Min-Soo Ahn

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.

OBJECTIVES This 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. BACKGROUND The prognostic significance and optimal cutoff of HTPR might differ according to a given clinical condition, such as AMI and ethnicity. METHODS On-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. RESULTS The 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). CONCLUSIONS Increased 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.

Comparison of sirolimus-eluting stent and paclitaxel-eluting stent for long-term cardiac adverse events in diabetic patients: the Korean Multicenter Angioplasty Team (KOMATE) Registry.

Background: There is some controversy on long‐term cardiac outcomes between sirolimus‐eluting stents (SES) and paclitaxel‐eluting stents (PES) in diabetes mellitus (DM). We compared cardiac adverse events after SES and PES implantation in patients with DM over a period of 3 year. Methods: A total of 634 patients with DM treated with SES (n = 428) or PES (n = 206) were consecutively enrolled in the KOMATE registry from 2003 to 2004. We assessed major adverse cardiac events (MACEs, cardiovascular death, nonfatal myocardial infarction, ischemia driven target vessel revascularization) and stent thrombosis (ST) according to the definitions set by the Academic Research Consortium. Results: Propensity score (PS) analysis was performed to adjust different baseline characteristics. The mean follow‐up duration was 38 ± 8 month (at least 36 month and up to 53 month). The 3‐year MACE rate did not show a significant difference between the two groups [52 (12.1%) in SES vs. 29 (14.1%) in PES, P = 0.496]. The definite and probable ST at 3 year were similar in both SES and PES [12 (2.8%) in SES vs. 7 (3.4%) in PES, P = 0.681]. There were no differences in hazard ratio for MACE and ST between two stents [MACE, crude: 0.844 (0.536–1.330) and adjusted for PS: 0.858 (0.530–1.389); ST, crude: 0.820 (0.323–2.083) and adjusted for PS: 0.960 (0.357–2.587)]. Conclusions: The present study demonstrated that long‐tem cardiac outcomes including ST were not significantly different between SES and PES in patients with DM.

Genotype- and Phenotype-Directed Personalization of Antiplatelet Treatment in Patients with Non-ST Elevation Acute Coronary Syndromes Undergoing Coronary Stenting

Background and Objectives We evaluated the effectiveness of genotype- and phenotype-directed individualization of P2Y12 inhibitors to decrease high on-treatment platelet reactivity (HOPR). Subjects and Methods Sixty-five patients undergoing percutaneous coronary intervention for non-ST elevation acute coronary syndromes were randomly assigned to genotype- or phenotype-directed treatment. All patients were screened for CYP2C19*2, *3, or *17 alleles by using the Verigene CLO assay (Nanosphere, Northbrook, IL, USA). The P2Y12 reaction unit (PRU) was measured using the VerifyNow P2Y12 assay (Accumetrics, San Diego, CA, USA). 21 CYP2C19 *2 or *3 carriers (65.6%) and 11 patients with HOPR (33.3%), defined as a PRU value ≥230, were given 90 mg ticagrelor twice daily; non-carriers and patients without HOPR were given 75 mg clopidogrel daily. The primary endpoint was the percentage of patients with HOPR after 30 days of treatment. Results PRU decreased following both genotype- and phenotype-directed therapies (242±83 vs. 109±90, p<0.001 in the genotype-directed group; 216±74 vs. 109±90, p=0.001 in the phenotype-directed group). Five subjects (16.2%) in the genotype-directed group and one (3.3%) in the phenotype-directed group had HOPR at day 30 (p=0.086). All patients with HOPR at the baseline who received ticagrelor had a PRU value of <230 after 30 days of treatment. Conversely, clopidogrel did not lower the number of patients with HOPR at the baseline. Conclusion Tailored antiplatelet therapy according to point-of-care genetic and phenotypic testing may be effective in decreasing HOPR after 30 days.

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 optimal time of B-type natriuretic peptide sampling associated with post-myocardial infarction remodelling after primary percutaneous coronary intervention

Aims To find the optimal time to evaluate plasma B-type natriuretic peptide (BNP), which is related to post-myocardial infarction remodelling (PMIR), we measured serial plasma BNP levels according to time protocols after primary percutaneous coronary intervention (PCI). Background It has been established that plasma BNP levels can predict the development of PMIR in patients with ST-elevation myocardial infarction (STEMI). However, the time of plasma BNP sampling associated with PMIR is still controversial. Methods We analysed 42 patients who were diagnosed as PMIR on six-month follow-up echocardiography among 131 patients with STEMI. We then compared clinical variables including plasma BNP between the remodelling group and the non-remodelling group. The plasma BNP level was obtained on hospital admission (acute phase), at two to five days (early phase), three to four weeks (late phase) and at the six-month follow up (long term). Results Early-phase and long-term BNP levels were higher in the remodelling group. The serial plasma BNP levels, according to study protocols, showed a biphasic pattern of elevation. In multiple logistic regression analyses, early-phase BNP [odds ratio (OR): 1.013, p < 0.01] and acute-phase BNP levels (OR: 1.007, p = 0.02) were independent predictors of PMIR. However, early-phase BNP level was statistically a more powerful predictor of PMIR during follow up. Conclusion Consecutive BNP levels after primary PCI showed a biphasic peak elevation during follow up. Earlyphase plasma BNP level was an independent predictor of PMIR in patients with STEMI.

BLEEDING RISK AND MAJOR ADVERSE EVENTS IN PATIENTS WITH PREVIOUS ULCER ON ORAL ANTICOAGULATION THERAPY: A MULTICENTER STUDY

Bleeding is the major concern for anticoagulation (OAC), especially in high bleeding risk patients. This multicenter study evaluated the safety and efficacy of OAC in AF patients with the history of ulcer. The study included 754 AF patients with healed ulcer at six tertiary hospitals. We compared

IMPACT OF CHRONIC KIDNEY DISEASE ON CLINICAL OUTCOMES IN PATIENTS WITH DIABETES MELLITUS UNDERWENT PERCUTANEOUS CORONARY INTERVENTION USING DRUG-ELUTING STENT

Although there have been few studies regarding the adverse effect of chronic kidney disease (CKD) on clinical outcomes in diabetic patients undergoing percutaneous coronary intervention (PCI), most studies were conducted in the era of bare metal stent or 1st generation drug-eluting stent (DES). It

PREDICTORS FOR CHANGES IN REFERENCE VESSEL DIAMETER IN PATIENTS WITH CORONARY ARTERY DISEASE

Selection of the appropriate stent diameter may be important during percutaneous coronary intervention (PCI) for preventing late stent thrombosis. We evaluated the predictors for changes in reference vessel diameter (RVD) in patients with coronary artery disease (CAD). 1,081 patients (1,688 lesions