The vascular endothelium is a dynamic endocrine organ that regulates vascular tone, local homeostasis, and the fibro-inflammatory - proliferative process. These responses are mediated by various substances released from the endothelium in response to physiologic stimuli, including prostacyclin, endothelin and, most importantly, nitric oxide (NO). NO mediates vasodilation and inhibits platelet aggregation, thrombus formation, expression of adhesion molecules and chemokines for leukocytes, and oxidative stress. It also attenuates growth and proliferation of vascular smooth muscle cells. Risk factors for atherosclerosis, such as hypercholesterolemia, hypertension, diabetes and cigarette smoking, impair endothelial function, which leads to atherosclerosis and results in ischemic manifestations such as acute coronary syndrome and stroke. Thus, therapeutic intervention aimed at increasing NO bioavailability by statins or angiotensin-converting enzyme inhibitors might improve patient prognosis. Vascular endothelial function is an important and clinically relevant therapeutic target for cardiovascular disease. (Circ J 2002; 66: 529 - 533)

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Although it is commonly believed that ischemia does not develop during coronary intervention in patients with rich collateral circulation to the target vessel, ST changes are often observed. the study group comprised 40 consecutive patients who underwent elective percutaneous coronary angioplasty and who had rich collateral vessels to the target lesions. None had side branches in the target vessel that would be occluded by the angioplasty balloon. During the intervention, the 12-lead electrocardiogram was monitored for any change in the ST-T segment and 13 (32.5%) showed significant ST changes. Of these, 3 had ST changes with every balloon inflation and the remaining 10 patients had ST changes with the second or subsequent inflations. Myocardial ischemia caused by balloon inflation is not uncommon during coronary angioplasty in patients with rich collaterals to the target vessel. The collateral circulation may stop functioning very early after improvement in the forward flow of the target vessel. (Circ J 2002; 66: 534 - 536)

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The present study was undertaken to assess whether repeated measurement of cardiac ¹²³I-metaiodobenzylguanidine (MIBG) imaging parameters before and after optimized treatments is useful for predicting the prognosis of patients with congestive heart failure (CHF) resulting from dilated cardiomyopathy (DCM). The subjects were 85 consecutive patients with DCM who had a left ventricular ejection fraction (LVEF) of less than 45%. The MIBG and the concentrations of neurohumoral factors were measured at baseline and after 6 months of optimized treatments. Cox proportional hazards analysis was performed to assess the various parameters before and after treatment. Twenty-three patients had a cardiac event (12 died; 11 hospitalized) during a mean follow-up period of 2 years. Although there was no difference between the baseline heart to mediastinum (H/M) ratio measured by MIBG between survivors and nonsurvivors, the H/M ratio was significantly decreased in nonsurvivors after 6 months. Multivariate analysis revealed that a high plasma concentration of brain natriuretic peptide level after 6 months (p=0.0049) and absolute changes in the H/M ratio (p=0.0046) were independent predictors of mortality. Comparison of the H/M ratio on MIBG imaging before and after optimized additional treatment provided useful information for predicting mortality and was independent of clinical and neurohumoral factors previously shown to be associated with poor prognosis in patients with DCM. (Circ J 2002; 66: 537 - 543)

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Arterial grafts are frequently used in modern coronary artery bypass grafting (CABG) and the benefit of the 2 internal mammary arteries (IMA) has already been established. However, the choice of the third arterial conduit, in addition to the IMA, is controversial. We have retrospectively analized perioperative and the follow-up results of patients who underwent CABG with triple arterial bypass using either the radial artery (RA) or the gastroepiploic artery (GEA) in conjunction with the bilateral IMA (BIMA). Between December 1995 and June 2001, 1,516 consecutive isolated CABG operations were performed at Shin-Tokyo Hospital. Among them the RA and BIMA were used in 96 patients (78 males, 18 females; mean age, 63.2±6.7 years, group R), and the GEA and BIMA in 123 patients (101 males, 22 females; mean age, 61.0±11.6 years, group G). Their perioperative and follow-up data were studied. The preoperative risk factors were similar between the 2 groups, except that there were significantly fewer patients with renal dysfunction in group R. The surgical results did not differ between the 2 groups; however, the GEA was more commonly used for revascularization of the right coronary artery, while the RA was used for the diagonal, circumflex or right coronary arteries. Surgical mortality and morbidity rates were not significantly different. During the follow-up period of 2.3±1.6 years, the event-free rates as well as the survival rates were not significantly different. CABG with either the RA or the GEA in conjunction with the BIMA can be performed safely. The surgical results as well as the follow-up results were acceptable and no significant differences between the 2 groups were observed. (Circ J 2002; 66: 544 - 548)

