic coronary angiography and perform interventional procedures. Intracoronary optical coherence tomography is currently considered the most advanced imaging modality. it provides, compared to intravascular ultrasound, better resolution (at least >10 times), allowing the detailed characterization of the superficial structure of the vessel wall. it provides, compared to intravascular ultrasound, better resolution (at least >10 times), allowing the detailed characterization of the superficial structure of the vessel wall. оно обеспечивает, по сравнению с внутрисосудистым УЗИ, лучшее разрешение (по крайней мере, >10 раз), что позволяет детально охарактеризовать поверхностную структуру стенки сосуда. it provides, compared to intravascular ultrasound, a better resolution (at least >10 times), which allows a detailed characterization of the surface structure of the vessel wall.与血管内超声相比，它提供了更好的分辨率（至少> 10 倍），允许详细表征血管壁的表面结构。与血管内超声相比，它提供了更好的分辨率（至少> 10），允许详细表征血管壁的表面结构。 Compared to intravascular ultrasound, it provides a better resolution (at least 10 times), which allows a detailed characterization of the surface structure of the vessel wall. In vivo imaging studies consistent with histological findings suggest that chronic inflammation and/or endothelial dysfunction may induce advanced neoatherosclerosis in HMS and DES. Thus, neoatherosclerosis has become a prime suspect in the pathogenesis of late stent failure. Key words: coronary stent, stent thrombosis, restenosis, neoatherosclerosis.
Stented percutaneous coronary intervention (PCI) is the most widely used procedure for the treatment of symptomatic coronary artery disease, and the technique continues to evolve. 1 Although drug eluting stents (DES) minimize the limitations of uncoated stents (UES), late complications such as in stent thrombosis (ST) and in stent restenosis (ISR) can occur with stent implantation, and serious concerns remain. 2-5
If ST is a potentially catastrophic event, the acceptance that ISR is a relatively benign disease has recently been challenged by evidence for acute coronary syndrome (ACS) in patients with ISR. four
Today, intracoronary optical coherence tomography (OCT)6-9 is considered a state-of-the-art imaging modality offering better resolution than intravascular ultrasound (IVUS). In vivo imaging studies10-12 consistent with histological findings show a “new” vascular response mechanism after stent implantation with de novo “neoatherosclerosis” within BMS and DES.
In 1964 Charles Theodore Dotter and Melvin P. Judkins described the first angioplasty. In 1978, Andreas Grunzig performed the first balloon angioplasty (the old conventional balloon angioplasty); it was a revolutionary treatment, but it also had the disadvantages of acute vascular closure and restenosis. 13 This led to the discovery of coronary stents: Puel and Sigwart installed the first coronary stent in 1986, providing a stent to prevent acute vessel closure and late systolic retraction. 14 Although these initial stents prevented abrupt closure of the vessel, they caused severe endothelial damage and inflammation. More recently, two landmark studies, the Belgian-Dutch Stent Study 15 and the Stent Restenosis Study 16, have advocated the safety of dual antiplatelet therapy (DAPT) stenting and/or appropriate deployment methods. 17,18 Following these trials, the number of PCIs performed increased significantly.
However, the problem of iatrogenic in-stent neointima hyperplasia after BMS placement was quickly identified, resulting in ISR in 20–30% of treated lesions. DES19 was introduced in 2001 to minimize the need for restenosis and reoperation. DES has increased the confidence of cardiologists by allowing the treatment of an increasing number of complex lesions that were previously considered treatable with coronary artery bypass grafting. In 2005, 80–90% of all PCIs were accompanied by DES.
Everything has its drawbacks, and since 2005 concerns about the safety of “first generation” DES have increased, new generation stents such as 20,21 have been developed and introduced. 22 Since then, efforts to improve the performance of stents have grown rapidly, and exciting new technologies have continued to be discovered and quickly brought to market.
BMS is a fine wire mesh tube. After first experience with Wall mount, Gianturco-Roubin mount and Palmaz-Schatz mount, many different BMS are now available.
