Treatment strategies for patients with heart failure and left ventricular systolic dysfunction continue to evolve as the complex pathophysiology of this disease is better understood. A number of advances have been made in recent years, most notably the addition of β-receptor antagonists. In addition, recent studies have provided important information regarding the utility of angiotensin receptor antagonists, aldosterone receptor antagonists, and natriuretic peptides in the management of heart failure. Nonpharmacologic advances include resynchronization therapy, which appears to confer symptomatic improvement in some patients, and improvements in ventricular assist device technology. As the importance of neurohormonal activation in the progression of heart failure becomes increasingly apparent, new therapeutic strategies targeting these neurohormonal systems are being investigated. (Circ J 2002; 66: 117 - 121)

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The aim of present study was to compare the predictive characteristics and cost - benefit of measuring the concentration of blood brain natriuretic peptide (BNP), compared with electrocardiography (ECG), chest radiography and echocardiography, as a diagnostic test for heart disease. The study group comprised 130 untreated patients who had symptoms suggestive of heart disease. According to the results of additional examinations and follow-up checks, 86 patients were diagnosed as having heart disease and 44 patients were judged free of heart disease. Positive findings in each test suggestive of heart disease were checked in accordance with criteria, and the number of positive and negative cases for each test was calculated. The predictive characteristics, such as specificity, sensitivity, accuracy, positive and negative predictive values, of each test and the cost - benefit value were calculated and analyzed statistically. The sensitivity, specificity and accuracy of blood BNP and echocardiography were significantly greater than those of ECG and chest radiography. Echocardiography had a significantly lower cost - benefit value compared with measuring blood BNP concentration. Thus, the blood BNP concentration had significantly higher predictive characteristics than ECG and chest radiography, and a cost-benefit value significantly greater than that of echocardiography. (Circ J 2002; 66: 122 - 126)

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Recent studies have demonstrated that elevated levels of cholesterol in the form of remnant-like particles (RLP-C) induce deterioration of endothelial function during the fasting state, but it is not known whether postprandial RLP-C elevation has the same effect. The objective of this study was to assess the effect of postprandial RLP-C elevation on endothelial function in 24 fasting normolipidemic subjects. Flow-mediated dilatation (FMD) during reactive hyperemia in the brachial artery was investigated. Serum lipids and lipoproteins during fasting and 4 h after regular fat-loading were measured. Subjects were divided into 2 groups: the high responders (postprandial RLP-C level >7.5 mg/dl, n=8) and the normal responders (postprandial RLP-C level ≤7.5 mg/dl, n=16). Significant increases in the level of both triglycerides and RLP-C were observed in the high responders. Basal FMD in the high responders (4.3±3.0%) was significantly lower than that in the normal responders (8.3±2.4%) (p<0.01), but FMD after the fat-loading in both groups did not change significantly. The change in RLP-C levels during the fat-loading test correlated significantly with basal FMD (r=-0.588, p<0.01). Multiple regression analysis showed a significant correlation between basal FMD and the change in RLP-C levels (r=-0.488, p<0.02). The results of this study suggest that postprandial RLP-C elevation could be associated with atherosclerotic progression even in normolipidemic subjects. (Circ J 2002; 66: 127 - 132)

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Although fulminant myocarditis is known as a fatal disease, patients have been able to recover and return to normal life with the help of mechanical cardiopulmonary support. However, therapeutic guidelines for using percutaneous cardiopulmonary support (PCPS) for fulminant myocarditis have not been established, and the clinical course and long-term prognosis of such patients are still controversial issues. The present national survey considered the current situation of patients as the basis for proposing therapeutic guidelines. Thirty of 52 patients (57.7%) survived and returned to social life. Important factors concerning the prognosis were the severity and grade of cardiac and renal dysfunction, the adjusted support flow rate to enable recovery from circulatory failure, and prevention of circulatory disturbances of the legs and multiple organ failure directly associated with PCPS. With regard to the long-term prognosis of patients treated with PCPS, the readmission rate was 10%, the exacerbation rate was 3.3%, and mortality was 10% during the average follow-up period of 962 days. Optimal management of the mechanical cardiopulmonary support and curative treatment for the myocarditis further improve the outcome of this disease. (Circ J 2002; 66: 133 - 144)

