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In-stent restenosis (ISR) develops primarily due to neointimal hyperplasia. Gallic acid (GA) has anti-inflammatory, antioxidant, and cardioprotective effects. This study sought to investigate the effects of GA on neointimal hyperplasia and proliferation and migration of vascular smooth muscle cells (VSMCs) in a pig ISR model. In vitro proliferation and migration experiments were confirmed, after VSMCs were treated with plateletderived growth factor (PDGF-BB) and GA (100 µM) using a 3‑(4,5‑dimethylthiazol)‑ 2,5‑diphenyltetrazolium bromide (MTT) assay and a scratch wound assay for 24 hours and 48 hours. A bare metal stent (BMS) was implanted in the pig coronary artery to induce ISR with overdilation (1.1-1.2:1), and GA (10 mg/kg/day) was administered for 4 weeks. At the 4-week follow-up, optical coherence tomography (OCT) and histopathological analyses were performed. GA decreased the proliferation of VSMCs by PDGF-BB for 24 hours (89.24±24.56% vs. 170.04±19.98%, p＜0.001) and 48 hours (124.87±7.35% vs. 187.64±4.83%, p＜0.001). GA inhibited the migration of VSMCs induced by PDGF-BB for 24 hours (26.73±2.38% vs. 65.38±9.73%, p＜0.001) and 48 hours (32.96±3.04% vs. 77.04±10.07%, p＜0.001). Using OCT, % neointimal hyperplasia was shown to have significantly decreased in the GA group compared with control vehicle group (28.25± 10.07% vs. 37.60±10.84%, p＜0.001). GA effectively reduced neointimal hyperplasia by inhibiting the proliferation and migration of VSMCs in a pig ISR model. GA could be a potential treatment strategy for reducing ISR after stent implantation.
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There are limited data on outcomes after implantation of everolimus-eluting stents (EES) in East Asian patients with small vessel coronary lesions. A total of 1,600 patients treated with XIENCE EES (Abbott Vascular, CA, USA) were divided into the small vessel group treated with one ≤2.5 mm stent (n=119) and the non-small vessel group treated with one ≥2.75 mm stent (n=933). The primary end point was a patient-oriented composite outcome (POCO), a composite of all-cause death, myocardial infarction (MI), and any repeat revascularization at 12 months. The key secondary end point was a device-oriented composite outcome (DOCO), a composite of cardiovascular death, target-vessel MI, and target lesion revascularization at 12 months. The small vessel group was more often female, hypertensive, less likely to present with ST-elevation MI, and more often treated for the left circumflex artery, whereas the non-small vessel group more often had type B2/C lesions, underwent intravascular ultrasound, and received unfractionated heparin. In the propensity matched cohort, the mean stent diameter was 2.5±0.0 mm and 3.1±0.4 mm in the small and non-small vessel groups, respectively. Propensity-adjusted POCO at 12 months was 6.0% in the small vessel group and 4.3% in the non-small vessel group (p=0.558). There was no significant difference in DOCO at 12 months (small vessel group: 4.3% and non-small vessel group: 1.7%, p=0.270).Outcomes of XIENCE EES for small vessel disease were comparable to those for non-small vessel disease at 12-month clinical follow-up in real-world Korean patients.
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Background/Aims@#Due to limited real-world evidence on the association between time to presentation (T2P) and outcomes following acute myocardial infarction and diabetes (AMI-DM), we investigated the characteristics of patients with AMI-DM and their outcomes based on their T2P. @*Methods@#4,455 patients with AMI-DM from a Korean nationwide observational cohort (2011–2015) were divided into early and late presenters according to symptom-to-door time. The effects of T2P on three-year all-cause mortality were estimated using inverse probability of treatment weighting (IPTW) and survival analysis. @*Results@#The incidence of all-cause mortality was consistently higher in late presenters than in early presenters (11.4 vs. 17.2%; p < 0.001). In the IPTW-adjusted dataset, the incidence of all-cause mortality was numerically higher in late presenters than in early presenters (9.1 vs. 12.4%; p = 0.072). In the survival analysis, the cumulative incidence of all-cause mortality was significantly higher in late presenters than in early presenters before and after IPTW. In the subgroup with ST-elevation myocardial infarction, late presenters had a higher incidence of cardiac death than early presenters before (4.8 vs. 10.5%; p < 0.001) and after IPTW (4.2 vs. 9.7%; p = 0.034). In the initial glycated hemoglobin (HbA1c)-stratified analysis, these effects were attenuated in patients with HbA1c ≥ 9.0% before (adjusted hazard ratio [HR]: 1.45, 95% confidence interval [CI]: 0.80-2.64) and after IPTW (adjusted HR: 0.82, 95% CI: 0.40-1.67). @*Conclusions@#Late presentation was associated with higher mortality in patients with AMI-DM; therefore, multifaceted and systematic interventions are needed to decrease pre-hospital delays.
