A survey by the Japanese Coronary Intervention Study (JCIS) group revealed that 109,788 percutaneous coronary intervention (PCI) procedures were performed at 1,023 laboratories during 1997. The present study aimed to describe the demographic and clinical characteristics, treatment strategies, in-hospital outcomes, and long-term outcomes of these patients. A total of 10,642 PCIs performed in 8,814 patients, which corresponded to approximately 10% of the overall PCIs, were selected at random. The mean patient age was 65 years, and 75% were males. The patients often had extensive coronary risk factors. The most prevalent clinical diagnosis was stable angina (36%), followed by myocardial infarction (MI) excluding acute myocardial infarction (AMI; 28%) and AMI (25%). Plain old balloon angioplasty was used as the sole procedure in 58% of lesions for which an attempt to heal was made, and coronary stent placement in 38%. Angiographic success was achieved in 92% of attempted lesions. Mortality, MI and emergency coronary artery bypass grafting (CABG) rates during the hospitalization were 2.6%, 2.0% and 0.7%, respectively. In-hospital mortality rate for AMI was 7.6%, whereas that for elective PCI in cases without AMI was 0.6%. The overall mortality for 1.8 years was 8%. Repeat PCI was performed for 35% and CABG for 6% during the follow-up period. In Japan, PCI was performed in patients with coronary artery disease and extensive risk factors, but a high rate of angiographic success was achieved. The rates of in-hospital mortality and emergency CABG were low in non-AMI patients, but the 1-year rate of repeat PCI was as high as 32%. (Circ J 2002; 66: 10 - 19)

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The Japanese Coronary Intervention Study (JCIS) has revealed that 17,667 coronary artery bypass grafting (CABG) procedures were performed at 477 facilities during 1997, and this report describes the demographic and clinical characteristics, treatment strategies, and the in-hospital and the long-term outcomes in patients treated with CABG in Japan. A total of 1,862 CABG cases, which corresponded to approximately 10% of the overall CABGs, were selected at random. The mean age was 65 years, and 76% of cases were males. The most prevalent clinical diagnosis was stable angina (54%), followed by myocardial infarction (MI) excluding acute myocardial infarction (AMI) (48%), unstable angina (25%), and AMI (5%). A large proportion of cases had multivessel coronary artery disease: 3-vessel disease (56%) and left main trunk disease (29%). The CABG procedures were emergency in 16%, and 93% of anastomotic sites were patent. In-hospital mortality and MI occurred in 5.1% and 3.5% of cases, respectively. The in-hospital mortality rate for emergency CABG was 12.0%, whereas that for elective CABG was 3.8%. The overall mortality rate during the follow-up period of 2.3 years was 10%. During the follow-up period, MI and angina occurred in 2% and 8% of cases, respectively. Percutaneous coronary intervention (PCI) was performed for 8%, and repeat CABG for 0.8%. In Japan, CABG was performed in patients with multivessel coronary artery disease with extensive risk factors. Angiographically determined success was achieved in 93% and the need for subsequent revascularization was relatively low. (Circ J 2002; 66: 20 - 29)

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It is well known that coronary flow reserve (CFR) is decreased in patients with hypertrophic cardiomyopathy (HCM), but it is unclear whether coronary endothelial function is impaired. Coronary endothelial function and CFR in the coronary macro- and microcirculation was evaluated in 14 patients with HCM and 11 control subjects. Acetylcholine (ACh), bradykinin (BK) and papaverine were infused into the left coronary artery. Coronary cross-sectional area was determined by quantitative coronary angiography and coronary blood flow (CBF) was determined by the product of the coronary cross-sectional area and CBF velocity measured by an intracoronary Doppler guidewire. Acetylcholine at 100 μg induced diffuse coronary spasms of the left anterior descending coronary arteries in 3 of the patients with HCM. The changes in the diameter of the left anterior descending coronary artery and the increases in CBF induced by BK (0.2, 0.6, and 2.0 μg/min) did not differ between the 2 groups. CFR was lower in the HCM group than in the control group (p<0.01). Moreover, the ratio of BK-induced CBF increase to papaverine-induced CBF increase was comparable between the 2 groups. Endothelium-dependent vasodilation of the epicardial and resistance coronary arteries induced by BK was preserved despite the decreased CFR in patients with HCM. (Circ J 2002; 66: 30 - 34)

