Levels of plasma Quaking and cyclooxygenase-2 predict in-stent restenosis in patients with coronary artery disease after percutaneous coronary intervention / 中南大学学报(医学版)

OBJECTIVES@#Percutaneous coronary intervention (PCI) is one of the important methods for the treatment of coronary artery disease (CAD). In-sent restenosis (ISR) after PCI for patients suffered from CAD is considered to be an essential factor affecting long-term outcomes and prognosis of this disease. This study aims to investigate the correlation between plasma Quaking (QKI) and cyclooxygenase-2 (COX-2) levels and ISR in patients with CAD.@*METHODS@#A total of 218 consecutive CAD patients who underwent coronary angiography and coronary arterial stenting from September 2019 to September 2020 in the Department of Cardiology of Xiangya Hospital of Central South University were enrolled in this study, and 35 matched individuals from the physical examination center were served as a control group. After admission, clinical data of these 2 groups were collected. Plasma QKI and COX-2 levels were measured by enzyme linked immunosorbent assay (ELISA). Follow-up angiography was performed 12 months after PCI. CAD patients were divided into a NISR group (n=160) and an ISR group (n=58) according to the occurrence of ISR based on the coronary angiography. The clinical data, coronary angiography, and stent features between the NISR group and the ISR group were compared, and multivariate logistic regression was used to explore the factors influencing ISR. The occurrence of major adverse cardiovascular events (MACE) 1 year after operation was recorded. Fifty-eight patients with ISR were divided into an MACE group (n=24) and a non-MACE group (n=34), classified according to the occurrence of MACE, and the plasma levels of QKI and COX-2 were compared between the 2 groups. Receiver operating characteristic (ROC) curves were utilized to analyze the diagnostic value of plamsa levels of QKI and COX-2 for ISR and MACE occurrences in patients after PCI.@*RESULTS@#Compared with control group, plasma levels of QKI and COX-2 in the CAD group decreased significantly (all P<0.001). Compared with the NISR group, the plasma levels of QKI and COX-2 also decreased obviously in the ISR group (all P<0.001), while the levels of high sensitivity C-reactive protein (hs-CRP) and glycosylated hemoglobin (HbAlc) significantly increased (all P<0.001). The level of COX-2 was negatively correlated with hs-CRP (r=-0.385, P=0.003). Multivariate logistic regression analysis showed that high level of plasma QKI and COX-2 were protective factors for in-stent restenosis after PCI, while hs-CRP was a risk factor. ROC curve analysis showed that the sensitivity and specificity of plasma QKI for evaluating the predictive value of ISR were 77.5% and 66.5%, respectively, and the sensitivity and specificity of plasma COX-2 for evaluating the predictive value of ISR were 80.0% and 70.7%, respectively. The sensitivity and specificity of plasma QKI combined with COX-2 for evaluating the predictive value of ISR were 81.3% and 74.1%, respectively. The sensitivity and specificity of plasma QKI for evaluating the prognosis of ISR were 75.0% and 64.7%, respectively. The sensitivity and specificity of plasma COX-2 for evaluating the prognosis of ISR were 75.0% and 70.6%, respectively. The sensitivity and specificity of plasma QKI combined with COX-2 for prognostic evaluation of ISR were 81.7% and 79.4%, respectively. The sensitivity and specificity of plasma COX-2 combined with QKI for evaluating ISR and MACE occurrences in patients after PCI were better than those of COX-2 or QKI alone (P<0.001).@*CONCLUSIONS@#High level of plasma QKI and COX-2 might be a protective factor for ISR, which can also predict ISR patient's prognosis.

Perfil Aterosclerótico da Artéria Carótida como Preditor de Risco para Reestenose após Implante de Stent Coronário / Carotid Artery Atherosclerotic Profile as Risk Predictor for Restenosis After Coronary Stenting

Resumo Fundamento: A incidência de reestenose da artéria coronária após o implante de um stent não farmacológico é mais baixa que na angioplastia com balão; no entanto, ainda apresenta altas taxas. Objetivo: O objetivo deste estudo foi identificar novos indicadores de risco para reestenose de stent usando ultrassonografia das carótidas que, em conjunto com indicadores já existentes, ajudariam na escolha do stent. Métodos: Realizamos um estudo prospectivo transversal incluindo 121 pacientes consecutivos com doença arterial coronariana que foram submetidos à intervenção coronária percutânea com angiografia nos 12 meses anteriores. Após os casos de reestenose de stent serem identificados, os pacientes foram submetidos à ultrassonografia de carótidas para avaliar a espessura da camada íntima média e placas ateroscleróticas. Os dados foram analisados por regressão múltipla de Cox. O nível de significância foi p<0,05. Resultados: A idade mediana dos pacientes foi de 60 anos (1º quartil = 55, 3º quartil = 68), e 64,5% dos pacientes eram do sexo masculino. A angiografia coronária mostrou que 57 pacientes (47,1%) apresentaram reestenose de stent. Cinquenta e cinco pacientes (45,5%) apresentaram placas ateroscleróticas ecolucentes nas artérias carótidas e 54,5% apresentaram placas ecogênicas ou nenhuma placa. Dos pacientes que apresentaram placas ecolucentes, 90,9% apresentaram reestenose do stent coronário, e daqueles com placas ecogênicas ou nenhuma placa, 10,6% apresentaram reestenose de stent. A presença de placas ecolucentes nas artérias carótidas aumentou o risco de reestenose de stent coronário em 8,21 vezes (RR=8,21;IC95%: 3,58-18,82; p<0,001). Conclusões: A presença de placas ateroscleróticas ecolucentes na artéria carótida constitui um preditor de risco de reestenose de stent coronário e deve ser considerada na escolha do tipo de stenta ser usado na angioplastia coronária.

