Evaluation of neointimal coverage of overlapping sirolimus- eluting stents by optical coherence tomography

Background Although overlapping sirolimus-eluting stents are often used in long lesions during percutaneous coronary intervention, it was not clear how intimal hyperplasia at the overlapping segments compares with that of single-layer sirolimus-eluting stents.Methods Optical coherence tomography （OCT） examinations were performed on 22 patients in whom overlapping sirolimus-eluting stents （SESs） were implanted. OCT images were analyzed off-line after the procedure. Still frames were selected and classified, and the length of overlap, lumen loss, and average neointimal thickness on the strut were measured. The stent strut was classified into well-apposed to vessel wall with apparent neointimat coverage （type A）, well-apposed to vessel wall without neointimal coverage （type B）, malapposed to the vessel wall without neointimal coveraae （tvDe C）, and strut located at a major side branch （type D）.Results Tlqere was no statistically significant difference between strut coverage types within overlapping and non-overlapping segments, but a greater percentage of type C struts were observed within the overlapping segments （5.2% vs 1.4%, P 〉0.05）. Neither neointimal thickness （（175.0±59.9） μm vs （168.3±90.2）μm, P=0.715） nor lumen loss （（1.61±0.55） mm^2 vs （1.48±0.37） mm^2, P=0.397） was statistically different between the two segments. One patient was diagnosed with suspected in-stent thrombosis at 6 months. Although no specific characteristics of thrombosis were seen on the OCT images, a greater number of malapposed struts without neointima coverage were observed.Conclusions About 90% struts were completely covered by neointimal proliferation at 12 months follow-up, and the thicknesses of neointima on overlapping and non-overlapping segments were similar. Most of type C struts at the overlapping segments were found on the inside layer stents. Delayed antiplatelet therapy was beneficial for the patients with incompletely covered struts.

~rognostic value of baseline C-reactive protein levels in patients mdergoing coronary revascularization

Background C-reactive protein （CRP） is a lowly expressed marker for inflammatory response. This study aimed to evaluate the prognostic value of baseline CRP levels in patients undergoing coronary revascularization in the context of modern medical treatment. Methods This was a retrospective study in a single center. Four hundred and fourteen patients were enrolled, who underwent coronary revascularization and received adequate medication for secondary prevention of coronary heart disease. The study compared the follow-up clinical outcomes between high level CRP group （CRP 〉5 mg/L） and low level one. The median follow-up time was 551 days. Results Compared with low CRP group, the relative risk （RR） of the major adverse cardiovascular and cerebral events （MACCE） in high CRP group was 5.131 （95% CI： 1.864-14.123, P=0.002）. There were no significant differences in death myocardial infarction and stroke during the follow-up between two groups, but a higher risk of re-revascularization was found in high CRP group （RR 6.008, 95% CI： 1.667-21.665, P=0.006）. Cox regression analysis showed that only CRP level could contribute to MACCE during the follow-up. MACCE-free rate was much lower in high CRP group （Kaplan-Meier log-rank P 〈0.001）. Conclusion In the context of modern medical treatment, the baseline level of CRP is an independent predictor for long-term prognosis in patients with coronary revascularization.

Comparison of drug eluting stent implantation with coronary artery bypass surgery in the treatment of patients with chronic total occlusion and multiple vessel disease