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To assess the role of insulin in ventricular repolarization in patients with congenital long QT syndrome (LQTS), an oral glucose tolerance (OGT) test was performed in 11 patients with LQTS and in 11 control cases without QT prolongation. Plasma glucose, potassium level and the immunoreactive insulin concentration (IRI) were measured, and the QT interval and T wave morphology on 12-lead ECG were analyzed during fasting and after glucose load. The LQTS group had a higher incidence of changes in T wave morphology, such as biphasic, bifid or notched T wave, after glucose load than the control group (11 of 11 patients [100%] vs 0 of 11 [0%]; p<0.00001). The T wave changes returned to baseline at 180 min after glucose load in 7 patients. The maximal QT interval and QT dispersion increased significantly and returned to baseline level in response to IRI after glucose load in LQTS, whereas the QT interval was unaffected in the control group. After glucose load, ventricular arrhythmias and T wave alternans were observed in 3 and 1 patients with LQTS, respectively, but none in the control group. The findings suggest that glucose-induced insulin secretion plays a role in inducing abnormalities and inhomogeneity of ventricular repolarization in patients with LQTS. (Circ J 2002; 66: 35 - 40)

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The present study sought to determine whether myocardial fatty acid metabolism as assessed with iodine-123-labeled 15-(p-iodophenyl)-3-R, S-methylpentadecanoic acid (BMIPP) scintigraphy is impaired in patients with aortic valve disease (AVD) and whether the degree of the metabolic abnormality reflects the severity of AVD. BMIPP scintigraphy was performed in 12 patients with aortic stenosis (AS), 14 patients with aortic regurgitation (AR), and 9 healthy volunteers, and from that the heart - mediastinum uptake ratio (H/M ratio) corrected by the left ventricular (LV) mass (U/Mass ratio) and the myocardial washout rate (WR) were obtained. The H/M ratio tended to be higher in patients than in healthy volunteers (3.3±0.7 for AS, 3.5±0.5 for AR, 3.0±0.3 for healthy volunteers), and the WR was significantly higher in patients than in healthy volunteers (42.8 ±9.1% for AS, 35.7±6.5% for AR, 19.6±9.1% for healthy volunteers, p<0.01). In the AS patients, the U/Mass ratio showed significant negative correlations (r=-0.79 to -0.90, all p<0.01) and the WR showed significant positive correlations (r=0.61 to 0.82, all p<0.01) with transaortic pressure gradient, LV wall thickness, and LV mass. Similarly, in AR patients these BMIPP parameters showed proportional changes to the LV volumes and LV mass (r=-0.79 to -0.83, all p<0.01 for U/Mass ratio, r=0.55 to 0.70, p<0.05 to <0.01 for WR). In the 9 patients who underwent aortic valve replacement, the BMIPP parameters tended to normalize with increasing U/Mass ratio (0.90 ±0.41 × 10^-2/g to 1.34±0.59 × 10^-2/g, p<0.05) and decreasing WR (41.9±8.8% to 35.4 ±9.2%, p<0.01) after surgery. Myocardial fatty acid metabolism as assessed with BMIPP scintigraphy was impaired in patients with aortic valve disease and the U/Mass ratio and WR reflect the severity. These parameters may be useful for the noninvasive assessment of the myocardial metabolic abnormalities caused by hemodynamic overload. (Circ J 2002; 66: 41 - 46)

