Atherosclerosis is responsible for more than half of all deaths in Western countries. Numerous studies have reported that accumulation of smooth muscle cells (SMCs) plays a principal role in atherogenesis, post-angioplasty restenosis and transplantation-associated vasculopathy. Although much effort has been devoted to targeting the migration and proliferation of medial SMCs, effective therapy to prevent occlusive vascular remodeling has not been established. Recently, it was suggested that bone marrow-derived precursors can give rise to vascular cells that contribute to the repair, remodeling, and lesion formation of the arterial wall under certain circumstances. This review highlights the recent findings on circulating vascular precursors and describes the potential therapeutic strategies for vascular diseases, targeting mobilization, homing, differentiation and proliferation of circulating progenitor cells. (Circ J 2003; 67: 983 - 991)

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The incidence, manifestation and management of arrhythmia in congenital heart disease (CHD) during pregnancy were evaluated in a multicenter study. Of 126 pregnancies in patients with CHD in 17 institutions from January 1991 to December 2000, 29 cases of pregnancy in 27 patients after cardiac repair (mean age, 29±4.9 years) were identified with arrhythmias (supraventricular tachyarrhythmia (SVT) in 15, ventricular tachycardia (VT) in 9, high-grade atrioventricular block in 4 and sick sinus syndrome in 3) (group A) and 29 control pregnancies from 29 patients with repaired CHD and no arrhythmias (group B). SVT tended to require anti-arrhythmic medication more than VT (10/15 vs 2/9, p=0.04). Nine different types of anti-arrhythmic agents were successfully administered without maternal complications. There were no maternal deaths in either group. In the comparison of group A with group B, there was lower cardiac functional class (8/29, p=0.04), higher incidence of polysplenia (4/29, p=0.04), and higher incidence of low-birthweight infant (7/29, p=0.02) in the former. It appears that there is a high prevalence of arrhythmias during pregnancy in patients with repaired CHD. Patients with CHD and low cardiac functional class and/or polysplenia could have arrhythmia during pregnancy that results in a low-birthweight infant. Meticulous care for these patients during pregnancy is recommended. (Circ J 2003; 67: 992 - 997)

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The evaluation of myocardial perfusion and tissue characteristics gives useful information regarding the indication for surgery. In the present study, two-phase contrast enhanced electron beam computed tomography (EBT) was used to quantitatively examine myocardial perfusion and the tissue characteristics of the left ventricular (LV) myocardium in congenital aortic stenosis (AS). The AS group comprised 15 patients and the control group had 14 non-AS patients. Myocardial ischemia and tissue characteristics were evaluated by the ratio of the incremental CT number of the myocardium (M) and the lumen (L) of the LV (M/L) in, the early phase with and without dipyridamole (Dp) loading and in the late phase after enhancement (respectively). In a comparison between the AS group and the controls, mean early M/Ls were significantly lower in the AS group than in the controls (20±5% vs 37±10%, p<0.01) and mean late M/Ls in the AS group were also significantly lower (47±11% vs 62±13%, p<0.01). In the AS patients, early M/Ls in the subendocardial and apical regions were especially lower than those of other segments, but the late M/Ls in these segments were inversely higher than those of other segments. These results suggest 2 things: (1) the existence of latent LV myocardial ischemia in AS patients, which is probably because of a hypertrophied LV wall, in turn caused by afterload, and (2) the presence of more myocardial ischemia and interstitial fibrosis in the subendocardial and apical regions of the AS heart. Using Dp loading for the AS patients increased the clarity of the contrast images. Contrast-enhanced EBT is useful for evaluating myocardial characteristics and perfusion in AS, and gives new insight into the LV wall characteristics in AS, as well as an indication for surgical correction of congenital AS. (Circ J 2003; 67: 998 - 1002)