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Brugada syndrome (BS) is associated with sudden cardiac death and the markers for ventricular fibrillation (VF) remain unclear, so the activation - recovery interval (ARI) dispersion and recovery time (RT) dispersion were investigated as possible markers in 20 subjects with BS (BS group) and 22 healthy individuals (H group). The 20 BS subjects were divided into 8 cases with documented VF (BS-VF group), 3 of which had recurrences, and 12 without (BS-N group). The corrected dispersion measurements from the standard 12-lead ECG of the QT interval (QTcd), ARI (ARIcd) and RT (RTcd) were compared among the groups. There were significant differences noted between the BS-VF and BS-N groups for the ARIcd and the RTcd, but not for the QTcd. Further, there were critical differences, 150 ms^1/2, observed for the ARIcd and RTcd, and these were associated with a prolongation of the maximum ARI or RT, shortening of the minimum ARI or RT, and prolongation only of the maximum QT for the QTcd. Susceptibility to VF may be predicted by the ARIcd or RTcd in BS. (Circ J 2002; 66: 549 - 552)

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A multicenter, placebo-controlled, randomized, double-blind trial compared the preventive effect of aprindine and digoxin on the recurrence of atrial fibrillation (AF) with placebo, and also compare the effectiveness of these 2 drugs in the prevention of AF. Patients with symptomatic paroxysmal or persistent AF who had converted to sinus rhythm (SR) were randomly assigned aprindine (40 mg/day), digoxin (0.25 mg/day) or placebo and followed up on an outpatient basis every 2 weeks for 6 months. Of the 141 patients from 36 participating centers, 47 were given aprindine, 47 digoxin, and 47 were on placebo. After the 6-month follow-up, the Kaplan-Meier estimates of the percentage of patients remaining free of recurrent symptomatic AF on aprindine, digoxin and placebo were 33.3%, 29.2% and 21.5%, respectively. In patients remaining in SR for 15 days after from the start of follow-up, freedom from recurrence was significantly more prevalent in the aprindine group than in the placebo group (p=0.0414), but there was no significant difference between the digoxin and placebo groups. The rate of adverse events was similar in the 3 groups. In conclusion, neither aprindine nor digoxin had a significant effect on preventing relapse of symptomatic AF; however, recurrence of AF occurred later with aprindine than with placebo or digoxin. (Circ J 2002; 66: 553 - 556)

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The long-term prognosis of patients with mildly dilated cardiomyopathy (MDCM) was investigated in 21 patients. MDCM was defined as left ventricular ejection fraction ≤40% and left ventricular end-diastolic volume ≤120 ml/m² by left ventriculography. During a follow-up period of 6.8±3.7 years, there were 9 cardiac events (5 heart failure deaths, 2 sudden deaths, and 2 re-hospitalizations for heart failure). Only in the patients without cardiac events was there a significant decrease in left ventricular size (end-diastolic dimension decreased from 58±6 mm to 50±8 mm, p<0.001) and an improvement in systolic function (fractional shortening increased from 17±5% to 26±11%, p=0.007). However, left atrial dilation was observed in the patients with an event (from 39±5 mm to 43±5 mm, p=0.02). Based on proportional hazard analysis, left ventricular end-diastolic pressure and mean pulmonary artery pressure at diagnosis and left atrial dimension at the time of follow-up were significant predictors of poor outcome. A subset of patients with MDCM has impaired hemodynamics at diagnosis, left atrial dilation at follow-up and a poor prognosis, and must be followed carefully even if the left ventricular dilatation is mild. (Circ J 2002; 66: 557 - 560)