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The long-term effects of the 3-hydoxy-3-methyl-glutaryl coenzyme A reductase inhibitor, pravastatin, on exercise electrocardiography (ECG) test performance and cardiovascular mortality and morbidity were compared with those of conventional lipid-lowering drugs in hypercholesterolemic patients with no history of myocardial infarction or stroke. One thousand two hundred and seventeen patients were randomly assigned with mean serum cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol levels of 6.98±0.91 mmol/L, 2.08±1.87 mmol/L, 1.38±0.44 mmol/L, and 5.07±1.14 mmol/L, respectively, and received either pravastatin at a dose of 10-20 mg/day (group P) or one of the conventional lipid-lowering drugs such as fibrates, nicotinic acid, and probucol (group C). The numbers of patients available for analysis in groups P and C were 305 and 278 at year 1, 261 and 216 at year 2, 206 and 184 at year 3, 159 and 122 at year 4, and 103 and 81 at year 5. Over the 3.2 year mean follow-up period, the reduction in serum LDL cholesterol levels was significantly greater (p<0.01) in group P (-24.3%) than in group C (-16.0%). Serum HDL cholesterol levels increased in group P (+11.6%), but decreased in group C (-0.3%) (p<0.01). There were no significant differences in the rate of patients who exhibited ischemic changes to exercise ECG test (ischemic responders) between the 2 groups. Coronary heart diseases (CHD) occurred in 6 patients in group P and 13 in group C; pravastatin significantly reduced CHD risk (reduction rate 0.369; 95% confidence interval 0.140-0.970; p<0.05). No significant differences existed between the treatment groups in terms of the number of strokes (group P, 6; group C, 7) or deaths unrelated to CHD (group P, 3; group C, 2). Although pravastatin did not improve the proportion of ischemic responders on exercise testing, it reduced CHD risk and serum LDL cholesterol levels more significantly than conventional lipid-lowering drugs without adversely affecting the risk of stroke and non-CHD death in hypercholesterolemic patients. (Circ J 2002; 66: 47 - 52)

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Heart rate is largely affected by the autonomic nervous system. However, little is known about the anatomic pathway of autonomic nerve fibers innervating the sinus node. The present study: (1) evaluates the effects of cavotricuspid isthmus ablation for common atrial flutter (AFL) on autonomic nervous function by using heart rate variability analysis, and (2) investigates the distribution of autonomic nerve pathways innervating the sinus node. Twelve patients with paroxysmal common atrial flutter who maintained sinus rhythm both before and after radiofrequency ablation were selected for the study. Holter ambulatory recordings were performed before and after (2.3±1.0 days) radiofrequency ablation of cavotricuspid isthmus. Heart rate and time domain (SDANN, rMSSD, pNN50) and frequency domain (low frequency (LF), high frequency (HF), LF/HF) analysis of heart rate variability were compared before and after ablation. Mean heart rate did not change significantly after ablation (59±6 vs 61±9 beats/min); parasympathetic indices of heart rate variability (SDANN, rMSSD, pNN50, HF) did not change significantly (110±37 vs 117±20 ms; 32±21 vs 28±9 ms; 4.8±0.9 vs 4.7±0.7 ln(ms²)); and sympathetic indices of heart rate variability (LF/HF) did not change significantly (1.1±0.2 vs 1.2±0.1). Cavotricuspid isthmus ablation for atrial flutter did not significantly change heart rate and heart rate variability because parasympathetic and sympathetic fibers innervating the sinus node are scarce in this region. (Circ J 2002; 66: 53 - 57)

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Reduced bioavailability of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide (NO) synthase, and the resulting decrease in NO in the coronary circulation may be involved in the pathogenesis of coronary spasm. The present study investigated the effects of BH4 on the vascular response to acetylcholine (ACh) in 28 patients with vasospastic angina (VA) using quantitative angiography. After recording the vascular responses to ACh (3 and 30 μg/min), either BH4 (1 mg/min) or saline was infused into the coronary artery for 2 min before and during a subsequent infusion of ACh. With the 3 μg/min dose of ACh, BH4 attenuated the ACh-induced decrease in coronary diameter in both the nonspastic segments (-1.1 ±2.2% ACh vs 6.0±2.8% ACh+BH4) and spastic segments (-6.3±2.7% ACh vs 2.9±2.7% ACh+BH4), but did not influence the ACh-induced coronary spasm at 30 μg/min (-57.3±2.4% ACh vs -55.3 ±2.4% ACh+BH4). In the control patients, saline did not influence either the spastic or nonspastic vasoconstrictor responses to ACh. Acute administration of BH4 improves coronary endothelial function, but does not prevent coronary spasm in patients with VA. (Circ J 2002; 66: 58 - 62)

