g-Jin Youn

A Randomized, Open-Label, Multicenter Trial for the Safety and Efficacy of Adult Mesenchymal Stem Cells after Acute Myocardial Infarction

Recent studies suggest that the intracoronary administration of bone marrow (BM)-derived mesenchymal stem cells (MSCs) may improve left ventricular function in patients with acute myocardial infarction (AMI). However, there is still argumentative for the safety and efficacy of MSCs in the AMI setting. We thus performed a randomized pilot study to investigate the safety and efficacy of MSCs in patients with AMI. Eighty patients with AMI after successful reperfusion therapy were randomly assigned and received an intracoronary administration of autologous BM-derived MSCs into the infarct related artery at 1 month. During follow-up period, 58 patients completed the trial. The primary endpoint was changes in left ventricular ejection fraction (LVEF) by single-photon emission computed tomography (SPECT) at 6 month. We also evaluated treatment-related adverse events. The absolute improvement in the LVEF by SPECT at 6 month was greater in the BM-derived MSCs group than in the control group (5.9%±8.5% vs 1.6%±7.0%; P=0.037). There was no treatment-related toxicity during intracoronary administration of MSCs. No significant adverse cardiovascular events occurred during follow-up. In conclusion, the intracoronary infusion of human BM-derived MSCs at 1 month is tolerable and safe with modest improvement in LVEF at 6-month follow-up by SPECT. (ClinicalTrials.gov registration number: NCT01392105)

Different prognostic significance of high on-treatment platelet reactivity as assessed by the VerifyNow P2Y12 assay after coronary stenting in patients with and without acute myocardial infarction.

OBJECTIVESnThis study compared the prognostic role of high on-treatment platelet reactivity (HTPR) in predicting thrombotic events in a Korean population undergoing percutaneous coronary intervention (PCI) in the acute myocardial infarction (AMI) and non-AMI setting.nnnBACKGROUNDnThe prognostic significance and optimal cutoff of HTPR might differ according to a given clinical condition, such as AMI and ethnicity.nnnMETHODSnOn-treatment platelet reactivity was measured with a VerifyNow P2Y12 assay (Accumetrics, San Diego, California) in 1,226 patients (824 men; age 65 ± 10 years), including 413 AMI cases, 12 to 24 h after PCI between March 2008 and March 2010. The prevalence of cardiovascular (CV) events defined as a composite of death from CV causes, nonfatal myocardial infarction, or stent thrombosis at 1-year follow-up were compared according to HTPR between patients with and without AMI.nnnRESULTSnThe optimal cutoff for HTPR was 272 IU of the P2Y(12) reaction unit (PRU) (area under the curve: 0.708; 95% confidence interval [CI]: 0.607 to 0.809, p = 0.03), which was the upper-tertile threshold. Among AMI patients, 1-year CV events occurred more frequently in patients with versus without HTPR (n = 14 [8.8%] vs. n = 1 [0.4%], p < 0.001), whereas there was no difference in the composite endpoint on the basis of HTPR in patients without AMI (n = 7 [2.8%] vs. n = 8 [1.4%], p = 0.193).nnnCONCLUSIONSnIncreased residual platelet reactivity is related to post-discharge CV events in subjects with AMI, whereas the prognostic significance of HTPR seems to be attenuated in patients with stable coronary disease after PCI.

Intravascular Ultrasound-Guided Percutaneous Coronary Intervention Improves the Clinical Outcome in Patients Undergoing Multiple Overlapping Drug-Eluting Stents Implantation

