Attenuation of ischemia-reperfusion injury by intracoronary chelating agent administration.

Ischemia-reperfusion (IR) injury accelerates myocardial injury sustained during the myocardial ischemic period and thus abrogates the benefit of reperfusion therapy in patients with acute myocardial infarction. We investigated the efficacy of intracoronary ethylenediaminetetraacetic acid (EDTA) administration as an adjunctive treatment to coronary intervention to reduce IR injury in a swine model. We occluded the left anterior descending artery for 1 h. From the time of reperfusion, we infused 50 mL of EDTA-based chelating agent via the coronary artery in the EDTA group and normal saline in the control group. IR injury was identified by myocardial edema on echocardiography. Tetrazolium chloride assay revealed that the infarct size was significantly lower in the EDTA group than in the control group, and the salvage percentage was higher. Electron microscopy demonstrated that the mitochondrial loss in the cardiomyocytes of the infarcted area was significantly lower in the EDTA group than in the control group. Echocardiography after 4 weeks showed that the remodeling of the left ventricle was significantly less in the EDTA group than in the control group: end-diastolic dimension 38.8 ± 3.3 mm vs. 43.9 ± 3.7 mm (n = 10, p = 0.0089). Left ventricular ejection fraction was higher in the EDTA group (45.3 ± 10.3 vs. 34.4 ± 11.8, n = 10, respectively, p = 0.031). In a swine model, intracoronary administration of an EDTA chelating agent reduced infarct size, mitochondrial damage, and post-infarct remodeling. This result warrants further clinical study evaluating the efficacy of the EDTA chelating agent in patients with ST-segment elevation myocardial infarction.

Association of Plasma Marker of Oxidized Lipid with Histologic Plaque Instability in Patients with Peripheral Artery Disease.

BACKGROUND: The association between oxidized low-density lipoprotein (OxLDL) and plaque instability in coronary and carotid artery disease is well established. However, the association between OxLDL and the histologic changes of plaque in peripheral artery disease has not been clearly elucidated. This study aims to investigate the association between plasma OxLDL and histologic plaque instability in patients with peripheral artery disease. METHODS: Prospectively obtained plaques from 48 patients who underwent endovascular atherectomy (n = 20), surgical endarterectomy (n = 9), or bypass surgery (n = 19) for treatment of atherosclerotic femoropopliteal artery disease were evaluated for histologic fibrosis, sclerosis, calcification, necrosis, cholesterol cleft, and foamy macrophages using hematoxylin and eosin, oil red O, and immunohistochemical staining. Unstable plaques were defined as plaques that were positive for foamy macrophages and with lipid content of more than 10% of the total plaque area. Plasma OxLDL levels were measured using an enzyme-linked immunosorbent assay (Mercodia AB, Uppsala, Sweden). RESULTS: Of the 48 patients, 26 (54%) had unstable plaques. The unstable plaque group was younger, had fewer angiographic total occlusions, less calcification, and more CD68-positive and LOX-1-positive cells than the stable plaque group. Plasma OxLDL levels were significantly higher in the unstable plaque group than in the stable plaque group (57.4 ± 13.9 vs. 47.2 ± 13.6 U/L, P = 0.014). Multivariate analysis revealed that plasma OxLDL level, smoking, angiographic nontotal occlusion, and statin nonuse were independent predictors of unstable plaque. CONCLUSIONS: Among patients with peripheral artery disease, the histologic instability of femoropopliteal plaque was independently associated with high plasma OxLDL, smoking, nontotal occlusion, and statin nonuse. Further large-scale studies are necessary to evaluate the role of noninvasive OxLDL measurement for predicting plaque instability and future adverse vascular event.

Differential impact of smoking on cardiac or non-cardiac death according to age.

