Antiarrhythmic Effect of Artemisinin in an Ex-vivo Model of Brugada Syndrome Induced by NS5806.

BACKGROUND AND OBJECTIVES: Brugada syndrome (BrS) is an inherited arrhythmia syndrome that presents as sudden cardiac death (SCD) without structural heart disease. One of the mechanisms of SCD has been suggested to be related to the uneven dispersion of transient outward potassium current (Ito) channels between the epicardium and endocardium, thus inducing ventricular tachyarrhythmia. Artemisinin is widely used as an antimalarial drug. Its antiarrhythmic effect, which includes suppression of Ito channels, has been previously reported. We investigated the effect of artemisinin on the suppression of electrocardiographic manifestations in a canine experimental model of BrS. METHODS: Transmural pseudo-electrocardiograms and epicardial/endocardial transmembrane action potentials (APs) were recorded from coronary-perfused canine right ventricular wedge preparations (n=8). To mimic the BrS phenotypes, acetylcholine (3 µM), calcium channel blocker verapamil (1 µM), and Ito agonist NS5806 (6-10 µM) were used. Artemisinin (100-150 µM) was then perfused to ameliorate the ventricular tachyarrhythmia in the BrS models. RESULTS: The provocation agents induced prominent J waves in all the models on the pseudo-electrocardiograms. The epicardial AP dome was attenuated. Ventricular tachyarrhythmia was induced in six out of 8 preparations. Artemisinin suppressed ventricular tachyarrhythmia in all 6 of these preparations and recovered the AP dome of the right ventricular epicardium in all preparations (n=8). J wave areas and epicardial notch indexes were also significantly decreased after artemisinin perfusion. CONCLUSIONS: Our findings suggest that artemisinin has an antiarrhythmic effect on wedge preparation models of BrS. It might work by inhibition of potassium channels including Ito channels, subsequently suppressing ventricular tachycardia/ventricular fibrillation.

Experimental verification of the value of the Tpeak -Tend interval in ventricular arrhythmia inducibility in an early repolarization syndrome model.

INTRODUCTION: In patients with early repolarization patterns on ECG, many researchers have studied to find predictors of fatal arrhythmia. However, there are no satisfying clinical predictors. We evaluated the value of the Tpeak -Tend interval on pseudo-ECG in canine myocardial wedge preparation models of early repolarization syndrome. METHODS AND RESULTS: Transmural pseudo-ECG and endocardial/epicardial action potentials were recorded from coronary-perfused canine left ventricular wedge preparations (n = 34). The Ito agonist NS5806 (8-10 µM), the calcium channel blocker verapamil (3 µM) and acetylcholine (2-3 µM) were used to mimic the disease model. A ventricular arrhythmia induction test was performed. QTpeak , QTend , Tpeak -Tend , and Tpeak -Tend /QTend were measured at 15 to 20 minutes after the provocative agent infusion. Polymorphic ventricular tachycardias (pVT) developed in 23 of the 34 preparations (67%). The maximal values of Tpeak -Tend and Tpeak -Tend /QTend were recorded just before pVT induction. At baseline, without the provocative agents, Tpeak -Tend and Tpeak -Tend /QTend were not different between pVT-induced and pVT-noninduced preparations. The Tpeak -Tend of the pVT-induced preparations was longer than that of non-induced preparations (58 ± 26.8 msec vs 33 ± 6.8 msec, P < .001). The Tpeak -Tend /QTend of pVT- induced preparations was larger than that of noninduced preparations (0.220 ± 0.1017 vs 0.128 ± 0.0312, P < .001). The transmural and epicardial dispersion of repolarization of pVT-induced preparations were larger than those of pVT-noninduced preparations. The transmural dispersion of repolarization showed a positive correlation with Tpeak -Tend . CONCLUSION: Tpeak -Tend predicted malignant ventricular arrhythmias in early repolarization syndrome models. Tpeak -Tend reflects the repolarization heterogeneity of ventricular myocardium.

N-terminal pro-B-type natriuretic peptide level is depressed in patients with significant coronary artery disease who have high body mass index.