Abstract Background: The incidence of restenosis of the coronary artery after a bare-metal stent implant has been lower than in simple balloon angioplasty; however, it still shows relatively high rates. Objective: The aim of this study was to find new risk indicators for in-stent restenosis using carotid ultrasonography, that, in addition to the already existing indicators, would help in decision-making for stent selection. Methods: We carried out a cross-sectional prospective study including 121 consecutive patients with chronic coronary artery disease who had undergone percutaneous coronary intervention with repeat angiography in the previous 12 months. After all cases of in-stent restenosis were identified, patients underwent carotid ultrasonography to evaluate carotid intima-media thickness and atherosclerosis plaques. The data were analyzed by Cox multiple regression. The significance level was set a p<0.05. Results: Median age of patients was 60 years (1st quartile = 55, 3rd quartile = 68), and 64.5% of patients were male. Coronary angiography showed that 57 patients (47.1%) presented in-stent restenosis. Fifty-five patients (45.5%) had echolucent atherosclerotic plaques in carotid arteries and 54.5% had echogenic plaques or no plaques. Of patients with who had echolucent plaques, 90.9% presented coronary in-stent restenosis. Of those who had echogenic plaques or no plaques, 10.6% presented in-stent restenosis. The presence of echolucent plaques in carotid arteries increased the risk of coronary in-stent restenosis by 8.21 times (RR=8.21; 95%CI: 3.58-18.82; p<0.001). Conclusions: The presence of echolucent atherosclerotic plaques in carotid artery constitutes a risk predictor of coronary instent restenosis and should be considered in the selection of the type of stent to be used in coronary angioplasty.

Application of Rotarex mechanical thrombectomy system in treating in-stent restenosis of lower extremity arteriosclerosis obliterans / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the role of Rotarex mechanical thrombectomy system in treating instent restenosis of peripheral artery disease (PAD).@*METHODS@#The clinical data of 7 in-stent restenosis (ISR) cases of lower extremity PAD from June 2017 to Dec 2018 were retrospectively analyzed. There were 5 males and 2 females and the mean age was (70.0±7.6) years from 59.0 to 76.0 years. All the cases were treated by Rotarex mechanical thrombectomy system. In the 7 cases, time interval from the previous stent implantation to ischemia recurrence was 1.0 to 72.0 months, and the median time was 6.0 months. The period from ischemia recurrence to endovascular therapy was 3 days to 2 years, and the median time was 62 days. Rotarex mechanical debulking catheter and percutaneous transluminal angioplasty (PTA) were used in all the cases, and the stent was used only when it was necessary. Anticoagulation was used for 24 hours after procedures and then antiplatelet agents were used as usual. Doppler ultrasonography was taken during the followed-up.@*RESULTS@#All the 7 cases were successful in technology, 3 of which were implanted with new stents for the fracture of the old ones. while for the other four cases, no new stent was implanted. The ankle-brachial index (ABI) increased from 0.31±0.08 to 0.86±0.08 after treatment (t=-12.84, P < 0.001). Thrombectomy was applied urgently in one case because of acute thrombosis in the stent, and the result was good. There was no other complications in hospital. All the patients were followed up for 5.0-22.0 months, and the median time was 14.0 months. No death and amputation occurred during the follow-up. One patient stopped antiplatelet agents because of gastrointestinal bleeding, which resulted in acute thrombosis. in-stent restenosis reappeared in 3 cases.@*CONCLUSION@#Debulking using Rotarex catheter is safe and effective in treating in-stent restenosis of PAD, especially in reducing stents implantation, but is not good at dealing with old thrombus and proliferating intima, and can do nothing about fractured stents and hyperplasia of intima, so it needs to be combined with stents and drug coated balloons.

Cut-off values of lesion and vessel quantitative flow ratio in de novo coronary lesion post-drug-coated balloon therapy predicting vessel restenosis at mid-term follow-up / 中华医学杂志(英文版)

