K.S. Cha

Mesenchymal stem cells overexpressing GCP-2 improve heart function through enhanced angiogenic properties in a myocardial infarction model

AIMS In this study, our aim was to evaluate the angio-vasculogenic properties of human adipose tissue-derived mesenchymal stem cells overexpressing the granulocyte chemotactic protein (GCP)-2 (hASCs/GCP-2) and to determine possible therapeutic effects in an experimental ischaemic heart model. METHODS AND RESULTS Quantitative real-time (qRT)-PCR results revealed that hASCs/GCP-2 expressed significantly higher levels of pro-angiogenic genes, including vascular endothelial growth factor (VEGF)-A, hepatocyte growth factor (HGF), and interleukin (IL)-8, when compared with control-vector transduced hASCs or human umbilical vascular endothelial cells (HUVECs). In addition, the anti-apoptotic insulin-like growth factor (IGF)-1 and Akt-1 were also highly up-regulated in the hASCs/GCP-2 cells. In vitro cell migration and proliferation assays showed that hASCs/GCP-2-derived conditioned media (CM) significantly accelerated the migration and proliferation of fibroblast cells. Examination of in vitro endothelial differentiation showed that hASCs/GCP-2 cells spontaneously formed vascular-like structures and highly expressed endothelial-specific genes and proteins. In vivo study results of our mouse myocardial infarction (MI) model revealed that hASCs/GCP-2 implantation improved the cardiac function and reduced the infarct size. Finally, transplanted hASCs/GCP-2 cells unexpectedly differentiated into endothelial cells and the engraftment rate was significantly higher than control groups. CONCLUSION We suggest that overexpression of GCP-2 in stem cells has the potential to enhance their angiogenic and survival properties.

Clinical influence of early follow-up glycosylated hemoglobin levels on cardiovascular outcomes in diabetic patients with ST-segment elevation myocardial infarction after coronary reperfusion

ObjectiveRecent studies have shown continuous control of diabetes is important for favorable outcomes in patients with ST-segment elevation myocardial infarction (STEMI). This study aimed to evaluate the clinical influence of postprocedural glycosylated hemoglobin A1c (HbA1c) levels on major adverse cardiac events (MACE) in diabetic patients with STEMI after coronary reperfusion. Patients and methodsA total of 303 patients with diabetes and STEMI undergoing a primary percutaneous coronary intervention were enrolled in this study. All eligible patients were divided into the following three groups on the basis of follow-up HbA1c (FU-HbA1c) levels, which were measured at a median of 85 days after the procedure: optimal, FU-HbA1c<7%; suboptimal, 7%⩽FU-HbA1c<9%; and poor, FU-HbA1c≥9%. We analyzed the 12-month cumulative MACE, defined as mortality, nonfatal myocardial infarction, and revascularization. In addition, we investigated FU-HbA1c levels as a predictor of MACE. ResultsThe incidence rates of MACE differed significantly between groups (6.4 vs. 13.6 vs. 19.6%; P=0.048). Moreover, the risk was increased in each successive group (hazard ratio: 1.00 vs. 2.19 vs. 3.68; P=0.046). Each 1% increase in the FU-HbA1c level posed a 26.6% relative increased risk of MACE (P=0.031). The optimal cutoff value for FU-HbA1c in predicting MACE was 7.45%. ConclusionThis study showed that higher levels of early FU-HbA1c after reperfusion in diabetic patients with STEMI were associated with increased 12-month MACE, suggesting continuous serum glucose level control even after reperfusion is important for a better outcome. FU-HbA1c seems to be a useful marker for predicting clinical outcome.

A new risk score for ventricular tachyarrhythmia in acute myocardial infarction with preserved left ventricular ejection fraction

BACKGROUND Ventricular tachycardia or fibrillation (VT/VF) is a major cause of sudden cardiac death after acute myocardial infarction (AMI). This study aims to investigate the clinical characteristics and outcomes of VT/VF, to identify the variables associated with VT/VF, and to construct a new scoring system. METHODS Patients with relatively preserved left ventricular ejection fraction (LVEF) (≥40%) included in the Korea Acute Myocardial Infarction Registry-National Institutes of Health registry were enrolled in this study. Among 13,109 patients in the registry, a total of 10,334 (78.8%) had relatively preserved LVEF after AMI. Patients were divided into two groups based on whether they experienced life-threatening VT/VF during hospitalization or not. The predictors for VT/VF during hospitalization were assessed. In-hospital mortality and complications were recorded. RESULTS A total of 358 (3.5%) experienced life-threatening VT/VF. The VT/VF group was at an increased risk of in-hospital mortality (odds ratio 2.99) and cardiac death (odds ratio 3.40). Variables of diagnosis, Killip class, smoking, initial rhythm, left bundle branch block, and LVEF were significant indicators of VT/VF. A new risk score system yielded acceptable discrimination function (c-statistics=0.773). CONCLUSIONS Relatively preserved LVEF patients could still be at risk of life-threatening VT/VF, which is related to a poor prognosis during the admission period. This new scoring system can be adopted to stratify the risk of VT/VF.