The aim of this study was to determine how body mass index (BMI) influences the N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in patients with significant coronary artery disease (CAD). A total of 348 patients (61.5 +/- 9.2 years, male 67.5%) who had normal left ventricular systolic function were enrolled. All patients underwent percutaneous coronary intervention. We excluded patients with acute myocardial infarction, chronic heart failure, or renal dysfunction. Baseline NT-proBNP level was measured on admission. All underwent follow-up (F-U) coronary angiography (CAG) and the F-U NT-proBNP level was measured before F-U CAG. The patients were divided into two groups: an NT-proBNP < 100 pg/mL group (group I, n = 228) and an NT-proBNP > 200 pg/mL group (group II, n = 120). BMI was significantly higher in group I than that in group II (26.5 +/- 2.2 versus 22.9 +/- 2.5 kg/m 2, P < 0.001). The level of NT-proBNP was negatively correlated with BMI and the levels of hemoglobin and apolipoprotein A1, and positively correlated with age, lipoprotein (a), and the Gensini score. In multivariate analysis, BMI was significantly related to a low NT-proBNP level in patients with CAD (odds ratio, 6.83; 95% confidence interval, 2.67-17.47; P < 0.001). The NT-proBNP level was not elevated in patients with a high BMI despite having significant CAD, and BMI was significantly related to a low NT-proBNP level in patients with significant CAD.

Carotid artery intima-media thickness in Behcet's disease patients without significant cardiovascular involvement.

BACKGROUND/AIMS: Behcet's disease (BD) is a systemic disorder associated with a characteristic vasculitis that can involve both veins and arteries of all sizes. Endothelial activation or injury is a characteristic feature of BD. Endothelial dysfunction is widely regarded as being the initial lesion in the development of atherosclerosis. The carotid artery intima-media thickness (IMT) is a widely accepted marker of subclinical atherosclerosis, We aimed to determine the carotid IMT in BD patients with using high-resolution B-mode Doppler ultrasonography. METHODS: We studied 40 patients (24 males, mean age: 39.1+/-8.5 years) who were diagnosed by the international diagnostic criteria of Behcet's disease and 20 healthy controls (13 males, mean age: 40.2+/-5.1 years), and the two groups were matched by age and gender. No subject in either group had a history of atherosclerosis or its complications. The clinical data, including the age of onset, the duration of disease, a history of medication, the activity score and the laboratory data were analyzed. RESULTS: The carotid IMT in the BD group was significantly higher than that in the control group (0.71+/-0.22 mm vs. 0.59+/-0.09 mm, respectively, p<0.01). Cardiac and major vessel involvements were not identified in the BD group. However, minor vascular involvements were documented in 2 patients with deep vein thrombosis, in 4 patients with superficial thrombophlebitis and in 2 patients with pseudoaneurysm. The carotid IMT in the patients with posterior uveitis or retinal vasculitis was higher than that of the patients without these findings (0.85+/-0.21 mm vs. 0.64+/-0.10 mm, respectively, p=0.007), but there was no difference of the IMT according to minor vascular involvement. CONCLUSIONS: Despite that there was no significant cardiovascular involvement in the BD patients, the carotid IMT was significantly higher in the BD patients as compared with the healthy controls.

Anti-inflammatory effect of abciximab-coated stent in a porcine coronary restenosis model.

The aim of this study was to examine the anti-inflammatory effect of abciximab-coated stent in a porcine coronary overstretch restenosis model. Ten abciximab-coated stents, ten sirolimus-eluting stents (SES), and ten paclitaxel-eluting stents (PES) were deployed with oversizing (stent/artery ratio 1.3:1) in porcine coronary arteries, and histopathologic analysis was done at 28 days after stenting. There were no significant differences in the neointima area normalized to injury score and inflammation score among the three stent groups (1.58 +/- 0.43 mm(2), 1.57 +/-0.39 mm(2) in abciximab-coated stent group vs. 1.69 +/- 0.57 mm(2), 1.72 +/- 0.49 mm(2) in the SES group vs. 1.92 +/- 0.86 mm(2), 1.79 +/- 0.87 mm(2) in the PES group, respectively). In the neointima, most inflammatory cells were lymphohistiocytes. Significant positive correlations were found between the extent of inflammatory reaction and the neointima area (r=0.567, p<0.001) and percent area stenosis (r=0.587, p<0.001). Significant correlations were found between the injury score and neointimal area (r=0.645, p<0.001), between the injury score and the inflammation score (r=0.837, p<0.001), and between the inflammation score and neointimal area (r=0.536, p=0.001). There was no significant difference in the inflammatory cell counts normalized to injury score among the three stent groups (75.5 +/- 23.1/microL in abciximabcoated stent group vs. 78.8 +/- 33.2/microL in the SES group vs. 130.3 +/- 46.9/microL in the PES group). Abciximab-coated stent showed comparable inhibition of inflammatory cell infiltration and neointimal hyperplasia with other drug-eluting stents in a porcine coronary restenosis model.