Three different designs are available: serpentine, tubular mesh and slotted tube. Coil designs consist of metal wires or strips forming a round coil shape; in tubular mesh designs, wire rolled together into a mesh forms a tube; slotted designs consist of metal tubes that are laser cut. These devices vary in composition (stainless steel, nichrome, cobalt chrome), design (various spacer shapes and widths, diameters and lengths, radial strength, radiopacity), and delivery systems (self-expanding or balloon-expandable).
As a rule, the new BMS consists of a cobalt-chromium alloy, resulting in thinner struts, improved driving performance and retained mechanical strength.
They consist of a metal stent platform (usually stainless steel) and are coated with a polymer that releases anti-proliferative and/or anti-inflammatory therapeutic agents.
Sirolimus (also known as rapamycin) was originally developed as an antifungal agent. Its mechanism of action is associated with blocking cell cycle progression by blocking the transition from G1 phase to S phase and inhibiting neointima formation. In 2001, the “first human” experience with SES showed promising results, leading to the development of the Cypher stent. 23 Large trials have demonstrated its effectiveness in preventing IR. 24
Paclitaxel was originally approved for the treatment of ovarian cancer, but its potent cytostatic properties—the drug stabilizes microtubules during mitosis, causes cell cycle arrest, and inhibits neointimal formation—make it a compound for Taxus Express PES. The TAXUS V and VI trials demonstrated the long-term efficacy of PES in high-risk complex coronary heart disease. 25,26 The subsequent TAXUS Liberté featured a stainless steel platform for ease of delivery.
Strong evidence from two systematic reviews and meta-analyses suggests that SES has an advantage over PES due to lower rates of IVR and target vessel revascularization (TVA), as well as a trend towards an increase in acute myocardial infarction (AMI) in the PES cohort. 27.28
Second generation devices have reduced shaft thickness, improved flexibility/deliverability, improved polymer biocompatibility/drug clearance profiles, and superior reendothelialization kinetics. In current practice, these are the most advanced DES designs and major coronary stents implanted worldwide.
Taxus Elements takes this one step further with a unique polymer designed for maximum early release and a new platinum-chromium spacer system that provides thinner spacers and increased radiopacity. The PERSEUS 29 study noted similar results between Element and Taxus Express for up to 12 months. However, there are not enough trials comparing yew elements with other second generation DESs.
The Endeavor Zotarolimus Coated Stent (ZES) is based on a stronger cobalt-chromium stent platform with higher flexibility and a smaller stent strut. Zotarolimus is a sirolimus analogue with similar immunosuppressive effects, but with increased lipophilicity to improve localization in the vessel wall. ZES uses a new phosphorylcholine polymer coating designed to maximize biocompatibility and minimize inflammation. Most drugs are washed out in the initial phase of injury, followed by arterial repair. After the first ENDEAVOR trial, the subsequent ENDEAVOR III trial compared ZES with SES, which showed higher late lumen loss and HR but fewer serious adverse cardiovascular events (MACEs) than SES. 30 The ENDEAVOR IV study comparing ZES with PES again found a higher incidence of SIS but a lower incidence of MI, presumably due to the very common ST in the ZES group. 31 However, the PROTECT study failed to demonstrate a difference in ST frequency between the Endeavor and Cypher stents. 32
The Endeavor Resolute is an improved version of the Endeavor stent with a new three-layer polymer. The newer Resolute Integrity (sometimes referred to as third generation DES) is based on a new platform with higher delivery capabilities (the Integrity BMS platform) and a new, more biocompatible three-layer polymer that can suppress the initial inflammatory response and elute more of the drug over the next 60 days. A trial comparing Resolute with Xience V (everolimus eluting stent [EES]) demonstrated that the Resolute system was equally effective in terms of mortality and target lesion failure. 33.34
Everolimus, a sirolimus derivative, is also a cell cycle inhibitor used in the development of EES Xience (Multi-link Vision BMS platform)/Promus (Platinum Chromium platform). The SPIRIT 35-37 trial demonstrated improved outcomes and reduced MACE with Xience V compared to PES, while the EXCELLENT trial demonstrated that EES was as good as SES in suppressing late loss at 9 months and clinical events at 12 months. 38 Finally, the Xience stent has been shown to be superior to BMS in the setting of ST elevation myocardial infarction (MI). 39