Background In patients with chronic total occlusion （CTO） and multivessel coronary artery disease, the comparison of surgical and the percutaneous revascularization strategies has rarely been conducted. The aim of this study was to compare long term clinical outcomes of drug eluting stent （DES） implantation with coronary artery bypass surgery （CABG）in the patients with CTO and multivessel disease.Methods From a prospective registry of 6000 patients in our institution, we included patients with CTO and multivessel coronary artery disease who underwent either CABG （n=679） or DES （n=267） treatment. Their propensity risk score was used for adjusting baseline differences.Results At a median follow-up of three years, propensity score adjusted Cox regression analysis showed that the rate of major adverse cardiac cerebrovascular events （MACCE） was lower in CABG group （12.7% vs. 24.3%, hazard ratio （HR） 1.969, 95% Cl 1.219-3.179, P=0.006） mainly due to lower rate of target vessel revascularization in CABG group than in DES group （3.1% vs. 17.2%, HR 16.14, 95% CI 5.739-45.391, P ＜0.001）. The incidence of cardiac death or myocardial infarction （composite end point） was not significantly different between these two groups. On multivariate analysis, the significant predictors of MACCE were only the type of revascularization. Age, left ventricular ejection fraction （LVEF）, and complete revascularization were identified as significant predictors of composite end points.Conclusions Our study shows that in patients with CTO and multivessel coronary disease, DES can offer comparable long term outcomes in cardiac death and myocardial infraction free survival in comparison with CABG. However, there is an increased rate of MACCE which results from more repeat revascularizations. Obtaining a complete revascularization is crucial for decreasing adverse cardiac events.

Coronary stenting versus bypass surgery in heart failure patients with preserved ejection fraction

Background The optimal revascularization strategy in patients with heart failure with preserved ejection fraction （HFPEF） remains unclear. The aim of the present study was to compare the effects of percutaneous coronary intervention （PCI） and coronary artery bypass grafting （CABG） in patients with HFPEF. Methods From July 2003 through September 2005, a total of 920 patients with coronary artery disease （CAD） and HFPEF （ejection fraction 〉50%） underwent PCI （n=350） or CABG （n=570）. We compared the groups with respect to the primary outcome of mortality, and the secondary outcomes of main adverse cardiac and cerebral vascular events （MACCE）, including death, myocardial infarction, stroke and repeat revascularization, at a median follow-up of 543 days. Results In-hospital mortality was significantly lower in the PCI group than in the CABG group （0.3% vs. 2.5%, adjusted P=0.016）. During follow-up, there was no significant difference in the two groups with regard to mortality rates （2.3% vs. 3.5%, adjusted P=0.423）. Patients receiving PCI had higher MACCE rates as compared with patients receiving CABG （13.4% vs. 4.0%, adjusted P 〈0.001）, mainly due to higher rate of repeat revascularization （adjusted P 〈0.001）. Independent predictors of mortality were age, New York Heart Association （NYHA） class and chronic total occlusion. Conclusion Among patients with CAD and HFPEF, PCI was shown to be as good as CABG with respect to the mortality rate, although there was a higher rate of repeat revascularization in patients undergoing PCI.

Clinical outcomes and cost-utility after sirolimus-eluting versus bare metal stent implantation

Background Randomized studies have shown beneficial effects of drug-eluting stent （DES） in reducing the risk of repeated revascularization. Other studies have shown higher proportion of death, myocardial infarction （MI） and increased cost concerning DES. However the long term safety and effectiveness of DES have been questioned recently.Methods To compare long term clinical outcomes, health-related quality of life （HRQOL） and cost-utility after sirolimus-eluting stent （SES） and bare metal stent （BMS） implantation in angina patients in China, 1241 patients undergoing percutaneous coronary revascularization （PCl） with either SES （n=632） or BMS （n=609） were enrolled continuously in this prospective, nonrandomized, multi-center registry study.Results Totally 1570 stents were implanted for 1334 lesions. Follow-up was completed in 1205 （97.1%） patients at 12 months. Rates of MI, all causes of death were similar between the two groups. Significant differences were found at rate of cardiovascular re-hospitalization （136 （22.4%） in BMS group vs. 68 （10.8%） in SES group, P=0.001） and recurrent angina （149 （24.5%） vs. 71 （11.3%）, P=0.001）. Dramatic difference was observed when compared the baseline and 9-month HRQOL scores intra-group （P 〈0.001）. However no significant difference was found inter-group either in baseline or follow-up HRQOL. Compared with SES, the total cost in BMS was significantly lower on discharge （62 546.0 vs. 78 245.0 Yuan, P=0.001）. And follow-up expenditure was remarkably higher in the BMS group than that in the SES group （13 412.0 vs. 8 812.0 Yuan, P=0.0001）.Conclusions There were no significant differences on death, in-stent thrombosis, MI irrespective of stent type. SES was superior to BMS on improvement of life quality. SES was with higher cost-utility compared to BMS.