Usefulness of preprocedural N-terminal pro-brain natriuretic peptide in predicting angiographic no-reflow phenomenon during stent implantation in patients with ST-segment elevation acute myocardial infarction.

The no-reflow phenomenon after primary percutaneous coronary intervention (PCI) is associated with larger infarct size, worse functional recovery, and higher incidence of complication after acute ST-elevation myocardial infarction (STEMI). The aim of this study was to assess the relation between preprocedural N-terminal pro-brain-type natriuretic peptide (NT-pro-BNP) and angiographic no-reflow phenomenon. We measured preprocedural serum NT-pro-BNP level in 159 consecutive patients with acute STEMI (aged 63 +/- 12 years; 72% men) before PCI. Angiographic no-reflow after PCI was defined as Thrombolysis In Myocardial Infarction (TIMI) flow grade <3. Baseline characteristics, including time from chest pain onset, between the no-reflow (n = 67) and normal-reflow groups (n = 92) were similar. NT-pro-BNP was significantly higher in the no-reflow group than the normal reflow group (1,982 +/- 3,314 vs 415 +/- 632 pg/ml; p = 0.005). Also, high-sensitivity C-reactive protein, monocytes, and troponin-T were significantly higher in the no-reflow group than the normal-reflow group. In the no-reflow group, NT-pro-BNP was much higher in patients with TIMI flow grade 0 (n = 41; 2,290 +/- 3,495 pg/ml) than those with TIMI grade 1 or 2 (n = 26; 1,575 +/- 2,340 pg/ml), but without significant difference. The area under the receiver-operating characteristic curve for NT-pro-BNP was 0.78, and the optimal cut-off value identified using receiver-operating characteristic curve analysis was 500 pg/ml. At the standard cut-off value of >500 pg/ml, increased NT-pro-BNP showed a high probability of no-reflow phenomenon (odds ratio 4.42, 95% confidence interval 1.15 to 17.00, p = 0.028). In conclusion, preprocedural NT-pro-BNP may be a strong predictor of the development of no-reflow phenomenon after PCI in patients with acute STEMI.

Relationship between peripheral monocytosis and nonrecovery of left ventricular function in patients with left ventricular dysfunction complicated with acute myocardial infarction.

BACKGROUND: Although ischemic heart failure is a major cause of mortality after acute myocardial infarction (AMI), the factors that may influence the nonrecovery of left ventricular function (LVF) after an AMI are still unclear. The aim of this study was to identify predictors of nonrecovery of LVF in patients with left ventricular (LV) dysfunction (defined as an echocardiographic ejection fraction (EF)<40%) complicated with AMI who undergo successful primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: LVF recovery was defined as improvement of LVEF more than 10% compared with baseline LVEF at follow-up. One hundred and eight patients with LV dysfunction after AMI were divided into 2 groups according to the LVF recovery at follow-up: patients with LVF recovery (n=64) vs patients without LVF recovery (n=44). The follow-up LVEF was measured at 8+/-4 months after PCI. Patients without LVF recovery were older (76+/-13 years vs 59+/-14 years, p=0.023) and the baseline peak monocyte count, creatine kinase, and troponin I levels were significantly higher in patients without LVF recovery than in patients with LVF recovery. Delta LVEF (follow-up LVEF-baseline LVEF) correlated with baseline peak monocyte count (r=-0.417, p<0.001), baseline peak creatine kinase (r=-0.269, p=0.005), and baseline peak troponin I levels (r=-0.256, p=0.007). Multivariate analyses showed that baseline peak monocyte count and old age were the independent predictors of nonrecovery of LVF (hazard ratio; 3.38, 95% confidence interval (CI): 1.16-5.43, p=0.012, and hazard ratio; 2.38, 95% CI: 1.09-4.87, p=0.025, respectively). CONCLUSION: Peripheral monocytosis is associated with nonrecovery of LVF in patients with LV dysfunction complicating an AMI who underwent successful primary PCI. These results suggest an important role of monocytes in the expansion of the infarct and the development of chronic ischemic heart failure after reperfusion therapy.

