To analyze the recent change in the long-term survival of patients with dilated cardiomyopathy (DCM), the present study comprised consecutive 111 patients with ejection fraction <50% and left ventricular end-diastolic diameter >58 mm, who were admitted to hospital from January 1983 to December 1994. The patients were divided into 2 groups: group A who were diagnosed before 1989 and group B diagnosed after 1990. Basic characteristics at diagnosis, including age, NYHA functional class, left ventricular end-diastolic diameter and ejection fraction, were similar between these 2 groups. Calculated survival rate at 5 years was 90.0% in group B in contrast to 62.3% in group A. Event-free survival also improved in group B. In group B, β-blockers and angiotensin converting enzyme inhibitors were more frequently used than in group A (p<0.0001) whereas digitalis and other positive inotropic agents were significantly less used. Left ventricular ejection fraction was significantly improved during the follow-up period in patients treated with β-blockers compared with those not treated with β-blockers. These data indicate a significant improvement in the survival of patients with dilated cardiomyopathy after 1990, which may be explained by the change of medical treatment, especially the use of β-blockers. (Jpn Circ J 1999; 63: 333 - 338)

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Understanding the causes of syncope in patients with arrhythmia is important in determining the therapeutic interventions. Neurally mediated syncope (NMS) was evaluated in 55 patients with various arrhythmias. The head-up tilt test with or without isoproterenol infusion induced NMS in 41 (74%) patients. When these patients was categorized into 3 types, depending on the development of syncope, vasodilatation was significant in a majority of patients. In 46% of patients with tachyarrythmias, NMS was accompanied by an increase in extrasystole. It was concluded that the evaluation of vasodilatation is important for the preventive strategy of NMS in patients with arrhythmias and that NMS may induce arrhythmias. (Jpn Circ J 1999; 63: 339 - 342)

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The present study undertook an extensive analysis of the histopathological findings of the atrioventricular conduction system in 14 elderly patients treated with permanent pacemakers for sick sinus syndrome (SSS). Special attention was given to the lowest Wenckebach block points of atrioventricular conduction during rapid atrial pacing, and ventricular rate or duration of ventricular pause during chronic atrial fibrillation. An electrophysiological study (EPS) was conducted under sinus rhythm in 13 patients and under junctional escape rhythm in 1 patient. Three of the 14 cases showed a lower Wenckebach block point of 130 beats/min or less. Two of these 3 cases showed excessive fatty infiltration around the atrionodal junction area and into the atrophic atrioventricular node (AVN) itself. Of the 6 patients who had chronic atrial fibrillation after pacemaker implantation, 2 cases showed a slow ventricular response of less than 60 beats/min and/or a long ventricular pause of 3.3 s. One of the 2 cases showed a lower Wenckebach block point of 130 beats/min at the time of EPS. The other, who later progressed to idiopathic atriomegaly, also showed marked fatty infiltration around the AVN. This fatty lesion was closely associated with diffuse disruption of the muscular fibers connecting the atrophic AVN with the atrium. In addition, most of the remaining cases also had an atrophic AVN. In conclusion, a sparse or absent atrionodal connection and an atrophic AVN due to excessive fatty infiltration in the atrionodal transitional area should be investigated in atrioventricular conduction disturbances in the elderly with SSS. (Jpn Circ J 1999; 63: 343 - 349)