BACKGROUND@#Drug-coated balloons (DCBs) have emerged as potential alternatives to drug-eluting stents in specific lesion subsets for de novo coronary lesions. Quantitative flow ratio (QFR) is a method based on the three-dimensional quantitative coronary angiography and contrast flow velocity during coronary angiography (CAG), obviating the need for an invasive fractional flow reserve procedural. This study aimed to assess the serial angiographic changes of de novo lesions post-DCB therapy and further explore the cut-off values of lesion and vessel QFR, which predict vessel restenosis (diameter stenosis [DS] ≥50%) at mid-term follow-up.@*METHODS@#The data of patients who underwent DCB therapy between January 2014 and December 2019 from the multicenter hospital were retrospectively collected for QFR analysis. From their QFR performances, which were analyzed by CAG images at follow-up, we divided them into two groups: group A, showing target vessel DS ≥50%, and group B, showing target vessel DS <50%. The median follow-up time was 287 days in group A and 227 days in group B. We compared the clinical characteristics, parameters during DCB therapy, and QFR performances, which were analyzed by CAG images between the two groups, in need to explore the cut-off value of lesion/vessel QFR which can predict vessel restenosis. Student's t test was used for the comparison of normally distributed continuous data, Mann-Whitney U test for the comparison of non-normally distributed continuous data, and receiver operating characteristic (ROC) curves for the evaluation of QFR performance which can predict vessel restenosis (DS ≥50%) at mid-term follow-up using the area under the curve (AUC).@*RESULTS@#A total of 112 patients with 112 target vessels were enrolled in this study. Group A had 41 patients, while group B had 71. Vessel QFR and lesion QFR were lower in group A than in group B post-DCB therapy, and the cut-off values of lesion QFR and vessel QFR in the ROC analysis to predict target vessel DS ≥50% post-DCB therapy were 0.905 (AUC, 0.741 [95% confidence interval, CI: 0.645, 0.837]; sensitivity, 0.817; specificity, 0.561; P < 0.001) and 0.890 (AUC, 0.796 [95% CI: 0.709, 0.882]; sensitivity, 0.746; specificity, 0.780; P < 0.001).@*CONCLUSIONS@#The cut-off values of lesion QFR and vessel QFR can assist in predicting the angiographic changes post-DCB therapy. When lesion/vessel QFR values are <0.905/0.890 post-DCB therapy, a higher risk of vessel restenosis is potentially predicted at follow-up.

Efficacy of drug coated balloon versus conventional balloon in the treatment of coronary de novo bifurcation lesions: a meta-analysis / 中华心血管病杂志

Objective: To systematically evaluate the efficacy of drug coated balloon (DCB) versus conventional balloon in the treatment of coronary de novo bifurcation lesions. Methods: The databases of PubMed, Embase, Cochrane Library, Web of science, CNKI (China National Knowledge Infrastructure), Wanfang database, VIP, China Biology Medicine disc, Chinese clinical trial registry, American clinical trial registry and cardiovascular related websites until September 2020 were retrieved for collecting the randomized controlled trials (RCT) comparing DCB versus conventional balloon in the treatment of coronary de novo bifurcation lesions. The risk of bias of included studies was assessed using the Cochrane risk assessment tool. The meta-analysis was performed by using Revman 5.3 and Stata 14.0 software. Results: Seven RCTs with a total of 613 patients were included in this meta-analysis. Among the included studies, 4 articles reached the low risk of bias, and the other 3 articles reached the medium risk of bias. The results of meta-analysis showed that there was no significant difference in the major adverse cardiac events (RR=0.65, 95%CI 0.39-1.08, P=0.10), myocardial infarction (RR=0.68, 95%CI 0.25-1.80, P=0.43), target lesion revascularization (RR=0.94, 95%CI 0.53-1.67, P=0.83) between DCB group and conventional balloon group. Late lumen loss of side branch was less in the DCB group than that in the conventional balloon group (WMD=-0.25, 95%CI -0.41--0.09, P<0.01) and the risk of side branch restenosis was also lower in the DCB group than that in the conventional balloon group (RR=0.47, 95%CI 0.22-0.98, P<0.05). However, subgroup analysis showed that the conclusions of domestic studies and foreign studies on late lumen loss and side branch restenosis were inconsistent. The meta-analysis based on domestic literature showed that the risk of side branch restenosis after DCB treatment was lower compared with conventional balloon group (RR=0.29, 95%CI 0.15-0.57, P<0.05), while this parameter derived from foreign literatures remained unchanged between two groups (P=0.53). The meta-analysis results of domestic literature showed that late lumen loss in DCB group was less than that in conventional balloon group (WMD=-0.32, 95%CI -0.51--0.13, P<0.05), but this phenomenon was not observed in foreign literatures (P=0.30). Conclusions: The use of DCB in the treatment of coronary de novo bifurcation lesions has the potential to reduce the rate of restenosis and late lumen loss of side branch compared with conventional balloon group. However, due to the limitation on quantity, quality and results of published studies, more high-quality and large scale RCTs are still needed to confirm these findings.

Advances in Preparation and Evaluation of Non-vascular Drug-eluting Stents / 中国医疗器械杂志

In recent years, the application of stent intervention in the treatment of non-vascular stenosis caused by benign and malignant factors has been widely concerned by researchers at home and abroad. The high incidence of malignant tumor diseases, further promotes the development of stent intervention. The conventional bare stents are prone to irritate luminal mucosa and produce restenosis and other complications. The emergence of drug-eluting stent is expected to solve this problem and become one of the important development trends of non-vascular stents. In this paper, the drug loading materials, drug loading layer drugs, preparation technology and quality evaluation methods of non-vascular drugeluting stent are described based on the recent research and clinical application documents, so as to provide basis and direction for the follow-up research and development.

