Kwon Sam Kim

Cardioprotective Effects of Exenatide in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention Results of Exenatide Myocardial Protection in Revascularization Study

Objective—Experimental evidence suggests that exenatide, a glucagon-like peptide 1 receptor analogue, has significant cardiovascular protective effects in various conditions. We examined whether routine use of exenatide at the time of primary percutaneous coronary intervention would reduce infarct size in patients with ST-segment–elevation myocardial infarction. Approach and Results—Fifty-eight patients with ST-segment–elevation myocardial infarction and thrombolysis in myocardial infarction flow 0 were enrolled in the study and randomly assigned to receive either exenatide or placebo (saline) subcutaneously. Infarct size was assessed by measuring the release of creatine kinase-MB and troponin I during 72 hours and by performing cardiac magnetic resonance imaging at 1 month after infarction. Routine and speckle tracking echocardiography was performed at initial presentation and at 3 days and 6 months after primary percutaneous coronary intervention. The exenatide and control groups had similar results with respect to ischemia time, demographic characteristics, and ejection fraction before primary percutaneous coronary intervention. The releases of creatine kinase-MB and troponin I were significantly reduced in the exenatide group. In 58 patients evaluated with cardiac magnetic resonance, the absolute mass of delayed hyperenhancement was significantly reduced in the exenatide group as compared with the control group (12.8±11.7 versus 26.4±11.6 g; P<0.01). At 6 months, the exenatide group showed a significantly lower value of E/E′ with improved strain parameters. No significant adverse effects of exenatide administration were detected. Conclusions—In patients with ST-segment–elevation myocardial infarction, adjunctive exenatide therapy with primary percutaneous coronary intervention was associated with reduction of infarct size and improvement of subclinical left ventricular function.

Preventive Effects of Exenatide on Endothelial Dysfunction Induced by Ischemia-Reperfusion Injury via KATP Channels

Objective—The purpose of this study was to evaluate whether exenatide administration can prevent impairment in endothelium-dependent vasodilatation induced by ischemia-reperfusion (IR) injury and whether this effect is mediated by KATP channel opening. Methods and Results—In a double-blind, placebo-controlled, crossover design, 20 volunteers were randomly assigned to 2 groups: subcutaneous exenatide (10 &mgr;g) or placebo administration. At 30 minutes after the study drug administration, endothelium-dependent flow-mediated dilatation (FMD) of the radial artery was measured before and after IR (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion) injury. Seven days later, both groups were crossed over and received the other treatment (ie, placebo or exenatide) and underwent the same protocol. Pre-IR radial artery diameter, FMD, and baseline radial artery diameter after IR injury were similar between 2 groups (P=no significant difference). After placebo administration, IR significantly blunted FMD (before IR: 12.0±6.23%; after IR: 4.6±3.57%, P=0.02). Exenatide prevented this impairment (FMD before IR: 15.0±7.14%; FMD after IR: 15.0±5.96%, P=no significant difference; P<0.001 compared with placebo). In a separate protocol, this protective effect was completely abolished by pretreatment with glibenclamide (glyburide, 5 mg), a blocker of KATP channels (n=7; FMD before IR: 12.0±2.2%; after IR: 3.2±2.1%, P<0.001). Conclusion—The present study demonstrates that subcutaneous exenatide protects IR-induced endothelial dysfunction through opening of KATP channels in human IR injury model.

Impact of glutathione S-transferase M1 and T1 gene polymorphisms on the smoking-related coronary artery disease.