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The homeobox transcription factor CSX/NKX2.5, which is a vertebrate homologue of the Drosophila gene tinman, is essential for cardiac development. It is expressed in the early cardiac mesoderm and in heart muscle lineage throughout life. Homozygous deletion of CSX/NKX2.5 causes early embryonic lethality in mice because cardiac development is arrested at the linear heart tube stage. Heterozygous mutation of human CSX/NKX2.5 has been associated with various congenital heart diseases such as atrial septal defect (ASD), ventricular septal defect, tetralogy of Fallot, and tricuspid valve abnormalities, including Ebstein's anomaly. Additionally, CSX/NKX2.5 mutation causes atrioventricular (AV) conduction block with or without associated congenital heart diseases. Ten different heterozygous mutations have been already reported and a new point mutation, which is a C-to-A transition (Cys264ter) at nucleotide 901 of CSX/NKX2.5, results in the production of a truncated protein occurring COOH-terminal to the homeodomain of CSX/NKX2.5. The mutation was found in a patient with familial ASD and first-degree AV block; 4 members from 3 generations had secundum-type ASD and first-degree AV block. (Circ J 2002; 66: 561 - 563)

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Aortic regurgitation (AR) is not a rare complication of Takayasu's disease and is now considered as an important risk factor related to mortality. Aortic-valve replacement surgery is the only curative treatment, but cardiac function and mortality after surgery have not been reported, so a follow-up study in 10 patients with Takayasu's disease complicated by AR was performed. Six patients underwent aortic-valve replacement surgery and all had improvement of the ejection fraction and a decrease in the size of the left ventricle size on echocardiography. Three of the 6 cases had a remote cardiovascular event. Detailed pathological examination carried out in one case of the aortic valve and aortic specimen from surgery showed only lymphoid cell infiltration around the capillary in the ascending aorta, and no other inflammatory change. Inflammation was well controlled at surgery by pre-operative steroid therapy, so early and aggressive aortic-valve replacement surgery with peri-operative immunosuppressive therapy should be considered for patients with Takayasu's disease. (Circ J 2002; 66: 564 - 566)

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Electrocardiographic (ECG) changes are often associated with subarachnoid hemorrhage (SAH), but it is not well known whether these have prognostic value. The present study retrospectively investigated 122 consecutive patients with SAH caused by ruptured aneurysms. The patients were classified based on the in-hospital outcome into 80 survivors and 42 nonsurvivors. In nonsurvivors, abnormalities often observed on the 12-lead ECG on arrival at hospital were abnormal Q wave, ST depression, and T wave inversion. The ECG score was defined as the total number of leads that had any of these 3 ECG abnormalities. Univariate analysis revealed a strong correlation of in-hospital death with the ECG score, the neurological status estimated by the grading of Hunt and Kosnik, age, and QTc interval. In age- and sex-adjusted multiple logistic regression analysis, the ECG score was the most powerful risk stratifier (ECG score ≥6 vs ECG score <6; p=0.0026, odds ratio 14.39, 95% confidence interval 2.54-81.71). The ECG score, a new and simple method of semi-quantification, was a powerful risk predictor in the present patients with SAH. (Circ J 2002; 66: 567 - 570)