Tobacco smoking causes cardiovascular diseases, lung disease, and various cancers. Understanding the population-based characteristics associated with smoking and the cause of death is important to improve survival. This study sought to evaluate the differential impact of smoking on cardiac or non-cardiac death according to age. Data from 514,866 healthy adults who underwent national health screening in South Korea were analyzed. The participants were divided into three groups: never-smoker, ex-smoker or current smoker according to the smoking status. The incidence rates and hazard ratios (HRs) of cardiac or non-cardiac deaths according to smoking status and age groups during the 10-year follow-up were calculated to evaluate the differential risk of smoking. Over the follow-up period, 6,192 and 24,443 cardiac and non-cardiac deaths had occurred, respectively. The estimated incidence rate of cardiac and non-cardiac death gradually increased in older age groups and was higher in current smokers and ex-smokers than that in never-smokers among all age groups. After adjustment of covariates, the HRs for cardiac death of current smokers compared to never-smokers were the highest in individuals in their 40's (1.82; 95% CI, 1.45-2.28); this gradually decreased to 0.96 (95% CI, 0.67-1.38) in individuals >80 years. In contrast, the HRs for non-cardiac death peaked in individuals in their 50's, (HR 1.69, 95% CI 1.57-1.82) and was sustained in those >80 years (HR 1.40, 95% CI 1.17-1.69). Ex-smokers did not show elevated risk of cardiac death compared to never-smokers in any age group, whereas they showed significantly higher risk of non-cardiac death in their 60's and 70's (HR, 1.29; 95% CI, 1.19-1.39; HR 1.22, 95% CI, 1.12-1.32, respectively). Acute myocardial infarction and lung cancer showed patterns similar to those of cardiac and non-cardiac death, respectively. Smoking was associated with higher relative risk of cardiac death in the middle-aged group and non-cardiac death in the older age group. Ex-smokers in the older age group had elevated risk of non-cardiac death. To prevent early cardiac death and late non-cardiac death, smoking cessation should be emphasized as early as possible.

Gender differences of in-hospital outcomes in patients undergoing percutaneous coronary intervention in the drug-eluting stent era.

Most studies on gender difference of the in-hospital outcome of percutaneous coronary intervention (PCI) were performed in the pre-drug-eluting stents (DES) era. This study was performed to investigate whether gender influences the in-hospital outcome of PCI in the DES era.A total of 44,967 PCI procedure between January and December of 2014 from the nationwide PCI registry database in Korea were analyzed. The study population was male predominant (70.2%). We examined the association of gender with unadjusted and adjusted in-hospital mortality and composite events of PCI, including mortality, nonfatal myocardial infarction, stent thrombosis, stroke, urgent repeat PCI and bleeding requiring transfusion.Most of the study patients (91.3%) received DES. The incidence rates of in-hospital mortality (2.95% vs 1.99%, P <.001) and composite events (7.01% vs 5.48%, P <.001) were significantly higher in women compared to men. Unadjusted analyses showed that women had a 1.49 times higher risk of in-hospital mortality and a 1.30 times higher risk of composite events than men (P <.001 for each). After adjustment for potential confounders, female gender was not a risk factor for mortality (P = .258), but the risk of composite events remained 1.20 times higher in women than in men (P = .008).Among patients undergoing PCI in the contemporary DES era, female gender was associated with an increased risk of in-hospital composite events, but not in-hospital mortality. More careful attention should be emphasized to minimize procedure-related risks and to improve prognosis in women undergoing PCI.

Comparison of Minimally Invasive Direct Coronary Artery Bypass and Percutaneous Coronary Intervention Using Second-Generation Drug-Eluting Stents for Coronary Artery Disease　- Propensity Score-Matched Analysis.

BACKGROUND: Some studies comparing minimally invasive direct coronary artery bypass (MIDCAB) and percutaneous coronary intervention (PCI) have reported MIDCAB's superiority, but they did not investigate contemporary PCI with newer generation drug-eluting stents (DES). We compared clinical outcomes after MIDCAB with previously reported outcomes after PCI with second-generation DES.Methods and Results:We retrospectively reviewed the records of patients treated with MIDCAB. Baseline characteristics and clinical outcomes after MIDCAB were compared with those for left anterior descending artery disease treated via PCI. The primary outcomes were major adverse cardiovascular and cerebrovascular events (MACCE), a composite of cardiovascular death, non-fatal myocardial infarction, ischemic stroke, and target vessel revascularization (TVR). A propensity score-matching (PSM) analysis was conducted to adjust for between-group differences in baseline characteristics. We analyzed 77 patients treated with MIDCAB and 2,206 treated with PCI. The MIDCAB group was older and had more severe coronary disease and a higher incidence of left ventricular dysfunction. Over a 3-year follow-up, the PCI group had favorable MACCE outcomes. After PSM, there were no between-group differences in MACCE (MIDCAB, 15.6% vs. PCI, 23.4%; hazard ratio [HR], 0.80; 95% CI: 0.38-1.68, P=0.548) or TVR (MIDCAB, 2.6% vs. PCI, 5.2%; HR, 0.51; 95% CI: 0.10-3.09, P=0.509). CONCLUSIONS: Clinical outcomes were similar between MIDCAB and PCI using second-generation DES over 3 years of follow-up.

