Keiji Ujino

Elevated levels of neopterin are associated with carotid plaques with complex morphology in patients with stable angina pectoris

OBJECTIVE Neopterin is an activation marker for monocytes/macrophages, and circulating levels of neopterin are elevated in patients with coronary complex lesions in unstable angina pectoris. We investigated the possible association between neopterin and complex carotid plaques which may be associated with the risk of ischemic stroke in patients with stable angina pectoris (SAP). METHODS We measured plasma levels of neopterin in 102 patients with SAP and carotid ultrasound was performed for evaluation of the presence of carotid plaques and plaque surface characteristics categorized as complex or noncomplex. In addition, endarterectomy specimens of extracranial high-grade carotid stenosis with complex plaques from five patients with SAP were immunohistochemically examined with antibodies to smooth muscle cells, endothelial cells, platelets, macrophages, and T cells. RESULTS Plasma neopterin levels were significantly higher in patients with complex carotid plaques than in those with noncomplex plaques (median [interquartile range]: 24.2 [19.2-39.3]nmol/L vs. 19.4 [11.9-25.1]nmol/L; P=0.01) or without any plaques (18.8 [14.9-23.6]nmol/L; P=0.001). On multivariate logistic analyses after adjustment for traditional atherosclerotic risk factors, multi-vessel coronary disease and high sensitivity C-reactive protein, neopterin levels were independently associated with the presence of complex carotid plaques (adjusted OR 2.21 per SD increase, 95%CI 1.13-4.33, P=0.02). Immunohistochemical staining revealed abundant neopterin-positive macrophages in carotid complex lesions. CONCLUSION These findings demonstrate that carotid plaques with complex morphology have increased circulating neopterin levels and immunohistochemical localization of neopterin in patients with SAP. Neopterin can be considered an important biomarker of plaque destabilization in carotid artery atherosclerotic lesions in this population.

Comparison of determinations of left atrial volume by the biplane area-length and Simpson's methods using 64-slice computed tomography

OBJECTIVES There is increasing evidence that left atrial (LA) size is an important predictor of adverse cardiovascular outcomes such as atrial fibrillation, stroke, and congestive heart failure. The aim of this study was to determine whether there is a difference in results of quantification of LA volume by the area-length and Simpsons methods using multislice computed tomography (MSCT). METHODS AND RESULTS The study population consisted of 51 patients with sinus rhythm (sinus group) and 20 patients with atrial fibrillation (af group) clinically indicated for MSCT angiography for evaluation of coronary arteries. Maximum LA volume, obtained at end-systole from the phase immediately preceding mitral valve opening, was measured using the area-length and Simpsons methods. In the sinus group, the mean LA volumes, indexed to body surface area, were 48.4+/-17.9 ml/m(2) with the area-length method and 48.3+/-17.0 ml/m(2) with the Simpsons method. In the af group, the mean indexed LA volumes with the area-length method and the Simposons method were 91.5+/-47.5 ml/m(2) and 90.3+/-45.9 ml/m(2), respectively. LA volumes calculated by the area-length method exhibited a strong linear relationship and agreement with those calculated using Simpsons method in both the groups (sinus group: r=0.99, P<0.0001, af group: r=0.99, P<0.0001). CONCLUSIONS The area-length method is a simple and reproducible means of assessment of LA volume. Standardization of LA volume assessment using MSCT is important for serial follow-up and meaningful communication of results of testing among institutions and physicians.

Long-acting calcium channel antagonist pranidipine prevents ventricular remodeling after myocardial infarction in rats