Glutathione S-transferase (GST) plays a key role in the detoxification of xenobiotic atherogen generated by smoking. To analyze the effect of GSTM1/T1 gene polymorphisms on the development of smoking-related coronary artery disease (CAD), 775 Korean patients who underwent coronary angiography were enrolled. The subjects were classified by luminal diameter stenosis into group A (>50%), B (20-50%), or C (<20%). GSTM1 and GSTT1 gene polymorphisms were analyzed using multiplex polymerase chain reaction (PCR) for GSTM1/T1 genes and CYP1A1 gene for internal control. Of 775 subjects, 403 patients belonged to group A. They had higher risk factors for CAD than group B (N=260) and group C (N=112). The genotype frequencies of null GSTM1 and GSTT1 showed no significant differences among 3 groups. Considering the effect of GSTM1 gene polymorphisms on the smoking-related CAD, smokers with GSTM1 null genotype had more increased risk for CAD than non-smoker with GSTM1 positive genotype (odds ratios [OR], 2.07, confidence interval [CI], 1.06-4.07). Also the effect of GSTT1 gene polymorphism on smoking-related CAD showed the same tendency as GSTM1 gene (OR, 2.00, CI, 1.05-3.84). This effect of GSTM1/T1 null genotype on smoking-related CAD was augmented when both gene polymorphisms were considered simultaneously (OR, 2.76, CI, 1.17-6.52). We concluded that GSTM1/T1 null genotype contributed to the pathogenesis of smoking-related CAD to some degree.

Prognostic Value of Serial Global Longitudinal Strain Measured by Two-Dimensional Speckle Tracking Echocardiography in Patients With ST-Segment Elevation Myocardial Infarction

The aim of this study was to determine whether assessment of global longitudinal strain (GLS) before revascularization could predict adverse cardiac events after ST-segment elevation myocardial infarction (STEMI). In addition, the relation between GLS and cardiac biomarkers was investigated. From July 2006 through December 2009, 98 patients with first STEMI underwent conventional and speckle tracking echocardiography at initial presentation and 3 days after primary coronary intervention. Patients were divided into 3 groups according to percent changes of GLS compared to baseline GLS values: group 1, improved GLS >10%; group 2, unchanged GLS from -10% to 10%; and group 3, decreased GLS <-10%. Subsequent complications including all-cause mortality and readmission because of congestive heart failure during a 6-month period of follow-up were prospectively evaluated. After coronary intervention, GLS was improved in 29 patients (30%, group 1), unchanged in 55 patients (56%, group 2), and worsened in 14 patients (14%, group 3). Complications developed in 7 patients (group 1, n = 0, 0%; group 2, n = 2, 28%; group 3, n = 5, 72%, p <0.01). Multivariate Cox analysis showed an independent association of GLS before and after coronary intervention with subsequent complications. Significant correlations were observed between GLS and cardiac biomarkers. In conclusion, GLS assessment before coronary intervention was a good predictor of complications in patients with STEMI comparable to predictions using GLS after intervention at 6-month follow-up.

Serial assessment of left ventricular remodeling by measurement of left ventricular torsion using speckle tracking echocardiography in patients with acute myocardial infarction.

The relation between remodeling and left ventricular (LV) torsion has not yet been fully investigated. The aim of this study was to determine whether LV torsion assessed by speckle tracking imaging can predict progressive LV dilation after acute myocardial infarction (AMI). From January 2006 through June 2008, 91 patients with AMI who were successfully treated with primary coronary intervention underwent conventional and speckle tracking echocardiographies at initial presentation and 3 days and 6 months after first AMI. Patients were divided into 2 groups based on presence of LV remodeling (increase of LV end-diastolic volume >20%) at 6-month follow-up. LV remodeling developed in 23 patients. At initial presentation, LV end-diastolic volume was not significantly different between the no-remodeling and remodeling groups (91.27 ± 35.68 vs 85.74 ± 28.89 ml, p = 0.51), but LV torsion (2.23 ± 0.67 vs 1.70 ± 0.58°/cm, p <0.05) was significantly decreased in the remodeling group. At 6-month follow-up speckle tracking echocardiography, apical rotation and global torsion in patients with remodeling were 6.7 ± 2.6 (p <0.05) and 1.7 ± 0.7°/cm (p = 0.76 from baseline), respectively, and in patients without remodeling, 8.8 ± 3.4 (p <0.01) and 2.5 ± 0.7°/cm (p <0.01 from baseline), respectively. According to receiver operating characteristic analysis, LV torsion of 1.9°/cm (area under curve 0.79, sensitivity 75%, specificity 78%) at initial presentation was selected as a significant predictor of remodeling. In conclusion, decreased LV torsion assessed by speckle tracking echocardiography may predict late LV remodeling after reperfusion therapy after AMI.

Comparison of peripheral arterial tonometry and flow-mediated vasodilation for assessment of the severity and complexity of coronary artery disease.