Custo-efetividade do Stent Farmacológico na Intervenção Coronariana Percutânea no SUS / Cost-effectiveness of Drug-Eluting Stents in Percutaneous Coronary Intervention in Brazils Unified Public Health System (SUS)

Resumo Fundamento O uso do stent farmacológico (SF) comparado ao stent não farmacológico (SNF) na intervenção coronariana percutânea (ICP) reduziu o percentual de reestenose, porém sem impacto na mortalidade, com aumento no custo. A literatura carece de estudos randomizados que comparem economicamente esses dois grupos de stents na realidade do Sistema Único de Saúde (SUS). Objetivo Estimar a razão custo-efetividade incremental (RCEI) entre SF e SNF na coronariopatia uniarterial em pacientes do SUS Métodos Pacientes com coronariopatia uniarterial sintomática foram randomizados em 3 anos para uso de SF ou SNF durante a ICP, na proporção de 1:2, com seguimento clínico de 12 meses. Foram avaliados reestenose intrastent (RIS), revascularização da lesão-alvo (RLA), eventos adversos maiores e custo-efetividade (CE) de cada grupo. Os valores de p < 0,05 foram considerados significativos. Resultados No grupo SF, dos 74 pacientes (96,1%) que completaram o acompanhamento, ocorreu RIS em 1(1,4%), RLA em 1 (1,4%), óbito em 1 (1,4%), sem trombose. No grupo SNF, dos 141 pacientes (91,5%),ocorreu RIS em 14 (10,1%), RLA em 10 (7,3%), óbito em 3 (2,1%) e trombose em 1 (0,74%). Na análise econômica, o custo do procedimento foi de R$ 5.722,21 no grupo SF e de R$4.085,21 no grupo SNF. A diferença de efetividade a favor do grupo SF por RIS e RLA foi 8,7% e 5,9%, respectivamente, com RCEI de R$ 18.816,09 e R$ 27.745,76. Conclusões No SUS, o SF foi custo-efetivo, em concordância com o limiar de CE preconizado pela Organização Mundial da Saúde. (Arq Bras Cardiol. 2020; 115(1):80-89)

Abstract Background The use of drug-eluting stents (DESs), compared with bare-metal stents (BMSs), in percutaneous coronary intervention (PCI) has reduced the rate of restenosis, without an impact on mortality but with an increase in costs. Medical literature lacks randomized studies that economically compare these 2 stent types within the reality of the Brazilian Unified Public Health System (SUS). Objective To estimate the incremental cost-effectiveness ratio (ICER) between DES and BMS in SUS patients with single-vessel coronary artery disease. Methods Over a 3-year period, patients with symptomatic single-vessel coronary artery disease were randomized in a 1:2 ratio to receive a DES or BMS during PCI, with a 1-year clinical follow-up. The evaluation included in-stent restenosis (ISR), target lesion revascularization (TLR), major adverse events, and cost-effectiveness for each group. P-values <0.05 were considered significant. Results In the DES group, of 74 patients (96.1%) who completed the follow-up, 1 developed ISR (1.4%), 1 had TLR (1.4%), and 1 died (1.4%), with no cases of thrombosis. In the BMS group, of 141 patients (91.5%), ISR occurred in 14 (10.1%), TLR in 10 (7.3%), death in 3 (2.1%), and thrombosis in 1 (0.74%). In the economic analysis, the cost of the procedure was R$ 5,722.21 in the DES group and R$ 4,085.21 in the BMS group. The effectiveness by ISR and TLR was 8.7% for DES and 5.9% for BMS, with an ICER of R$ 18,816.09 and R$ 27,745.76, respectively. Conclusions In the SUS, DESs were cost-effective in accordance with the cost-effectiveness threshold recommended by the World Health Organization (Arq Bras Cardiol. 2020; 115(1):80-89)

Association of CMTM5 gene expression with the risk of in-stent restenosis in patients with coronary artery disease after drug-eluting stent implantation and the effects and mechanisms of CMTM5 on human vascular endothelial cells / 北京大学学报(医学版)

OBJECTIVE@#To elucidate the correlation between CKLF-like marvel transmembrane domain containing member (CMTM5) gene and the risk of in-stent restenosis (ISR) with coronary artery disease (CAD) patients and to detect the effects and mechanisms of CMTM5-stimulated genes on human vascular endothelial cells (ECs) proliferation and migration.@*METHODS@#A total of 124 hospitalized patients in Shijitan Hospital were enrolled in this study. All the CAD patients were detected with platelet reactivity and grouped into two groups according to platelet reactivity; ISR was conformed by coronary angiography; RT-PCR method was used to detect CMTM5 gene expression; The CMTM5 over expression, reduction and control EC lines were established; Cell count, MTT, Brdu and flow cytometry methods were used to detect the proliferation of ECs, scratch and transwell experiments to test the migration of ECs, Western blot was used to detect signal path expressions.@*RESULTS@#CMTM5 gene expression in HAPR (High on aspirin platelet reactivity) group was 1.72 times compared with No-HAPR group, which was significantly higher than No-HAPR group. HAPR group ISR rate was 25.8% (8 cases), the incidence of No-HAPR ISR group was 9.7% (9 cases), and the results showed that in HAPR group, the incidence of ISR was significantly higher than that in No-HAPR group (P=0.04, OR=0.04, 95%CI=1.16－7.52), which showed that CMTM5 gene was significantly correlated with the risk of ISR. In HAPR group ISR rate was 25.8% (8 cases), the incidence of ISR in No-HAPR group was 9.7% (9 cases), and the results showed that the risk of ISR in HAPR group was significantly higher than that in No-HAPR group. All the results showed that CMTM5 was significantly correlated with the risk of ISR in CAD patients (P < 0.05). CMTM5 overexpression inhibited the proliferation and migration ability of ECs (P < 0.05), PI3K/Akt signaling pathways were involved in the role of regulation on ECs.@*CONCLUSION@#Our results revealed that CMTM5 gene was closely related with ISR, CMTM5 overexpression may repress ECs proliferation and migration through regulating PI3K-Akt signaling.

