Cardiac transplantation has been established as a therapeutic strategy for patients with end-stage heart failure. In Japan, however, cardiac transplantation has not been performed since the first case in 1968, and even now, after legislation for the approval of brain death was passed in 1997, it is still not performed regularly. Following long and steady efforts to enlighten Japanese society about the concept of brain death and the importance of organ transplantation, the first cardiac transplantation under the new legislation was successfully performed at Osaka University Hospital on February 1999. The patient was 47-year-old male in the dilated phase of hypertrophic cardiomyopathy who had been supported with an implantable left ventricular assist device. This article briefly reviews the situation prior to the first case of cardiac transplantation under the new legislation and discusses the current status of the therapy in Japan.

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During the past 2 years since new legislation for organ transplantation from brain-dead donors came into effect in Japan, 3 cardiac transplants have been carried out, 2 of which were performed at the National Cardiovascular Center (NCVC). The recipient cases were 46- and 25-year-old male patients who suffered from end-stage dilated cardiomyopathy and had been listed for cardiac transplantation in the Japan Organ Transplantation Network as status I candidates. The first patient was supported by the use of a paracorporeal air-driven left ventricular assist device of the NCVC type, and had a moderate degree of renal and hepatic dysfunction at the time of transplantation. Donor hearts were transported from distant hospitals (Tokyo and Miyagi prefecture) and the transportation time was 1 h 33 min and 2 h 4 min, respectively. The operation was performed by the standard technique (Lower-Shumway) in the first patient and by the bicaval anastomosis technique in the second patient. Reperfusion of the transplanted heart was performed retrogradely through the coronary sinus utilizing leukocyte-depleted blood with a gradual increase in temperature. Total ischemic time was 3 h 34 min and 3 h 35 min, respectively. Weaning from the cardiopulmonary bypass was easy and uneventful in each patient. Immunosuppressive therapy was conducted with OKT-3 induction in the first patient because of the coexisting renal dysfunction and with a triple immunosuppressive regimen for both patients. Routine endomyocardial biopsy showed acute rejection of less than grade Ib, and the patients were discharged on the 65th and 46th postoperative day, respectively. At present, both patients are in the NYHA class I state and are ready to return to work. The uneventful recovery seen in these patients shows the advances made in transplant medicine, including the progress and improvement of immunosuppressive therapy, surgical techniques, myocardial protection, and detection and treatment of infection. Further efforts are required to fully establish the cardiac transplantation program in Japan.

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The purpose of the present study was to determine whether parameters of left atrial appendage (LAA) function, assessed by transesophageal echocardiography (TEE), could predict the clinical outcome in patients with dilated cardiomyopathy (DCM). Fifty-five patients (20 had ischemic cardiomyopathy; mean age, 56±14 years) who underwent TEE to evaluate LAA function from 1992 to 1996 were studied. After a mean follow-up period of 34±13 months, 16 patients died; the cause was cardiac in 14 and noncardiac in 2. Patients who died of cardiac cause had a lower LAA emptying velocity than survivors (38±18 vs 54±18 cm/s, p=0.01). There were, however, no significant differences between survivors and nonsurvivors with regard to the maximal LAA area (4.3±1.3 vs 4.5±0.9 cm², p=0.55), minimal LAA area (2.4±1.1 vs 2.9±1.1 cm², p=0.13), and LAA ejection fraction (46±16 vs 36±18%, p=0.05). On the Cox proportional hazards model analysis, LAA emptying velocity <50 cm/s (chi-square 5.9, p=0.02), LAA ejection fraction <43% (chi-square 5.6, p=0.02), female gender (chi-square 5.2, p=0.02), pulmonary artery wedge pressure ≥14 mmHg (chi-square 4.8, p=0.03), E/A ratio ≥1.3 (chi-square 4.6, p=0.03), deceleration time <148 ms (chi-square 4.6, p=0.03), and cardiothoracic ratio ≥54% (chi-square 4.3, p=0.04) were significantly related to cardiac death. The stepwise multivariate analysis revealed that LAA emptying velocity (chi-square 6.1, p=0.01) and gender (chi-square 5.4, p=0.02) were the independent predictors for outcome. In conclusion, the parameters of LAA function may be useful predictors of the clinical outcome in patients with DCM.

