Sang Jin Ha

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.

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.

Green tea consumption improves endothelial function but not circulating endothelial progenitor cells in patients with chronic renal failure

This study was designed to determine the effect of green tea consumption in patients with chronic kidney disease (CKD) on flow-mediated endothelium-dependent vasodilation (FMD) and the number of circulating endothelial progenitor cells (EPCs). Forty patients with CKD requiring chronic dialysis were enrolled. The patients were divided into two groups: the catechin group that consumed green tea (5 g/day for 1 month) and the control group that consumed water. The number of EPCs, inflammatory markers, oxidative stress, and FMD were determined at baseline and 4 weeks after green tea consumption. Clinical characteristics, oxidative stress, inflammatory markers, and circulating EPCs number were not significantly different. FMD was significantly improved after 4 weeks in the catechin group (from 5.68±2.67% to 8.66±3.46%, p=0.002). Short-term green tea consumption induced a rapid improvement in FMD, but did not improve circulating EPC levels in patients with CKD.

Impact of gender differences on long-term outcomes after successful percutaneous coronary intervention in patients with acute myocardial infarction

Abstract Many observational and randomized studies have suggested that women have a higher short-term mortality after acute myocardial infarction (AMI) following primary percutaneous coronary intervention (PCI). However, little is known about the effect of gender differences on short- and long-term outcomes in the drug-eluting stent (DES) era. To evaluate the clinical outcomes of women who have undergone PCI with DES, we analyzed 3298 consecutive eligible patients using the Korea Acute Myocardial Infarction Registry (KAMIR). No differences in primary PCI success rates were found between women and men. On univariate analysis, women showed worse outcomes than men for one-month major adverse cardiac event (MACE) (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.81–2.92) and 12-month MACE (OR, 1.64; 95% CI, 1.36–1.97). On multivariable analysis, older age (OR, 1.03; 95% CI, 1.02–1.05), dyslipidemia (OR, 2.28; 95% CI, 1.16–4.49), smoking (OR, 1.54; 95% CI, 1.07–2.21) and Killip class (OR, 3.63; 95% CI, 2.76–4.91), but not gender, were associated with one-month MACE in this national registry. In 12-month MACE, old age, ischemic heart disease history, diabetes, dyslipidemia, and Killip class were independent predictors of patients undergoing primary PCI with DES. Older age and additional comorbidities, but not gender, are likely to explain the deteriorating short- and long-term outcomes in the DES era.

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.

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.

Acute regional myocarditis with normal ventricular wall motion diagnosed by two-dimensional speckle tracking imaging.