Clinical characteristics of early and late drug-eluting stent in-stent restenosis and mid-term prognosis after repeated percutaneous coronary intervention / 中华医学杂志(英文版)

BACKGROUND@#The mechanism and characteristics of early and late drug-eluting stent in-stent restenosis (DES-ISR) have not been fully clarified. Whether there are different outcomes among those patients being irrespective of their repeated treatments remain a knowledge gap.@*METHODS@#A total of 250 patients who underwent initial stent implantation in our hospital, and then were readmitted to receive treatment for the reason of recurrent significant DES-ISR in 2016 were involved. The patients were categorized as early ISR (<12 months; E-ISR; n = 32) and late ISR (≥12 months; L-ISR; n = 218). Associations between patient characteristics and clinical performance, as well as clinical outcomes after a repeated percutaneous coronary intervention (PCI) were evaluated. Primary composite endpoint of major adverse cardiac events (MACEs) included cardiac death, non-fatal myocardial infarction (MI), or target lesion revascularization (TLR).@*RESULTS@#Most baseline characteristics are similar in both groups, except for the period of ISR, initial pre-procedure thrombolysis in myocardial infarction, and some serum biochemical indicators. The incidence of MACE (37.5% vs. 5.5%; P < 0.001) and TLR (37.5% vs. 5.0%; P < 0.001) is higher in the E-ISR group. After multivariate analysis, E-ISR (odds ratio [OR], 13.267; [95% CI 4.984-35.311]; P < 0.001) and left ventricular systolic dysfunction (odds ratio [OR], 6.317; [95% CI 1.145-34.843]; P = 0.034) are the independent predictors for MACE among DES-ISR patients in the mid-term follow-up of 12 months.@*CONCLUSIONS@#Early ISR and left ventricular systolic dysfunction are associated with MACE during the mid-term follow-up period for DES-ISR patients. The results may benefit the risk stratification and secondary prevention for DES-ISR patients in clinical practice.

Impact factors of in-stent restenosis following successful stent implantation for acquired severe pulmonary vein stenosis post atrial fibrillation ablation / 中华心血管病杂志

Objective: To investigate the influencing factors of in-stent restenosis (ISR) following successful stent implantation in patients with ablation-associated severe pulmonary vein stenosis (PVS) who undergo atrial fibrillation ablation. Methods: Data of patients who underwent pulmonary vein angiography to confirm PVS after radiofrequency ablation for atrial fibrillation (AF) and received pulmonary vein stenting at Shanghai Chest Hospital from March 2010 to December 2017 were retrospectively analysed. All patients were followed up for a long period of time (pulmonary vein contract-enhanced CT within 6 to 12 months after operation was performed, and pulmonary angiography was performed if CT indicated stenosis>50%). The incidence of ISR was recorded. According to angiography, the patients were divided into ISR group and non-ISR group. The clinical and intraoperative imaging characteristics and interventional data were compared between the two groups. Logistic regression was used to analyse the influencing factors of ISR. Results: A total of 47 patients ((47.1±12.2) years old) were enrolled in this study, including 28 males(59.6%). There were 19 cases in ISR group and 28 cases in non-ISR group. Compared with the non-ISR group, the ISR group received more pulmonary vein isolation ((2.8±0.9) vs. (1.8±1.3), P=0.02), and the interval between last ablation and stenting was longer ((19.4±9.6) vs. (13.0±12.4), P=0.03). The incidence of ISR in patients with stent diameter≤8 mm was significantly higher than those with stent diameter>8 mm (33.3%(20/60) vs. 8.1%(3/37), P<0.01). Logistic regression analysis found that the number of radiofrequency ablation>1 (OR=2.1, 95%CI 1.3-3.9, P=0.02), and the time from the last ablation to stent placement>12 months (OR=1.5, 95%CI 1.1-2.5, P=0.03), reference diameter of stenosed distal vessel (OR=0.7, 95%CI 0.5-0.9, P=0.04), post procedural minimal luminal diameter (OR=0.4, 95%CI 0.2-0.8, P=0.02) and stent diameter (OR=0.6, 95%CI 0.3-0.9, P=0.03) were independent factors of ISR. Conclusions: The greater number of radiofrequency ablations and the longer time from the last ablation to stent placement increase the risk of ISR. The larger reference diameter of the stenosed distal vessel, stent diameter and post procedural minimal luminal diameter are the protective factors of ISR.