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Serum uric acid (UA) has been proposed as a marker for impaired oxidative metabolism and the present study investigated whether serum UA level increases in proportion to the severity of pulmonary thromboembolism (PTE) in 193 patients. Serum UA was repeatedly measured after treatment of PTE in 76 patients. Right heart catheterization was performed in a subgroup of patients (n=104). Serum UA on admission was significantly elevated in patients with acute PTE (6.2±2.3 mg/dl) and those with chronic PTE (7.0±2.1 mg/dl) compared with age-matched controls (4.5±0.9 mg/ml). In particular, serum UA was markedly higher in the 27 patients who died during hospitalization than in the remaining survivors (8.3 ±2.2 vs 6.5±2.2 mg/dl, p<0.001). In acute PTE, serum UA negatively correlated with cardiac output, but not significantly with mean pulmonary arterial pressure. In chronic PTE, serum UA negatively correlated with cardiac output and positively correlated with mean pulmonary arterial pressure. Serum UA significantly decreased from 6.7±2.0 to 5.8 ±1.9 mg/dl with treatment, associated with an increase in cardiac output and in PaO₂. Serum UA increases in proportion to the severity of PTE, and thereby may serve as a potential indicator of the efficacy of treatment of PTE. (Circ J 2002; 66: 571 - 575)

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The efficacy and safety of fibrinolysis and subsequent transluminal (FAST) therapy were evaluated in 195 patients with acute myocardial infarction (AMI) for the early achievement of thrombolysis-in-myocardial-infarction grade 3 (TIMI-3) flow in the infarct-related artery. Intravenous thrombolysis using the optimal dose of a thrombolytic agent was initiated immediately after arrival in the emergency room, followed by coronary angiography and adjuvant percutaneous coronary intervention. A comparison of the thrombolysis alone (n=83) and thrombolysis plus intervention (n=112) groups showed significant differences in the time interval from hospital arrival to achievement of TIMI-3 flow (66.2±23.7 vs 111.6 ±29.6 min, p<0.0001), creatine kinase-MB release (295 ±201 vs 468±322 U/L, p=0.0003) and peak troponin T (23.6±16.9 vs 38.9±25.9 ng/ml, p<0.0001). No significant differences were observed in either 30-day mortality or complications. The TIMI-3 flow at the initial angiography was significantly higher with a single bolus of mutant tissue-type plasminogen activator (t-PA) monteplase than with an accelerated infusion of t-PA (60% vs 32%, p=0.005). In conclusion, the early restoration of TIMI-3 flow by FAST therapy reduced the degree of myocardial damage with a low risk of complications. TIMI-3 flow was achieved at an earlier stage with monteplase and this agent may be beneficial in the FAST therapy. (Circ J 2002; 66: 576 - 582)

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Exercise capacity is often reduced in patients with atrial fibrillation (AF), but very few studies have focused on changes in endothelial function as a potential mechanism for the exercise limitation. The present study used using venous occlusion plethysmography to investigate whether nitric oxide (NO)-mediated vasodilatation is attenuated during exercise in patients with AF by measuring forearm blood flow (FBF) in 10 patients at rest and immediately after 2 levels of rhythmic handgrip exercise, before and after inhibition of NO synthesis with N^G-monomethyl-L-arginine (L-NMMA, 100μmol). The measurements were repeated 1 day after restoration of sinus rhythm by cardioversion. FBF responses to graded doses of acetylcholine (ACh) were also observed before and after cardioversion. Heart rate decreased after cardioversion, but blood pressure did not change. FBF at rest was not affected by cardioversion, but at the highest level of exercise it increased from 28.4±2.3 ml · min^-1 · dl^-1 before to 39.4±3.2 ml · min^-1 · dl^-1 after cardioversion (p<0.05). L-NMMA significantly decreased FBF at rest (p<0.01) and depressed the increase in FBF response to exercise after (p<0.01), but not before cardioversion. The FBF response to ACh was also accelerated significantly after cardioversion. The present results provide new evidence that NO bioavailability is depressed at rest and during exercise in patients with AF. (Circ J 2002; 66: 583 - 588)