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To examine the mechanism of myocardial ischemia in hypertrophic cardiomyopathy (HCM), coronary flow velocity was measured in the left anterior descending coronary artery (LAD) using a Doppler guide wire in 11 patients with HCM and in 8 normal controls. The average peak velocity (APV), percent increase of APV (%APV), and APV during systole (Vs) and diastole (Vd) were calculated at rest and during rapid atrial pacing. The APV in HCM reached a peak value at a heart rate of 90 beats/min, while in the controls the APV increased continuously until the heart rate reached 130 beats/min [%APV (130 beats/min); 103±30% in HCM vs 139±23% in controls, p<0.04]. During rapid atrial pacing, Vs in the controls increased, whereas Vs in HCM decreased further. During high-rate pacing, Vd in HCM reached a peak value at a heart rate of 90 beats/min, whereas in the controls, Vd increased continuously until the heart rate reached 130 beats/min. The acceleration rate of early diastolic flow was significantly lower in HCM than in the controls (1.85±0.66 vs 3.18±1.62 m/s², p<0.03). This abnormal response might be due to an increase in the reverse systolic flow and a decrease in the diastolic flow, probably caused by a slow acceleration of early diastolic flow velocity in the LAD. (Jpn Circ J 1999; 63: 350 - 356)

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Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) have both shown strong angiogenetic effects in ischemic animal models and it has been reported that these growth factors were increased after acute myocardial ischemia. However, there have been few reports on the serum levels of bFGF and VEGF after acute myocardial infarction (AMI), in particular there has not been a comparative study of bFGF and VEGF in human subjects. The time course of circulating levels of bFGF and VEGF was examined in 36 patients with AMI who were within 24 h of the onset of the AMI. The serum bFGF and VEGF levels of 50 age- and sex-matched healthy volunteers served as the baseline value. All the patients had undergone coronary angiography on the day of admission (Day 0), but prior to that the serum bFGF and VEGF levels were examined by enzyme-linked immunoassay. The serum bFGF and VEGF levels were also evaluated on Days 7, 14 and 28. Creatine kinase, myosin light chain I and troponin-T were measured subsequently and radionuclide examinations were performed during the early phase of AMI to determine the infarct size. The serum bFGF levels were significantly increased at Day 0 and were maintained until Days 7 and 14. Although serum VEGF levels at Day 0 were similar to the baseline values, they showed a remarkable increase by Days 7 and 14. A high serum level of bFGF was detected in the acute phase of AMI, and a later increase in VEGF was determined in the sub-acute phase, which suggest that these 2 growth factors play an important role at different time points of the reconstructing process of infarcted myocardial tissue. (Jpn Circ J 1999; 63: 357 - 361)

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Although acute myocardial infarction (AMI) may involve both plaque rupture and ischemia-reperfusion injury, the pathogenesis of these phenomena is unclear. To elucidate the pathogenesis of AMI, serial measurements of platelet activating factor (PAF), interleukin-6 and cell adhesion molecules were made in patients with AMI. The PAF levels were measured upon hospital admission and at 24 and 72 h in 8 patients with AMI. Serum levels of interleukin-6, soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured upon admission and at 24 h and 4 weeks in 30 patients with AMI and 15 patients with stable effort angina. PAF levels were higher in patients with AMI than in normal volunteers; the increased levels lasting at least 72 h. In contrast, interleukin-6 increased at 24 h. sE-selectin was elevated at admission and sVCAM-1 increased later. sE-selectin levels upon admission in patients with additional ST-segment elevation after reperfusion were significantly higher than those in patients without ST-elevation. In patients with AMI, the time-course of changes in blood levels of cytokines varied according to the individual substances. Although it is unclear what is the precise role of each of the cytokines in the pathophysiology of AMI, sE-selectin may be possibly related to the reperfusion injury in the infarcted myocardium. (Jpn Circ J 1999; 63: 362 - 366)

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Left ventricular hypertrophy (LVH) is an adaptive change in response to hypertensive pressure overload. Some evidence indicates that the decrease in sarcoplasmic reticulum (SR) Ca²⁺-ATPase mRNA expression, which may contribute to a diastolic dysfunction of the heart, occurs in the experimental pressure overload model. Also, recent studies have demonstrated that angiotensin II (Ang II) and angiotensin II receptor type 1 (AT₁) play important roles in LVH. The purpose of this study was to investigate the function of the SR and the role of AT₁ in genetic hypertension in spontaneously hypertensive rats (SHR) at ages 10 and 18 weeks. In SHR, cardiac hypertrophy has already developed at 10 weeks of age. SR Ca²⁺-ATPase activity and mRNA expression were significantly lower in SHR than in Wistar-Kyoto rats (WKY). Plasma renin activity in SHR was unchanged compared with WKY, whereas the Ang II concentration in SHR was significantly higher than that in WKY. AT₁ mRNA expression in SHR was similar to that in WKY. These results suggest that in the early stage of hypertension in SHR Ang II may stimulate hypertrophy in the cardiomyocytes through the AT₁, which is not downregulated by a high concentration of Ang II. (Jpn Circ J 1999; 63: 367 - 372)