Clinical Outcomes and Cost-Effectiveness Analysis of FFR Compared with Angiography in Multivessel Disease Patient / Impacto Clínico e Custo-Efetividade da FFR em Comparação à Angiografia em Pacientes com Doenças Multiarteriais Submetidos à ICP

Abstract Background: In multivessel disease patients with moderate stenosis, fractional flow reserve (FFR) allows the analysis of the lesions and guides treatment, and could contribute to the cost-effectiveness (CE) of non-pharmacological stents (NPS). Objectives: To evaluate CE and clinical impact of FFR-guided versus angiography-guided angioplasty (ANGIO) in multivessel patients using NPS. Methods: Multivessel disease patients were prospectively randomized to FFR or ANGIO groups during a 5 year-period and followed for < 12 months. Outcomes measures were major adverse cardiac events (MACE), restenosis and CE. Results: We studied 69 patients, 47 (68.1%) men, aged 62.0 ± 9.0 years, 34 (49.2%) in FFR group and 53 (50.7%) in ANGIO group, with stable angina or acute coronary syndrome. In FFR, there were 26 patients with biarterial disease (76.5%) and 8 (23.5%) with triarterial disease, and in ANGIO, 24 (68.6%) with biarterial and 11 (31.4%) with triarterial disease. Twelve MACEs were observed - 3 deaths: 2 (5.8%) in FFR and 1 (2.8%) in ANGIO, 9 (13.0%) angina: 4(11.7%) in FFR and 5(14.2%) in ANGIO, 6 restenosis: 2(5.8%) in FFR and 4 (11.4%) in ANGIO. Angiography detected 87(53.0%) lesions in FFR, 39(23.7%) with PCI and 48(29.3%) with medical treatment; and 77 (47.0%) lesions in ANGIO, all treated with angioplasty. Thirty-nine (33.3%) stents were registered in FFR (0.45 ± 0.50 stents/lesion) and 78 (1.05 ± 0.22 stents/lesion) in ANGIO (p = 0.0001), 51.4% greater in ANGIO than FFR. CE analysis revealed a cost of BRL 5,045.97 BRL 5,430.60 in ANGIO and FFR, respectively. The difference of effectiveness was of 1.82%. Conclusion: FFR reduced the number of lesions treated and stents, and the need for target-lesion revascularization, with a CE comparable with that of angiography.

Resumo Fundamentos: Em pacientes multiarteriais e lesões moderadas, a reserva de fluxo fracionada (FFR) avalia cada lesão e direciona o tratamento, podendo ser útil no custo-efetividade (CE) de implante de stents não farmacológicos (SNF). Objetivos: Avaliar CE e impacto clínico da angioplastia + FFR versus angioplastia + angiografia (ANGIO), em multiarteriais, utilizando SNF. Métodos: pacientes com doença multiarteriais foram randomizados prospectivamente durante ±5 anos para FFR ou ANGIO, e acompanhados por até 12 meses. Foram avaliados eventos cardíacos maiores (ECAM), reestenose e CE. Resultados: foram incluídos 69 pacientes, 47(68,1%) homens, 34(49,2%) no FFR e 35(50,7%) no ANGIO, idade 62,0 ± 9,0 anos, com angina estável e Síndrome Coronariana Aguda estabilizada. No FFR, havia 26 com doença (76,5%) biarterial e 8 (23,5%) triarterial, e no grupo ANGIO, 24(68,6%) biarteriais e 11(31,4%) triarteriais. Ocorreram 12(17,3%) ECAM - 3(4,3%) óbitos: 2(5,8%) no FFR e 1(2,8%) no ANGIO, 9(13,0%) anginas, 4(11,7%) no FFR e 5(14,2%) no ANGIO, 6 reestenoses: 2(5,8%) no FFR e 4 (11,4%) no ANGIO. Angiografia detectou 87(53,0%) lesões no FFR, 39(23,7%) com ICP e 48(29,3%) com tratamento clínico; e 77(47,0%) lesões no ANGIO, todas submetidas à angioplastia. Quanto aos stents, registrou-se 39(33,3%) (0,45 ± 0,50 stents/lesão) no FFR e 78(66,6%) (1,05 ± 0,22 stents/lesão) no ANGIO (p = 0,0001); ANGIO utilizou 51,4% a mais que o FFR. Análise de CE revelou um custo de R$5045,97 e R$5.430,60 nos grupos ANGIO e FFR, respectivamente. A diferença de efetividade foi 1,82%. Conclusões: FFR diminuiu o número de lesões tratadas e de stents e necessidade de revascularização do vaso-alvo, com CE comparável ao da angiografia.

In-stent restenosis assessed with frequency domain optical coherence tomography shows smooth coronary arterial healing process in second-generation drug-eluting stents

INTRODUCTION@#The pathophysiology and mechanism of in-stent restenosis (ISR) after implantation of second-generation drug-eluting stents (DESs) are not fully clear. We compared the morphological characteristics of ISR between first- and second-generation DESs using frequency domain optical coherence tomography (OCT).@*METHODS@#Patients who underwent follow-up coronary angiography (CAG) after first-generation (CYPHER™ and TAXUS™) and second-generation (Nobori®, PROMUS Element™, Resolute Integrity and XIENCE) DES implantations were examined. ISR was defined as lesions of over 50% diameter stenosis at follow-up CAG. Frequency domain OCT was performed at the time of revascularisation of ISR. Tissue morphology was assessed at minimum lumen area. OCT images of DESs at both early (≤ 1 year) and late (> 1 year) phase follow-up were compared.@*RESULTS@#On qualitative OCT assessment, the ratios of homogeneous, layered, heterogeneous without-attenuation and heterogeneous with-attenuation morphologies were 57.1%, 17.1%, 20.0% and 5.7%, respectively, for second-generation DES ISR (n = 35), and 16.7%, 25.0%, 25.0% and 33.3%, respectively, for first-generation DES ISR (n = 36). At late phase follow-up, homogeneous morphology was significantly more common for second-generation DES ISR compared to first-generation DES ISR (first-generation: 8.0% vs. second-generation: 50.0%; p < 0.01) while heterogeneous with-attenuation morphology was significantly more common for first-generation DES ISR (first-generation: 44.0% vs. second-generation: 5.6%; p < 0.01).@*CONCLUSION@#Homogeneous tissue morphology was more frequently found for second-generation than first-generation DES ISR, especially in the late phase. This suggested that neointimal hyperplasia was the main mechanism in second-generation DES ISR, and that the neointima was stabilised, much like in bare metal stent implantation.