Background and Objectives Stented segment length is a predictive factor for restenosis and stent thrombosis still in the drug-eluting stent (DES) era, and the benefit of routine intravascular ultrasound (IVUS) is still unclear. The aim of the present study was to investigate whether IVUS-guided percutaneous coronary intervention (PCI) improved the vascular outcomes as compared with conventional PCI in the treatment of diffuse coronary artery disease. Subjects and Methods From our registry database from January 2006 to May 2009, we identified 85 consecutive patients with de novo coronary lesions treated with at least 64 mm of multiple, overlapping DES. The 2-year rate of major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, non-fatal myocardial infarction, target lesion revascularization (TLR), or stent thrombosis, was compared according to the use of IVUS. Results The 2-year MACE rate was lower in the IVUS-guided group than that of the angiography-guided group (8% vs. 33.3%, p=0.005). The incidence of TLR was lower in patients with IVUS use than in those without IVUS use (0% vs. 27.8%, p<0.001). On Cox proportional hazard analysis, no IVUS use {hazard ratio (HR) 5.917, 95% confidence interval (CI) 1.037-33.770, p=0.045} and age (HR 1.097, 95% CI 1.006-1.138, p=0.032) were unfavorable predictors for the 2-year MACE. Conclusion The use of IVUS may improve the effectiveness and safety of multiple overlapping drug-eluting stenting for long, diffuse coronary lesions.

Urinary levels of 8-iso-prostaglandin f2α and 8-hydroxydeoxyguanine as markers of oxidative stress in patients with coronary artery disease.

Background and Objectives The objective of this study was to determine if urinary levels of 8-iso-prostaglandin F2α (8-iso-PGF2α) and 8-hydroxydeoxyguanine (8-OHdG) could be used as markers of the oxidative stress in significant coronary artery disease (CAD). Subjects and Methods We conducted a case-control study in 104 subjects assessed by coronary angiography with the following diagnoses: 35 consecutive cases of significant CAD and 69 cases of non-CAD with stable angina. We compared the urinary levels of 8-iso-PGF 2α and 8-OHdG, as measured by immunoassay between the 2 groups. Results History of hypertension was significantly higher and high density lipoprotein-cholesterol level significantly lower in the CAD group compared with those in the non-CAD group. Median levels of 8-iso-PGF2α were significantly higher in the CAD group compared with the non-CAD group (9.2 vs. 6.0 ng/mg, p=0.001). There were no significant differences in 8-OHdG values between the 2 groups. The odds ratio of 8-iso-PGF2α for CAD in the highest tertile compared with that in the lowest tertile was 7.39 (95% confidence interval; 1.71-31.91). There was no significant difference in median values of 8-iso-PGF2α between single- and multi-vessel CAD. Conclusion Urinary 8-iso-PGF 2α was independently associated with significant CAD in this case-control study.

The clustering patterns of metabolic risk factors and its association with sub-clinical atherosclerosis in Korean population

Background and aims: Metabolic syndrome (MetS) is considered to be an insulin-resistance syndrome, but recent evidence suggests that MetS has multiple physiological origins which may be related to atherosclerosis. This study investigated clustering patterns of metabolic risk factors and its association with sub-clinical atherosclerosis. Subjects and methods: This study used factor analysis of 11 metabolic factors in 1374 individuals to define clustering patterns and determine their association with carotid intima-media thickness (CIMT). Eleven metabolic factors were used: body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), fasting blood insulin (FBI), serum triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), homeostasis model assessment-insulin resistance (HOMA-IR), high-sensitivity C-reactive protein (hsCRP) and adiponectin. Two regression analyses were done, the first using individual metabolic variables and the second using each factor from the factor analysis to evaluate their relationships with CIMT. Results: Four clustering patterns, insulin-resistance factor (FBG, FBI, HOMA-IR), obesity-inflammatory factor (BMI, WC, hsCRP), blood pressure factor (SBP, DBP) and lipid metabolic factor (HDL-C, TG, adiponectin) were categorized. In a multivariate regression model after adjustment for age, sex, low-density lipoprotein cholesterol and smoking history (pack year), insulin resistance factor (B = 11.09, p = 0.026), obesity-inflammatory factor (B = 18.50, p < 0.001), blood pressure factor (B = 12.84, p = 0.010) and lipid metabolic factor (B = − 11.55, p = 0.023) were found to be significantly associated with CIMT. Conclusion: In conclusion, metabolic risk factors have four distinct clustering patterns that are independently associated with sub-clinical atherosclerosis.