ObjectiveNoninvasive flow-mediated vasodilation (FMD) is a widely used method to assess endothelial function, but its technical difficulty and problems remain obstacles for use in clinical practice. Reactive hyperemia-peripheral arterial tonometry (RH-PAT) was developed as a simpler and more reproducible method. We compared FMD and RH-PAT in patients with stable angina. Furthermore, the differences in these two techniques according to coronary artery disease (CAD) severity and complexity were also assessed. Materials and methodsWe consecutively enrolled 80 patients who underwent elective coronary angiography. Endothelial function was assessed before angiography using brachial artery FMD and RH-PAT. The complexity and extent of the coronary lesions were assessed angiographically. The extent of CAD was defined as the number of diseased coronary arteries (>70%) and complexity of CAD was assessed by the SYNTAX score algorithm. ResultsIn the overall study group (61±9 years, 57% men), the mean FMD was 8.5±5.1% and the mean reactive hyperemia index (RHI) measured by RH-PAT was 1.7±0.4. A significant correlation was observed between FMD and RHI irrespective of sex, diabetes, or presence of CAD. FMD and RHI were significantly lower in patients with multivessel and complex CAD. A receiver-operating characteristic curve analysis showed that both techniques were comparable in terms of predicting the presence of CAD and complexity. ConclusionAssessment of RH-PAT could be a less operator-dependent and noninvasive method of evaluating vascular endothelial function in patients with stable angina.

Platelet reactivity after receiving clopidogrel compared with ticagrelor in patients with kidney failure treated with hemodialysis: a randomized crossover study.

BACKGROUND Patients with kidney failure treated with maintenance hemodialysis (HD) are poor responders to clopidogrel. More beneficial platelet-inhibiting strategies in HD patients therefore are required. STUDY DESIGN Single-center, prospective, randomized, crossover study. SETTING & PARTICIPANTS 25 HD patients in Seoul, Korea. INTERVENTION Patients were randomly assigned to receive clopidogrel (300mg loading, 75mg once daily for maintenance dose) or ticagrelor (180mg loading, 90mg twice daily for maintenance dose) for 14 days, and after a 14-day washout period, crossover treatment for another 14 days. All patients received aspirin (100mg/d). OUTCOMES & MEASUREMENTS Platelet function was evaluated predosing and at 1, 5, and 48 hours and 14 days after the first loading dose. During the offset phase, platelet function was assessed at 1 hour and 2, 4, and 14 days after the last dose by light transmittance aggregometry and the VerifyNow P2Y12 assay, and patients were genotyped for the CYP2C19*2 allele. Maximal extent of aggregation, inhibition of platelet aggregation (IPA), P2Y12 reaction units (PRUs), and percentage of inhibition were evaluated. We performed per-protocol analysis, excluding patients who did not complete the protocol. RESULTS 9 patients did not complete the protocol (7 patients due to adverse events; 2, nonadherence). Higher IPA occurred with ticagrelor than with clopidogrel at 1, 5, and 48 hours and 14 days after loading. By 5 hours after loading, a greater proportion of patients in the ticagrelor group than in the clopidogrel group achieved IPA>50% (75% vs 12%, respectively; P<0.05) and IPA>70% (44% vs 0%, respectively; P<0.05). Rates (slope) of onset and offset of the antiplatelet effect were faster in patients receiving ticagrelor than for those receiving clopidogrel (P<0.05). Regardless of CYP2C19*2 allele, the ticagrelor group had significantly lower PRUs at all times than the clopidogrel group. LIMITATIONS Single-center study with a small number of patients, not a double-blind study, and not intention-to-treat analysis. CONCLUSIONS Ticagrelor may result in more rapid and greater platelet inhibition than clopidogrel in patients with kidney failure receiving HD.