Effects of Rosuvastatin on Apolipoprotein J in Balloon-Injured Carotid Artery in Rats / Efeitos da Rosuvastatina sobre Apolipoproteína J em Artérias de Ratos Lesionadas com Balão

Abstract Background: Restenosis after percutaneous coronary intervention in coronary heart disease remains an unsolved problem. Clusterin (CLU) (or Apolipoprotein [Apo] J) levels have been reported to be elevated during the progression of postangioplasty restenosis and atherosclerosis. However, its role in neointimal hyperplasia is still controversial. Objective: To elucidate the role Apo J in neointimal hyperplasia in a rat carotid artery model in vivo with or without rosuvastatin administration. Methods: Male Wistar rats were randomly divided into three groups: the control group (n = 20), the model group (n = 20) and the statin intervention group (n = 32). The rats in the intervention group were given 10mg /kg dose of rosuvastatin. A 2F Fogarty catheter was introduced to induce vascular injury. Neointima formation was analyzed 1, 2, 3 and 4 weeks after balloon injury. The level of Apo J was measured by real-time PCR, immunohistochemistry and western blotting. Results: Intimal/medial area ratio (intimal/medial, I/M) was increased after balloon-injury and reached the maximum value at 4weeks in the model group; I/M was slightly increased at 2 weeks and stopped increasing after rosuvastatin administration. The mRNA and protein levels of Apo J in carotid arteries were significantly upregulated after rosuvastatin administration as compared with the model group, and reached maximum values at 2 weeks, which was earlier than in the model group (3 weeks). Conclusion: Apo J served as an acute phase reactant after balloon injury in rat carotid arteries. Rosuvastatin may reduce the neointima formation through up-regulation of Apo J. Our results suggest that Apo J exerts a protective role in the restenosis after balloon-injury in rats.

Resumo Fundamento: A reestenose após intervenção coronária percutânea (ICP) após doença coronariana continua um problema não solucionado. Estudos relataram que os níveis de clusterina (CLU), também chamada de apolipoproteína (Apo) J, encontram-se elevados na progressão da reestenose pós-angioplastia e na aterosclerose. Contudo, seu papel na hihperplasia neointimal ainda é controverso. Objetivo: Elucidar o papel da Apo J na hiperplasia neointimal na artéria carótida utilizando um modelo experimental com ratos in vivo, com e sem intervenção com rosuvastatina. Métodos: ratos Wistar machos foram divididos aleatoriamente em três grupos - grupo controle (n = 20), grupo modelo (n = 20), e grupo intervenção com estatina (n = 32). Os ratos no grupo intervenção receberam 10 mg/kg de rosuvastatina. Um cateter Fogarty 2 F foi introduzido para induzir lesão vascular. A formação de neoíntima foi analisada 1, 2, 3 e 4 semanas após lesão com balão. Concentrações de Apo J foram medidas por PCR em tempo real, imuno-histoquímica e western blotting. Resultados: A razão área íntima/média (I/M) aumentou após a lesão com balão e atingiu o valor máximo 4 semanas pós-lesão no grupo modelo; observou-se um pequeno aumento na I/M na semana 2, que cessou após a administração de rosuvastatina. Os níveis de mRNA e proteína da Apo J nas artérias carótidas aumentaram significativamente após administração de rosuvastatina em comparação ao grupo modelo, atingindo o máximo na semana 2, mais cedo em comparação ao grupo modelo (semana 3). Conclusão: A Apo J atuou como reagente de fase aguda após lesão com balão nas artérias carótidas de ratos. A rosuvastatina pode reduzir a formação de neoíntoma por aumento de Apo J. Nossos resultados sugerem que a Apo J exerce um papel protetor na reestenose após lesão com balão em ratos.

Stents farmacológicos: estado atual / Drug-eluting stents: state-of-the-art

Stents farmacológicos foram desenvolvidos para reduzir a resposta proliferativa neointimal e consequentemente a reestenose, mais frequente limitação da intervenção coronária percutânea com balão e stents não faramcológicos. O desenvolvimento destes dispositivos baseia-se no maior entendimento da biologia da reestenose, na seleção de fármacos anti-proliferativos adequados para os diversos mecanismos envolvidos nesta complicação e no uso de plataformas/polímeros adequados para entrega do fármaco. Consequentemente o desempenho destes dispositivos depende da perfeita interação de todos estes elementos. As abordagens atuais para minimizar a reestenose são revisados neste capítulo. Embora a primeira geração dos stents farmacológicos tenha sido focada na eficácia em reduzir a reestenose, questões relacionadas à sua segurança surgiram, comprometendo seu uso mais disseminado. As novas gerações de stents farmacológicos com polímeros duráveis ou bioabsorvíveis conseguiu reduzir as taxas de nova intervenção e de trombose. Embora o modelo ideal de stent farmacológico ainda esteja em investigação, é certo que esta tecnologia já se estabeleceu como primeira linha na intervenção coronária percutânea contemporânea