EPCs are a subset of circulating cells involved in vascular homeostasis and endothelial repair. Increased EPC at the site of vascular injury will promote early re-endothelialization, potentially reducing the risk of ST. EPC Biology’s first foray into stent design is the Genous stent, coated with anti-CD34 antibodies, capable of binding circulating EPCs via its hematopoietic markers to enhance re-endothelialization. While initial studies have been encouraging, recent evidence points to high TVR rates. 40
Given the potentially detrimental effects of polymer-induced delayed healing that are associated with ST risk, bioresorbable polymers offer the benefits of DES by avoiding longstanding concerns about polymer persistence. To date, various bioresorbable systems have been approved (eg, Nobori and Biomatrix, biolimus eluting stent, Synergy, EES, Ultimaster, SES), but the literature supporting their long-term results is limited. 41
Bioabsorbable materials have the theoretical advantage of providing mechanical support initially when elastic recoil is taken into account and reducing the long-term risks associated with existing metal struts. New technologies have led to the development of lactic acid polymers (poly-l-lactic acid [PLLA]), but many stent systems are in development, although finding the ideal balance between drug elution and degradation kinetics remains a challenge. The ABSORB study demonstrated the safety and efficacy of everolimus-coated PLLA stents. 43 The revision of the second generation Absorb stent was better than the previous one with a good 2-year follow-up. 44 The current ABSORB II study, the first randomized trial comparing the Absorb stent with the Xience Prime stent, should provide additional data, and the first available results are promising. 45 However, the ideal conditions, optimal implantation technique, and safety profile in coronary artery disease need to be clarified.
Thrombosis in both BMS and DES has adverse clinical outcomes. In a registry of patients implanted with DES,47 24% of ST cases resulted in death, 60% in non-fatal MI, and 7% in unstable angina. PCI for urgent ST is usually suboptimal, with recurrence in 12% of cases. 48
Extended ST has potentially adverse clinical outcomes. In the BASKET-LATE study, 6–18 months after stent placement, rates of cardiac mortality and non-fatal MI were higher in the DES group than in the SMP group (4.9% and 1.3%, respectively). 20 A meta-analysis of nine studies in which 5261 patients were randomized to SES, PES, or BMS showed that after 4 years of follow-up, SES (0.6% versus 0%, p = 0.025) and PES (0.7%) ) increased the incidence of very late ST compared with BMS by 0.2%, p = 0.028). 49 In contrast, in a meta-analysis including 5108 patients, 21 a 60% relative increase in mortality or MI was reported with SES compared with BMS (p = 0.03), while PES was associated with a nonsignificant increase of 15% (see – up to 9 months to 3 years).
Numerous registries, randomized trials, and meta-analyses have examined the relative risk of ST after BMS and DES implantation and have reported conflicting results. In a registry of 6906 patients treated with BMS or DES, there were no differences in clinical outcomes or ST rates at 1 year of follow-up. 48 In another registry of 8146 patients, the risk of persistent ST excess was found to be 0.6% per year compared with BMS. 49 A meta-analysis of studies comparing SES or PES with SMPs showed an increased risk of mortality and MI with first-generation DES compared with SMPs, 21 and another meta-analysis of 4545 patients randomized to SES or ST between PES and BMS at 4 years of follow-up. 50 Other real-world studies have demonstrated an increased risk of progressive ST and MI in patients treated with first-generation DES after discontinuation of DAPT. 51
Given conflicting data, several pooled analyzes and meta-analyses collectively determined that DES and first-generation SGM did not differ significantly in risk of death or MI, but SES and PES had an increased risk of very common ST compared to SGM. To review the available evidence, the US Food and Drug Administration (FDA) appointed an expert panel53 that issued a statement recognizing that first-generation DES is effective as labeled and that the risk of very advanced stages ST is small, but not large. , Significant increase. As a result, the FDA and association recommend extending the DAPT period to 1 year, although there is little evidence to support this claim.