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The present study investigated the contractile reserve of myocardium exhibiting reverse redistribution (RRD) of thallium-201 (²⁰¹Tl) after acute myocardial infarction. Forty patients experiencing their first acute myocardial infarction underwent resting ²⁰¹Tl single-photon emission computed tomography (SPECT) and low-dose (5-10μg·kg^-1·min^-1) dobutamine stress echocardiography (DSE) within 4 weeks after the onset of infarction. The left ventricle was divided into 13 segments for analysis. The severity of defects in ²⁰¹Tl SPECT and the extent of wall motion abnormality in DSE were visually assessed and scored. The sum of each defect score and wall motion score of infarct-related segments were defined as total defect score (TDS) and total wall motion score (TWM), respectively. Quantitative analysis of ²⁰¹Tl uptake was also performed. Resting ²⁰¹Tl SPECT revealed RRD in 16 patients (group RRD), fixed defect (FIX) in 23 patients (group FIX), and redistribution in one. There was a significant difference in improvement of TWM between rest and stress in TWM in both the RRD and FIX groups (p<0.0001, each case). The improvement of TWM with dobutamine was significantly greater in RRD than in FIX (1.6±1.0 vs 0.6±0.7, p=0.001). There was a positive correlation between the magnitude of RRD and improvement of TWM with dobutamine (r=0.48, p=0.002). Myocardium exhibiting RRD on ²⁰¹Tl SPECT in patients with acute myocardial infarction has greater contractile reserve than that exhibiting a fixed defect.

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Myocardial remodeling is an important predictor for the development of dilated cardiomyopathy (DCM). Matrix metalloproteinases (MMPs) are the family of proteins responsible for extracellular remodeling, and tissue inhibitors of metalloproteinases (TIMPs) tightly control their activity. In the present study, the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 was determined by immunohistochemistry in right ventricular endomyocardial biopsy samples from 16 patients with idiopathic DCM, and its clinical significance was evaluated by comparison with parameters of cardiac function. To obtain a semi-quantitative assessment of MMP and TIMP expression, the average number of positive cells per high power field was counted. The left ventricular ejection fraction (LVEF) significantly correlated with the expression of both MMP-2 (r=-0.68) and TIMP-2 (r=-0.58). Patients were classified into 2 groups according to the degree of MMP-2 expression: strongly positive and weakly positive. LVEF, left ventricular (LV) end-diastolic pressure, right ventricular end-diastolic pressure, pulmonary capillary wedge pressure and the plasma norepinephrine level were significantly greater in the strongly positive group (p<0.05). In conclusion, the expression of MMPs and TIMPs in the cardiac matrix of patients with idiopathic DCM is closely associated with myocardial remodeling and subsequent deterioration of LV performance. These findings suggest new therapeutic targets for patients with idiopathic DCM.

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This analysis was carried out to clarify the capacity of metoprolol to prevent cardiac events in Japanese post-myocardial infarction patients during a follow-up period of 16.3 months. Cardiac events occurred in 44 of 650 patients treated without β-blockers (6.8%) and in 13 of 432 patients treated with metoprolol (3.0%), which represents a significant decline in the incidence of cardiac events among patients receiving metoprolol (p<0.01, odds ratio 0.43, 95% confidence interval 0.23-0.80). Because this was a retrospective analysis, there were unavoidable differences in the backgrounds of the patients in the 2 groups. Subgroup analyses, each focusing on a specific patient characteristic, were therefore performed. These showed that metoprolol effectively reduced cardiac events in many subgroups. Furthermore, multivariate analysis carried out to exclude any modification based on the differences in patient background confirmed metoprolol to be effective in reducing subsequent cardiac events in post-myocardial infarction patients. A large, randomized, placebo-controlled clinical trial needs to be performed in the Japanese population to confirm the present result.