Comparision of high sensitivity C-reactive protein and matrix metalloproteinase 9 in patients with unstable angina between with and without significant coronary artery plaques

Background Inflammation within vulnerable coronary plaques may cause unstable angina by promoting rupture and erosion. C-reactive protein （CRP） is the most reliable and accessible test method for clinical use for identifying coronary artery disease event. Matrix metalloproteinase 9 （MMP-9） is highly over-expressed in the vulnerable regions of a plaque. Our aim was to evaluate the plasma levels of MMP-9 and hsCRP in subjects with both unstable angina and coronary plaques, as well as in those with unstable angina without coronary plaques.

Thorombolytic therapy with rescue percutaneous coronary intervention versus primary percutaneous coronary intervention in patients with acute myocardial infarction： a multicenter randomized clinical trial

Background Although thrombolytic therapy with rescue percutaneous coronary intervention （PCI） is a common treatment strategy for ST-segment elevation acute myocardial infarction （STEMI）, scant data are available on its efficacy relative to primary PCI, and comparison was therefore the aim of this study. Methods This multicenter, open-label, randomized, parallel trial was conducted in 12 hospitals on patients （age 〈70 years） with STEMI who presented within 12 hours of symptom onset （mean interval 〉3 hours）. Patients were randomized to three groups： primary PCI group （n=101）; recombinant staphylokinase （r-Sak） group （n=-104）; and recombinant tissue-type plasminogen activator （rt-PA） group （n=-106）. For all patients allocated to the thrombolytic therapy arm, coronary angiography was performed at 90 minutes after drug therapy to confirm infarct-related artery （IRA） patency; rescue PCI was performed in cases with TIMI flow grade 〈2. Bare-metal stent implantation was planned for all patients. Results After randomization it required an average of 113.4 minutes to start thrombolytic therapy （door-to-needle time）and 141.2 minutes to perform first balloon inflation in the IRA （door to balloon time）. Rates of IRA patency （TIMI flow grade 2 or 3） and TIMI flow grade 3 were significantly lower in the thrombolysis group at 90 minutes after drug therapy than in the primary PCI group at the end of the procedure （70.5% vs. 98.0%, P 〈0.0001, and 53.0% vs. 85.9%, P 〈0.0001, respectively）. Rescue PCI with stenting was performed in 117 patients （55.7%） in the thrombolytic therapy arm. Rates of patency and TIMI flow grade 3 were still significantly lower in the rescue PCI than in the primary PCI group （88.9% vs. 97.9%, P=-0.0222, and 68.4% vs. 85.0%, P=0.0190, respectively）. At 30 days post-therapy, mortality rate was significantly higher in the thrombolysis combined with rescue PCI group than in primary PCI group （7.1% vs. 0, P=0.0034）. Rates of death/MI and bleeding complications were significantly higher in the thrombolysis with rescue PCI group than in the primary PCI group （10.0% vs. 1.0%, P=-0.0380, and 28.10% vs. 8.91%, P=-0.O001, respectively）. Conclusions Thrombolytic therapy with rescue PCI was associated with significantly lower rates of coronary patency and TIMI flow grade 3, but with significantly higher rates of mortality, death/MI and hemorrhagic complications at 30 days, as compared with primary PCI in this group of Chinese STEMI patients with late presentation and delayed treatments.