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The combination of a change in lifestyle toward Western habits and an aging society, has led to a steady increase in the incidence of atherosclerotic diseases in the Japanese population. Coronary artery disease (CAD), carotid stenosis (CS), and peripheral artery disease (PAD) are major manifestations of generalized atherosclerosis and increase the risk of cardiovascular events. However, the incidence of CS and PAD in Japanese patients with CAD is not well known, so the present study investigated this in 380 consecutive patients with CAD undergoing elective coronary aorta bypass grafting (CABG) at Kishiwada Tokushukai Hospital between October 1999 and October 2001. The coexistence of CS and PAD in all patients was preoperatively evaluated by duplex ultrasonography and the ankle - brachial index (ABI). The average age of the study population was 66.09.1 years (range, 42-87). The number of male patients was 293 (77.1%). The incidence of CS was 13.7% and 15.3% for PAD. Multivariate logistic regression analysis demonstrated that no particular traditional atherosclerotic risk factor, such as hypertension, hyperlipidemia, diabetes mellitus, and smoking, was able to predict either CS or PAD, but CS and PAD were independent predictors of each other. The results of the study suggest that CS and PAD were not only highly prevalent but also strongly associated with each other in this cohort of CAD patients. Accordingly, extracoronary atherosclerotic disease should be assessed in Japanese CAD patients. (Circ J 2003; 67: 1003 - 1006)

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The objective of this study was to determine who is at risk for cardiac events among young patients with long QT syndrome (LQTS) with or without a past history of LQTS-related cardiac events. The subjects were young patients with LQTS who had visited one of 36 hospitals from January 1997 to August 2000 in Japan. To predict the risk factors for cardiac events, stepwise regression analyses were performed for a total of 197 cases. There were 7 of 129 cases (5%) without a past history and 32 of the 68 (47%) cases with a past history of LQTS-related cardiac events that experienced new events after diagnosis (p<0.0001). Patients with a family history showed a higher incidence of symptoms both before and after diagnosis than patients with sporadic occurrence. Analyses revealed that noncompliance with medication and a lower age at diagnosis were significant predictors for the group with a past history. A negative predictive value <4 points was 100% in the group without a past history. To prevent future cardiac events, compliance with medication must be improved in those with a past history. A total LQTS score <4 points was useful to predict the absence of cardiac events in the group without a past history. (Circ J 2003; 67: 1007 - 1012)

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Histological abnormalities of the atherosclerotic lesion are closely related to the stability of the plaque. Specifically, the plaque is likely to be unstable if the fibrous cap is thin. However, ultrasonic characterization of the atherosclerotic lesion has not been done from this viewpoint. Thus, in the present study ultrasonic tissue characterization of the carotid atherosclerotic lesion was attempted to assess the stability of the plaque. Integrated ultrasonic backscatter (IBS) in the atherosclerotic lesion was compared with histological findings of the respective tissue in 35 patients with carotid artery stenosis who underwent carotid endarterectomy. Carotid IBS was determined by locating the region-of-interest (ROI) in the center of the atherosclerotic lesion and calibrating by subtracting the IBS in the tunica externa of the vessel from the IBS of the ROI. IBS was also determined at the interface of the plaque, and at this site it was analyzed in relation to the thickness of the fibrous cap. Lipid content, fibrous tissue, thrombus, hemorrhage and calcification were histologically assessed in the respective tissue. Carotid IBS in the lipid lesion (-22.5±4.1 dB) was significantly different from that of fibrous, hemorrhagic or calcified lesions (-11.1±7.1, -27.5±4.1, +2.1±6.5 dB, respectively), but there was no significant difference in IBS between the lipid lesion and thrombus (-15.2±8.8 dB). IBS was lower in the thin fibrous cap than in the thick lesion (-10.9±6.4 vs -2.4±6.2 dB, p<0.001). IBS can be used to characterize atherosclerotic lesions in the carotid artery; a low value at the interface suggests a thin fibrous cap, which is frequently associated with unstable plaque. (Circ J 2003; 67: 1013 - 1016)

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Nonischemic dilated cardiomyopathy (DCM) is associated with a high risk of sudden cardiac death. Signal-averaged electrocardiography (SAECG) is a useful clinical tool for detecting late ventricular potentials (LP). Gap junction alterations have recently been shown to be involved in the pathogenesis of ventricular arrhythmias in DCM; however, the possible relationship between gap junctional connexin43 (Cx43) expression and SAECG has not yet been evaluated. In the present study 16 patients (47±13 years) with DCM who had undergone SAECG testing were evaluated. In each patient, the expression of Cx43 proteins was qualitatively and quantitatively determined using immunoconfocal microscopy and right ventricular biopsy specimens. The level of expression of Cx43 protein was defined as the proportion of tissue area occupied by Cx43 (percent tissue area) in each test area. The abundance and distribution of the Cx43 signal was assessed in relation to LP. Late ventricular potentials were positive in 5 patients (LP (+) group) and negative in 11 patients (LP (-) group). The incidence of sustained ventricular tachycardia in the LP (+) group was higher than that in the LP (-) group (80% vs 18%, p=0.04). The percent tissue area of Cx43 in the LP (+) group was significantly lower than that in the LP (-) group (p=0.02). Furthermore, Cx43 protein in the LP (+) group was distributed more heterogeneously than that in the LP (-) group (p=0.001). The heterogeneous expression of Cx43 protein may contribute to impaired ventricular conduction, which may be related to the LP detected on SAECG. (Circ J 2003; 67: 1017 - 1021)