To the Editor, Acute myocarditis associated with a normal left ventricular (LV) ejection fraction is challenging to diagnose. Echocardiography is the initial imaging modality used, but diagnostic accuracy is limited, especially in patients with chest pain in whom LV function and size are almost always normal [1]. The current reference standard for noninvasive diagnosis of myocarditis is cardiac magnetic resonance (CMR) imaging [2]. Here we describe a case of a 19-year-old man who presented with severe chest pain that mimicked acute coronary syndrome but was subsequently diagnosed with acute regional myocarditis by two-dimensional (2D) speckle echocardiography. The patient was successfully treated medically for myocarditis. A 19-year-old male with no cardiovascular risk factors was admitted due to chest discomfort and fever. On admission, blood pressure, heart rate and body temperature were 140/65 mmHg, 92 beats per minute, and 38℃, respectively. Initial electrocardiography showed upwardly concave ST elevations in II, III, and aVF leads, with no reciprocal change in the anterior chest lead. Laboratory tests revealed elevated serum C-reactive protein (CRP) and cardiac biomarker (CRP, 1.5 mg/L; creatine kinase [CK], 616 IU/L; CK-MB, 53.0 IU/L; and troponin-I, 4.81 ng/mL). A 2D-echocardiogram showed normal regional wall motion with preserved LV systolic and diastolic function, but automated function imaging, which was assessed by a 2D speckle-tracking imaging (STI), showed a decreased peak in the systolic longitudinal strain of the basal inferior and lateral walls (Fig. 1D, Bulls eye view) and the circumferential strain also decreased in the basal inferior and lateral walls (Fig. 2). Strain curves showed that abnormal longitudinal systolic shortening was detected by strain echocardiography in the lateral and posterior wall, where there were abnormalities indicating longitudinal strain such as a reduced systolic shortening and a postsystolic peak (Fig. 1A, yellow line; Fig. 1B, red line); however, longitudinal systolic shortening in the anterior, inferior and septal walls was normal (Fig. 1C). This pattern was also observed in the circumferential strain curve (Fig. 2). Elevated cardiac biomarkers and decreased regional peak systolic strain usually suggest regional coronary ischemia. However, in this patient, ischemic disease was extremely unlikely due to his young age, lack of family history of coronary artery disease, and lack of regional wall motion abnormalities on the conventional 2D echocardiogram, despite a decreased regional peak longitudinal strain. Therefore, conservative treatment was initiated, including pain medications and diuretics, rather than invasive procedures such as a coronary angiography or myocardial biopsy. To confirm the diagnosis and to examine the change in the myocardium, CMR imaging was performed on the day following admission. Gadolinium-enhanced CMR on the fifth day of admission demonstrated subepicardial delayed hyperenhancement at the basal inferior, lateral wall and the mid lateral wall on short axis, 10 minutes after the enhancement of the image in accordance with myocarditis (Fig. 3). Surprisingly, abnormalities in automated functional imaging and strain curve analysis correlate closely with findings on CMR imaging. Antigen tests for cosackie and influenza viruses were positive. With the suspicion of acute viral myocarditis associated with influenza, we prescribed tamiflu (Genentech, Basel, Switzerland) for 5 days. The patients clinical signs resolved along with the normalization of the ST segment changes and the serum CK level. Figure 1 Two-dimensional speckle tracking imaging. Strain curves showed that abnormal longitudinal systolic shortening was detected by strain echocardiography in the lateral and posterior wall, where there were abnormalities indicating longitudinal strain such ... Figure 2 Two-dimensional segmental circumferential strain curves and color M mode depicting attenuated strain in inferior and lateral segments at the mid-ventricular level. Figure 3 (A, B) Cardiac magnetic resonance imaging showed subepicardial delayed hyperenhancement at the basal inferior, lateral, and mid lateral walls on short axis on a 10 minute-delayed enhancement image. Acute myocarditis has myriad presentations, and often mimics acute coronary syndrome at initial presentation. CMR imaging and myocardial biopsy at the initial acute presentation is not feasible for a differential diagnosis and cannot confirm myocarditis. However, conventional 2D echocardiography, plus strain imaging were crucial in this case to determine the best course of treatment. This case demonstrated that decreased myocardial strain as assessed by 2D speckle echocardiography and different strain curve pattern such as reduction in systolic shortening and postsystolic peak may lead clinicians to the accurate diagnosis of acute myocarditis in patients with chest pain and elevated cardiac biomarkers, but normal wall motion, mimicking acute coronary syndrome. Although the diagnosis of myocarditis has traditionally required a histologic diagnosis, according to the classic Dallas criteria, new diagnostic strategies such as CMR can strongly indicate and diagnose myocarditis. CMR imaging can characterize tissue according to water content and changes in contrast kinetics, which allows visualization of the entire myocardium. Thus, it is well suited to detect patchy myocarditic lesions [3]. Recently, CMR imaging has become the noninvasive diagnostic tool of choice to diagnose myocarditis, and is recommended in patients whose symptoms suggest this condition [2]. However, CMR does have some disadvantages, notably its high cost and the time needed to perform it; therefore, it is not feasible in an acute emergency setting. Conventional 2D echocardiography has traditionally played a limited role in the diagnostic armamentarium for acute myocarditis due to the lack of specific distinguishing features and/or apparently normal examinations encountered in less severe forms of myocarditis [1]. Nevertheless, segmental and global wall motion abnormalities do occur, and patterns of hypertrophic, dilated, and restrictive cardiomyopathy have been reported in histologically proven myocarditis [1]. The advent of novel echocardiographic modalities, such as strain echocardiography, has dramatically expanded the scope of echocardiography, which provides an accurate bedside assessment of regional contractility and can identify longitudinal myocardial dysfunction derived from edema in acute myocarditis [4,5]. Particularly for myocardial damage of only the epicardial layer of the ventricular wall during acute myocarditis, Doppler echocardiography can identify longitudinal segmental myocardial dysfunction derived from edema [5]. These newer techniques are more efficacious than conventional echocardiography in the diagnosis of myocarditis. Interestingly, decreased myocardial longitudinal strain and circumferential strain assessed by the 2D speckle tracking technique, in the absence of wall motion abnormalities, may represent a useful additional diagnostic finding in acute regional myocarditis, while longitudinal segmental myocardial dysfunction derived from edema also supports the diagnosis. This methodological improvement allowed us to evaluate myocardial damage using CMR rather than subjecting the patient to invasive methods such as coronary angiography. In conclusion, in young patients with chest pain who have elevated cardiac biomarkers and dynamic EKG changes but who do not fit the signalment for coronary disease, 2D STI analysis, including longitudinal and circumferential strain, can help physicians to diagnose acute myocarditis and to devise an appropriate treatment plan.