Proliferation, migration and apoptosis activities of endothelial progenitor cells in acute coronary syndrome

Background There are numerous articles on the endothelial progenitor cells （EPCs） in different disease conditions. However, the functional properties of EPCs in acute coronary syndrome （ACS） are still uncertain. Here we aimed to study the number and functions of EPCs in ACS patients. Methods Patients were enrolled with admitted ACS （n=25） and another 25 gender-, age-, atherosclerotic risk factors-matched stable coronary artery disease （CAD） controls. EPCs were defined as CD34＋/CD133＋/VEGFR-2＋ and quantified by flow cytometry. Moreover, functional properties of EPCs including colony-forming unit （CFU）, proliferation, migration as well as apoptosis were evaluated and compared between the two groups. Plasma matrix metalloproteinase-9 （MMP-9） was detected in all patients as well. Results The two groups had similar medication and clinical characteristics on admission. The EPCs in ACS patients were more than 2.6 times that in stable CAD subjects （15.6±2.7 vs. 6.0±0.8 /100 000 events, P 〈0.01）. CFU was not statistically different between the two groups （10.8±2.9 vs. 8.2±1.8, number/well, P 〉0.05）. Furthermore, EPCs isolated from ACS patients were significantly impaired in their proliferation （0.498±0.035 vs. 0.895±0.067, OD value, P〈0.01） and migration capacity （20.5±3.4 vs. 30.7±4.3, number/well, P 〈0.01） compared with controls. Moreover, the apoptosis cell in cultured EPCs was drastically increased in ACS group （（18.3±2.. 1 ）% vs. （7.8±0.4）%, P 〈0.01）. Conclusions Patients with ACS exhibited apparently increased circulating EPCs as well as cultured apoptosis percentage together with a remarkable impairment of proliferation and migration activities compared with stable CAD subjects.

Association between non-alcoholic fatty liver disease and coronary artery disease severity

Background Both non-alcoholic fatty liver disease （NAFLD） and coronary artery disease （CAD） are closely associated with many metabolic disorders. Invasive coronary angiography （CAG） is a common approach as an intervention for CAD.However, the association between angiographic severity of coronary artery and NAFLD remains controversial. This study aimed to evaluate the relationship between NAFLD and CAD.Methods Totally 542 consecutive patients who planned to undergo CAG due to a suspected CAD were enrolled.Abdominal computed tomography （CT） was performed before angiography to detect NAFLD. CAD was defined as stenosis of at least 50% in at least one major coronary artery. The severity of CAD was assessed by the number of vessels affected and the vessel score multiplied by the severity score （Gensini score）. Significant stenosis was defined as 70% or greater reduction in lumen diameter. A probability value of P 〈0.05 was considered statistically significant.Results Of 542 patients studied, 248 （45.8%） were found to have NAFLD by abdominal CT, and 382 patients （88%）were found to have significant CAD by CAG. Age, diabetes mellitus, waist circumference, body mass index, and obesity were associated with NAFLD. According to the results of Logistic regression analysis, the presence of NAFLD independently increased the risk for CAD, as seen in CAG （odds ratio （OR）, 95% confidence interval （CI）： 7.585（4.617-12.461）; P 〈0.001）. NAFLD was significantly more common in patients as CAD severity increased （P〈0.001）.Conclusions The presence of NAFLD is associated with high severity of CAD, requiring that patients with abdominal obesity be also investigated for NAFLD. Patients with NAFLD should be closely followed up for the presence and severity of CAD.

Effect of Kuanxiong Aerosol(宽胸气雾剂)on Patients with Angina Pectoris:A Non-inferiority Multi-center Randomized Controlled Trial