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Free radical generation was studied by the electron spin resonance (ESR) technique using α-phenyl N tert butyl nitrone (PBN) in a brief ischemia-reperfusion model of the canine heart, and correlated with biochemical changes of the sarcoplasmic reticulum (SR). ESR spectra (aH = 0.3-0.4 mT, aN = 1.43-1.58 mT) were observed as PBN spin adducts, which peaked at levels 5-fold above the control levels at 5 min after reperfusion. The simulated coupling constants of PBN spin adducts suggested that the sample should contain at least 2 carbon-centered radicals at 5 min after reperfusion (radical A: aH = 0.350 mT, aN = 1.485 mT; radical B: aH = 0.370 mT, aN = 1.615 mT). At this time point, a significant reduction in Ca-ATPase activity of the SR was found without degradation of the major ATPase protein. Superoxide dismutase (SOD) significantly reduced the intensity of the PBN spin adduct signals and preserved the Ca-ATPase activity of the SR to 80% of the control level. Reperfusion injury after brief ischemia may be the result of inactivation of intracellular Ca-ATPase by free radicals generated during reperfusion, and SOD contributes to the protective effect by scavenging the radicals. (Jpn Circ J 1999; 63: 373 - 378)

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Using doxycycline (DOXY), fluorescence spectrum analysis was performed on arteriosclerotic lesions, and the efficacy of this method was examined in basic and clinical studies. In the basic study, DOXY 50 mg was administered intravenously to arteriosclerotic rabbits, and the thoracoabdominal aorta removed. Fluorescence spectral analysis was performed on each specimen, and the fluorescence spectral pattern, peak intensity and degree of intimal hypertrophy were studied. In the clinical study, DOXY 200 mg was administered intravenously to 6 human subjects with stable angina and coronary arterial stenosis of greater than 90%, and coronary angiography, coronary angioscopy and fluorescence spectral analysis were performed. DOXY accumulation in the arteriosclerotic intima of rabbit aortae was confirmed. The fluorescence spectrum was monomodal, peaking at around 532 nm. In the noncalcification group, significant correlation was observed between peak intensity and arteriosclerotic intimal thickness. Using DOXY as a fluorescent marker, it was possible to assess the level of arteriosclerotic intimal hypertrophy. Clinically, it was possible to obtain the DOXY spectrum of the coronary arteries. (Jpn Circ J 1999; 63: 379 - 386)

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This study was performed to demonstrate accumulation of the photosensitizer hematoporphyrin derivative (HPD) in atherosclerosis and to determine whether intimal hyperplasia, the main cause of restenosis after angioplasty, can be inhibited by photodynamic therapy (PDT). Forty Japanese White rabbits were subjected to balloon endothelial injury in the common iliac artery. Five groups of rabbits, ie, immediately after, or 3, 7, 14 or 28 days after the balloon injury, were injected with HPD. These rabbits were sacrificed 24 h after HPD administration, and HPD fluorescence was investigated in the injured arteries by fluorescence microscopy. Other groups of rabbits were injected with HPD 24 h before PDT, and they were then subjected to intravascular Hg-Xe flash-lamp irradiation immediately after (0D-PDT), or 3 days (3D-PDT), 7 days (7D-PDT), or 14 days (14D-PDT) after the balloon injury. All rabbits were sacrificed 28 days after the balloon injury, and histological sections of PDT-treated arteries were examined by light microscopy. Slight, uniform HPD accumulation was observed in the injured media immediately after the balloon injury, and throughout the entire media and the neointima on day 7. On day 14, HPD accumulation had diminished in the media and increased in the intima, and on day 28 no HPD remained in the media. In the 0D- or 3D-PDT groups, no inhibition of intimal hyperplasia was observed. In contrast, there was significant inhibition of intimal hyperplasia in the 7D- and 14D-PDT groups, and the most effective inhibition was in the 7D-PDT group. This study demonstrated that PDT with HPD inhibits smooth muscle cell growth and decreases the intimal hyperplasia response in rabbits. (Jpn Circ J 1999; 63: 387 - 393)