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Risk stratification according to the EuroSCORE additive model of 803 consecutive patients undergoing heart and thoracic aorta surgery using cardiopulmonary bypass from August 1994 to December 2000 was performed. The population was divided into 5 clinically relevant risk categories: 0-2% risk, 3-5% risk, 6-8% risk, 9-11% risk, and 12+% risk. Observed and predicted mortalities were compared within 3 groups of patients divided by year of operation (early: August 1994 to September 1996, n=260; middle: October 1996 to September 1998, n=259; late: October 1998 to December 2000, n=284). Overall hospital mortality was 4.5%; predicted mortality was 5.3% in the early, 5.1% in the middle, and 5.4% in the late period; observed mortality was 6.5%, 3.9%, and 3.2%, respectively (p=0.0024 in early vs late). In the early period, observed mortality was lower than predicted mortality in the 0-2% and 3-5% risk categories, but higher in the other categories. Moreover, observed mortality increased markedly with the increase in predicted mortality. In the late period, observed mortality was lower than predicted mortality in all 5 risk categories. The EuroSCORE is clinically relevant index for constructing a risk stratification scoring system for Japanese cardiovascular patients as well and shows that the quality of surgical care has improved gradually over the years. (Circ J 2002; 66: 145 - 148)

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The long-term beneficial effects of pimobendan in the treatment of chronic heart failure (CHF) have not been established, so the present trial compared pimobendan (1.25 or 2.5 mg twice daily) vs placebo in 306 patients with stable New York Heart Association class IIm or III CHF, and a radionuclide or echocardiographic left ventricular ejection fraction (LVEF) ≤45% despite optimal treatment with conventional therapy, for up to 52 weeks in a double-blind protocol. At the end of the 52 weeks of treatment, combined adverse cardiac events had occurred in 19 patients in the pimobendan group (15.9%) vs 33 patients in the placebo group (26.3%). The cumulative incidence of combined adverse cardiac events was 45% lower (95% confidence interval of hazard ratio: 0.31-0.97, log-rank test: p=0.035) in the pimobendan group than in the placebo group. Death and hospitalization for cardiac causes occurred in 12 patients in the pimobendan group (10.1%), vs 19 patients in the placebo group (15.3%), but without significant difference. Treatment with pimobendan also increased the mean Specific Activity Scale score from 4.39±0.12 at baseline to 4.68±0.15 at 52 weeks (p<0.05). In conclusion, long-term treatment with pimobendan significantly lowered morbidity and improved the physical activity of patients with mild to moderate CHF. (Circ J 2002; 66: 149 - 157)

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Homocysteine induces endothelial injury and inhibits endothelial cell proliferation, which is a key role in angiogenesis. The purpose of this study was to investigate whether the plasma level of homocysteine is associated with the development of collaterals in patients with single-vessel coronary artery disease (CAD). Among a series of 105 male patients with angiographic estimation, 49 with single-vessel CAD were intensively investigated. Development of collaterals was classified by Rentrop's method. Univariate and multivariate analyses revealed that hyperhomocysteinemia negatively affected the development of collaterals (p=0.0015 and 0.0011, odds ratio 0.69, 95% confidence interval 0.52-0.90), whereas the duration of angina and percent stenosis evaluated by quantitative coronary angiography had a positive affect. Moreover, the level of homocysteine in the group with poorly developed collaterals (n=7, Rentrop class 0 and 1) was significantly higher than that in the group with well-developed collaterals (n=12, Rentrop class 2 and 3) of the patients with single-vessel disease showing total occlusion (p=0.034). This study clearly demonstrates that the plasma level of homocysteine is independently and inversely associated with the development of collateral circulation in CAD patients. Homocysteine might be a new undesirable aspect of ischemic heart disease through its inhibition of collateral development. (Circ J 2002; 66: 158 - 162)

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The adenine/cytosine¹¹⁶⁶ (A/C¹¹⁶⁶) polymorphism of the angiotensin-II type 1 receptor (AGTR1) gene is presumed to be associated with mitral valve prolapse syndrome (MVPS) in Caucasians. To investigate whether a similar association exists among the Chinese population in Taiwan, 100 patients with MVP diagnosed by echocardiography and 100 normal subjects were studied by polymerase chain reaction-based restriction analysis. The difference in genotype (χ²=0.24; p=0.89) and allelic (Yates' χ²=0.06; p=0.81) frequencies between the groups were not significant. Further categorization of the MVP patients into mild and severe subgroups also revealed no statistical difference from the controls. It was concluded that A/C¹¹⁶⁶ polymorphism of the AGTR1 gene is not a suitable genetic marker of MVPS in Taiwan Chinese. (Circ J 2002; 66: 163 - 166)