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Dobutamine (DOB) stress radionuclide ventriculography (RVG) is proposed for evaluating left ventricular performance in patients with Kawasaki disease (KD). Dobutamine stress RVG, up to 15 μg · kg^-1 · min ^-1, was performed in 40 patients with a history of KD, some of whom had a perfusion defect (PD group) on dipyridamole stress thallium-201 myocardial imaging, some of whom had no perfusion defects (NPD group), and some of whom had no coronary artery lesions (C group). No significant differences in either systolic or diastolic indices of the left ventricle at rest were observed between the 3 groups. Although hemodynamic responses were similar in all patients after DOB stress, early diastolic index of the first third filling fraction decreased only in the PD group and was significantly lower in this group compared with the C group (p<0.01). The asynchrony index increased significantly in those patients with coronary stenosis after DOB stress (p<0.05). No serious side-effects were observed during the study. Even late after onset, patients with myocardial ischemia as a result of KD still had impaired early diastolic filling and asynchronous relaxation of the left ventricle. As an alternative to exercise testing, DOB stress RVG is a safe and promising means for serially evaluating left ventricular performance in patients with KD. (Circ J 2002; 66: 63 - 69)

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Atrial resynchronization resulting from simultaneous pacing of the atria may adjust inter- or intra-atrial asynchrony and prevent atrial fibrillation (AF). The purpose of this study was to assess the efficacy of bi-atrial pacing (BAP) in preventing AF, and the safety of this system. The effect of BAP was compared with single site right atrial pacing (RAP) in 6 patients with sick sinus syndrome and paroxysmal AF in a prospective switchover trial. P wave duration was significantly reduced during BAP (p<0.01). Pacing threshold, atrial wave amplitude and the lead impedance presented no significant differences at implant, 1 week and 3 months after implantation, respectively (NS). The number of AF episodes significantly decreased during both RAP and BAP compared with the control (p<0.01). Although the number of premature atrial contractions was significantly less during BAP than RAP (p<0.05), there were no significant differences of AF episodes between the two. The percentage of pacing was achieved in only 70% during both pacing modes. BAP was safe and reliable in this follow-up period and can prevent AF. These findings provide encouragement for further study and observation of BAP to prevent AF. (Circ J 2002; 66: 70 - 74)

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Cross-sectional surveillance was carried out in long-lived Uygur in China to investigate blood pressure (BP) and pulse rate (PR) variation in centenarians. The study group comprised 33 centenarians (age ≥100 years), 103 longevous subjects (age 90-99 years) and 100 elderly (age 65-70 years) subjects. Office BP was measured, and 24-h noninvasive ambulatory blood pressure monitoring (ABPM) was performed. The office BP was higher and hypertension occurred more frequently in the centenarians than in either the longevous or elderly subjects. Mean 24-h systolic and diastolic BP was higher in the centenarians than in the other 2 groups. However, mean 24-h PR did not differ between them. Day - night differences in systolic BP decreased, and the non-dipper-type BP pattern was common in the centenarians (79.1% vs 68% and 63.6% in longevous and elderly subjects, respectively). Circadian BP was characterized by 3 peaks in longevous subjects and multiple peaks in centenarians. Morning rising and nocturnal dipping of BP were observed in both longevous and elderly subjects. In conclusion, BP in longevous and elderly Uygur was characterized by circadian rhythmicity, but the nocturnal fall in BP was not seen in centenarians. Differences in day - night BP and circadian rhythmicity may decrease with advancing age, especially in centenarians. (Circ J 2002; 66: 75 - 79)

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Whether cyclical changes in energy-related phosphate metabolites arise during a cardiac cycle in isolated rat hearts and are affected by differences in myosin isozyme composition was determined. Myocardial adenosine triphosphate (ATP), phosphocreatine (PCr), inorganic phosphate (Pi), and intracellular pH in normal, hypothyroid and hyperthyroid rat hearts were measured using the pacing-gated ³¹P nuclear magnetic resonance technique. Maximal decrease in ATP and PCr, and maximal increase in Pi at the peak-systole in normal rat hearts were observed. In hypothyroid and hyperthyroid rats, similar cyclical changes in phosphate metabolites were observed during the cycle. However, the magnitude of fluctuations was smaller in hypothyroid rats and larger in hyperthyroid rats compared with that observed in normal rats. Cardiac myosin isozyme patterns were also different amongst the experimental groups. The results suggest that cyclical changes and the magnitude of fluctuations in energy-related phosphate metabolites during a cardiac cycle may depend on the cardiac workload and the intrinsic properties in the enzyme kinetics of myosin. (Circ J 2002; 66: 80 -86)