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To evaluate whether or not β-blockers can improve the condition of patients with heart failure treated with a combination of diuretics, digitalis and angiotensin-converting enzyme inhibitor (ACEI), 52 patients with chronic heart failure who have been treated with ACEI for more than 6 months were enrolled. They were divided into 2 groups: 26 patients continued the same therapy another 6 months or more (group A), and 26 patients were given oral metoprolol for 6 months or more, in addition to the ACEI (group B). Echocardiographic parameters and atrial and brain natriuretic peptides (ANP, BNP) were measured. The left ventricular dimensions at end-diastole and end-systole were significantly decreased and fractional shortening was significantly increased in group B after 6 months’ treatment with the β-blocker, but these parameters remained unchanged in group A. Plasma levels of both ANP and BNP were significantly decreased in group B, but remained unchanged in group A. These results indicate that concomitant β-blocker therapy can improve left ventricular function and attenuate plasma ANP and BNP levels in patients with chronic heart failure treated with ACEI.

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The aim of the present investigation was to compare the hemodynamic and thermal responses to a 30-min aerobic exercise between middle- or old-aged patients with normal left ventricular function and those with left ventricular dysfunction. Constant-load sitting ergometer exercise of approximately 90% of the subject’s oxygen uptake (VO₂) at the anaerobic threshold for 30min was conducted in 21 patients with left ventricular dysfunction (61±10 years, left ventricular ejection fraction (LVEF) 35±7%) and 24 patients with normal left ventricular function (59±9 years, LVEF 71±7%). Heart rate (HR), blood pressure, deep temperatures in the forehead and thigh, and forearm skin blood flow (SkBF) were measured every minute, and cardiac output (CO) and stroke volume (SV) were determined every 10min with the dye-dilution technique during the exercise. Patients of both groups exhibited a progressive elevation in each temperature and an increase in SkBF during the exercise. Although the VO₂ and CO remained stable, almost the same magnitude of decrease in SV as increase in HR was seen after the 10th min of exercise in both groups. The magnitude of the decrease in SV was greater in old-aged than middle-aged patients with left ventricular dysfunction. Thus, the downward drift in SV during a 30-min constant-load aerobic exercise might not be influenced by left ventricular function, but intensified by aging in patients with left ventricular dysfunction.

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The present study investigated the serial changes in serum magnesium (Mg) and erythrocyte concentration of Mg in patients with acute myocardial infarction (AMI) and the relationship between these changes and left ventricular ejection fraction (LVEF) at 1 month after the onset of infarction. The study group comprised 26 patients with AMI (mean age, 57.9±8.9 years). Serum Mg and erythrocyte Mg were measured on hospital days 1, 2, 4, 7 and 21. The change in erythrocyte Mg during the acute phase was calculated as a ratio: [(erythrocyte Mg at day 2)- (erythrocyte Mg at day 1)]/(erythrocyte Mg at day 1). The change in serum Mg was calculated similarly. The following results were obtained. (1) Serum Mg tended to increase from the onset of myocardial infarction (day 1: 1.86±0.19, day 2: 1.93±0.22, day 4: 2.17±0.23; day 7: 2.25±0.20; day 21: 2.12±0.15 mg/dl). (2) Erythrocyte Mg on day 2 and day 4 showed a significant decrease compared with day 1 (day 1: 2.45±0.40, day 2: 2.09±0.41, day 4: 2.07±0.37, day 7: 2.22±0.33, day 7: 2.34±0.28 mg/dl per 400×10⁴/mm³ cells). (3) A significant positive correlation was observed between the change in serum Mg and LVEF (r=0.55, p<0.05), and a significant negative correlation was observed between the change in erythrocyte Mg and LVEF (r=-0.57, p<0.05). Thus, it was concluded that an extracellular shift in intracellular Mg occurred during the first 2 days after the onset of myocardial infarction. This responsive increase in the extracellular Mg level may be an important factor for maintaining left ventricular function in patients 1 month after the onset of AMI.

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A 32-year-old woman was admitted with the diagnosis of congestive heart failure (CHF) without organic heart disease after peripheral blood stem cell transplantation (PBSCT) for malignant lymphoma. Various cytokines have been reported to be released from stem cells after PBSCT and some have a suppressive effect on myocardial contractility; elevated levels of cytokines have been reported in dilated cardiomyopathy (DCM) and/or CHF patients. In the present case, elevated levels of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) were observed, and there was a parallel relationship between the recovery of cardiac function and the decreased of these cytokines, strongly suggesting that the release of IL-6 and TNF-α after PBSCT might have been important in the pathogenesis of the CHF.