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In this study, the endothelin-1 (ET-1) and nitric oxide (NO) concentrations in slow coronary flow (SCF) patients were assessed before and at the peak of the exercise stress test and compared with the values from healthy controls. The study population was 25 patients who underwent coronary angiography and were diagnosed as SCF (11 females (44%), aged 56.7±9.8 years), and 20 normal subjects (9 females (45%), aged 54.3±9.2 years). Mean TIMI frame count in the patients was 54.1±13.4. Blood samples were drawn at rest and immediately at the end of exercise testing. The baseline ET-1 concentrations of the control subjects were lower than those of the patients (7.0±4.5 pg/ml vs 11.1±5.9 pg/ml p<0.0001) and this difference increased after exercise (6.2±4.3 pg/ml vs 20.1 ±10.4 pg/ml, p<0.0001). Post-exercise ET-1 concentrations were significantly higher than baseline in patients with SCF (p<0.0001) and a reduction in the ET-1 concentrations was observed in control subjects (p<0.05). Baseline NO concentrations of the patients were lower than those of the control subjects (27 ±5.1 μmol/L vs 31.2±4.9 μmol/L, p=0.0001). Although the NO concentrations in both groups were significantly increased after exercise (29.4 ±5.9 μmol/L vs 33.3±5.6 μmol/L, p<0.05 for both), the difference was not significant. A significant negative correlation among post-exercise ET-1 concentrations and maximal heart rate, exercise duration and exercise rate - pressure product, and a significant positive correlation among post-exercise NO concentrations and maximal heart rate and exercise duration were observed in both groups. The results of this study show that endothelial function (assessed by ET-1 and NO concentrations) and its response to exercise were abnormal in SCF patients compared with healthy subjects, and this may play some pathophysiologic role. (Circ J 2003; 67: 1022 - 1028)

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Although patients with medically treated vasospastic angina have a good outcome, few data exist regarding the role of underlying lesion severity associated with or without hyperlipidemia in the prognosis. Therefore, the aim of the present study was to assess the relationship between the long-term outcome of vasospastic angina and the factors influencing its prognosis. A total of 256 patients (219 men, 37 women; mean age, 54.1±9.2) who had coronary spasm with or without underlying lesions and were being treated with calcium channel antagonists were enrolled and followed for 13.6±3.7 years. Cardiac events consisted of cardiac death and ischemic events, which included acute myocardial infarction and unstable angina. Cox analysis selected coronary artery stenosis (CAS, ≥50%) and risk factors such as age, hypertension, diabetes mellitus, low-density lipoprotein-cholesterol (LDL-C), sex and smoking. There were 19 cases of cardiac death (7.4%) and 58 of ischemic events (22.7%) during the follow-up period. The presence of significant CAS was an independent predictor of event-free survival (hazard ratio (HR) =2.84, 95% confidence interval (CI) =1.79-4.52, p<0.0001). In 193 patients without significant CAS, there were 10 cases of cardiac death (5.2%, p<0.05) and 34 of ischemic events (17.6%, p<0.01). In that group, high LDL-C was the independent predictor of event-free survival (HR = 3.89, 95% CI = 1.20-12.6, p=0.02). Kaplan-Meier survival analysis revealed significantly lower event-free survival in patients with than in those without lesions (p<0.0001 by log-rank test). These results demonstrate that the most important factor for long-term prognosis of vasospastic angina treated with calcium channel antagonists is significant CAS. High LDL-C, which might alter the underlying coronary endothelial function and/or accelerate atherosclerotic lesions, could also contribute to the occurrence of cardiac events, particularly in patients without significant CAS. (Circ J 2003; 67: 1029 - 1035)

