Thrombus aspiration therapy allows for the examination of thrombus and atheroma fragments in acute coronary syndrome (ACS). Inflammatory cells and platelet activation play key roles in thrombus formation in ACS. However, histopathologic evaluation of thrombi in ACS has not been adequately addressed. We performed histologic analysis of tissue samples obtained by thrombus aspiration therapy. We studied 165 samples from patients with ACS. The area of each sample, percentage of red thrombus, and percentage of white thrombus were measured. Samples were stained immunohistochemically with antibodies against macrophages, activated platelets, and interleukin (IL)-5. Seventy-six samples included atheroma fragments. Macrophages, neutrophils, and activated platelets were observed in thrombi and in atheroma fragments. Eosinophil infiltration was also observed predominantly in the area between white thrombus and red thrombus in 106 samples. We categorized all samples into 3 groups according to the grade of eosinophil infiltration (eos-, eos+, eos++ group). Sample area in the eos++ group was greater than that in the eos- group (P < 0.0001). In addition, the percentage of the red thrombus areas in the eos++ group and the eos+ group was greater than that in the eos- group (P < 0.009, P < 0.02, respectively). However, there was no difference in the percentage of white thrombus area between the 3 groups. Staining for IL-5 was identified in inflammatory cells within thrombi. Eosinophils may play an important role in coronary occlusion by promoting thrombus growth.

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The aim of the present study was to clarify the effects of phase II cardiac rehabilitation (CR) on job stress and health-related quality of life (HRQOL) after return to work in middle-aged patients with acute myocardial infarction (AMI). A total of 109 middle-aged outpatients (57 ± 7 years) who completed a phase I CR program after AMI were enrolled, 72 of whom participated in a phase II CR program for 5 months after hospital discharge (CR group) and 37 who discontinued the phase II CR program after the discharge (non-CR group). Job stress was assessed at 6 months after the AMI using a brief job stress questionnaire containing questions related to job stressors, worksite support, level of satisfaction with work or daily life, and psychological distress. HRQOL was assessed using the short-form 36-item health survey (SF-36) at hospital discharge and at 3 and 6 months after the AMI. There were no significant differences in clinical and occupational characteristics between the CR and non-CR groups. The CR group patients exhibited significantly better results for job stressors and psychological distress and higher SF-36 scores at 6 months after the AMI, as compared with those in the non-CR group. These findings suggest that discontinuing a phase II CR program induced chronic psychosocial stress after return to work in these middle-aged post-AMI patients.

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Hepatocyte growth-promoting factor (pHGF) has the greatest potential as a therapeutic agent for vascular growth factor. The aim of this study was to investigate the effect of pHGF on myocardial ischemia and exercise capacity in patients with severe coronary artery disease (CAD).
Forty-nine patients were enrolled for a two week treatment period. Treadmill graded exercise tests with gas analysis were conducted before and after therapy. Serum levels of HGF were significantly elevated after therapy. The degrees of exercise-induced ST segment depression were decreased more significantly in the pHGF group. Similar differences were also found in the maximum heart rate and the maximum heart rate when the ST segment was depressed 1 mm while undergoing the treadmill graded exercise test. Both were increased more significantly in the pHGF group. Total exercise time, systolic blood pressure in the peak of exercise, the length of time that ST segment depression of 1 mm is needed, and total work all were increased in both groups after intervention. Furthermore, total exercise time and total work were increased more significantly in the pHGF group.
The levels of HGF increased significantly after pHGF treatment. pHGF could favorably improve exercise-induced myocardial ischemia and enhance exercise capacity in patients with severe CAD.