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Although long-term survival of diabetic patients with multivessel coronary disease has been reported to be better in those treated with bypass surgery than with coronary angioplasty, it is unclear if diabetic patients who undergo coronary angioplasty show better long-term survival than those treated medically. Between 1985 and 1994, 667 consecutive patients with isolated severe (≥90% diameter stenosis) proximal left anterior descending (LAD) coronary artery disease were divided into 4 groups according to the initial therapeutic choice and their diabetic status: of 225 diabetic patients, 104 were treated medically and 121 underwent coronary angioplasty; of 442 non-diabetic patients, 215 were treated medically and 227 underwent coronary angioplasty. The primary end-point of follow-up was death from any cause, and the secondary end-point was cardiac death. Cox's proportional hazard model was used to assess the relative risk of baseline variables. The mean follow-up interval was 6.5±3.0 years. The relative distribution of baseline parameters of medically treated patients to those treated with coronary angioplasty was identical in diabetic and non-diabetic patients. Although non-diabetic patients who underwent coronary angioplasty showed better long-term survival than those treated medically, this survival advantage was not observed in diabetic patients. After adjustment of parameters using Cox's proportional hazard model, age over 65 years, coronary angioplasty and low left ventricular ejection fraction were independent determinants of total death. Long-term survival in non-diabetic patients with severe LAD coronary artery disease is more favorable in patients treated with coronary angioplasty than those treated medically, but this advantage is overridden when the patients are diabetic. (Circ J 2002; 66: 589 - 594)

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To test the hypothesis that coronary revascularization improves long-term prognosis in patients with hemodialysis, 80 of 121 patients (66%) on maintenance hemodialysis who had undergone initial coronary angiography had bypass surgery, catheter angioplasty, or both between 1983 and 1999. Multivessel disease was more frequent (p=0.01) and the duration of hemodialysis therapy was shorter (p=0.01) in patients with diabetes (n=61), than in nondiabetic patients (n=60). Of the patients who underwent revascularization, complete revascularization was achieved in 75% of those with diabetic nephropathy (30/40) and 83% in a similar number of nondiabetic patients (33/40). The 5-year survival rate from initiation of hemodialysis was 79% in diabetic and 96% in non-diabetic patients (p<0.01), exceeding published Japanese (53% vs 70%) and US (26% vs 60%) survival rates. When survival was studied from the date of revascularization, predictors of outcome were age and achievement of complete revascularization. Surprisingly, diabetes was not a predictor of survival outcome. Complete revascularization improves long-term survival in both diabetic and nondiabetic patients. (Circ J 2002; 66: 595 - 599)

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The efficacy and safety of amiodarone in the management of atrial fibrillation (AF) or flutter in 108 Japanese patients with heart failure was retrospectively examined. Thirty-four (41%) of the 82 patients who were in sinus rhythm after 1 month of amiodarone administration had their first recurrence, 70% of cases occurring within 1 year of initiation. The cumulative rates of maintenance of sinus rhythm were 0.68, 0.55, and 0.47 at 1, 3, and 5 years, respectively. Amiodarone was more effective in maintaining sinus rhythm in patients with paroxysmal AF or flutter than in those with the persistent form (p<0.05). The cumulative rates for cases that remained in permanent AF were 0.04, 0.11, and 0.14 at 1, 3, and 5 years, respectively. Apart from suppressing AF, the mean heart rate during Holter monitoring was significantly decreased with amiodarone therapy in cases of permanent AF. Adverse effects requiring the discontinuation of amiodarone therapy occurred in 16% of patients. Low-dose amiodarone therapy may prevent AF or flutter in Japanese patients with heart failure. (Circ J 2002; 66: 600 - 604)