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The differential diagnosis of wide QRS premature contractions is often inaccurate in most ECG machines with automatic computer-assisted diagnosis. The purpose of the present study was to improve the accuracy of the automated differential diagnosis between premature ventricular contractions (PVC) and supraventricular contractions with aberrant conduction (A-PSC). The study investigated 180 consecutive electrocardiograms (ECGs) with wide QRS premature contractions picked up from 3,723 in the ECG database. A new algorithm, Detection of Wide QRS Complex → Second Derivative → Absolute Value → Smoothing → T Wave Subtraction → P' Detection, was compared with a conventional QRS morphology algorithm and P' algorithm without T wave subtraction. The rate of false positives was reduced step by step (22.3% in the conventional algorithm, 7.8% in the P' without T subtraction algorithm and 3.0% in the P' with T subtraction algorithm), resulting in a marked increase in diagnostic accuracy for A-PSC from 77.2% to 90.6% and 95.0%, respectively. In a general population with external samples, the newest algorithm showed 77.8% sensitivity, 99% specificity, and 98.9% accuracy for diagnosis of A-PSC. The new algorithm for differential diagnosis of wide QRS complexes is simple, reliable, and easy to apply to most 12-lead ECG machines with computer-assisted automatic diagnosis. (Circ J 2003; 67: 1036 - 1040)

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In the present study, the intravascular ultrasound (IVUS) morphologic appearance of coronary atherosclerotic plaque associated with focal spasm was prospectively studied in 45 patients with or without focal coronary spasm provoked by ergonovine or acetylcholine. The percent plaque area and plaque arc were determined from the IVUS images at the sites of spasm. Calcified lesion was defined as the presence of high-intensity echo with acoustic shadowing. Twenty-three patients had focal coronary spasm defined as angiographic narrowing >75% and IVUS demonstrated atherosclerotic plaque in these 23 sites. In the 22 patients without focal spasm, IVUS demonstrated 18 atherosclerotic lesions in 17 patients and the remaining 5 patients did not have significant lesions. There was no difference in the percent plaque area and plaque arc between plaque lesions with (47±10%, 298±71°) and without (39±15%, 249±83°) coronary spasm. Interestingly, calcified lesion was less frequently present at the sites with than at those without spasm (p<0.05). These results indicate that the presence of plaque without calcification is likely to be related to the occurrence of focal vasospasm, although the severity and distribution of the disease did not differ between each patient group. (Circ J 2003; 67: 1041 - 1045)

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EPC-K1, a hydroxyl radical scavenger synthesized by phosphate linkage of vitamin E and vitamin C, prevents myocardial reperfusion injury in vivo; however, the direct effects of EPC-K1 on coronary arteries are unknown. These experiments were undertaken to define possible mechanisms through which EPC-K1 imparts its protective action on the coronary vasculature. EPC-K1 (10^-5 to 10^-1 mg/ml) induced concentration-dependent relaxation in contracted canine coronary artery segments with endothelium, but no change in tension of arterial segments without endothelium (p<0.05, ANOVA). Endothelium-dependent relaxation to EPC-K1 was inhibited by N^G-monomethyl-_L-arginine (_L-NMMA) (10^-5 mol/L). Inhibition of relaxation by _L-NMMA was reversed by the addition of _L-arginine (10^-4 mol/L), but not by _D-arginine (10 ^-4 mol/L). Subsequent exposure of canine coronary artery segments with intact endothelium to hydroxyl radicals for 30 min (generated by FeSO₄ [0.56 mmol/L] + H₂O₂ [0.56 mmol/L]) impaired endothelium-dependent relaxation. However, pretreating the vascular segments with EPC-K1 (10^-4 mg/ml) prevented hydroxyl radical-mediated endothelial cell injury and maintained endothelium-dependent relaxation. These experiments indicate that EPC-K1 stimulates the release of endothelium-derived nitric oxide, an endogenous vasodilator and inhibitor of platelet and leukocyte activation and adhesion, from the coronary artery endothelium. Additionally, EPC-K1 scavenges hydroxyl radicals that mediate endothelial cell injury. These 2 independent and important actions are possible mechanisms by which EPC-K1 prevents reperfusion injury in the ischemic heart. (Circ J 2003; 67: 1046 - 1052)