Usefulness of serum N-terminal pro-brain natriuretic peptide to predict in-stent restenosis in patients with preserved left ventricular function and normal troponin I levels.

The level of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is a strong predictor of mortality in patients with acute coronary syndrome and may be a strong prognostic marker in patients with chronic coronary artery disease. We investigated whether NT-pro-BNP could predict in-stent restenosis (ISR) in asymptomatic patients with preserved left ventricular (LV) systolic function who underwent percutaneous coronary intervention. We measured serum NT-pro-BNP levels in 249 patients (61 +/- 9 years of age; 73% men) with preserved LV systolic function (ejection fraction >50%) who underwent follow-up coronary angiography. Initial diagnoses were stable angina in 50 (20%), unstable angina in 133 (53%), and myocardial infarction in 66 (27%). Baseline characteristics between groups with ISR (n = 92) and without ISR (n = 157) were similar. The level of NT-pro-BNP was higher in patients with ISR than in those without ISR (222 +/- 327 vs 94 +/- 136 pg/ml, p = 0.001). In the ISR group, NT-pro-BNP level was higher in patients with left anterior descending coronary artery ISR (n = 53, 312 +/- 479 pg/ml) than in those with left circumflex coronary artery ISR (n = 19, 115 +/- 98 pg/ml, p = 0.018). At the standard cutoff of >200 pg/ml, a high NT-pro-BNP level indicated a high probability of ISR (odds ratio 2.18, 95% confidence interval 1.0 to 4.5, p = 0.038). In multivariate analysis, NT-pro-BNP level was an independent predictor for ISR. In conclusion, NT-pro-BNP could be a predictor of ISR in asymptomatic patients with preserved LV systolic function.

Impact of postprocedure minimum stent area on long-term results following abciximab-coated stent implantation: an intravascular ultrasound analysis.

BACKGROUND: Smaller postprocedural minimum stent areas (MSA) measured by intravascular ultrasound (IVUS) have been associated with higher restenosis rates. METHODS: This was a single-center, prospective, randomized trial and we assessed the predictive value of MSA for long-term patency and the incidence and extent of incomplete stent apposition (ISA) following abciximab-coated stent (n=69) compared to bare metal stent (BMS) implantation (n=69). All patients underwent IVUS follow-up at 6 months. RESULTS: At follow-up coronary angiogram, the restenosis rate and late loss were 12%, 0.30+/-0.24 mm in abciximab-coated stent group and 29%, 0.68+/-0.36 mm in BMS group (p=0.011, 0.010, respectively). At follow-up IVUS, intrastent lumen area was significantly larger and intrastent neointimal hyperplasia area was significantly smaller in abciximab-coated stent group than those in BMS group (5.9+/-1.6 mm(2) vs. 4.5+/-1.7 mm(2), p=0.001, and 1.9+/-1.5 mm(2) vs. 3.3+/-1.9 mm(2), p<0.001, respectively). Target lesion revascularization occurred in 9%, 0%, and 0% in abciximab-coated stent group and 19%, 4%, and 1% in BMS group in lesions with a MSA <6.0 mm(2), from 6 to 7.5 mm(2), and >7.5 mm(2), respectively. Late-acquired ISA at follow-up was observed in 7 patients and there was no difference in the incidence of ISA between both groups [abciximab-coated stent: n=3 (4%) vs. BMS: n=4 (6%), p=0.698]. CONCLUSION: Abciximab-coated stent reduced restenosis and had a considerably lower optimal MSA threshold compared to BMS and showed lower incidence of late-acquired ISA.