Biochemical and clinical correlation of intraplaque neovascularization using contrast-enhanced ultrasound of the carotid artery

OBJECTIVE Several biomarkers reflecting inflammatory or proteolytic activity have been known to represent plaque vulnerability. Moreover, a recent study confirmed that contrast-enhanced ultrasound (CEUS) can visualize intraplaque neovascularization (IPN) and demonstrate plaque vulnerability. In this study, we tried to demonstrate that IPN detected by CEUS was correlated with several well-known biomarkers and clinical outcome in patients with coronary artery disease (CAD). METHODS Patients with stable CAD were screened by conventional carotid ultrasound and patients with carotid plaque thickness more than 2 mm were performed by CEUS for the presence of IPN. Plasma levels of biomarkers and clinical outcomes were evaluated. RESULTS Among consecutive 89 patients fulfilled the inclusion criteria, 30 patients without IPN (group 1) and 59 patients with IPN (group 2) were analyzed. There were no significant difference in baseline characteristics except for mean age (62.9±10.1 yrs versus 68.4±9.6 yrs, p=0.015). On multivariate analysis, only MMP-9 (p=0.021, 95% CI 1.002-1.027) showed a significant association with IPN. But patients with IPN showed only trend for a history of cardiovascular disease (CVD) (44% versus 30%, p=0.19) and one-year cardiovascular events (CVE) (6.8% versus 3.3%, p=0.50) compared to group 1. Maximum plaque thickness (p=0.04, 95% CI 1.230-6.322) showed a significant correlation with the clinical outcome including CVD or CVE. CONCLUSION MMP-9 correlated with IPN on CEUS. For clinical implication, however, large prospective studies are needed.

Effect of Platelet Reactivity, Endothelial Function, and Inflammatory Status on Outcomes in Patients With Stable Angina Pectoris on Clopidogrel Therapy

Although high on-treatment platelet reactivity (HTPR) is an important predictor of clinical outcomes in patients undergoing coronary stenting, it is unknown whether endothelial dysfunction and HTPR are associated. We examined the platelet function, peripheral vascular function, endothelial progenitor cell (EPC) number, platelet activation markers, high-sensitivity C-reactive protein (hs-CRP) level, and clinical outcomes in patients receiving chronic clopidogrel therapy. We consecutively enrolled 91 patients who underwent follow-up angiography because of chest discomfort. All patients took aspirin and clopidogrel for an average of 498 ± 138 days. Platelet reactivity was assessed by light transmittance aggregometry (maximal platelet aggregation by 5 μmol/L of adenosine diphosphate ≤50% in group 1 [optimal response] and >50% as group 2 [HTPR]). Flow-mediated dilation of the brachial artery and brachial-ankle pulse wave velocity (PWV), numbers of EPCs isolated from peripheral blood, platelet activation markers (soluble CD40 ligand and soluble P-selectin), and hs-CRP levels were assessed before follow-up angiography. There were no significant differences in baseline characteristics and previous percutaneous coronary intervention (PCI) data between groups 1 (n = 59) and 2 (n = 32). Group 2 showed poorer flow-mediated dilation (6.1 ± 4.1% vs 12.9 ± 6.2%, p <0.001), pulse wave velocity (1925.4 ± 362.2 vs 1571.0 ± 306.5 ms, p <0.001), and lower circulating EPCs by flow cytometry (21.9 ± 14.7 vs 65.2 ± 30.1 per 10 fields, p <0.001) compared with group 1. Significantly higher levels of soluble CD40 ligand, soluble P-selectin, and hs-CRP were observed in group 2. In multivariate analysis, elevated hs-CRP level, but not HTPR, was independently associated with repeated PCI. In patients with angina, HTPR was associated endothelial dysfunction and elevated hs-CRP, although elevated hs-CRP level was significantly associated with poorer outcomes.

A case of systemic amyloidosis following ankylosing spondylitis associated with congestive heart failure.

Secondary (amyloid A [AA]) amyloidosis is a systemic disease characterized by amyloid deposition in many organs, leading to impaired function. Although cardiac involvement may occur with AA amyloidosis, significant deposition of amyloid in the heart is considered an infrequent observation and is rarely the cause of death. It occurs in 5% of patients with poorly controlled chronic inflammatory disease, mainly rheumatoid arthritis, ankylosing spondylitis, and familial Mediterranean fever. The authors report a case of AA amyloidosis diagnosed by rectal and skin biopsies, with cardiac involvement demonstrated by typical echocardiographic features in the presence of low voltage on electrocardiography.