Efficacy of IntraCoronary Erythropoietin Delivery BEfore Reperfusion-Gauging Infarct Size in Patients with Acute ST-segment Elevation Myocardial Infarction (ICEBERG).

Previous clinical studies have shown inconsistent results regarding the effect of erythropoietin in ST-segment elevation myocardial infarction (STEMI). This study investigated whether directed intracoronary infusion of darbepoetin-α into ischemic myocardium before reperfusion would reduce infarct size or post-infarct remodeling in STEMI patients.Eighty STEMI patients received one of the following treatments simultaneously with the first balloon inflation: intracoronary darbepoetin-α 300 µg (n = 40) or saline (n = 40), administered via the over-the-wire balloon system. The primary endpoint was infarct size estimated by serial cardiac enzyme levels after procedure. The secondary endpoints were (1) infarct size and proportion of salvaged myocardium measured with cardiac magnetic resonance (CMR) at baseline; (2) post-infarct remodeling (PIR), defined as an increase in left ventricular end-diastolic volume more than 20% at 4 months compared to the baseline on CMR; and (3) composite cardiovascular endpoints assessed at 4 months.The peak CK-MB [median 270.0 (interquartile range 139.8-356.3) versus 231.5 (131.0-408.5) ng/mL, P = 0.55] and troponin-I [128.5 (63.5-227.8) versus 109.0 (43.8-220.0) ng/mL, P = 0.52) ] did not differ between the darbepoetin-α and control group. Fifty-seven patients completed the baseline and 4-month follow-up CMR. There were no differences in infarct size [30.6 (18.1-49.8) versus 31.5 (22.5-47.3) cm3, P = 0.91), proportion of salvaged myocardium [26.7% (15.9-42.6%) versus 35.8% (22.4-48.8%), P = 0.12) or PIR (8.0% versus 6.7%, P = 0.62) between the two groups. Composite cardiovascular outcomes did not differ between the two groups.In conclusion, administration of intracoronary darbepoetin-α before reperfusion did not reduce infarct size or post-infarct remodeling in STEMI patients.

Clinical and Computed Tomography Angiographic Predictors of Coronary Lesions That Later Progressed to Chronic Total Occlusion.

OBJECTIVES: This study aimed to investigate clinical and coronary computed tomographic angiography (CTA) characteristics of lesions that progressed to chronic total occlusion (CTO). BACKGROUND: CTO is one of the most common reasons for referral to coronary artery bypass surgery. Prediction and adequate early management for future CTO lesions may be beneficial. METHODS: The study evaluated patients with at least 1 vessel with a diameter stenosis of ≥70% on invasive coronary angiography (ICA) who underwent previous coronary CTA >12 months before ICA, from 2006 to 2015. The study compared the baseline clinical and coronary CTA characteristics of the patients with future CTO lesions with those of the patients with future non-CTO lesions (patient-level analysis) and compared coronary CTA findings between the future CTO lesion with the most stenotic non-CTO lesion in each CTO patient (lesion-level analysis). RESULTS: Among the 216 patients, 32 (14.8%) had a CTO lesion on ICA. In patient-level analysis, no significant differences in clinical characteristics were found, whereas the coronary CTA culprit lesions of the CTO group had a smaller minimal lumen diameter (MLD) with more adverse plaque characteristics. In lesion-level analysis, future CTO lesions had a smaller MLD, a smaller reference segment diameter (RD), and longer lesion length. These lesions were more likely to be noncalcified plaques with a noneccentric cross-sectional distribution, and had a higher remodeling index, lower mean plaque attenuation (MPA), and more napkin-ring signs. In multivariate analysis and receiver-operating characteristic curve analysis, MLD of <2.0 mm, RD of <3.2 mm, and MPA of <50 Hounsfield units were independent predictors of future CTO lesions. The risk of CTO development in lesions with triple risk factors was 14-fold higher than that of the lesions with no risk factors. CONCLUSIONS: Lesions that progressed to CTO had more severe baseline coronary CTA features than non-CTO lesions. A small MLD, small RD, and low MPA were independent predictors of progression to CTO.

Effect of tailored use of tirofiban in patients with Non-ST-elevation acute coronary syndrome undergoing percutaneous coronary intervention: a randomized controlled trial.