Effect of cilostazol addition or clopidogrel doubling on platelet function profiles in diabetic patients undergoing a percutaneous coronary intervention.

BackgroundWe investigated the pharmacodynamic effect of cilostazol addition (100 mg twice, Triple) or clopidogrel doubling (150 mg daily, Double) on standard dual antiplatelet therapy in type 2 diabetes mellitus (T2DM) patients with clopidogrel resistance undergoing a percutaneous coronary intervention. Methods and resultsThis was a prospective, randomized, cross-over platelet function study. Percent inhibition less than 20% was used as the cutoff value of clopidogrel resistance. After percutaneous coronary intervention, a total of 50 T2DM patients with clopidogrel resistance were assigned to receive cilostazol 100 mg twice daily or clopidogrel 150 mg daily for 28 days; afterwards, they received cross-over treatment for another 28 days. Eight patients were excluded because of side effects and follow-up loss. The platelet function test using VerifyNow was performed at three time points: at baseline (T0), 28 days after randomization (T1), and 28 days after cross-over treatment (T2).A total of 42 T2DM patients completed the study protocol. The clopidogrel resistance improved significantly following cilostazol addition or clopidogrel doubling treatment compared with baseline (52.9±27.0 in Triple, 45.4±16.8% in Double, P<0.001 in both). This effect continued after cross-over treatment (58.1±26.1 and 41.0±20.0%, respectively, both P<0.05). A head-to-head comparison between two groups showed a lower P2Y12 reaction unit (PRU) and higher percentage of platelet inhibition in the Triple than those in the Double group (PRU, 138.7±88.2 vs. 198.8±19.5, P=0.049; %platelet inhibition, 58.1±26.1 vs. 40.97±20.0, P=0.048). ConclusionAdjunctive treatment with cilostazol in T2DM patients on standard dual antiplatelet therapy might be a more effective strategy for overcoming clopidogrel resistance than clopidogrel doubling treatment.

Exenatide Prevents Morphological and Structural Changes of Mitochondria Following Ischaemia-Reperfusion Injury

BACKGROUND Exenatide exerts cardioprotective effects by attenuating ischaemic reperfusion (IR) injury, possibly through activating the opening of mitochondrial ATP-sensitive potassium channels. We used atomic force microscopy (AFM) to investigate changes in mitochondrial morphology and properties in order to assess exenatide-mediated cardioprotection in IR injury. METHODS We used an in vivo Sprague-Dawley rat IR model and ex vivo Langendorff injury model. In the left anterior descending artery (LAD) occlusion model, animals were randomly divided into three groups: sham-operated rats (Sham, n=5), IR-injured rats treated with placebo (IR, n=6), and IR-injured treated with exenatide (IR + EXE, n=6). For the Langendorff model, rats were randomly divided into two groups: IR injury with placebo (IR, n=4) and IR injury with exenatide (IR+EXE, n=4). Morphological and mechanical changes of mitochondria were analysed by AFM. RESULTS Exenatide pre-treatment improved cardiac function as evidenced by improvement in echocardiographic results. The ratio of infarct area (IA) to risk area (RA) was significantly reduced in exenatide-treated rats. According to AFM, IR significantly increased the area of isolated mitochondria, indicative of mitochondrial swelling. Treatment with exenatide reduced the mitochondrial area and ameliorated the adhesion force of mitochondrial surfaces. CONCLUSIONS Exenatide pre-treatment improves morphological and mechanical characteristics of mitochondria in response to IR injury in a rat model. These alterations in mitochondrial characteristics appear to play a cardioprotective role against IR injury.