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There are 2 types of transient outward currents (I_to) in the hearts of various mammals: a 4-aminopyridine (4-AP) sensitive K⁺ current and a 4-AP resistant Ca²⁺ activated current, carried by Cl^-, (referred to as I_to1 and I_to2, respectively). However, the I_to has been considered to be absent in guinea-pig ventricular myocytes and so this study tested the hypothesis that I_to1 is generally absent in guinea-pig ventricular myocytes, but I_to2 appears under the condition of Ca²⁺ overload. Membrane currents were recorded by the whole-cell patch-clamp technique and Ca²⁺ overload was achieved by adding internal, and eliminating external, Na⁺ with subsequent enhancement of Ca²⁺ influx via the Na⁺-Ca²⁺ exchange. Under physiological conditions, I_to could not be elicited by 300 ms-test pulse from -70 mV to 0 mV (n=32). However, under Ca²⁺ overload, a biphasic current resulting from the overlap of the L-type Ca²⁺ channel current and I_to was elicited (n=38). This I_to was resistant to 4-AP (3 mmol/L, n=30) but sensitive to both anthrancene-9-carboxylic acid (9-AC, 3 mmol/L, n=8) and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (100 μmol/L, n=3). Replacing K⁺ with Cs⁺ on both sides of the membrane failed to abolish I_to (n=38). I_to disappeared by lowering the external Cl- (n=3). The amplitude of I_to was dependent on that of the L-type Ca²⁺ channel current (n=4). Because Ca²⁺ release from the sarcoplasmic reticulum was prevented by caffeine (5 mmol/L), I_to was negligible (n=6). These results suggest that I_to1 is absent, but Ca²⁺ overload evokes I_to2 in guinea-pig ventricular myocytes. (Circ J 2002; 66: 87 - 92)

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Because many endogenous substances, including adenosine, contribute to the pathophysiology of ischemic hearts, the present study was designed to investigate the transcription responses of murine hearts to ischemia with or without administration of an inhibitor of adenosine receptor, 8-sulfophenyltheophylline (8SPT). Sixty minutes after ligation of the proximal site of the left coronary artery with (n=9) or without (n=9) 8SPT, the hearts were excised to obtain mRNA for cDNA array analysis. In 18,376 cDNA, 2 known genes were upregulated over 10-fold, and 11 known genes were upregulated 5.0-9.9-fold. 8SPT reduced the expressed gene to the control levels. Furthermore, 32 unknown genes were also upregulated over 5.0-fold. In contrast, 11 known genes were downregulated below 0.2-fold, and 64% of the downregulated genes were restored by 8SPT. The 7 unknown genes were downregulated to levels below 0.2-fold. Therefore, it was concluded that the cardiac expression of 24 known and 39 unknown genes was modulated by ischemic stress, and that these genes appeared to be related to the pathophysiology of the ischemic heart because endogenous adenosine modulated their expression. (Circ J 2002; 66: 93 - 96)

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The purpose of this study was to evaluate the electrical remodeling of the ventricular myocardium in the experimental autoimmune myocarditis (EAM) model in Lewis rats. EAM was induced by immunization with cardiac myosin. During the active myocarditis phase, the effective refractory period (ERP), the duration of the monophasic action potential (MAPD) was extracted from the left ventricular free wall, and the mRNA levels of Kv1.4, 4.2, 4.3 and L type Ca²⁺ channel were determined by RNase protection assays. The inducibility of ventricular arrhythmia was higher in EAM rats than in the control rat, and the direct relationship between the coupling intervals of the premature stimulus and the ventricular arrhythmia in EAM rats. The ERP was prolonged in EAM rats compared with the control group. The MAPDs determined as 20% and 90% repolarization time, were both longer in EAM rats than in the controls. The level of expression of Kv4.2 mRNA was reduced in EAM rats in comparison with the controls, whereas those of Kv1.4, 4.3 and the L type Ca²⁺ channel were unchanged. Ventricular vulnerability was higher in EAM rats than in the control rats, and some of the ventricular arrhythmias observed in the EAM group seemed to be based on triggered activity. The level of expression of Kv4.2 mRNA was significantly reduced, and this change was compatible with prolongation of the action potential duration. (Circ J 2002; 66: 97 - 103)