As mentioned earlier, second generation DES have been developed with improved design features. CoCr-EES has undergone the most extensive clinical research. In a meta-analysis by Baber et al.54 of 17,101 patients, CoCr-EES significantly reduced definite/probable ST and MI compared with PES, SES, and ZES at 21 months. Finally, Palmerini et al showed in a meta-analysis of 16,775 patients that CoCr-EES has a significantly lower early, late, 1- and 2-year defined ST compared to other pooled DES. 55 Real-life studies have demonstrated a reduction in the risk of ST with CoCr-EES compared with first-generation DES. 56
Re-ZES was compared with CoCr-EES in the RESOLUTE-AC and TWENTE studies. 33,57 There was no significant difference in mortality, myocardial infarction, or defined ST segment between the two stents.
In a network meta-analysis of 50,844 patients, including 49 RCTs,58 CoCr-EES was associated with a significantly lower incidence of defined ST than BMS, a finding not seen with other DES; the decline was not only at “significantly early” and after 30 days (58). odds ratio [OR] 0.21, 95% confidence interval [CI] 0.11-0.42) and at 1 year (OR 0.27, 95% CI 0.08-0.74) and 2 years (OR 0.35, 95% CI 0.17–0.69). Compared to PES, SES, and ZES, CoCr-EES was associated with a lower ST rate at 1 year.
Early ST is associated with various factors. Underlying plaque morphology and thrombus burden seem to influence the outcome after PCI;59 deeper struts penetration by necrotic core (NC) prolapse, long medial tear within the stent, suboptimal stenting with residual edge dissections or significant edge stenosis, incomplete apposition, and incomplete expansion of implanted stent may increase the risk of ST.60 Therapeutic regimen of antiplatelet drugs does not substantially influence incidence of early ST: in a randomized trial comparing BMSs with DESs, the rates of acute and subacute ST during DAPT were similar (<1%).61 So, early ST seems to be primarily related to underlying treated lesions and to procedural factors. Underlying plaque morphology and thrombus burden seem to influence the outcome after PCI;59 deeper struts penetration by necrotic core (NC) prolapse, long medial tear within the stent, suboptimal stenting with residual edge dissections or significant edge stenosis, incomplete apposition, and incomplete expansion of implanted stent may increase the risk of ST.60 Therapeutic regimen of antiplatelet drugs does not substantially influence incidence of early ST: in a randomized trial comparing BMSs with DESs, the rates of acute and subacute ST during DAPT were similar (<1%) .61 So, early ST seems to be primarily related to underlying treated lesions and to procedural factors. Морфология лежащей в основе бляшки и тромбоз, по-видимому, влияют на исход после ЧКВ;59 более глубокая пенетрация распорок из-за пролапса некротического ядра (NC), длинного медиального разрыва внутри стента, субоптимального стентирования с остаточными краевыми расслоениями или значительным краевым стенозом, неполной аппозицией и неполным расширением имплантированного стента может увеличить риск ST.60 Терапевтический режим антитромбоцитарных препаратов не оказывает существенного влияния на частоту раннего ST: в рандомизированном исследовании, сравнивающем BMS и DES, частота острого и подострого ST во время DAPT была одинаковой (<1%) .61 Таким образом, ранняя ST, по-видимому, в первую очередь связана с лежащими в основе пролеченными поражениями и процедурными факторами. Underlying plaque morphology and thrombosis appear to influence outcome after PCI;59 deeper strut penetration due to necrotic nucleus (NC) prolapse, long medial tear within the stent, suboptimal stenting with residual marginal delaminations or significant marginal stenosis, incomplete apposition and incomplete expansion of an implanted stent may increase the risk of ST.60 Therapeutic regimen of antiplatelet drugs does not significantly affect the incidence of early ST: in a randomized trial comparing BMS and DES, the incidence of acute and subacute ST during DAPT was the same (<1%) .61 Thus, early ST appears to be primarily related to underlying treated lesions and procedural factors.