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To clarify whether the myocardial perfusion abnormalities observed on harmonic power Doppler imaging (HPDI) during hyperemia are related to a decrease in coronary flow velocity reserve (CFVR), HPDI and CFVR were measured in the left anterior descending coronary artery (LAD) territory of 75 patients. During continuous infusion of Levovist, dual-frame triggered apical 4-chamber views were obtained at rest and during adenosine triphosphate (ATP) infusion. The persistence of perfusion defects during ATP infusion or stress-induced defects in the LAD territory was defined as abnormal. Both HPDI and coronary flow velocity recordings of adequate quality were successfully obtained in 73 patients, and 37 patients showed abnormal myocardial perfusion. CFVR was significantly lower in patients with abnormal perfusion than in patients who had normal findings (1.38 ±0.38 vs 2.60±0.76, p<0.001). A CFVR less than 1.9 had a sensitivity of 89% (33/37) and a specificity of 89% (32/36) for predicting the presence of abnormal myocardial perfusion. This study demonstrates that myocardial perfusion abnormalities observed during HPDI using ATP stress are closely correlated to a decrease in CFVR and may reflect significant stenosis or microvascular damage in the LAD territory. (Circ J 2002; 66: 167 - 172)

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The aim of this study was to clarify whether atherosclerotic plaque morphology, as defined by quantitative analysis with intravascular ultrasound (IVUS) images, was related to the immunohistochemical findings. Twenty-five coronary lesions in 25 patients who had ultrasound guidance during directional coronary atherectomy (DCA) were enrolled. The lesions retrieved by DCA were analyzed and divided into 3 groups (lesions infiltrated with both macrophages and lymphocytes: group IML; lesions infiltrated with macrophages but not lymphocytes: group IM; and non-infiltrated lesions: group NI). The mean plaque echo level divided by the mean adventitia echo level (MPEL/MAEL) and the heterogeneity of the distribution of plaque echo levels (HDPEL) were calculated. The proportion of patients with acute coronary syndromes was significantly different among the groups: IML (n=14), IM (n=5), and NI (71%, 0% and 17%, respectively; p<0.01). The pre-DCA HDPEL value was highest in group IML and lowest in group NI; however, no significant differences in MPEL/MAEL values were found. The results suggest that plaque morphology, as defined by IVUS images, was related to the immunohistochemical findings. The increase in HDPEL correlated with the presence of immune inflammation. (Circ J 2002; 66: 173 - 177)

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To assess the changes in treatment and outcome of acute myocardial infarction (AMI) over a 15-year period, the medical records of 1,437 patients with AMI who underwent emergency coronary angiography within 24 h of the onset of chest pain at Hiroshima City Hospital from 1985 to 1999 were reviewed. The patients were divided into 3 groups in chronological order: group 1 (1985-89, n=439), group 2 (1990-94, n=453) and group 3 (1995-99, n=545). Conventional balloon angioplasty and thrombolysis were frequently performed in group 1 (56% and 29%, respectively) and group 2 (71% and 13%, respectively), whereas coronary stenting and conventional balloon angioplasty were more often performed in group 3 (57% and 23%, respectively). The achievement of TIMI grade 3 flow improved in the chronological order (62%, 80% and 85%, respectively; p<0.001). The incidence of reinfarction was lower in group 3 (4.2%) than groups 1 and 2 (8.0% and 7.5%, respectively; p=0.007), and in-hospital mortality decreased from group 1 to group 3 (11.8%, 8.2% and 5.5%, respectively; p=0.002). Stenting is now the most frequently chosen treatment for AMI and sustained TIMI grade 3 flow is obtained in most of the cases, with the result that mortality has reduced by 50% in the past decade. (Circ J 2002; 66: 178 - 181)

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Chronotropic, inotropic and coronary vasodilator actions of the clinically available ampoule preparation of Salvia miltiorrhiza/Dalbergia odorifera mixture were examined using canine isolated, blood-perfused heart preparations. The mixture slightly decreased the sinoatrial rate and significantly increased coronary blood flow, but hardly affected the developed tension of the papillary muscle. The effect on coronary blood flow was induced by at least a 10-fold smaller dose than that which induced the chronotropic effect. These results were quite similar to those of a typical calcium channel blocker, verapamil, used in a previous study, suggesting that the Salvia miltiorrhiza/Dalbergia odorifera mixture may have potential as an anti-anginal drug. (Circ J 2002; 66: 182 - 184)