Objective： To evaluate the effect and safety of Kuanxiong Aerosol （宽胸气雾剂, KA） on patients with angina pectoris. Methods： Block randomization was performed to randomly allocate 750 patients into KA （376 cases） and control groups （374 cases）. During an angina attack, the KA group received 3 consecutive sublingual sprays of KA （0.6 mL per spray）. The control group received 1 sublingual nitroglycerin tablet （NT, 0.5 rag/tablet）. Log-rank tests and Kaplan-Meier estimations were used to estimate the angina remission rates at 6 time-points after treatment （1,2, 3, 4, 5, and 〉5 min）. Logistic regression analysis was performed to observe the factors influencing the rate of effective angina remission, and the remission rates and incidences of adverse reactions were compared for different Canadian Cardiovascular Society （CCS） classes of angina. Results： The 5-min remission rates in the KA and control groups were not significantly different （94.41% vs. 90.64%, P〉0.05）. The angina CCS class significantly influenced the rate of remission （95% confidence interval = 0.483-0.740, P〈0.01）. In the CCS subgroup analysis, the 3- and 5-min remission rates for KA and NT were similar in the CCS I and IV subgroups （P〉0.05）, while they were significantly better for KA in the CCS Ⅱ and Ⅲ subgroups （P〈0.05 or P〈0.01）. Furthermore, the inciden0ce of adverse reactions was significantly lower in the KA group than in the control group for the CCS Ⅱ and Ⅲ subgroups （9.29% vs. 26.22%, 10.13% vs. 20.88%, P〈0.05 or P〈0.01）. Conclusions： KA is not inferior to NT in the remission of angina. Furthermore, in CCS Ⅱ and Ⅲ patients, KA is superior to NT, with a lower incidence of adverse reactions. （Registration No. ChiCTR- IPR-15007204）

Effectiveness of Integrative Medicine Therapy on Coronary Artery Disease Prognosis: A Real-World Study

Objective: To evaluate the effectiveness of integrative medicine(IM) on patients with coronary artery disease(CAD) and investigate the prognostic factors of CAD in a real-world setting. Methods: A total of 1,087 hospitalized patients with CAD from four hospitals in Beijing, China were consecutively selected between August 2011 and February 2012. The patients were assigned to two groups based on the treatment: Chinese medicine(CM) plus conventional treatment, i.e., IM therapy(IM group); or conventional treatment alone(CT group). The endpoint was major adverse cardiac events [MACE; including cardiac death, myocardial infarction(MI), and revascularization]. Results: A total of 1,040 patients finished the 2-year follow-up. Of them, 49.4%(514/1,040) received IM therapy. During the 2-year follow-up, the total incidence of MACE was 11.3%. Most of the events involved revascularization(9.3%). Cardiac death/MI occurred in 3.0% of cases. For revascularization, logistic stepwise regression analysis revealed that age 65 years [odds ratio(OR), 2.224], MI(OR, 2.561), diabetes mellitus(OR, 1.650), multi-vessel lesions(OR, 2.554), baseline high sensitivity C-reactive protein level 3 mg/L(OR, 1.678), and moderate or severe anxiety/depression(OR, 1.849) were negative predictors(P<0.05); while anti-platelet agents(OR, 0.422), β-blockers(OR, 0.626), statins(OR, 0.318), and IM therapy(OR, 0.583) were protective predictors(P<0.05). For cardiac death/MI, age 65 years(OR, 6.389) and heart failure(OR, 7.969) were negative predictors(P<0.05), while statin use(OR, 0.323) was a protective predictor(P<0.05) and IM therapy showed a beneficial tendency(OR, 0.587), although the difference was not statistically significant(P=0.218). Conclusion: In a real-world setting, for patients with CAD, IM therapy was associated with a decreased incidence of revascularization and showed a potential benefit in reducing the incidence of cardiac death or MI.

Combined effect of atorvastatin and probucol on plasma cystatin C levels and severity of coronary lesion in patients with borderline coronary lesion