潜在的斑块形态和血栓负荷似乎影响PCI 后的结果；59 坏死核心(NC) 脱垂导致的更深的支柱穿透、支架内长的内侧撕裂、具有残余边缘剥离或显着边缘狭窄的次优支架、不完全并置和不完全扩张60 抗血小板药物的治疗方案不会显着影响早期ST 的发生率：在一项比较BMS 与DES 的随机试验中，DAPT 期间急性和亚急性ST 的发生率相似（<1%） .61 因此，早期ST 似乎主要与潜在的治疗病变和手术因素有关。潜在 的 斑块 形态 和 血栓 似乎 影响 影响 pci 后 结果 ； ； ； ； ； 坏 死 核心 核心 核心 核心 核心 核心 脱垂 导致 的 深 的 支柱 穿透 、 内长 的 内侧 、 具有 残余 边缘 或 显着 边缘 狭窄 次 次 次 次 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的 的优 支架 、 不 完全 并置和 不 扩张 扩张 扩张 抗血 小板 药物 的 治疗 方案 不 显着 影响 影响 早期 的 ： 在 项 比较 比较 bms 与 des 的 中 ， dapt 期间 急性 亚急性 的 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生 发生率相似（<1%） .61 The underlying plaque morphology and thrombosis appear to influence outcomes after PCI; 59 Deeper strut penetration due to necrotic nucleus (NC) prolapse, medial ruptures in stent length, secondary dissection with residual margins, or significant margin narrowing Optimal stenting, incomplete apposition, and incomplete expansion60 Antiplatelet regimen has no significant effect on early ST incidence: incidence of acute and subacute ST during DAPT in a randomized trial comparing BMS and DES. are primarily related to underlying therapeutic lesions and surgical factors.
Today, the focus is on late/very late ST. While procedural and technical factors seem to play a major role in the development of acute and subacute ST, the mechanism of delayed thrombotic events appears to be more complex. It has been suggested that certain patient characteristics may be risk factors for progressive and very advanced ST: diabetes mellitus, ACS at the time of initial surgery, renal failure, advanced age, reduced ejection fraction, major adverse cardiac events within 30 days of initial surgery. For BMS and DES, procedural variables such as small vessel size, bifurcations, multivascular disease, calcification, complete occlusion, long stents appear to be associated with the risk of progressive ST. 62,63 Poor response to antiplatelet therapy is a major risk factor for progressive DES thrombosis 51 . This response may be due to patient non-compliance, underdosing, drug interactions, comorbidities affecting drug response, receptor-level genetic polymorphism (especially clopidogrel resistance), and activation of other pathways for platelet activation. Stent neoatherosclerosis is considered an important mechanism for late stent failure, including late ST64 (section “Stent Neoatherosclerosis”). The intact endothelium separates the thrombosed vessel wall and stent posts from the bloodstream and secretes antithrombotic and vasodilatory substances. DES exposes the vessel wall to anti-proliferative drugs and a drug-release platform, with varying effects on healing and endothelial function, with a risk of late thrombosis. 65 Pathological studies have shown that strong first-generation DES polymers can contribute to chronic inflammation, chronic fibrin deposition, poor endothelial healing, and consequently increased risk of thrombosis. 3 Late hypersensitivity to DES appears to be another mechanism leading to ST. Virmani et al. [66] reported postmortem findings after ST showing aneurysm expansion in the stent segment with local hypersensitivity reactions consisting of T-lymphocytes and eosinophils; these findings may reflect the influence of indestructible polymers. 67 Stent misfit may be due to suboptimal stent expansion or occur several months after PCI. Although procedural malapposition is a risk factor for acute and subacute ST, the clinical significance of acquired stent malapposition may depend on aggressive arterial remodeling or drug-induced delayed healing, but its clinical relevance is controversial. 68
The protective effects of second-generation DES may include faster and more intact endothelialization, as well as differences in stent alloy and structure, strut thickness, polymer properties, and antiproliferative drug type, dose, and kinetics.