BACKGROUND: We conducted a randomized controlled trial to investigate whether an additional platelet inhibition with tirofiban would reduce the extent of myocardial damage and prevent periprocedural myonecrosis in patients with Non-ST-elevation acute coronary syndrome (NSTE-ACS) with a high residual platelet activity (HPR). METHODS: Patients with an HPR, defined as P2Y12 reaction unit (PRU) > 230, were randomly assigned to group A (tirofiban treatment, n = 30) or C1 (n = 30) and patients without an HPR to C2 (n = 78). Periprocedural myocardial damage was assessed using the area under the curve (AUC) of serial cardiac enzyme levels from the time of the procedure to post-36 h. Periprocedural myonecrosis incidence was evaluated. RESULTS: The troponin I AUC was not different between the groups (197.2 [41.5395.7], 37.9 [8.9313.9], 121.3 [43.7481.8] h∙ng/mL; p = 0.088). The results did not change when the baseline levels were adjusted (365.3 [279.5, 451.1], 293.0 [207.1, 379.0], and 298.0 [244.7, 351.3] h∙ng/mL; p = 0.487). The rate of periprocedural myonecrosis was also not different between the groups (53.0% vs. 50.0% vs. 33.3%, p = 0.092). The CK-MB isoenzyme analysis showed similar results. No difference in complications was noted. CONCLUSION: Additional tirofiban administration was not beneficial to patients with NSTE-ACS even with an HPR. TRIAL REGISTRATION: Clinical trial no. NCT03114995 , registered 11 April, 2017, retrospectively.

The Effect of Cilostazol on the Angiographic Outcome of Drug-Eluting Coronary Stents Angiographic Analysis of the CILON-T (Influence of CILostazol-Based Triple Antiplatelet Therapy ON Ischemi Complication after Drug-Eluting StenT Implantation) Trial.

It is not clear if anti-restonotic effect of cilostazol is consistent for different types of drug-eluting stents (DES).The purpose of this study was to compare the anti-proliferative effect of cilostazol between DAT and TAT with consideration of confounding influences of DES type.Nine hundred and fifteen patients were randomized to either dual antiplatelet therapy (DAT; aspirin and clopidogrel) or triple antiplatelet therapy (TAT; aspirin, clopidogrel, and cilostazol) in the previous CILON-T trial. After excluding 70 patients who received both or neither stents, we analyzed 845 patients who received exclusively PES or ZES, and compared in-stent late loss at 6 months between both antiplatelet regimens (DAT versus TAT).Baseline angiographic and clinical characteristics were similar between the DAT (656 lesions in 425 patients) and the TAT group (600 lesions in 420 patients). The 6-month follow-up angiography was completed in 745 patients (88.2%). Quantitative coronary angiography showed that TAT significantly reduced in-stent late loss (DAT 0.62 ± 0.62 mm versus TAT 0.54 ± 0.49 mm, P = 0.015). Stent type, diabetes or lesion length did not interact with difference of late loss. However, reduction of late loss by cilostazol did not lead to a significant reduction in the rate of target lesion revascularization (TLR) (DAT 7.8% versus TAT 6.9%, P = 0.69) due to a nonlinear relationship found between late loss and TLR.The TAT group showed less in-stent late loss as compared to the DAT group. This was consistently observed regardless of DES type, lesion length, or diabetic status. However, reduction of late loss by cilostazol did not lead to a significant reduction in TLR.

Relation between secondhand smoke exposure and cardiovascular risk factors in never smokers.

OBJECTIVE: Secondhand smoke exposure (SHSE) in nonsmokers has been associated with premature cardiovascular mortality and ischemic heart disease. We conducted a cross-sectional, population-based study evaluating the relationship between SHSE, measured by subjective and objective methods, and conventional cardiovascular risks such as blood pressure, lipid profiles, and fasting glucose. METHODS: We extracted information on 7376 healthy adults who had never smoked, for whom there were available urine cotinine levels, from the Korea National Health and Nutrition Examination Survey 2008-2011. SHSE was defined using self-report questionnaires and urine cotinine levels. The main outcomes included SBP and DBP, serum lipid profiles, and fasting glucose. RESULTS: The mean age of the study population was 45.4 ±â€Š0.4 years and 75.2% were women. Self-reported SHSE had no significant association with study outcomes except for DBP, which had marginally positive relationships (P = 0.060). Unadjusted analysis showed higher cotinine levels were associated with lower SBP, total cholesterol, LDL cholesterol, and triglyceride. All associations lost statistical significance after multivariable adjustment. Fasting glucose had a positive relationship with urine cotinine in quartiles but not with logarithm-transformed cotinine. CONCLUSION: Although SHSE is associated with increased risk of cardiovascular mortality and morbidity, we did not find any consistent relationship among SHSE and blood pressure, lipid, or fasting glucose levels in this cross-sectional study. Using objective measurements of urine cotinine did not alter this relationship. Further long-term prospective studies are needed to evaluate the effect of SHSE as a cardiovascular risk factor.