Background The plasma cystatin C concentration （PcyC） has been demonstrated to have prognostic value in acute coronary syndrome, but the study of PcyC in patients with borderline coronary lesions is limited. Moreover, the effects of atorvastatin and probucol on PcyC and the severity of coronary lesions are unknown. This study was to evaluate the effects of the combination of atorvastatin and probucol on PcyC and severity of coronary lesion in patients with borderline coronary lesions. Methods One hundred and thirty consecutive patients with borderline coronary lesions （40% to 60% isolated single stenosis assessed by quantitative coronary angiography） were enrolled into the borderline coronary lesion （BCL） group, and one hundred and thirty-six subjects without coronary lesions comprised the controls （CTR）. The subjects in the BCL group were randomized into routine treatment （RTT, n=60）, and combined treatment with atorvastatin 20 mg plus probucol 1.0 g daily added to routine medication （CBT, n=70）, both groups were treated for 6 months continuously. The levels of PcyC, high-sensitive C-reactive protein （hs-CRP）, total cholesterol （TC）, low-density lipoprotein cholesterol （LDL-C）, high-density lipoprotein cholesterol （HDL-C）, and triglycerides （TG） were determined. One hundred and four subjects in the BCL group were rechecked by coronary angiography. Results PcyC levels were significantly higher in the BCL group than in the CTR group; （2003.26＋825.73） ng/ml vs. （1897.83＋664.46） ng/ml （P 〈0.01）. Compared with patients in the RTT group, the levels of PcyC, TC, LDL-C, TG and hs-CRP were significantly lower in the CBT group （P 〈0.05）. Moreover, there was a trend towards a slight decrease in the RTT patients, （54.38＋10.67）% vs. （50.29＋9.89）% （P 〉0.05）, and a significant decrease in the CBT patients, （53.65＋9.48%） vs. （40.38＋12.93）% （P 〈0.05）, in the mean percent stenosis of borderline coronary lesions before and after six months of treatment. Conclusions Cystatin C played an important role in with the severity of coronary lesions. The combination the treatment of choice. the development of coronary artery disease, and was associated of atorvastatin and probucol decreased PcyC levels, and could be

A prospective multicenter parallel-controlled trial of TIVOLI biodegradable-polymer-based sirolimus-eluting stent compared to ENDEAVOR zotarolimus-eluting stent for the treatment of coronary artery disease： 8-month angiographic and 2-year clinical follow-up results

Background Available drug-eluting stents （DES） have achieved great success in reducing restenosis rates. Recently,investigators have demonstrated that the durable polymer carrier plays a significant role in DES-related hypersensitive reaction and delays vessel healing. TIVOLI stent is a novel sirolimus-eluting coronary stent with biodegradable coating containing sirolimus and polylactic-co-glycolic acid （PLGA） polymer. The present study sought to evaluate the effectiveness and safety of the TIVOLI biodegradable-polymer-based sirolimus-eluting stent in treating patients with coronary artery disease.Methods A prospective, multicenter clinical trial comparing TIVOLI biodegradable coated sirolimus-eluting stent with ENDEAVOR zotarolimus-eluting stent was conducted in 324 patients （TIVOLI group： 168 patients; ENDEAVOR group：156 patients） at 12 centers in China to demonstrate the non-inferiority of in-stent late loss with TIVOLI stent compared to ENDEAVOR stent in subjects with a maximum of two de novo native coronary artery lesions （lesion length ≤40 mm,reference vessel diameter 2.25-4.00 mm）. The primary end point was angiographic in-stent late loss at 8-month. The secondary end points were clinical outcomes at 2 years,including major adverse cardiac events （cardiac death,myocardial infarction, or target-lesion revascularization） and stent thrombosis.Results Angiographic late lumen loss at 8 months in the TIVOLI group was superior to the ENDEAVOR group （in-stent （0.25±0.33） mm vs. （0.57±0.55） mm, diff （95% CI）-0.23 （-0.32, -0.14）, P 〈0.0001; in-segment （0.25±-0.33） mm vs. （0.42±-0.55） mm, diff （95% CI） -0.13 （-0.23, -0.02）,P=0.0083）. The rate of in-stent binary restenosis at 8 months was reduced from 8.6% in the ENDEAVOR group to 2.9% in the TIVOLI group （P=0.0229）. Compared to ENDEAVOR stent, TIVOLI stent resulted in a significant reduction in target-lesion revascularization （4.2% vs. 9.6%, P=0.0495） at 2 years. The two-year major adverse cardiac events （MACE） rate was lower for the TIVOLI group, but not significantly different （6.6% vs. 10.9%, P=0.1630）.Conclusions TIVOLI was superior to ENDEAVOR stent with respect to late lumen loss at 8 months, and it yielded both lower rates of angiographic binary restenosis at 8 months and target lesion revascularization （TLR） at 2 years.The MACE rate at 2 years was comparable in both groups.