Compared to CoCr-EES, thin (81 µm) cobalt-chromium stent scaffolds, antithrombotic fluoropolymers, low polymer content, and drug loading may contribute to lower ST rates. Experimental studies have shown that thrombosis and platelet deposition are significantly lower in fluoropolymer-coated stents than in uncoated stents. 69 Whether other second-generation DESs have similar properties deserves further study.
Coronary stents improve the surgical success of coronary interventions compared to traditional percutaneous transluminal coronary angioplasty (PTCA), which has mechanical complications (vascular occlusion, dissection, etc.) and a high rate of restenoses (up to 40–50% of cases). By the end of the 1990s, almost 70% of PCIs were performed with BGM implantation. 70
然而，尽管技术、技术和药物治疗取得了进步，但BMS 植入后再狭窄的风险约为20%，在特定亚组中发生率> 40%。然而，尽管技术、技术和药物治疗取得了进步，但BMS However, despite advances in technology, techniques, and treatments, the risk of restenosis following BMS implantation is approximately 20%, with rates exceeding 40% in certain subgroups. 71 In general, clinical studies have shown that restenosis after BMS implantation, similar to that seen with conventional PTCA, peaks at 3–6 months and resolves at 1 year. 72
DES further reduces ISR rates,73 although this reduction is angiographically and clinically dependent. The DES polymer coating releases anti-inflammatory and anti-proliferative agents, inhibits neointima formation, and delays vascular repair by months or years. 74 In clinical and histological studies, persistent neointima growth has been observed over a long follow-up period after DES implantation, a phenomenon known as “late catch-up” 75.
Vascular injury during PCI induces a complex process of inflammation and repair over a relatively short period of time (weeks to months), resulting in endothelialization and neointimal coverage. According to histopathological observations, neointimal hyperplasia (HMS and DES) after stent implantation mainly consisted of proliferative smooth muscle cells in a proteoglycan-rich extracellular matrix. 70
Thus, neointimal hyperplasia is a repair process involving coagulation and inflammation factors, as well as cells that induce smooth muscle cell proliferation and extracellular matrix formation. Immediately after PCI, platelets and fibrin are deposited on the vessel wall and attract leukocytes through a series of cell adhesion molecules. Rolling leukocytes attach to attached platelets through an interaction between the leukocyte integrin Mac-1 (CD11b/CD18) and platelet glycoprotein Ibα 53 or fibrinogen associated with platelet glycoprotein IIb/IIIa. 76.77
According to new data, bone marrow progenitor cells are involved in vascular reactions and repair processes. Mobilization of EPC from bone marrow to peripheral blood promotes endothelial regeneration and postnatal neovascularization. It appears that bone marrow smooth muscle progenitor cells (SMPCs) migrate to the site of vascular injury, resulting in neointimal proliferation. 78 Previously, CD34-positive cells were considered as a fixed population of EPCs, further studies have shown that the CD34 surface antigen does indeed recognize undifferentiated bone marrow stem cells with the ability to differentiate into EPCs and PBMCs. Transdifferentiation of CD34-positive cells into an EPC or SMPC lineage is dependent on the local environment; ischemic conditions induce differentiation towards the EPC phenotype, which promotes reendothelialization, while inflammatory conditions induce differentiation towards the SMPC phenotype, which promotes neointimal proliferation. 79
Diabetes increases the risk of ISR by 30–50% after BMS implantation, and the higher rate of restenosis in diabetic compared to non-diabetic patients also persisted in the DES era. The mechanisms underlying this observation are likely multifactorial, including systemic (eg, variability in the inflammatory response) and anatomical (eg, smaller vessels, longer lesions, diffuse disease, etc.), which independently increase the risk of ISR. 70
Vessel diameter and lesion length independently affected ISR rates, with smaller diameter/longer lesions significantly increasing restenosis rates compared to larger diameter/shorter lesions. 71
First generation stent platforms showed thicker stent struts and higher ISRs compared to second generation stent platforms with thinner struts.