Effect of combination therapy with simvastatin and carvedilol in patients with left ventricular dysfunction complicated with acute myocardial infarction who underwent percutaneous coronary intervention.

BACKGROUND: This study assessed the effects of combination therapy with simvastatin and carvedilol on clinical outcome in patients with left ventricular (LV) dysfunction after acute myocardial infarction (AMI). METHODS AND RESULTS: The study retrospectively analyzed the data from 672 patients with LV dysfunction [LV ejection fraction (LVEF) <40%] complicated with AMI who underwent percutaneous coronary intervention (PCI). The patients were divided into 4 treatment groups: combination group (n=160), simvastatin only group (n=216), carvedilol only group (n=242), neither treatment group (n=54). At 6 months after PCI, the LVEF had improved most significantly in the combination group. During 1-year follow-up, cardiac death occurred most frequently in the neither treatment group compared with the other 3 groups (combination: 4%, simvastatin alone: 7%, carvedilol alone: 8%, neither: 17%, p<0.001 between neither treatment and other 3 groups). The results on major adverse cardiovascular events (MACE) showed that the combination of simvastatin and carvedilol was associated with a relative risk reduction of 53% (p<0.001), treatment with simvastatin alone with a relative risk reduction of 44% (p=0.001), and carvedilol alone with a relative risk reduction of 40% (p=0.003) compared with neither treatment. The independent predictors of 1-year MACE were neither treatment, elevated high sensitivity C-reactive protein (> or =0.5 mg/dl), and old age (>70 years). CONCLUSION: Combination therapy with simvastatin and carvedilol had a positive impact on the endpoints of cardiovascular death and MACE and seems to have an additive beneficial effect on these endpoints in patients with LV dysfunction complicated with AMI who underwent PCI.

Relation of soft plaque and elevated preprocedural high-sensitivity C-reactive protein levels to incidence of in-stent restenosis after successful coronary artery stenting.

Although various predictors relating to in-stent restenosis (ISR) have been demonstrated, the relation between the parameters of intravascular ultrasound and inflammatory markers and ISR has not been reported. This study included 120 patients who underwent stent implantation for angiographically significant stenosis. Patients were divided into a soft plaque group (n = 50) and a nonsoft plaque group (n = 70). All patients underwent angiographic and intravascular ultrasound follow-up at 6 months. The baseline high-sensitivity C-reactive protein (hs-CRP) level was significantly higher in the soft plaque group. The follow-up minimal lumen diameter was significantly smaller in the soft plaque group. Soft plaque was detected in 73% of the ISR group but only 27% of the non-ISR group. Also, ISR was observed in 44% of the soft plaque group in contrast to only 11% of the nonsoft plaque group. The neointimal area at the minimal lumen cross-sectional area at follow-up was significantly larger in the soft plaque group (3.7 +/- 1.5 vs 1.9 +/- 1.5 mm2, p < 0.001). In conclusion, in patients with soft plaque, an elevated hs-CRP level was significantly associated with ISR (63% vs 15%, p < 0.001). By multivariate analysis, the combination of soft plaque and elevated hs-CRP was the most significant independent predictor of ISR.

Varix of the right atrium.

A 68-year-old female patient was referred for the evaluation of an incidentally detected asymptomatic cardiac mass. Imaging studies showed a 3.0 x 2.4 cm, well circumscribed, round, cystic mass with a calcified nodule that was attached to the lower rim of the fossa ovalis in the right atrium. Under cardiopulmonary bypass, the right atrium was opened to reveal a well circumscribed, dark bluish, pedunculated mass. Histologically, the specimen was a unilocular cyst lined by flattened endothelium, with peripheral fibrin clots and dystrophic calcification of the wall. Immunohistochemical staining of the lining cells was positive for cluster designation 34, which represents hematopoietic progenitor cell antigen. The final pathologic diagnosis was compatible with varix of the heart, which should be considered for a cystic mass with a calcified nodule located in the right atrium, near the lower rim of the fossa ovalis.

N-terminal pro-B-type natriuretic Peptide predicts significant coronary artery lesion in the unstable angina patients with normal electrocardiogram, echocardiogram, and cardiac enzymes.