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The right ventricular ejection fraction (RVEF) can be shown theoretically as a mathematical function of the percent shortening in the 3 axial dimensions of the right ventricular cavity (the septum - free wall dimension (SF), the anterior - posterior dimension (AP), and the tricuspid valve - apex dimension (TA) or the long axis dimension (LA)). There is a need to decide which mechanism is the most important for the RVEF in cases with neither obvious regional wall motion abnormalities of the left ventricle nor right ventricular overload. Forty-four consecutive subjects (34 males/10 females) were enrolled: 16 had normal hemodynamic parameters without significant coronary artery stenosis, 15 had hypertrophic cardiomyopathy and 13 had dilated cardiomyopathy. Biplane right ventricular cineangiography was performed and the percent shortening of the SF, AP, and TA or LA were measured. The percent shortening in the SF (34.8±14.7%) was larger than that of the AP, TA, and LA (23.2±8.5, 21.0±8.3 and 18.3±7.0, respectively; all p<0.001). There was a linear correlation between the percent shortening of each dimension and the RVEF. The 95% confidence interval of the regression equation from the percent shortening of the SF and RVEF was located above those from the other percent shortenings, except for a lower RVEF. These results indicate that systolic shortening of the SF (ie, bellows action) plays an important role in the RVEF except for a lower ejection fraction. (Circ J 2002; 66: 605 - 609)

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A 54-year-old man, who had undergone atrial septal defect (ASD) closure 30 years previously, was admitted for exertional dyspnea and chest oppression. He presented with right pleural effusion and hepatomegaly. Hemodynamic characteristics were consistent with constrictive pericarditis caused by multiple cystic lesions anterior to the main pulmonary artery and right ventricle, and severe calcification over the posterior and diaphragmatic sides of the heart. Magnetic resonance imaging was useful for differential diagnosis of the cystic mass and at surgery, it was revealed that the cystic lesions were old hematoma without cells. Pericardiectomy and removal of the calcification were performed safely using an ultrasonic scalpel, without cardiopulmonary bypass, resulting in hemodynamic improvement and relief of his symptoms. (Circ J 2002; 66: 610 - 612)

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A 63-year-old Taiwan aboriginal male was admitted with exertional dyspnea, appetite loss and general fatigue. Echocardiography revealed moderate pericardial effusion and histological examination of the pericardiocentesis sample revealed an eosinophil-dominated bloody exudate. The larvae of Strongyloides stercoralis were detected in the pericardial specimen. After treatment with anti-nematodal agents, the eosinophilia decreased from 26% to 1% and the patient's symptoms improved. This is a rare case of Strongyloides-induced bloody pericardial effusion in a non-immunosuppressed patient. (Circ J 2002; 66: 613 - 614)

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An 80-year-old woman was admitted with cardiogenic shock; she arrived in a deep coma with systolic blood pressure of 44 mmHg. An electrocardiogram showed ST elevation in I, aV_L, V₅ and V₆, suggesting myocardial infarction in the lateral area of the left ventricle. A chest roentgenogram showed right pulmonary edema without cardiomegaly. Transthoracic and transesophageal echocardiograms revealed severe mitral regurgitation and a flailing anterior mitral valve leaflet, suggesting a ruptured papillary muscle. The patient was initially treated with high-dose dopamine, dobutamine and norepinephrine. Intraaortic balloon pumping was initiated after the patient's condition stabilized. She underwent emergency mitral valve replacement with a prosthetic valve. Complete rupture of the anterior papillary muscle was confirmed. Histological examination revealed necrosis of the anterior papillary muscle with inflammatory changes. She recovered uneventfully. Postoperative coronary angiography demonstrated subtotal occlusion of the first diagonal branch, and left ventriculography demonstrated akinesis of the lateral segment. This was a rare case in which subtotal occlusion of the first diagonal branch caused rupture of an anterior papillary muscle leading to severe mitral regurgitation. (Circ J 2002; 66: 615 - 618)

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A 60-year-old man with isolated noncompaction of the ventricular myocardium was evaluated by magnetic resonance imaging (MRI), which clearly showed excessively prominent trabeculations and deep intertrabecular recesses that correlated well with the findings on echocardiography and contrast enhanced computed tomography. On the T2-weighted and contrast enhanced MRI scans, the noncompacted myocardium was separated into 2 layers: a subendocardial and an endocardial layer. A difference in signal intensity may reflect myocardial damage that leads to ventricular dysfunction or arrhythmia. (Circ J 2002; 66: 619 - 621)

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