A laboratory association between hemoglobin and VerifyNow P2Y12 reaction unit: A systematic review and meta-analysis.

BACKGROUND: VerifyNow P2Y12 assay is used widely to evaluate residual platelet reactivity in patients taking P2Y12 receptor antagonists. However, a laboratory association between VerifyNow P2Y12 reaction unit (PRU) and hemoglobin, which might lead to wrong interpretation of the data, is reported. We performed these systematic review and meta-analysis to clearly define the relationship between PRU and hemoglobin and to elucidate whether the relationship, if any, is a true biological association or is just a laboratory error. METHODS: Through a comprehensive electronic and manual search, 10 studies were selected for the cohort level meta-analysis. Among 10 studies, we were able to retrieve the raw data of 5 studies, and a patient-level meta-analysis was performed. Potential publication bias was searched by funnel plot analysis and was actively adjusted, if present, by trim and fill method. RESULTS: The pooled analysis revealed a significant inverse correlation between PRU and hemoglobin (r=-0.349; P<.001; 10 studies with 4,793 patients). VerifyNow P2Y12 base unit, which reflects off-drug platelet reactivity, was also inversely correlated with hemoglobin (r=-0.526; P<.001; 8 studies with 4,395 patients). % Inhibition (r=0.081; P=.059; 6 studies with 3,832 patients) and ΔPRU (r=-0.037; P=.188; 5 studies with 3,521 patients) were not associated with hemoglobin. A significant inverse association between PRU and hemoglobin was also observed in the patient-level meta-analysis (3,533 patients pooled from 5 studies; r=-0.335; P<.001). Light transmission aggregometry (r=0.160; P=.072; 4 studies with 1,144 patients) and multiple electrode platelet aggregometry (r=-0.029; P=.394; 3 studies with 7,645 patients) showed no significant association with hemoglobin. CONCLUSIONS: A significant inverse association was observed between PRU and hemoglobin which is likely to be a laboratory error. Clinicians should be aware that this association might lead to wrong interpretation of the data.

Long-Term Prognostic Value of Late Gadolinium-Enhanced Magnetic Resonance Imaging in Patients With and Without Left Ventricular Dysfunction Undergoing Coronary Artery Bypass Grafting.

The value of late gadolinium-enhanced (LGE) magnetic resonance imaging (MRI) for the prediction of functional recovery after surgical revascularization has been previously established. However, the impact of LGE-MRI on the long-term prognosis after coronary artery bypass grafting (CABG) remains incompletely understood. Therefore, we aimed to evaluate the long-term prognostic value of LGE-MRI, based on the presence or absence of left ventricular (LV) dysfunction, in patients with coronary artery disease undergoing CABG. One hundred forty-six consecutive patients underwent cine- and LGE-MRI before CABG. Adverse cardiac events included cardiac death, nonfatal myocardial infarction, heart failure, and unstable angina. A 3-year landmark analysis of the primary end point was also performed for patients surviving beyond 3 years after CABG. During a median follow-up of 9.4 years, 44 patients (30%) experienced adverse cardiac events. Although a LV ejection fraction <50% was associated only with adverse cardiac events at 3 years after CABG, LGE was associated with a worse outcome both at and beyond 3 years after CABG. In the overall study population, LGE presence (adjusted hazard ratio [HR] 2.58; p = 0.027), score (adjusted HR 1.06; p <0.001), and extent (adjusted HR 1.08; p <0.001) were independent predictors of adverse cardiac events. Moreover, in both the LV ejection fraction <50% and ≥50% groups, the LGE extent was an independent predictor of adverse cardiac events. In conclusion, our qualitative and quantitative analyses of LGE-MRI provide long-term prognostic information after surgical revascularization. The LGE extent was a strong predictor of adverse cardiac events, independent of the LV function.

Cigarette Smoking Does Not Enhance Clopidogrel Responsiveness After Adjusting VerifyNow P2Y12 Reaction Unit for the Influence of Hemoglobin Level.