BACKGROUND: Brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are not specific for ventricular dysfunction and other cardiac processes, such as myocardial ischemia, may also cause elevation of these markers. METHODS AND RESULTS: To determine whether elevation of NT-proBNP without elevation of cardiac specific markers can predict coronary artery disease (CAD), the serum level of NT-proBNP was measured in 161 patients with unstable angina (61.0+/-8.1 years, male 54.0%) with normal ventricular function (left ventricular ejection fraction >55% and no regional wall motion abnormality by echocardiography) and normal troponin I level (<0.05 ng/ml). In these patients, levels of C-reactive protein and myoglobin were normal and none had Q wave on electrocardiographic (ECG). The NT-proBNP level was higher in patients with CAD (n=74) than in patients without CAD (n=87) (173.1+/-231.6 vs 68.1+/-62.5 pg/ml, p<0.001). At the standard cut-off point of >200 pg/ml, elevated NT-proBNP level shows high probability of CAD (odds ratio, 10.1; 95% confidence interval, 2.6-38.7, p=0.001). The NT-proBNP level positively correlated with the extent of CAD (r=0.329, p=0.001). In multivariate analysis, the NT-proBNP was an independent predictor of CAD. CONCLUSION: These results suggested that NT-proBNP is a useful screening test for CAD in the unstable angina patients with normal ECG, echocardiogram and cardiac enzyme levels.

Impact of preinterventional arterial remodeling on in-stent neointimal hyperplasia and in-stent restenosis after coronary stent implantation.

BACKGROUND: Patterns of arterial remodeling during the course of plaque development have been shown to play an important role in both the progression of de novo atherosclerosis and in the restenotic process following coronary intervention. The aim of the present prospective study was to evaluate the effect of pre-interventional arterial remodeling on in-stent neointimal hyperplasia (NIH) and in-stent restenosis (ISR) after stenting. METHODS AND RESULTS: Pre-interventional arterial remodeling was assessed in 85 native coronary lesions by using intravascular ultrasound (IVUS). The remodeling index (RI) was 1.09+/-0.20 in the positive remodeling (PR)/intermediate remodeling (IR) group and 0.84+/-0.12 in the negative remodeling (NR) group. The plaque plus media cross sectional area (P&M CSA) at pre-intervention and NIH CSA at follow-up in the minimal lumen CSA were significantly larger in the PR/IR group (9.2+/-2.9 mm2 vs 6.2+/-1.8 mm2, 3.3+/-1.2 mm2 vs 1.5+/-0.9 mm2; p = 0.001, p = 0.001, respectively). On 3-dimensional analysis of IVUS images at follow-up, the lumen volume was significantly smaller in the PR/IR group than that in the NR group (62+/-15 mm3 vs 75 +/-20 mm3; p = 0.001), and neointima hyperplasia volume was significantly larger in the PR/IR group than that in the NR group (46+/-15 mm3 vs 26+/-10 mm3; p = 0.001). A significant positive correlation was found between pre-interventional RI and follow-up NIH CSA (r = 0.25, p = 0.022). The incidence of ISR and repeat intervention was significantly higher in the PR/IR group (30.8% vs 18.2%, 28.8% vs 15.2%; p = 0.032, 0.035, respectively). CONCLUSION: Measuring pre-interventional arterial remodeling patterns by IVUS may be helpful to stratify lesions at high-risk of ISR.

Myocardial protective effects of nicorandil during percutaneous coronary intervention in patients with unstable angina.