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Left ventricular function after a left ventriculectomy was assessed in a patient with idiopathic dilated cardiomyopathy (DCM) who has survived longer than any other patient in Japan after this operation. The 19-year-old male had a history of cerebral infarction because of left ventricular thrombus associated with DCM. In order to remove the thrombus and improve left ventricular function, an approximately 12×4 cm piece of myocardial tissue was resected according to the methods of Batista's operation. Left ventricular diastolic dimension was temporarily reduced 1 month after surgery, but increased again. During the 45 months of follow-up, left ventricular diastolic dimension, cardiac output and New York Heart Association functional class remain unchanged from the preoperative values. (Circ J 2002; 66: 104 - 106)

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A 52-year-old Japanese man who had suffered from Behçet's disease since the age of 45 years was admitted to hospital for evaluation of syncope and heart murmur. Echocardiography and aortography revealed severe aortic regurgitation and cystic masses under the right coronary cusp and the left ventricular outflow tract, but no shunt jet. He was diagnosed with unruptured aneurysm of the sinus of Valsalva, and surgical closure of the orifice of the aneurysm was performed. The diameter of the orifice was 11 mm and the aneurysm was 15 mm in depth, and consisted of 2 chambers. Because the aortic regurgitation was reduced after patch closure of the orifice, aortic valve replacement was not performed. Unruptured aneurysm of the sinus of Valsalva is a rare clinical lesion, but patients with active inflammatory disease of the aorta, such as in Behçet's disease, should have periodic echocardiography for early detection of an aneurysm or valvular involvement, even if there are not any symptoms. (Circ J 2002; 66: 107 - 108)

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A 66-year-old woman admitted with dyspnea on exertion had atrial fibrillation and left ventricular dysfunction. Echocardiography revealed an atrial septal defect (ASD) and a soft, easily deformable thrombus in the dilated left atrium. The atrial mass suddenly disappeared on the 10th day after admission, and contrast-enhanced chest computed tomography and pulmonary blood flow scintigraphy showed that the thrombus had detached from the left atrium, floated into the right atrium through the ASD and caused pulmonary embolism. This is the first documented case of a left atrial thrombus causing pulmonary embolism by passing through an ASD. When an ASD is present, it is important to consider not only paradoxical thromboembolism (from the right to the left atrium), but also pulmonary embolism caused by thromboembolism from the left to the right atrium. (Circ J 2002; 66: 109 - 110)

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Diagnosis of primary tumors of the aorta is difficult. A patient who had a primary intimal sarcoma of the aorta with metastasis presented with obstructive symptoms and computed tomography showed a thrombus-like mass in the aorta. However, transesophageal echocardiography revealed an inhomogeneous and echo-dense mass with an outer membrane, unlike a thrombus, and suggestive of a primary aortic tumor. Pathologic examination of specimens from exploration and autopsy revealed a primary intimal sarcoma. (Circ J 2002; 66: 111 - 113)

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The plasma concentration of monocyte chemoattractant protein-1 (MCP-1) antigen is higher in patients with restenosis after coronary angioplasty than in those who do not restenose. In this study the MCP-1 expression of coronary atherectomy specimens was investigated by immunohistochemistry. Samples were obtained from 12 patients with restenosis and 15 with de novo lesions by directional coronary atherectomy. MCP-1 immunoreactivity was found in all patients in the restenosis group and in 8 of the de novo group. The frequency of macrophage expression was higher in the restenosis group than in de novo group. These results indicate that local expression of MCP-1 may be associated with the mechanisms of vascular remodeling after coronary angioplasty. (Circ J 2002; 66: 114 - 116)

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