Platelet Distribution Width on Admission Predicts In-Stent Restenosis in Patients with Coronary Artery Disease and Type 2 Diabetes Mellitus Treated with Percutaneous Coronary Intervention / 中华医学杂志(英文版)

<p><b>Background</b>It is known that there is a definite association between platelet distribution width (PDW) and poor prognosis in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). However, there are no data available regarding the prognostic significance of PDW for in-stent restenosis (ISR) in patients with CAD and T2DM. We aimed to determine the value of PDW on admission that predicted ISR in patients with CAD and T2DM.</p><p><b>Methods</b>Between January 2012 and December 2013, a total of 5232 consecutive patients diagnosed with CAD and T2DM undergoing percutaneous coronary intervention were admitted. Three years of retrospective follow-up was undertaken. A total of 438 patients with second angiography operations were included. ISR was defined as ≥50% luminal stenosis of the stent or peri-stent segments. Continuous data were presented as the mean ± standard deviation or median (P, P) and were compared by one-way analysis of variance or Kruskal-Wallis H-test. Categorical variables were presented as percentages and were compared by Chi-square test or Fisher's exact test. The association between PDW and ISR was calculated by logistic regression analysis. A two-sided value of P < 0.05 was considered statistically significant. Statistical analyses were performed by SPSS version 22.0 for windows.</p><p><b>Results</b>Fifty-nine patients with ISR, accounting for 13.5% of the total, were included. ISR was significantly more frequent in patients with higher PDW quartiles compared with lower quartiles. We observed that PDW had a strong relationship with mean platelet volume (r = 0.647, 95% confidence interval [CI]: 0.535-0.750, P < 0.0001). The receiver-operating characteristic curves showed that the PDW cutoff value for predicting ISR rate was 13.65 fl with sensitivity of 59.3% and specificity of 72.4% (area under curve [AUC] = 0.701, 95% CI: 0.625-0.777, P < 0.001). Multivariate analysis showed that the risk of ISR increased approximately 30% when PDW increased one unit (odds ratio [OR]: 1.289, 95% CI: 1.110-1.498, P = 0.001). Patients with higher PDW, defined as more than 13.65 fl, had a 4-fold higher risk of ISR compared with lower PDW (OR: 4.241, 95% CI: 1.879-9.572, P = 0.001). Furthermore, when patients were divided by PDW quartiles values, PDW was able to predict ISR (Q2: OR = 0.762, 95% CI: 0.189-3.062, P = 0.762; Q3: OR = 2.782, 95% CI: 0.865-8.954, P = 0.086; and Q4: OR = 3.849, 95% CI: 1.225-12.097, P = 0.021, respectively; P for trend <0.0001).</p><p><b>Conclusion</b>PDW is an independent predictor of ISR in patients with CAD and T2DM.</p>

Effects of miRNA-1,miRNA-21 in plasma on in-stent restenosis in patients with coronary heart disease and diabetes mellitus after percutaneous coronary intervention / 中国应用生理学杂志

OBJECTIVE@#To observe the expression differences of the plasma miRNA-1, miRNA-21 between patients with coronary heart disease (CHD) and without coronary artery lesions, between patients with in-stent restenosis (ISR) and none in-stent restenosis (NISR), and to study their predictive value for ISR occurred after percutaneous coronary intervention (PCI) in patients with CHD and diabetes mellitus (DM).@*METHODS@#The selected subjects were divided into CHD group in which patients were implemented stenting (=187), and control group in which patients were without coronary artery lesions (=195). According to the guidelines, the control group was divided into normal group (=150), simple-DM group (=45); the CHD group was divided into simple-CHD group (=119) and CHD-DM group (=68), the CHD group was also divided into ISR group (=48), NISR group (=139), and the ISR group was divided into simple-ISR group (=26) and ISR-DM group (=22) again. Plasma was collected from each group, and total RNA was extracted, the level of blood miRNA-1, miRNA-21 of each group was detected, and their level differences were analyzed.@*RESULTS@#Compared with control group, the level of miRNA-1 and miRNA-21 of CHD group was increased (<0.05); compared with NISR group, the level of miRNA-1 and miRNA-21 of ISR group was increased (<0.05). The incidence of ISR of CHD-DM group was obviously higher than that of simple-CHD group, ISR-DM group's level of miRNA-21 was higher than that of simple-ISR group (<0.05), and there was no difference of miRNA-1 level between ISR and ISR-DM group (<0.05). In Logistics, for CHD patents, the OR of DM, miRNA-1, miRNA-21 were 2.132, 3.066, 1.924 respectively (<0.05); for CHD patents with ISR, the OR of DM, miRNA-21 were 2.123, 3.066 respectively (<0.05); especially for CHD and DM patents with ISR, the OR of miRNA-21 was 9.148 (<0.05). In ROC curve, for CHD patients with ISR, the AUC of miRNA-1, miRNA-21 were 0.854, 0.857 respectively; for CHD-DM patients with ISR, the AUC of miRNA-21 was 0.783.@*CONCLUSIONS@#To predict the occurrence of ISR for CHD patients, the plasma miRNA-1 and miRNA-21 have a relatively high specificity and sensitivity, for CHD patients with DM, miRNA-21 may have a higher clinical value.