BACKGROUND: The purpose of the study was to prospectively evaluate the protective effect of nicorandil during percutaneous coronary intervention (PCI) in patients with unstable angina (UAP). METHODS AND RESULTS: Two hundred patients (61+/-10 year-old, male 143) diagnosed with UAP at an emergency medical center were randomly assigned to 2 groups: intravenous isosorbide dinitrate, Group I (n=100), or intravenous nicorandil, Group II (n=100). PCI was performed 12-48 h after infusion of each agent. Serum concentrations of creatine kinase-MB (CK-MB), cardiac troponin T (cTnT), and I (cTnI) were measured before and 6, 12, 24 h after PCI. Patients with non-coronary chest pain, requiring emergency coronary angiogram, temporary pacemaker or glycoprotein IIb/IIIa receptor blocker were excluded. PCI was successfully performed in 96 patients (Group I=54, 61.7+/-8.2 years, 32 males; Group II=42, 60.4+/-11.7 years, 27 males). No significant differences in clinical or coronary angiographic characteristics were observed between the 2 groups. The concentration of CK-MB was elevated in 9 patients (17%) of Group I and 6 (14%) of Group II, cTnT in 16 (30%), 6 (14%) and cTnI in 25 (46%), 9 (21%) after PCI. Elevation of any troponin was less frequent in Group II [28/54 (52%) vs 10/42 (24%) patients, p=0.01]. Major adverse coronary events during the 6-month clinical follow-up occurred in 9 (17%) of Group I and 5 patients of Group II (12%, p=NS). Follow-up echocardiography revealed lower left ventricular ejection fraction in Group I than in Group II (65.4+/-7.2% vs 71.0+/-6.7%, p=0.03). CONCLUSION: Nicorandil has a myocardial protective effect during PCI in patients with UAP.

Prognostic significance of simvastatin therapy in patients with ischemic heart failure who underwent percutaneous coronary intervention for acute myocardial infarction.

We prospectively followed 202 patients with ischemic heart failure who underwent percutaneous coronary intervention (PCI) for acute myocardial infarction (left ventricular [LV] ejection fraction <40%). Patients were divided into 2 groups: groups I (simvastatin group, n = 106, aged 60.8 +/- 10.3 years, men 71.7%) and II (non-simvastatin group, n = 96, aged 60.9 +/- 10.4 years, men 78.1%). During 1-year clinical follow-up, simvastatin therapy was associated with a significant reduction in mortality (1.9% vs 7.5%, p = 0.048), restenosis rate (25.7% vs 43.1%, p = 0.033), and repeat PCI rate (25.7% vs 43.1%, p = 0.033), and with significant improvement in LV ejection fraction (31% to 42% vs 32% to 39%, p = 0.042). The event-free survival rate was higher in group I than in group II (79.8% vs 57.0%, p = 0.001). In conclusion, simvastatin therapy improves LV systolic function and decreases mortality, restenosis, and repeat PCI rate in patients with ischemic heart failure who underwent PCI for acute myocardial infarction.

Predictive factors of major adverse cardiac events in acute myocardial infarction patients complicated by cardiogenic shock undergoing primary percutaneous coronary intervention.

BACKGROUND: The aim of this study was to assess in-hospital mortality and major adverse cardiac events (MACE) during long-term clinical follow-up of patients who developed cardiogenic shock (CS) after acute myocardial infarction (AMI) and who underwent primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: The data from 147 patients with CS after AMI (61.7 +/-10.4 years, M:F =156:99) who underwent primary PCI at Chonnam National University Hospital between January 1999 and December 2002 were analyzed: clinical characteristics, coronary angiographic findings and mortality during admission, and MACE during a 1-year clinical follow-up. Of the enrolled patients, 121 patients survived (group I, M:F =94:27) and 26 died (group II, M:F =14:12) during admission. By binary logistic regression analysis, in-hospital death was associated with low Thrombolysis In Myocardial Infarction (TIMI) flow after coronary revascularization (p=0.02, odds ratio (OR) =1.3). Eighty-nine patients (60.5%) survived without MACE during the 1-year clinical follow-up and MACE was associated with a C-reactive protein (CRP) of more than 1 mg/dl (p=0.002, OR =6.3) and low TIMI flow after coronary revascularization (p<0.001, OR =7.8). CONCLUSIONS: Primary PCI achieving TIMI 3 flow reduces in-hospital death in AMI with CS. High concentration of CRP and low TIMI flow are associated with MACE during long-term clinical follow-up.

Long-term clinical outcomes of platelet glycoprotein IIb/IIIa inhibitor combined with low molecular weight heparin in patients with acute coronary syndrome.