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The effects of a new benzopyran derivative, NIP-142, on atrial fibrillation (AF) and flutter (AFL) and on electrophysiological variables were studied in the dog. NIP-142 (3 mg/kg) was administered intravenously to pentobarbital-anesthetized beagles during vagally-induced AF and during AFL induced after placement of an intercaval crush. Isolated canine atrial tissues were studied using standard microelectrode technique. NIP-142 terminated AF in 5 of 6 dogs after an increase in fibrillation cycle length (CL) and prevented reinitiation of AF in all 6 dogs. NIP-142 terminated AFL in all 6 dogs without any appreciable change in flutter CL, and prevented reinitiation of AFL in all 6 dogs. NIP-142 prolonged atrial effective refractory periods (11±5%, 3±3%, 12±3%, and 10±5% from the baseline value at basic CLs of 150, 200, 300, and 350 ms, respectively) without changes in intraatrial conduction time. The prolongation of the atrial effective refractory period was greater in the presence of vagal stimulation. NIP-142 decreased action potential phase-1 notch and increased phase-2 plateau height without making any changes in the action potential duration, although it did reverse carbachol-induced shortening of the action potential duration. In conclusion, NIP-142 is effective in treating AFL and vagally-induced AF by prolonging atrial refractoriness. (Circ J 2002; 66: 185 - 191)

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Many studies have suggested that the renin -angiotensin system plays an important role in the left ventricular (LV) remodeling and cardiac dysfunction that occurs after myocardial infarction (MI). Although angiotensin II type 1A (AT1A) receptor knockout (KO) mice are reported to display less LV remodeling after MI, diastolic dysfunction has not been fully evaluated, so the present study measured transmitral inflow pattern in both AT1A receptor KO mice with MI (KO-MI) and wild type mice with MI (WT-MI). Cardiac geometry and function were examined by Doppler echocardiography and myocardial mRNA expression was determined by Northern blot analysis at 4 weeks after MI. The LV internal diastolic dimension of WT-MI was larger than that of the KO-MI (p<0.05). Marked increases in the E wave velocity and the ratio of the peak velocity of the E wave to the A wave were observed in the WT-MI (p<0.01). The deceleration rate of the E wave in KO-MI was lower than in WT-MI (p<0.05). mRNA expressions of ANP, BNP, collagen I and collagen III in the non-infarcted LV and RV of KO-MI were significantly lower than WT-MI. In conclusion, transmitral inflow abnormalities in KO-MI were attenuated compared with WT-MI. (Circ J 2002; 66: 192 - 196)

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Experiments were conducted to determine whether the medial amygdala could control hemodynamics through the GABA receptor in anesthetized rats. Bicuculline (10-100 pmol), a GABA_A antagonist, injected into the anterior basomedial amygdala (medial amygdala) produced dose-related increases in blood pressure (BP) and heart rate (HR). Following microinjection of a 100 pmol dose, plasma norepinephrine and epinephrine also rose significantly. In a group that had undergone bilateral adrenalectomy, the same dose of bicuculline into the same region of the amygdala caused similar increases in BP and HR to those produced in normal rats. Pretreatment with an intraperitoneal injection of hexamethonium prevented these responses. When bicuculline was given intravenously (100 pmol) it failed to effect these cardiovascular changes. Bicuculline-induced hypertension and tachycardia were inhibited by microinjection of muscimol, a GABA agonist, into the anterior basomedial amygdala. The results thus demonstrate that the influence of bicuculline on BP and HR is through action on the anterior basomedial amygdala and direct sympathetic outflow to heart and vascular smooth muscle. There is tonic GABAergic inhibition of sympathetic outflow in the medial amygdala that plays a part in regulating hemodynamics in the limbic system. (Circ J 2002; 66: 197 - 203)

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A primiparous woman with a St Jude Medical (SJM) mitral valve prosthesis and receiving anticoagulant drug delivered a healthy male infant by spontaneous normal vaginal delivery. Oral warfarin was replaced by subcutaneous heparin at the 6th week of gestation and the dosage of heparin was adjusted to maintain a partial thromboplastin time between 2.0 and 2.5 times the control value. Treatment with heparin was administered during the first trimester and the last 5 weeks of gestation. Warfarin was used between the 13th and 32nd week. Successful pregnancy and delivery in patients with a SJM mitral valve prostheses is possible with careful maintenance of anticoagulation. (Circ J 2002; 66: 204 - 206)