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A 61-year-old man was referred for cardiac investigation because embolism was suspected to be the cause of the sudden onset of severe pain in his right leg after a surgical procedure. The electrocardiogram revealed no atrial fibrillation. Transthoracic echocardiography demonstrated a tumor-like echo at the anterior mitral leaflet, and transesophageal echocardiography documented a mass 13×9 mm in size, attached by a stalk to the left atrial side of the anterior mitral leaflet. The other parts of the mitral valve appeared to be intact. At emergency surgery, the mass was located in the center of the left atrial side of the anterior mitral leaflet. It mimicked a myxoma and had a stalk arising from the anterior leaflet. After resection of the mitral valve mass, catheter thrombo-embolectomy was performed and several long pieces of fresh thrombus were removed. On histological examination, the mass consisted of fresh thrombus tissue. No cellular component or myxoma tissue was documented. The distal embolus also consisted of fresh thrombus tissue. This is the first case of a thrombus of the intact mitral valve without atrial fibrillation. (Jpn Circ J 1999; 63: 394 - 396)

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A 77-year-old woman with acute myocarditis developed cardiogenic shock soon after admission and was given mechanical cardiopulmonary support. Echocardiography revealed severe global left ventricular hypokinesia. After 5 days of mechanical support, left ventricular wall motion gradually began to improve, but the patient died of cardiac tamponade on day 13. At necropsy, a free wall rupture was found where the apical akinetic area bordered the basal portion, an area which had shown better wall motion. Left ventricular free wall rupture in acute myocarditis has not been reported, but this case indicates that it may occur in fulminant myocarditis when a cardiopulmonary support system is used. (Jpn Circ J 1999; 63: 397 - 399)

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Hemolytic anemia is a rare manifestation of infective endocarditis. A 19-year-old man with a small ventricular septal defect developed right-sided infective endocarditis with huge vegetations involving the tricuspid valve, the ventricular septal defect, and the pulmonary valve. Intravascular hemolysis was suggested by the presence of numerous fragmented erythrocytes, giant platelets and polychromasia of the red blood cells. The direct Coombs test was positive, and there were spherocytes and splenomegaly, findings that suggested an immune-mediated mechanism also played a role in the hemolysis. The hematological picture persisted despite antibiotic therapy and recovered only after surgical removal of the vegetations, tricuspid and pulmonary valvectomy, and patch closure of the ventricular septal defect. (Jpn Circ J 1999; 63: 400 - 403)

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A 47-year-old woman with a left-sided Kent bundle showed marked reduction of the ventriculoatrial conduction time during extrastimuli at the right ventricular apex and outflow tract. The degree of reduction was greater than 6 years ago. A `supernormal conduction' in the ventricle and the Kent bundle could have been responsible for this phenomenon. (Jpn Circ J 1999; 63: 404 - 406)