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BACKGROUND@#Current polymer-based drug-eluting stents (DESs) have fundamental issues about inflammation and delayed re-endothelializaton of the vessel wall. Substance-P (SP), which plays an important role in inflammation and endothelial cells, has not yet been applied to coronary stents. Therefore, this study compares poly lactic-co-glycolic acid (PLGA)-based everolimus-eluting stents (PLGA-EESs) versus 2-methacryloyloxyethyl phosphorylcholine (MPC)-based SP-eluting stents (MPC-SPs) in in-vitro and in-vivo models. @*METHODS@#The morphology of the stent surface and peptide/drug release kinetics from stents were evaluated. The invitro proliferative effect of SP released from MPC-SP is evaluated using human umbilical vein endothelial cell. Finally, the safety and efficacy of the stent are evaluated after inserting it into a pig’s coronary artery. @*RESULTS@#Similar to PLGA-EES, MPC-SP had a uniform surface morphology with very thin coating layer thickness (2.074 lm). MPC-SP showed sustained drug release of SP for over 2 weeks. Endothelial cell proliferation was significantly increased in groups treated with SP (n = 3) compared with the control (n = 3) and those with everolimus (n = 3) (SP:118.9 ± 7.61% vs. everolimus: 64.3 ± 12.37% vs. the control: 100 ± 6.64%, p < 0.05). In the animal study, the percent stenosis was higher in MPC-SP group (n = 7) compared to PLGA-EES group (n = 7) (MPC-SP: 28.6 ± 10.7% vs. PLGAEES: 16.7 ± 6.3%, p < 0.05). MPC-SP group showed, however, lower inflammation (MPC-SP: 0.3 ± 0.26 vs. PLGAEES: 1.2 ± 0.48, p < 0.05) and fibrin deposition (MPC-SP: 1.0 ± 0.73 vs. PLGA-EES: 1.5 ± 0.59, p < 0.05) around the stent strut. MPC-SP showed more increased expression of cluster of differentiation 31, suggesting enhanced reendothelialization. @*CONCLUSION@#Compared to PLGA-EES, MPC-SP demonstrated more decreased inflammation of the vascular wall and enhanced re-endothelialization and stent coverage. Hence, MPC-SP has the potential therapeutic benefits for the treatment of coronary artery disease by solving limitations of currently available DESs.
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BACKGROUND@#A drug-eluting stent (DES) is a highly beneficial medical device used to widen or unblock narrowed blood vessels. However, the drugs released by the implantation of DES may hinder the re-endothelialization process, increasing the risk of late thrombosis. We have developed a tacrolimus-eluting stent (TES) that as acts as a potent antiproliferative and immunosuppressive agent, enhancing endothelial regeneration. In addition, we assessed the safety and efficacy of TES through both in vitro and in vivo tests. @*METHODS@#Tacrolimus and Poly(lactic-co-glycolic acid) (PLGA) were applied to the metal stent using electrospinning equipment. The surface morphology of the stent was examined before and after coating using a scanning electron microscope (SEM) and energy dispersive X-rays (EDX). The drug release test was conducted through high-performance liquid chromatography (HPLC). Cell proliferation and migration assays were performed using smooth muscle cells (SMC).The stent was then inserted into the porcine coronary artery and monitored for a duration of 4 weeks. @*RESULTS@#SEM analysis confirmed that the coating surface was uniform. Furthermore, EDX analysis showed that the surface was coated with both polymer and drug components. The HPCL analysis of TCL at a wavelength of 215 nm revealed that the drug was continuously released over a period of 4 weeks. Smooth muscle cell migration was significantly decreased in the tacrolimus group (54.1% ± 11.90%) compared to the non-treated group (90.1% ± 4.86%). In animal experiments, the stenosis rate was significantly reduced in the TES group (29.6% ± 7.93%) compared to the bare metal stent group (41.3% ± 10.18%). Additionally, the fibrin score was found to be lower in the TES group compared to the group treated with a sirolimus-eluting stent (SES). @*CONCLUSION@#Similar to SES, TES reduces neointimal proliferation in a porcine coronary artery model, specifically decreasing the fibrins score. Therefore, tacrolimus could be considered a promising drug for reducing restenosis and thrombosis.