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Pulse-spray thrombolysis was performed in 2 patients with acute myocardial infarction (AMI) caused by thrombotic occlusion of coronary artery ectasia. Case 1, a 66-year-old woman with an inferior AMI underwent emergency coronary arteriography, which revealed occlusion of an ectatic right coronary artery. Primary balloon angioplasty failed to reestablish distal flow. Urokinase was administered through the pulse-spray infusion catheter (UltraFuse ™) and intravenous recombinant tissue plasminogen activator was also administered. Angiographic disappearance of the thrombus was observed within 30 min of starting the infusion, and there was only mild irregularity in the ectatic coronary artery. Case 2, a 45-year-old man with an inferior AMI underwent emergency coronary arteriography, which revealed occlusion of an ectatic right coronary artery. TIMI-3 flow was soon obtained after administration of 480,000 units of urokinase through the pulse-spray infusion catheter. There was diffuse right coronary ectasia without angiographic evidence of coronary stenosis. Coronary ectasia sometimes develops into AMI without the coexistence of coronary stenosis. Because a massive thrombus plays a major role, pulse-spray thrombolysis is a possible treatment in coronary artery ectasia with thrombotic occlusion. (Circ J 2002; 66: 207 - 210)

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A 16-year-old Japanese woman with infective endocarditis was admitted to hospital. An echocardiography exhibited a perivalvular pseudoaneurysm just under the mitral valve. Left ventriculography demonstrated that the aneurysm had a small neck and dyskinetic motion with oppression to the coronary sinus and right coronary artery. (Circ J 2002; 66: 211 - 212)

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A 76-year-old man with chest pain was admitted to hospital where electrocardiography (ECG) showed ST-segment elevation in leads V_1-4, indicative of acute anterior myocardial infarction. ST-segment elevation was also present in the right precordial leads V_4R-6R. Emergency coronary angiography revealed that the left coronary artery was dominant and did not have significant stenosis. Aortography showed ostial occlusion of the right coronary artery (RCA). Left ventriculography showed normal function and right ventriculography showed a dilated right ventricle and severe hypokinesis of the right ventricular free wall. Conservative treatment was selected because the patient's symptoms soon ameliorated and his hemodynamics was stable. ^99mTc-pyrophosphate and ²⁰¹Tl dual single-photon emission computed tomography showed uptake of ^99mTc-pyrophosphate in only the right ventricular free wall, but no uptake of ^99mTc-pyrophosphate and no perfusion defect of ²⁰¹Tl in the left ventricle. The peak creatine kinase (CK) and CK-MB were 1,381 IU/L and 127 IU/L, respectively. His natural course was favorable and the chest pain disappeared under medication. Two months after the onset, the ECG showed poor R progression in leads V_1-4 indicating an old anterior infarction. Coronary angiography confirmed the ostial stenosis of the hypoplastic RCA. This was a case of pure right ventricular free wall infarction because of the occlusion of the ostium of the hypoplastic RCA, but not of the right ventricular branch. Because the electrocardiographic findings resemble those of an acute anterior infarction, it is important to consider pure right ventricular infarction in the differential diagnosis. (Circ J 2002; 66: 213 - 215)

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Circulating levels of hepatocyte growth factor (HGF) are increased in the early stage of an acute myocardial infarction because of arterial thrombosis. The purpose of this study was to use a new sensitive enzyme-linked immunosorbent assay to investigate whether circulating HGF is increased in patients with cerebral infarction. Circulating HGF was measured in 32 patients with cerebral infarction on admission to hospital and on days 2, 3, 7 and 14 after the onset of symptoms. Serum HGF levels exceeded the mean value +2SD (329 pg/ml) measured in controls in 10 of 20 patients (50%) within 6 h after onset and in 15 of 32 patients (47%) within 24 h. Plasma D-dimer was increased in more than half of the patients with elevated HGF values. HGF levels in 16 patients who were measured serially were persistently increased throughout the study period. The results suggests that circulating HGF is a reliable early marker of cerebral infarction, and that this new sensitive HGF assay may be useful for diagnosing cerebral thrombosis. (Circ J 2002; 66: 216 - 218)

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