AS-2: Significance of Slow-Response to Clopidogrel Assessed by a Point-of-Care Assay in Acute Coronary Syndrome Patients Undergoing Coronary Stenting

Background: To prevent atherothrombotic events, clopidogrel and aspirin are routinely used to treat patients undergoing percutaneous coronary intervention (PCI). Despite clopidogrel therapy, patients undergoing PCI are at risk of recurrent coronary events. We sought to evaluate prospectively death and myocardial infarction (MI) in acute coronary syndrome patients and their response to clopidogrel. Methods: We enrolled 610 consecutive patients (pts; 160 males, 65.2 10.3 years) who received percutaneous coronary intervention (PCI) for acute coronary syndrome (unstable angina, non-ST elevation MI, and ST elevation MI) from January 2006 to January 2008. Endpoint was defined as cardiac death and stent thrombosis (ST) using definitions of the Academic Research Consortium. Aspirin and clopidogrel responsiveness were evaluated by VerifyNow tests (Accumetrics, San Diego, CA). Low response to clopidogrel was defined as the 20% inhibition of P2Y12 receptor. Results: Baseline demographic characteristics were similar between the normal group (370 pts) and the low-response group (240 pts). Cardiac death occurred in 7 pts (1.9%) in the normal group and 14 pts (5.8%) in low group (p 0.009). Stent thrombosis occurred in 5 pts in normal group (0.7%, 4 definite and 1 probable) and 10 pts in the low-response group (4.2%, 7 definite, 2 probable, and 1 possible; p 0.028). The association between cardiac death and low response to clopidogrel was evaluated with multivariable logistic regression models adjusted for age and sex. The adjusted odds ratio for cardiac death was 3.242 (p 0.013, 95% confidence interval 1.281–8.205). Conclusion: Low-response to clopidogrel measured with a pointof-care assay is an independent predictor of cardiac death and stent thrombosis in acute coronary syndrome patients undergoing PCI.

AS-267: The Impact of Intravascular Ultrasound for Late Stent Thrombosis after Drug-Eluting Stent Implantation

Background: Stent thrombosis (ST) is a serious complication of drugeluting stent (DES) implantation, regardless of the timing (acute, subacute, or late). The US Food and Drug Administration (FDA) panel accepts ST but rejects increased death/myocardial infarction (MI) risk for on-label DES use. To date, the safety and efficacy of intravascular ultrasound (IVUS) use in DES implantation has been well evaluated, but there are few data regarding IVUS for ST. We evaluated the impact of IVUS for ST in DES implantation. Methods: A total 1,448 patients with DES implantation were included from January 2006 to February 2008 and were divided into a phase I group (from January 2006 to December 2006; before IVUS use; n 731) and a phase II group (from March 2007 to February 2008; after IVUS use; n 717). ST was defined by the Academic Research Consortium (ARC) as reported at the Transcatheter Cardiovascular Therapeutics 2006 meeting. Results: The median follow-up duration was 6 months in both phases. In all, 31 (2.1%) ST occurred: 21 (2.9 %) in phase I (4 subacute, 17 late ST) and 10 (1.4%) in phase II (4 subacute, 6 late ST). The incidence of ST in phase I was higher than in phase II (2.9% vs 1.4 %, p 0.052) but was not significant. Subacute ST in phase I was not higher than phase II (0.5% vs 0.6 %, p 0.978). Late ST in phase I was significantly higher than in phase II (2.3% vs 0.8 %, p 0.023). The univariate logistic regression showed the hazard ratio (HR) for late ST was 0.376 (95% confidence interval [CI], 0.146–0.971) for IVUS use and 0.959 (95% CI, 0.936–0.981) for high-density lipoprotein (HDL). After adjustment for age, sex, and HDL, IVUS use showed a trend for predicting late ST (HR, 0.223; 95% CI, 0.049–1.003; p 0.050). Conclusion: The incidence of late ST was higher in phase I before IVUS use compared with phase II after IVUS use. The use of IVUS showed the trend for decreasing late ST, but a large-scale study is needed for the evaluation of the impact of IVUS use in DES implantation. AS-268