SummaryThe purpose of this study was to examine the effects of the long-acting calcium channel antagonist pranidipine on ventricular remodeling, systolic and diastolic cardiac function, circulating humoral factors, and cardiac mRNA expression in myocardial infarcted rats. Myocardial infarction (MI) was produced by ligation of the coronary artery in Wistar rats. Three mg/kg per day of pranidipine was randomly administered to the infarcted rats. Hemodynamic measurements, Doppler echocardiographic examinations, analyses of the plasma levels of humoral factors, and myocardial mRNA expression were performed at 4 weeks after myocardial infarction. Left ventricular end-diastolic pressure (LVEDP) and central venous pressure (CVP) increased to 24.2 ± 1.2mmHg and 5.4 ± 0.6mmHg. Pranidipine reduced LVEDP and CVP to 13.6 ± 1.4mmHg (P < 0.01) and 2.5 ± 0.4mmHg (P < 0.01). The weight of the left and right ventricles in MI was significantly higher than in the sham-operated rats (sham, 2.02 ± 0.04 and 0.47 ± 0.02g/kg; MI, 2.18 ± 0.05 and 0.79 ± 0.04g/kg;P < 0.01). Left ventricular end-diastolic dimension (LVDd) in MI increased to 10.3 ± 0.3mm (P < 0.01) (sham, 6.4 ± 0.3mm). Pranidipine prevented an increase in the weight of the left and right ventricles (2.02 ± 0.04 and 0.6 ± 0.03g/kg,P < 0.01) and LVDd (7.9 ± 0.2mm,P < 0.01 to MI). Plasma renin activity (PRA), and plasma epinephrine, norepinephrine, and dopamine concentrations in MI were higher than those of the sham-operated rats. Pranidipine decreased the PRA and plasma cathecolamine levels of the myocardial infarcted rats to the level of the sham-operated rats. Moreover, the rats in MI showed systolic dysfunction, shown by decreased fractional shortening (sham, 31 ± 2% vs MI, 15 ± 1%;P < 0.01) and diastolic dysfunction shown by the E-wave deceleration rate (sham, 12.8 ± 1.1 m/s2; MI, 32.6 ± 2.1m/s2;P < 0.01). Pranidipine significantly prevented systolic and diastolic dysfunction. The increases in β-myosin heavy chain (MHC), α-skeletal actin, and atrial natriuretic polypeptide mRNAs in the noninfarcted left ventricle and right ventricle at 4 weeks after the myocardial infarction were significantly suppressed by the treatment with pranidipine. On the other hand, depressed α-MHC was restored to normal levels by pranidipine in both regions. In conclusion, pranidipine prevents the left ventricular remodeling process accompanied by systolic and diastolic dysfunction, and inhibits abnormal cardiac gene expression after myocardial infarction.

Predictors of success of the modified maze procedure using radiofrequency device.

The modified maze procedure using radiofrequency devices has become an increasingly common surgical option for patients with atrial fibrillation. Several lesion sets have been proposed and tested, but it remains unclear which yields the best results. We studied 61 patients who underwent the modified maze procedure using radiofrequency devices from March 2005. The pulmonary veins were isolated separately on both sides, and a connecting lesion was made inferiorly in the early series of 30 patients (group 1). In 31 patients (group 2) treated from May 2007, we added a superior connecting lesion between both pulmonary veins (completing a box lesion), and also performed coronary sinus ablation from the epicardial side, using a monopolar device. At 6 months postoperatively, maintenance of sinus rhythm with and without antiarrhythmic medications was 70% and 63%, respectively in group 1, and 94% and 90% in group 2 (both p < 0.05). Multivariate analysis indicated that the box lesion with coronary sinus ablation was an independent predictor of the maintenance of sinus rhythm at 6 months. These 2 lesions should not be eliminated from the modified maze procedure.

Asymptomatic vascular rings of aorta in adult cardiac surgery patients.

A 70-year-old man presented with recurrent exertional chest oppression. His history included insulin-dependent diabetes, systemic hypertension, hypercholesterolemia, minor stroke, and myocardial infarction with a subsequent percutaneous catheter intervention. Coronary angiography showed severe 3-vessel disease with significant left main stenosis. A double aortic arch was identified incidentally by multidetector computed tomography (Figure 1). Both arches arose from the ascending aorta, gave rise to the common carotid and subclavian arteries, encircled the trachea and esophagus, and joined the descending aorta. The distal ascending aorta and Figure 1. Multidetector computed tomography demonstrating double aortic arch. The aortic arches were balanced and gave rise to the common carotid and subclavian arteries on each side.