BACKGROUND: Platelet activation and aggregation with resultant arterial thrombus formation play a pivotal role in the pathophysiology of acute coronary syndrome (ACS). In the present study the efficacy of tirofiban, a specific inhibitor of the platelet glycoprotein IIb/IIIa receptor, combined with heparin or low-molecular-weight heparin (dalteparin), was evaluated for the management of ACS. METHODS AND RESULTS: One hundred and sixty patients (60.9+/-11.1 years, 104 male) with unstable angina or non-ST elevation myocardial infarction and who had ST-T changes and elevated troponin were randomly assigned to 4 groups: group I (n=40: heparin alone), group II (n=40: dalteparin alone), group III (n=40: tirofiban + heparin) and group IV (n=40: tirofiban + dalteparin). The occurrence of major adverse cardiac events (MACE) was compared prospectively during a 6-month clinical follow-up. Percutaneous coronary intervention or coronary artery bypass graft was performed in 32 cases in group I, 29 in group II, 28 in group III and 31 in group IV (p=0.72). Minor bleeding complication developed in 2 patients (5.0%) in group I, 2 (5.0%) in group II, 4 (10.0%) in group III and 3 (7.5%) in group IV (p=0.78). During the follow-up MACE occurred in 10 patients (31.3%) in group I, 9 (31.0%) in group II, 4 (14.3%) in group III and 4 (12.9%) in group IV (p=0.02: Group I and II vs Group III and IV). CONCLUSIONS: Tirofiban combined with dalteparin was associated with relatively more bleeding complications in the short term, but was effective in reducing the incidence of MACE during long-term clinical follow-up in patients with ACS.

Airway hyperresponsiveness to hypertonic saline as a predictive index of exercise-induced bronchoconstriction.

BACKGROUND: Changes in airway mucosal osmolarity are an underlying mechanism of bronchoconstrictive responses to exercise and hypertonic saline (HS). The purpose of this study was to examine whether an osmotic challenge test using HS can predict exercise-induced bronchospasm (EIB) in asthma patients. METHODS: Thirty-six young male asthmatic patients underwent bronchial challenge tests based on 4.5% HS, exercise (> 24h later), and methacholine (MCh) at the Chonnam National University Hospital. The relationships between responses to HS and exercise, and between MCh and exercise were evaluated. RESULTS: The maximal fall in forced expiratory volume in one second following exercise was significantly higher in the HS-responders (n=19) than in the HS-nonresponders (n=17, 35.9 +/- 4.1% vs. 17.9 +/- 2.7%, p<0.001), and there was a significant correlation between the severity of EIB and HS-airway hyperresponsiveness (AHR). When compared with the MCh-AHR test in terms of predicting EIB, the HS-AHR test showed higher specificity (71.4% vs. 42.90%), but a lower sensitivity (58.6% vs. 89.7%) and negative predictive value (29.4% vs. 50.0%). At the moderate AHR cutoff value, the MCh-AHR test had a specificity that was comparable with and predictive values that were higher than those of the HS-AHR test. CONCLUSIONS: The HS-AHR test was more specific than the MCh-AHR test, but was less sensitive and had a poorer negative predictive value, which in combination preclude the use of the HS-AHR test as a screening tool for EIB. The MCh-AHR test had a cutoff value for moderate AHR that may be more useful for predicting EIB in asthmatic patients.

Effect of abciximab-coated stent on in-stent intimal hyperplasia in human coronary arteries.

The investigators tested whether abciximab-coated stents prevent neointimal hyperplasia (NIH) formation in coronary de novo lesions. Abciximab-coated stents were compared with control stents. All patients underwent follow-up coronary angiography and intravascular ultrasound (IVUS). All stents were successfully deployed, and patients were discharged home without clinical events. At follow-up coronary angiography, the restenosis rate and late loss were 14% and 0.33 +/- 0.28 mm in the abciximab-coated stent group and 28.6% and 0.64 +/- 0.32 mm in the control stent group (p = 0.099 and p = 0.014, respectively). At follow-up IVUS, the intrastent luminal area and intrastent NIH area were 5.7 +/- 1.6 and 2.0 +/- 1.6 mm(2), respectively, in the abciximab-coated stent group and 4.2 +/- 0.8 and 3.4 +/- 1.7 mm(2), respectively, in the control stent group (p = 0.001 and p = 0.001, respectively). Abciximab-coated stents are feasible and significantly inhibit NIH, with potential therapeutic benefit in preventing stent restenosis.