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The aim of this study was to evaluate the effectiveness of an angiotensin-converting enzyne inhibitor (ACEI, quinapril) or angiotensin II receptor blocker (ARB, candesartan) on atrial natriuretic peptide (ANP) activity in rats with hypertension induced by nitric oxide (NO) inhibition. ACEI and ARB have a number of pharmacologic effects, including blood pressure reduction, myocardial preservation, and an unknown effect in the circulation. The changes in ANP in NO inhibitor-induced hypertensive rats were evaluated in order to elucidate the interaction between ANP and NO in the regulation of blood pressure. Thirty-six rats were divided into 4 groups and administered the experimental agents for 8 weeks: group Control was given regular food (n=9), group N^G-nitro-L-arginine (L-NNA) was administered L-NNA (25 mg · kg^-1 · day^-1, n=9), group ACEI was administered L-NNA and quinapril (10 mg · kg^-1 · day^-1, n=9), and group ARB was administered L-NNA and candesartan (10 mg · kg^-1 · day^-1, n=9). Blood pressure, plasma ANP, atrial ANP, ANP mRNA, and ANP granules were measured. A significant elevation in blood pressure was observed in group L-NNA. However, there were no increases in plasma ANP (L-NNA: 138.8±64.4, Control: 86.7±36.4), ANP mRNA (L-NNA: 2.2±1.0, Control: 1.7±0.5) or ANP granules (L-NNA: 61.1±10.2, Control: 64.5±8.5). No increase in blood pressure was seen in groups ACEI and ARB. However, plasma ANP (ACEI: 1,392.3±1,034.4, ARB: 1,142.8±667.3), ANP mRNA (ACEI: 52.8±29.1, ARB: 42.9±21.2), and ANP granules (ACEI: 122.5±23.4, ARB: 136.3±33.2) increased significantly. NO inhibitor-induced hypertension caused no changes in ANP concentrations. However, the ACEI and ARB had a direct effect on the induction of ANP secretion. The findings suggest that ANP secretion is directly effected by ACEI and ARB, which seems to play a key role in lowering blood pressure, relieving heart failure symptoms, and preserving the myocardium. (Circ J 2003; 67: 1053 - 1058)

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A giant, high-flow coronary fistula is usually difficult to treat by transcatheter coil embolization, but the 0.052-inch Gianturco coil, which is larger and has a stronger shape memory than conventional coils, is now available. Using this device and additional conventional coils, a high-flow coronary artery fistula in a healthy 31-year-old man was successfully embolized. The new Gianturco coil widens the indication for the transcatheter embolization of coronary artery fistulas. (Circ J 2003; 67: 1059 - 1060)

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A 67-year-old man was transferred to hospital because of acute circulatory failure resulting from sustained left ventricular tachycardia (LVT) and dysfunction. Transthoracic echocardiography revealed severely impaired left ventricular contraction and dyskinesis of the apical wall. Neither anti-arrhythmic agents nor direct current cardioversion was effective; the patient was resuscitated by immediate use of percutaneous cardiopulmonary support and intraaortic balloon counterpulsation. Ventricular contraction returned to normal following restoration of normal sinus rhythm with amiodarone and cibenzoline. The pathogenesis of LVT accompanied by transient ventricular dyskinesis is discussed with regard to the efficient use of a mechanical circulatory support system in resuscitation. (Circ J 2003; 67: 1061 - 1063)

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Remarkable progress has been made in the treatment of coronary heart diseases because of a variety of new interventional devices, but as each new device or procedure has suitability for a particular type of patient or purpose, patient selection is increasingly important. Endoluminal perspective volume renderings of the coronary arteries of a 70-year-old male with old myocardial infarction and recurrent chest pain were carried out using electron-beam computed tomography. Conventional coronary angiography had revealed significant stenosis of the distal portion of the left anterior descending branch, and subsequent conventional balloon angioplasty had failed to expand the stenotic site. Perspective volume rendering images can distinguish differences in objects and evaluate the cross sectional area of the lumen and the morphology of calcification. In the present patient, a huge mass of calcified plaque occupied most of the lumen at a site corresponding to the angiographic site of stenosis. According to this finding, rotational atherectomy was indicated and had a good outcome. The qualitative information for characterizing and determining the morphology of atherosclerotic plaque provided by perspective volume rendering may be useful in selecting the appropriate intervention. (Circ J 2003; 67: 1064 - 1067)

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A 55 year-old man had a myxoma that originated in the left atrium and grew through a secundum atrial septal defect into the right atrium. The tumor, which was attached by a pedicle to the lateral wall of the left atrium near the right pulmonary vein, was resected under cardiopulmonary bypass. Transesophageal echocardiography was important in the successful outcome of surgical treatment. (Circ J 2003; 67: 1068 - 1069)

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Wrong:Kazuhiro Higuchi, MD;
Right:Hirokazu Higuchi, MD;

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