Benefit of IVUS-guided PCI in diabetic patients presented with acute myocardial infarction- from Korea acute myocardial infarction registry

Purpose: Intravascular ultrasonography (IVUS) has been widely used in percutaneous coronary intervention (PCI) field. Precise measurement of reference vessel and early detection of various complications which cannot be distinguished by angiographic image led the outcome of IVUS-guided PCI more favorable. However, its beneficial effect was not thoroughly evaluated in the setting of acute myocardial infarction. Some studies documented that in the cases of AMI, IVUS-guided PCI was not superior to the conventional angiography guided PCI. We hypothesized that certain subjects such as patients with diabetes mellitus (DM) might receive benefits from IVUS-guided PCI. Methods: Patients were from Korea Acute Myocardial Infarction Registry (KAMIR) data. KAMIR was the retrospective observational study from 52 tertiary hospitals commemorating of the 50th anniversary of Korea Society of Cardiology. From 16,264 patients, 3,339 of consecutive patients were enrolled in this study. Patients with DM presented with AMI and received PCI were divided to two groups according to the use of IVUS during the procedure; IVUS group (n=683, 20.5%) and control group (n=2,656, 79.5%). Primary outcome was major adverse cardiovascular event (MACE) at one year follow up. Secondary outcomes were each component of MACE and stent thrombosis. Results: Mean age was 63.1 years and almost 75% were male. Patients in the IVUS group were younger and had better Killip class, more anterior infarction and target organ damage than the control group. They received longer, larger and more stents compared to patients in the control group. One month MACE was significantly lower in the IVUS group compared to the control group (4.6% vs. 10.6%, p<0.0001). Except for the one month death rate, other components of one month MACE were similar between the two groups. One month death rate was significantly lower in the IVUS group. Similar pattern was shown in the one year MACE. One year MACE was significantly lower in the IVUS group (10.1% vs. 15.1%, p=0.001). Also, but for the lower rate of one year death rate, other components showed no significant differences between two groups. One year stent thrombosis was not different, too (1.6% vs. 2.4%). However, after the multivariate logistic regression analysis, use of IVUS was not a significant predictor neither for one month MACE nor for one year MACE. This results reveals that this registry data represents IVUS was mostly done in patients with hemodynamic stable. Conclusion: From our study, IVUS-guided PCI was not associated with favorable clinical outcomes in diabetic patients with AMI.

Predictive value of glycosylated hemoglobin on cardiovascular outcomes in prediabetic patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

Background: Prediabetes is well known to have a substantially greater cardiovascular risk as a result of insulin resistance, dysglycemia, dyslipidemia, hypertension, endothelial dysfunction or inflammation shown as in diabetes mellitus. Previous studies demonstrated impaired glucose tolerance and/or impaired fasting glucose are strong predictors of adverse outcome in acute coronary syndrome. However, the prognostic value of glycemic controlled level, determined by glycosylated hemoglobin (HbA1c), in prediabetic patients with ACS is still undefined. The aim of this study was to demonstrate the role of HbA1c at admission on major adverse cardiac events (MACE) in prediabetic patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods: Using data from Korea Working Group on Myocardial Infarction (Kormi; February 2008-December 2011), this observational study included 1,536 patients who had not been diagnosed with DM before or after admission (HbA1c at admission less than 6.5%) with STEMI undergoing primary PCI. Patients were divided into two groups based on HbA1c at admission: non-diabetic (HbA1c≤5.6%, n=607, 39.5%) and pre-diabetic group (5.7%≤HbA1c≤6.4%, n=929, 60.5%). Results: One-year cumulative MACE which was defined as a composite of mortality, nonfatal MI, repeated PCI or coronary artery bypass graft, was not different between two groups (7.4% vs 9.4%, p=0.182). After multivariate logistic analysis, HbA1c was not associated with occurrence of MACE (OR 1.009, 95% CI 0.579-1.759, p=0.975). We conducted subgroup analysis and divided pre-diabetic patients into two groups by the HbA1c level of 6.0%. Both of one-year cumulative MACE (11.1% versus 7.5%) and OR for MACE were lower (OR 0.586) in patients with higher HbA1c level, but did not show any statistical significances, either. Conclusion: This study demonstrated HbA1c level at admission was not significantly associated with cardiovascular outcomes in prediabetic Korean populations with STEMI undergoing primary PCI.