OBJECTIVES: The authors performed this analysis to examine whether the enhanced clopidogrel responsiveness in current smokers is maintained after adjusting the influence of hemoglobin on VerifyNow P2Y12 reaction unit (PRU). BACKGROUND: PRU is consistently reported to be lower in current smokers. However, PRU has a significant inverse relationship with hemoglobin level, and smokers have higher hemoglobin levels. Because the association between PRU and hemoglobin is likely to be an in vitro phenomenon, we hypothesized that the observed difference in PRU between nonsmokers and current smokers is the result of confounding effect of hemoglobin rather than true difference in platelet reactivity. METHODS: Three cohorts were combined for the analysis (SNUBH [Seoul National University Bundang Hospital], n = 459; CILON-T [influence of CILostazol-based triple antiplatelet therapy ON ischemic complication after drug-eluting stenT implantation], n = 715; HOST-ASSURE [Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen], n = 1,357). The final combined cohort consisted of 1,314 patients who underwent percutaneous coronary intervention and had VerifyNow P2Y12 assay results. General linear model (analysis of covariance) was used to control the effect of hemoglobin on PRU. RESULTS: A significant inverse correlation was observed between PRU and hemoglobin (r = -0.389; p < 0.001). Current smokers showed a significantly higher hemoglobin level (13.5 ± 1.6 vs. 14.4 ± 1.5; p < 0.001) but lower PRU level (230.1 ± 90.7 vs. 212.2 ± 83.6; p < 0.001). After adjusting the influence of hemoglobin on PRU, there was no difference in PRU between nonsmokers and current smokers (224.1 [95% confidence interval: 218.7 to 229.5] vs. 225.3 [95% confidence interval: 217.2 to 233.3]; p = 0.813). CONCLUSIONS: The observed difference in PRU between nonsmokers and current smokers is largely attributable to the difference in hemoglobin level. Enhanced clopidogrel responsiveness in cigarette smokers is not confirmed in this study and the concept of the smokers' paradox needs further validation.

Physiological and clinical relevance of anomalous right coronary artery originating from left sinus of Valsalva in adults.

OBJECTIVE: To examine physiological and clinical relevance of an anomalous right coronary artery originating from left sinus of Valsalva (right ACAOS) with interarterial course in adults. METHODS AND RESULTS: For physiological assessment, fractional flow reserve (FFR) during dobutamine challenge was measured in 37 consecutive adult patients with lone right ACAOS with interarterial course. At baseline, mean FFR was 0.91±0.06, declining to 0.89±0.06 upon dobutamine infusion (p<0.001). Dobutamine stress FFR was significant (≤0.8) in three patients (8.1%), two of whom were surgically treated. Following surgery, dobutamine stress FFR rose from 0.76 to 0.94 and 0.76 to 0.98. Remodelling index (r=0.583, p=0.002), minimal lumen area (diastole: r=0.580, p=0.002; systole: r=0.0618, p<0.001) and per cent area stenosis (r=-0.550, p=0.004), measured by intravascular ultrasound, correlated with dobutamine stress FFR. To assess the clinical relevance, follow-up data of 119 patients with lone right ACAOS with interarterial course were analysed retrospectively. Two deaths occurred during a median follow-up period of 4 years, for a mortality rate of 0.34 per 100 person-year. No instances of myocardial infarction were recorded and one patient did undergo surgical revascularisation in the course follow-up. CONCLUSIONS: Most instances of lone right ACAOS with interarterial course discovered in adults were physiologically insignificant and ran benign clinical courses. Conservative management may thus suffice in this setting if no definitive signs of myocardial ischaemia are evident.

Impact of smoking status on clinical outcomes after successful chronic total occlusion intervention: Korean national registry of CTO intervention.

OBJECTIVES: We sought to evaluate the effect of cigarette smoking on long-term outcomes after successful percutaneous coronary intervention for chronic total occlusion (CTO) lesions. BACKGROUND: Cigarette smoking promotes the progression of atherosclerosis but enhances the antiplatelet effect of clopidogrel. METHODS: The Korea National Registry of CTO Intervention included 2,167 patients with CTO lesions from 26 centers who were successfully revascularized with drug-eluting stents from 2007 to 2009. Thrombotic events were defined as the composite of cardiac death, nonfatal myocardial infarction, and stent thrombosis. RESULTS: Current-smokers had more favorable baseline characteristics such as a younger age and lower prevalence of hypertension and diabetes mellitus. At 1 year, current-smokers had a significantly lower thrombotic event rate (1.1% vs. 2.7%, P = 0.034), but a significantly higher target vessel revascularization (TVR) rate (7.2% vs. 4.2%, P = 0.017) compared with never-smokers. After adjustment, current-smoking was independently associated with a 72% decreased risk for thrombotic events, and 73% increased risk for TVR. CONCLUSIONS: In patients with a revascularized CTO lesion, cigarette smoking is associated with fewer thrombotic events but with a higher incidence of TVR. Patients with CTO may benefit from smoking cessation to reduce TVR in conjunction with the use of new more potent antiplatelet agents whose effect is independent of cigarette smoking to improve thrombotic events. © 2015 Wiley Periodicals, Inc.