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BACKGROUND@#Biodegradable poly (l-lactic acid) (PLLA), a bio safe polymer with a large elastic modulus, is widely used in biodegradable medical devices. However, because of its poor mechanical properties, a PLLA strut must be made twice as thick as a metal strut for adequate blood vessel support. Therefore, the mechanical properties of a drug-eluting metal-based stents (MBS) and a bioresorbable vascular scaffolds (BVS) were evaluated and their safety and efficacy were examined via a long-term rabbit iliac artery model. @*METHODS@#The surface morphologies of the MBSs and BVSs were investigated via optical and scanning electron microscopy. An everolimus-eluting (EE) BVS or an EE-MBS was implanted into rabbit iliac arteries at a 1.1:1 stent-toartery ratio. Twelve months afterward, stented iliac arteries from each group were analyzed via X-ray angiography, optical coherence tomography (OCT), and histopathologic evaluation. @*RESULTS@#Surface morphology analysis of the EE coating on the MBS confirmed that it was uniform and very thin (4.7 lm). Comparison of the mechanical properties of the EE-MBS and EE-BVS showed that the latter outperformed the former in all aspects (radial force (2.75 vs. 0.162 N/mm), foreshortening (0.24% vs. 1.9%), flexibility (0.52 vs. 0.19 N), and recoil (3.2% vs. 6.3%). At all time points, the percent area restenosis was increased in the EE-BVS group compared to the EE-MBS group. The OCT and histopathological analyses indicate no significant changes in strut thickness. @*CONCLUSION@#BVSs with thinner struts and shorter resorption times should be developed. A comparable long-term safety/efficacy evaluation after complete absorption of BVSs should be conducted.
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Background@#Lipoprotein(a) is a known independent risk factor for atherosclerotic cardiovascular disease. However, the prognostic impact of the baseline lipoprotein(a) levels on long-term clinical outcomes among patients with acute myocardial infarction remain unclear. @*Methods@#We analyzed 1,908 patients with acute myocardial infarction from November 2011 to October 2015 from a single center in Korea. They were divided into 3 groups according to their baseline lipoprotein(a) levels: groups I (< 30 mg/dL, n = 1,388), II (30–49 mg/dL, n = 263), and III (≥50 mg/dL, n = 257). Three-point major adverse cardiovascular events (a composite of nonfatal myocardial infarction, nonfatal stroke, and cardiac death) at 3 years were compared among the 3 groups. @*Results@#The patients were followed for 1094.0 (interquartile range, 1,033.8–1,095.0) days, during which a total of 326 (17.1%) three-point major adverse cardiovascular events occurred. Group III had higher rates of three-point major adverse cardiovascular events compared with Group I (23.0% vs. 15.7%; log-rank P = 0.009). In the subgroup analysis, group III had higher rates of three-point major adverse cardiovascular events compared with group I in patients with non-ST-segment elevation myocardial infarction (27.0% vs. 17.1%; log-rank P = 0.006), but not in patients with ST-segment elevation myocardial infarction (14.4% vs. 13.3%; logrank P = 0.597). However, in multivariable Cox time-to-event models, baseline lipoprotein(a) levels were not associated with an increased incidence of three-point major adverse cardiovascular events, regardless of the type of acute myocardial infarction. Sensitivity analyses in diverse subgroups showed similar findings to those of the main analysis. @*Conclusion@#Baseline lipoprotein(a) levels in Korean patients with acute myocardial infarction were not independently associated with increased major adverse cardiovascular events at 3 years.