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Enhanced external counterpulsation (EECP) is a noninvasive treatment for chronic stable angina, which works by recruiting and developing the coronary collateral vessels. Coronary perfusion and coronary flow reserve (CFR) were evaluated by nitrogen-13 (¹³N) ammonia positron emission tomography (PET) in a patient who had undergone EECP. The patient, who had 3-vessel coronary artery disease, required a percutaneous transluminal coronary angioplasty (PTCA) for the right coronary artery. The PTCA was successful, but 6 months later he again felt chest oppression. The coronary angiography showed re-stenosis at the PTCA site, and other progressive coronary stenosis. The patient was again treated with EECP for 35 h. The ¹³N-ammonia PET was performed both at baseline and during dipyridamole provocation, before and after EECP treatment. Coronary perfusion of each myocardial wall increased at the baseline (anterior: 0.52-0.75; septal: 0.48-0.66; lateral: 0.61-0.68; inferior: 0.46-0.57 ml min^-1 g^-1), and the CFRs in the septal and inferior walls (septal: 2.07-2.15; inferior: 1.99-2.06) also increased after the treatment. Thus, the EECP treatment improved both coronary perfusion at baseline and CFR, which suggests that it may be one of the choices for treatment of angina. (Jpn Circ J 1999; 63: 407 - 411)

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Takayasu's arteritis is a rare inflammatory aortoarteritis of unknown etiology and causes stenoocclusive disease of the aorta and its branches as well as aortic regurgitation. A surgical case of Takayasu's arteritis is presented. A 56-year-old female exhibited aortic regurgitation complicated by severe coarctation of the thoracoabdominal aorta due to Takayasu's arteritis. In this case, a 2-staged repair, consisting of an axillofemoral bypass and an aortic valve replacement, was successfully performed. (Jpn Circ J 1999; 63: 412 - 413)

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A 69-year-old woman with symptoms of congestive heart failure had a left atrial leiomyosarcoma, an extremely rare cardiac tumor, which obstructed the mitral valve and pulmonary veins. Surgical resection was performed, but no other adjuvant therapy was administered because the patient refused it. Recurrence of the tumor occurred soon after surgery and the patient died 81 days postoperatively. (Jpn Circ J 1999; 63: 414 - 415)

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This report describes a 49-year-old male with concealed Wolff-Parkinson-White syndrome in whom a true uncommon atrial flutter suddenly emerged 2 weeks after successful catheter ablation of a left-sided accessory pathway. The earliest atrial activation during the atrial flutter was recorded at the posterolateral mitral annulus 2 cm proximal to the previous successful ablation site for the accessory pathway. Two applications of radiofrequency (RF) current directed at the supravalvular mitral annulus could not terminate the atrial flutter. A subsequent delivery of RF current directed at the subvalvular annulus, where a local fragmented potential preceded the earliest atrial activation, eliminated the atrial flutter. (Jpn Circ J 1999; 63: 416 - 420)

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Two cases of QT prolongation and torsades de pointes (TdP) are presented. The patients had been taking clarithromycin (400 mg/day) for respiratory disease. Although erythromycin is reportedly associated with TdP, this is the first report of clarithromycin associated with TdP in the absence of other drugs already known to produce QT prolongation. (Jpn Circ J 1999; 63: 421 - 422)

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In a patient with severe ischemic heart disease and advanced human immunodeficiency virus (HIV) infection, vigorous perioperative treatment with anti-retroviral agents was given and coronary artery bypass surgery using cardiopulmonary bypass was successfully performed. This strategy could become the standard for patients with cardiovascular disease and advanced HIV infection. The following aspects of this case require further investigation: (1) lack of a reactive increase in the neutrophil count, (2) transient extreme reduction of lymphocytes, and (3) a relative decrease in the CD⁸⁺ cell ratio. (Jpn Circ J 1999; 63: 423 - 424)

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Atrial septal defect (ASD) is the most common form of congenital cardiac defect in humans. Recently, point mutations in the cardiac homeobox gene CSX/NKX2-5 have been reported to cause the autosomal dominant form of familial ASD. Notably, all the affected patients exhibit atrioventricular conduction disturbance and some of them died suddenly. The first case of familial ASD with a mutation of the CSX/NKX2-5 gene in a Japanese patient is reported here. Identification of CSX/NKX2-5 mutations in ASD patients would be very important because the existence of such mutations may predict sudden cardiac death. (Jpn Circ J 1999; 63: 425 - 426)

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