Different influences of hematocrit on the results of two Point-Of-Care platelet function tests, the VerifyNow assay and multiple electrode platelet aggregometry.

OBJECTIVE: Previous studies have reported a considerable association between the VerifyNow (Accumetrics, San Diego, CA, USA) P2Y12 assay results and hematocrit. No reports, however, have described an association between the multiple electrode platelet aggregometry (MEA; Dynabyte, Munich, Germany) adenosine diphosphate (ADP) assay results and hematocrit. This study was conducted to evaluate the influence of hematocrit on the results of 2 different point-of-care platelet function tests. METHODS: A total of 462 consecutive patients who were undergoing percutaneous coronary intervention were enrolled. Platelet function was evaluated with both the VerifyNow P2Y12 and MEA ADP assays. RESULTS: Anemic patients (n = 152, 32.9%) demonstrated a significantly higher rate of cardiac death, myocardial infarction, and stroke (5.3% vs. 2.3%, p = 0.046) during the follow-up (median: 18.8 months). Although the VerifyNow P2Y12 assay results demonstrated a significant inverse correlation with hematocrit (r = -0.409, p<0.001), there was no such correlation between the MEA ADP assay results and hematocrit (r = 0.039, p = 0.401). In the multivariate analysis, anemia was an independent predictor of high on-treatment platelet reactivity, defined as a VerifyNow P2Y12 reaction unit level of ≥252.5 (odds ratio = 2.21, 95% confidence interval = 1.39-3.52; p = 0.001). Importantly, this association was independent of an intrinsic change in platelet reactivity as measured by the MEA ADP assay. Adjusting for the influence of hematocrit improved the strength of the correlation between the VerifyNow P2Y12 and MEA ADP assay results. CONCLUSIONS: Hematocrit significantly influenced the VerifyNow P2Y12 assay results, a phenomenon that was presumably in-vitro. Hematocrit level should therefore be considered when interpreting results of the VerifyNow P2Y12 assay.

Cilostazol eliminates adverse smoking outcome in patients with drug-eluting stent implantation.

BACKGROUND: The present study investigated whether cilostazol can eliminate adverse smoking outcome after percutaneous coronary intervention (PCI). METHODS AND RESULTS: A total of 914 patients with successful drug-eluting stent (DES) implantation were randomly assigned to dual antiplatelet therapy (DAT; aspirin and clopidogrel, n=457) or to triple antiplatelet therapy (TAT; DAT with cilostazol, n=457). The effect of smoking on 2-year major adverse cardio/cerebrovascular events (MACCE) in both the TAT and DAT groups was evaluated. Total MACCE were not significantly different between the 2 anti-platelet regimens (9.8% in TAT vs. 11.4% in DAT groups, P=0.45), but the adverse effects of smoking on clinical outcome were different between DAT vs. TAT. Current smokers had a higher prevalence of MACCE than non-smokers in the DAT group (16.7% vs. 9.5%, P=0.04). In the TAT group, however, the adverse effect of smoking was abolished (9.2% vs. 10.1%, P=0.85). Regarding the effects of smoking on the antiplatelet effects of DAT or TAT, post-treatment platelet reactivity (in P2Y12 reaction units; PRU) in current smokers was not significantly lower than that in non-smokers in the DAT group, whereas, in the TAT group, it was significantly lower than that of non-smokers (189±88 vs. 216±89 PRU, P=0.01). CONCLUSIONS: Adverse clinical effects of smoking may be eliminated by the addition of cilostazol to DAT after DES implantation. This may be due to the stimulation of cilostazol's antiplatelet effects by smoking.

Platelet volume indices are associated with high residual platelet reactivity after antiplatelet therapy in patients undergoing percutaneous coronary intervention.