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Although higher red cell distribution width (RDW) has recently been reported to be associated with increased mortality independent of anemia in patients with heart failure and those with coronary artery disease (CAD), the mechanism underlying this association is unknown. We hypothesized that higher RDW may reflect neurohumoral activation and a chronic inflammatory state that each contribute to adverse clinical outcomes in these populations. We measured RDW and plasma levels of B-type natriuretic peptide (BNP) and high-sensitive C-reactive protein (hs-CRP) in 226 consecutive patients undergoing cardiac catheterization for CAD (age, 67 ± 8 years; males, 77%; RDW, 45.8 ± 3.3 fL; hemoglobin, 13.2 ± 1.4 g/dL; BNP, median [interquartile range], 26.0 [9.0-58.4] pg/mL; hs-CRP, 679 [345-1920] ng/mL).
Plasma BNP (r = 0.21, P < 0.01) but not hs-CRP (r = 0.04, P > 0.1) levels correlated with RDW. After adjustment for potential confounders including age, gender, body mass index, glomerular filtration rate, hemoglobin, and known hemodynamic determinants of BNP, including elevated left ventricular end-diastolic pressure and volume and slow left ventricular relaxation, RDW was independently predicted by BNP (r² = 0.058, P < 0.001). In conclusion, elevated BNP levels are independently associated with higher RDW in patients with CAD. Neurohumoral activation may be a mechanistic link between increased RDW and adverse clinical outcomes in this population.

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Indications for implantable cardioverter defibrillators (ICDs) are expanding. Defining long-term predictors of ICD therapies might help to identify those patients who will benefit most from implantation of an ICD. The objective of this study was to examine long-term predictors of appropriate ICD therapy among patients with coronary disease at high risk of sudden cardiac death.
An analysis of 245 patients with coronary disease, who had been implanted with an ICD for primary or secondary prevention of sudden cardiac death, was performed. Time to appropriate ICD therapy, defined as antitachycardia pacing or shock, was evaluated by the Kaplan-Meier method. Cox regression analysis was performed to determine hazard ratios for factors predicting appropriate ICD therapies.
During a mean (SD) follow-up of 41 (33) months, 115 patients (53%) experienced appropriate ICD therapy. Independent predictors of appropriate ICD therapy included advanced age, left ventricular ejection fraction (LVEF) < 35%, and impaired renal function, with covariate-adjusted hazard ratios of 1.36 per 10 years (95% CI, 1.11 - 1.66; P = 0.003), 1.78 (95% CI, 1.21 - 2.63; P = 0.004), and 1.59 (95% CI, 1.00 - 2.54; P = 0.050), respectively. Remote myocardial infarction (> 6 months prior to ICD implantation) was associated with higher probability of appropriate ICD therapy among patients with LVEF > 35% (adjusted HR 2.68 [95% CI, 1.05 - 6.86; P = 0.04]), but not among patients with LVEF < 35% (adjusted HR 1.09 [95% CI, 0.58 - 2.04; P = 0.79]).
Left ventricular ejection fraction, advanced age, and renal impairment are long-term predictors of appropriate ICD therapy in patients with coronary disease at high risk of sudden cardiac death. Patients with an ejection fraction above 35% have few arrhythmic events early after the myocardial infarction but appropriate therapies become more frequent late after the myocardial infarction, possibly due to progression of the disease.

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Cerebrovascular events increase with additional risk factors in patients with nonvalvular atrial fibrillation (NVAF). The relative risk proportional to the number of risk factors in Japanese patients has not been reported.
The prevalence of risk factors was investigated for over 2 years in a prospective cohort study of 265 patients with NVAF. The CHADS2 score is a widely used risk stratification scheme that includes age, hypertension, diabetes mellitus, previous stroke, and heart failure.
Cerebral infarction occurred in 23 patients. This group was significantly older and had a significantly higher prevalence of hypertension. The ratio of a CHADS2 score of 0 - 2 was 77% among patients without stroke, but 44% in the cerebral infarction group. Univariate logistic regression analysis showed that the predictive factors of cerebral infarction were: age (odds ratio (OR) 1.087 (confidence interval (CI) 1.032 - 1.145, P = 0.002), hypertension (OR 3.288 (CI 1.086 - 9.962, P = 0.03) and CHADS2 score (OR 1.762 (CI 1.222 - 2.543, P = 0.002). Furthermore, a CHADS2 score of 3 - 6 was associated with a greater risk of cerebral infarction (OR 4.420 (CI 1.838 - 10.631, P < 0.001).
The CHADS2 score was a useful marker of stroke risk in this Japanese population. An increased CHADS2 score was associated with an approximate 1.8-fold increase in risk.