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Primary malignant pericardial mesothelioma is a rare tumor and the case reported here presented as constrictive pericarditis. The patient’s symptoms progressed day by day despite treatment with digitalis, diuretics and catecholamines. Although a computed tomographic scan of the chest, echocardiography and pericardiocentesis were performed, a preoperative definitive diagnosis could not be obtained. Emergency pericardiectomy and partial resection of the tumor were carried out with the aid of a percutaneous cardiopulmonary supporting system, but the patient died of cardiac failure on postoperative day 3. The tumor appeared to be the biphasic type of diffuse malignant mesothelioma. The prognosis for pericardial mesothelioma is extremely poor due to its late presentation and difficulty in completely removing it surgically and, unfortunately, there still is not a radical therapy for this tumor.

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A patient with subacute pericarditis showed no evidence suggesting tuberculosis until pericardiectomy was performed because of hemodynamic deterioration. The excised pericardium had a rubbery fibroelastic consistency; histologically, there were granulomatous changes characteristic of tuberculosis. Although tuberculous pericarditis is a difficult diagnosis, this case illustrates the diagnostic and therapeutic importance of early pericardiectomy before myocardial inflammatory infiltration occurs together with end-stage pericardial fibrosis and calcification.

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A 31-year-old woman underwent radiofrequency catheter ablation of a concealed left posteroseptal accessory pathway associated with a coronary sinus diverticulum. The patient had previously undergone unsuccessful catheter ablation of the posteroseptal region of the mitral annulus. Coronary sinus venography revealed the presence of the diverticulum near the ostium. An electrogram in the neck of the diverticulum showed the shortest ventriculoatrial conduction time and a large accessory pathway potential during atrioventricular reciprocating tachycardia. The pathway was successfully ablated within the neck of the diverticulum. The findings in this case underscore the importance of coronary sinus venography before ablation.

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Two patients in whom coronary spasm was refractory to intracoronary injection of nitroglycerin were relieved by intracoronary administration of nicorandil (a nitrate and potassium channel opener) during catheterization. These findings suggest that nicorandil may prove useful as an additional therapeutic agent.

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Radiofrequency catheter ablation of accessory bypass tracts associated with the Wolff-Parkinson-White (WPW) syndrome has become an accepted and widespread therapy. When bypass tracts are located in the free wall of the left ventricle, complete atrioventricular (AV) block is an unusual complication. Two cases of symptomatic WPW syndrome with transient complete atrioventricular block during catheter ablation are described. The first case was a 14-year-old female with an accessory pathway located in the left posterior wall, and the second was a 72-year-old female with an accessory pathway located in the left lateral wall. Radiofrequency energy application resulted in transient complete AV block with escape rhythm. In the first case, AV conduction with left bundle branch block resumed the next day, whereas in the second case, AV conduction soon resumed with prolongation of atrio-His (AH) interval and no evidence of pre-excitation. This phenomenon could have been due to either trauma to the AV node during catheter entry into the left ventricle or compression of the AV node with a catheter shaft during ablation because both patients’ hearts were comparatively small.

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A 61-year-old man who had undergone substernal esophagogastric anastomosis for reconstruction after esophageal cancer, developed unstable angina 9 years later. Complete revascularization for triple-vessel disease was performed via a left thoracotomy approach under cardiopulmonary bypass. The successful results show that complete revascularization can be performed via this approach.

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Recent reports have shown that repeated tilt-table testing or tilt training is a very effective therapy for the treatment of neurocardiogenic syncope induced by head-up tilt testing. The present patient experienced repeated syncopal or presyncopal attacks and had shown prolonged asystole on an electrocardiogram during syncope. The presyncope could be reproducibly induced by head-up tilt testing. Oral propranolol and/or disopyramide therapies failed to prevent his symptoms. Tilt training (2 sessions/day) was repeated every day for 4 weeks at home, and then head-up tilt testing was performed again. The syncope or presyncope was not induced by head-up tilt testing. The patient has continued with this training and has had no symptoms during the follow-up period of 1 year.

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