AIM: It is well known that platelet volume indices are associated with adverse outcomes following percutaneous coronary intervention(PCI). In this study, we investigated the hypothesis whether the association between platelet size and clinical outcomes is the result of high residual platelet reactivity after antiplatelet therapy in patients with large platelets. METHODS: Between February 2010 and December 2011, a total of 462 consecutive patients with coronary artery disease who were scheduled to undergo planned PCI were enrolled in this study. The degree of platelet aggregation induced by arachidonic acid(AA) and adenosine diphosphate(ADP) was assessed using the Multiple Electrode Platelet Aggregometry(Multiplate(®), Dynabyte, Munich, Germany)(MEA) test. We simultaneously measured the mean platelet volume(MPV) in the same period(Sysmex XE-2100, Mundelein, IL). RESULTS: The study population consisted of 462 consecutive patients, including 371 stable angina patients and 91 acute coronary syndrome patients. The patients with large platelets(upper quintile of MPV ≥10.6 fL) had significantly high residual platelet reactivity after both aspirin(MEA ASP 9 [5-14] Units vs. 13 [8-18.5] Units, p < 0.001) and clopidogrel(MEA ADP 21 [15-30] Units vs. 24 [18.5-40] Units, p=0.003) treatment. According to a multivariate analysis, having large platelets was independently associated with high residual platelet reactivity after both aspirin (OR 2.52, 95% CI 1.50-4.24, p < 0.001) and clopidogrel(OR 2.86, 95% CI 1.59-5.15, p < 0.001) treatment. Platelet volume indices were not associated with any differences in the incidence of major adverse cardiac events during follow-up. CONCLUSIONS: Platelets with a higher volume are associated with high residual platelet reactivity after conventional dual antiplatelet therapy.

Randomized trial comparing the efficacy between different types of paclitaxel-eluting stents: the comparison of efficacy between COroflex PLEASe ANd Taxus stent (ECO-PLEASANT) randomized controlled trial.

AIMS: Paclitaxel-eluting stents (PESs) have been shown to inhibit neointimal hyperplasia after percutaneous coronary intervention. Coroflex Please (B Braun, Melsungen, Germany) is a newly developed PES. We compared the clinical and angiographic efficacy of Coroflex Please with Taxus Liberte (Boston Scientific, Natick, MA) in a real-world practice. METHODS AND RESULTS: We performed a prospective, open-label, randomized, controlled study that enrolled 945 patients undergoing percutaneous coronary interventions in 18 centers in Korea. The primary end point was clinically driven target vessel revascularization at 9 months. The baseline characteristics were mostly similar and comparable between 2 groups. At 9 months, the incidence of clinically driven target vessel revascularization was 14.6% for Coroflex and 6.4% for Taxus, which was significantly different (hazard ratio 2.43, 95% CI 1.50-3.94, noninferiority P value = 1.000). This is well corroborated by the difference of in-stent late loss between 2 stents (0.71 ± 0.64 mm vs 0.52 ± 0.50 mm, P < .001) by 9-month follow-up angiography (n = 415 vs 215). Among secondary clinical end points, stent thrombosis (definite and probable) for 1 year was 2.2% in Coroflex and 1.3% in Taxus (P = .317). Also, myocardial infarction for 9 months was higher in Coroflex group than that in Taxus (4.9% vs 1.6%, P = .012), which was partly contributed by the higher incidence of periprocedural myocardial infarction in Coroflex arm (2.2% vs 0.3%, P = .028). CONCLUSIONS: Coroflex Please was inferior to Taxus Liberte with regard to clinical and angiographic efficacy.

A single-center prospective randomized controlled trial evaluating the safety and efficacy of IntraCoronary Erythropoietin delivery BEfore Reperfusion: gauging infarct size in patients with acute ST-segment elevation myocardial infarction. Study design and rationale of the 'ICEBERG Trial'.

BACKGROUND: Erythropoietin (EPO) protected the myocardium from ischemia and reperfusion injury in preclinical studies. However, whether EPO can reduce myocardial injury in patients with acute myocardial infarction (MI) is controversial. The inconsistent results of previous studies have been attributed to differences in the doses, timing, and routes of administration of EPO. In this study, we will evaluate intracoronary treatment with a long-acting EPO analog, darbepoetin-α, administered immediately before reperfusion in patients with acute anterior ST-segment elevation MI. METHODS: This trial will be a single-center, prospective, randomized, two-arm, controlled trial with blind evaluation of the endpoints. At the time of the primary percutaneous coronary intervention, 80 patients will randomly receive one of the following treatments immediately before the first ballooning: intracoronary darbepoetin-α (ARANESP®; Jeil-Kirin Pharm., Korea) 300µg (n=40) or saline (n=40), administered via the over-the-wire balloon system. The objectives of this study are to evaluate the safety and efficacy of intracoronary darbepoetin-α therapy. DISCUSSION: This is the first study to evaluate the safety and efficacy of intracoronary darbepoetin-α treatment in patients with acute MI.