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The clinical usefulness of the Tei index, which reflects left ventricular (LV) systolic and diastolic function, is known to have prognostic value in patients with overt heart disease such as ischemic heart disease or congestive heart failure. Additionally, LV diastolic functional parameters such as the transmitral E/A (early to atrial velocity) ratio have been shown to have prognostic value in hypertensive patients. However, the clinical usefulness of the Tei index for hypertensive patients without overt heart disease has not yet been fully studied. We compared the Tei index between hypertensive and normotensive patients and examined independent determinants of the Tei index in hypertensive patients with preserved LV systolic function. Our subjects were 319 patients with cardiovascular risk factors including hypertension and diabetes, all of whom had preserved LV systolic function (LV ejection fraction ≥ 55%). They were divided into two groups: 100 normotensives (67 ± 11 years) and 219 hypertensives (69 ± 13 years). LV structural and functional parameters including transmitral E/A ratio and the Tei index were measured with Doppler echocardiography. The correlations of the transmitral E velocity to the Tei index (r = -0.311, P < 0.001) were the closest in all echocardiographic parameters in hypertensives. Stepwise regression analysis showed that E velocity (β coefficient = -0.315, P < 0.001) and relative wall thickness (β coefficient = 0.262, P < 0.001) were independently associated with the Tei index. The Tei index in hypertensives with preserved LV systolic function may be determined primarily by LV diastolic dysfunction during early diastole with LV concentric remodeling and may, together with the E/A ratio, have prognostic value in hypertensive patients.

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Endothelial function is impaired in hypertensive patients. Decreased nitric oxide and prostacyclin production as well as increased oxidative stress are involved in this abnormality.
The aim of the present study was to evaluate whether biomarkers of endothelial dysfunction and oxidative stress have diagnostic value in patients with essential hypertension.
We measured nitric oxide, prostacyclin, and oxidized-LDL levels and assessed oxidative status in 62 patients with diagnosed essential arterial hypertension and 45 healthy controls.
In the hypertensive group, among measured parameters, the median prostacyclin level was significantly lower, when compared to healthy controls (125.57 pg/mL, 25%; 75% quartile range: 84.99; 275.93 and 462.9 pg/mL, 25%; 75% quartile range: 107.69; 849.3, respectively, P = 0.009). The largest area under the ROC curve was found for prostacyclin; 0.647 (95% C.I. 0.549 to 0.737). In the analysis of logistic regression, the prostacyclin and oxidized-LDL cut-off values were associated with a 4.9 higher significant risk of hypertension (O.R. 4.91 and 4.99, respectively; P = 0.0008 and P = 0.00065, respectively). Oxidized-LDL, a biomarker of endothelial damage, was the only one that had a significant negative correlation with protective prostacyclin in hypertensive patients (r = -0.29, P = 0.02).
Of all the biomarkers prostacyclin and oxidized-LDL had the best diagnostic value for patients with hypertension.

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Septic shock has been reported as an independent risk factor for atrial fibrillation (AF), however, the mechanism remains unknown. We investigated whether lipopolysaccharide (LPS) could alter cardiac ion channel gene expression, thereby leading to atrial arrhythmogenesis.
LPS (2.5 mg/kg) was injected intraperitoneally into 10 week old Sprague-Dawley rats (n = 5). Hemodynamic data were obtained and the atrial appendages were removed after LPS injection (0, 3, 6, 12, and 24 hours) for an RNase protection assay for α1C, β2, α1G, and SCN5A. An electrophysiological study in isolated perfused hearts was performed before and 12 hours after the LPS injection. Heart rate and body temperature were significantly increased (P < 0.05) and mean blood pressure was slightly decreased (P < 0.1) at 12 hours after LPS injection. The mRNA levels of the L-type calcium channel gene (β2 and α1C) were significantly decreased at 6 and 12 hours after LPS injection. Atrial ERP became significantly shortened and the number of repetitive atrial responses induced by an extrastimulus were significantly increased after LPS injection.
LPS induced the down-regulation of L-type calcium channel gene expression and ERP shortening, which might be a mechanism underlying sepsis-induced AF.