Moreover, incidence of restenosis is associated with the stent length, nearly doubling for stent lengths >35 mm compared to those <20 mm. Moreover, the incidence of restenosis is associated with the stent length, nearly doubling for stent lengths >35 mm compared to those <20 mm. Кроме того, частота рестеноза связана с длиной стента, почти удваиваясь при длине стента >35 мм по сравнению с длиной стента <20 мм. In addition, the rate of restenosis is related to stent length, almost doubling with stent length >35 mm compared to stent length <20 mm.此外，再狭窄的发生率与支架长度有关，支架长度>35 mm 的支架长度几乎是<20 mm 的两倍。此外，再狭窄的发生率与支架长度有关，支架长度>35 mm Кроме того, частота рестеноза зависела от длины стента: длина стента >35 мм почти в два раза больше, чем стента <20 мм. In addition, the frequency of restenosis depended on the length of the stent: the length of the stent >35 mm is almost twice that of the stent <20 mm. The final minimum lumen diameter of the stent also played an important role: a smaller final minimum lumen diameter predicted a significantly increased risk of restenosis. 81.82
Traditionally, intimal hyperplasia after BMS implantation is considered stable, with an early peak between 6 months and 1 year followed by a late dormant period. An early peak of intimal growth followed by intimal regression with lumen enlargement several years after stent implantation has been previously reported; maturation of smooth muscle cells and changes in the extracellular matrix have been proposed as possible mechanisms for late neointima regression. 83 However, longer-term follow-up studies have shown a triphasic response after BMS placement with early restenosis, intermediate regression, and late luminal restenosis. 84
In the DES era, late neointimal growth was initially demonstrated after SES or PES implantation in animal models. 85 Several IVUS studies have shown early attenuation of intimal growth followed by late catching up over time after SES or RPE implantation, possibly due to an ongoing inflammatory process.86
Despite the “stability” traditionally attributed to ISR, about a third of patients with BMS ISR develop ACS. four
There is increasing evidence that chronic inflammation and/or endothelial insufficiency induce progressive neoatherosclerosis in HCM and DES (mainly first-generation DES), which may be an important mechanism for the development of progressive IR or progressive ST. Inoue et al [87] reported histological autopsy findings after implantation of Palmaz-Schatz coronary stents, suggesting that inflammation around the stent may precipitate new indolent atherosclerotic changes within the stent. Other studies10 have shown that restenotic tissue within 5-year CGM consists of recent onset atherosclerosis with or without peritoneal inflammation; specimens from ACS cases show typical vulnerable plaques in native coronary arteries Histological block morphology with foamy macrophages and cholesterol crystals. In addition, when comparing BMS and DES, a significant difference in time to the development of new atherosclerosis was noted. 11,12 The earliest atherosclerotic changes in foamy macrophage infiltration began 4 months after SES implantation, while the same changes in CGM lesions occurred after 2 years and remained a rare finding up to 4 years. In addition, DES stenting for unstable lesions such as thin tegmental fibroatherosclerosis (TCFA) or intimal rupture has a shorter time to development compared to BMS. Thus, neoatherosclerosis appears to be more common and occur earlier in first-generation DES than in BMS, possibly due to a different pathogenesis.
The impact of second generation DES or DES on development remains to be explored; although some existing observations of second generation DES88 suggest less inflammation, the incidence of neoatherosclerosis is similar compared to first generation, but further studies are still needed.