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The Guidelines of the 2019 European Society of Cardiology (ESC) and the 5th Society of Lipid and Atherosclerosis (KSoLA) for the Management of Dyslipidemia advocate a more intensive lipid-lowering strategy. However, there is a lack of evidence regarding the current status of lipid management in Korean patients in real-world practice. The Korean Society of Myocardial Infarction conducted a survey among its members of the Korean Society of Cardiology on the new lipid guidelines. Although most participants were aware of the changes in the ESC and the KSoLA guidelines, more than half of them did not agree with lowering the low-density lipoprotein cholesterol levels to < 55 mg/dL, because its safety and efficacy have not yet been proven in Koreans. A substantial disparity exists between lipid management guidelines and current clinical practices, highlighting the necessity for clinical research that specifically targets East Asians and Koreans to bridge this gap.
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Purpose@#This study aimed to compare long-term clinical outcomes according to the use of emergency medical services (EMS) in patients with ST-segment elevation myocardial infarction (STEMI) who arrived at the hospital within 12 hr of symptom onset. @*Materials and Methods@#A total of 13104 patients with acute myocardial infarction were enrolled in the Korea Acute Myocardial Infarction Registry–National Institutes of Health from October 2011 to December 2015. Of them, 2416 patients with STEMI who arrived at the hospital within 12 hr were divided into two groups: 987 patients in the EMS group and 1429 in the non-EMS group. Propensity score matching (PSM) was performed to reduce bias from confounding variables. After PSM, 796 patients in the EMS group and 796 patients in the non-EMS group were analyzed. The clinical outcomes during 3 years of clinical follow-up were compared between the two groups according to the use of EMS. @*Results@#The symptom-to-door time was significantly shorter in the EMS group than in the non-EMS group. The EMS group had more patients with high Killip class compared to the non-EMS group. The rates of all-cause death and major adverse cardiac events (MACE) were not significantly different between the two groups. After PSM, the rate of all-cause death and MACE were still not significantly different between the EMS and non-EMS groups. The predictors of mortality were high Killip class, renal dysfunction, old age, long door-to-balloon time, long symptom-to-door time, and heart failure. @*Conclusion@#EMS utilization was more frequent in high-risk patients. The use of EMS shortened the symptom-to-door time, but did not improve the prognosis in this cohort.
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Objective@#Data pertaining to the prognostic value of the combination of high neutrophilto-lymphocyte ratio (NLR) and anemia on admission in patients with ST-segment elevation myocardial infarction (STEMI) are limited. The objective of this study was to investigate the clinical value of baseline NLR in combination with anemia in predicting clinical outcomes after STEMI. @*Methods@#A total of 5,194 consecutive patients with STEMI within 12 hours of symptom onset from the Korea Acute Myocardial Infarction Registry-National Institute of Health database between 2011 and 2015 were categorized into 4 groups according to their NLR and hemoglobin levels: low NLR (<4) without anemia (n=2,722; reference group); high NLR (≥4) without anemia (n=1,527); low NLR with anemia (n=508); and high NLR with anemia (n=437). The co-primary outcomes were 180-day and 3-year all-cause mortality. @*Results@#Mortality rates significantly increased at the 3-year follow-up across the groups (3.3% vs. 5.4% vs. 16.5% vs. 21.7% for 180-day mortality and 5.3% vs. 9.0% vs. 23.8% vs. 33.4% for 3-year mortality; all p-trends <0.001). After adjusting for baseline covariates, the combination of high NLR and anemia was a significant predictor of 180-day mortality after STEMI with low NLR and no anemia as the reference (adjusted hazard ratio, 2.16; 95% confidence interval, 1.58–2.95; p<0.001). Similar findings were observed for the 3-year mortality. @*Conclusions@#This nationwide prospective cohort study showed that the combination of high NLR (≥4) and anemia is a strong predictor of all-cause mortality after STEMI.