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Ablation catheters with multiple electrodes are effective for the creation of linear atrial lesions but are associated with an increased risk of coagulum formation. In an animal study, we used a novel 9Fr deflectable ablation catheter with two saline/foam electrode pocket covered with 20 mm tubing. Each pocket contained six 2-mm long electrodes with a 1-mm interelectrode distance. Bipolar electrograms between the 3 distal and 3 proximal composite electrodes were recorded, and the pacing threshold was determined before and after radiofrequency (RF) ablation. Long linear lesions were created by applying RF energy for 90 seconds at 50 W during saline irrigation (0.4 mL/sec) between 1) the superior vena cava (SVC) and inferior vena cava (IVC), 2) SVC, fossa ovalis, and IVC, 3) transverse loop from the crista terminalis to the tricuspid valve (TV), and 4) TV and the IVC. Continuous transmural lesions were created only in a minority of cases, and lesion gaps were noted in the free wall lesions. No coagulum formation was observed after RF energy delivery. A long lesion can be created in the right atrium by using an irrigated balloon catheter, but continuous lesion formation was achieved only in a minority of animals.

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MicroRNA-1 (miR-1) is preferentially expressed in cardiac muscles, and the expression has been demonstrated to be involved in cardiac development and cardiovascular diseases. Here we report that miR-1 is closely related with ischemia/reperfusion injury in a rat model. The level of miR-1 is inversely correlated with Bcl-2 protein expression in cardiomyocytes of the I/R rat model. In vitro, the level of miR-1 was dramatically increased in response to H₂O₂. Overexpression of miR-1 facilitated H₂O₂-induced apoptosis in cardiomyocytes. Inhibition of miR-1 by antisense inhibitory oligonucleotides caused marked resistance to H₂O₂. Through bioinformatics, we identified the potential target sites for miR-1 on the 3’ UTR of Bcl-2. miR-1 significantly reduced the expression of Bcl-2 in the levels of mRNA and protein. The post-transcriptional repression of Bcl-2 was further confirmed by luciferase reporter experiments. These data demonstrated that miR-1 plays an important role in the regulation of cardiomyocyte apoptosis, which is involved in post-transcriptional repression of Bcl-2.

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The waveforms of myocardial tension and left ventricular (LV) pressure curves are useful for evaluating myocardial and LV performance, and especially for inotropism and lusitropism. Recently, we found that half-logistic (h-L) functions provide better fits for the two partial rising and two partial falling phases of the isovolumic LV pressure curve compared to mono-exponential (m-E) functions, and that the h-L time constants for the four sequential phases are superior inotropic and lusitropic indices compared to the m-E time constants. In the present study, we tested the hypothesis that the four sequential phases of the isometric tension curves in mammalian cardiac muscles could be curve-fitted accurately using h-L functions. The h-L and m-E curve-fits were compared for the four phases of the isometric twitch tension curves in 7 isolated rabbit right ventricular and 15 isolated mouse LV papillary muscles. The isometric tension curves were evaluated in the four temporal phases: from the beginning of twitch stimulation to the maximum of the first order time derivative of tension (dF/dt_max) (Phase I), from dF/dt_max to the peak tension (Phase II), from the peak tension to the minimum of the first order time derivative of tension (dF/dt_min) (Phase III), and from dF/dt_min to the resting tension (Phase IV). The mean h-L correlation coefficients (r) of 0.9958, 0.9996, 0.9995, and 0.9999 in rabbit and 0.9950, 0.9996, 0.9994, and 0.9997 in mouse for Phases I, II, III, and IV, respectively, were higher than the respective m-E r-values (P < 0.001). The h-L function quantifies the amplitudes and time courses of the two partial rising and two partial falling phases of the isometric tension curve, and the h-L time constants for the four partial phases serve as accurate and useful indices for estimation of inotropic and lusitropic effects.

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