The Japanese Rhythm Management Trial for Atrial Fibrillation (J-RHYTHM study) is a randomized comparative evaluation of rate control and rhythm control, both combined with antithrombotic therapy, as therapeutic strategies for the treatment of atrial fibrillation (AF). This study differs from the earlier AFFIRM and RACE studies in that it has a composite primary end-point representing mortality and also physical/psychological disablement (total mortality, symptomatic cerebral infarction, systemic embolism, major bleeding, hospitalization for heart failure requiring intravenous administration of diuretics, and patient disablement). Patients' will to change the therapeutic strategy to the other is also considered as an end-point representing disablement under the assigned strategy. The secondary end-point includes quality of life scores and the efficacy and safety of drugs used in treating AF. The J-RHYTHM study emphasizes patient-reported experience and perception of AF-specific disablement, and the safety of antiarrhythmics available in Japan; it will follow 2,600 patients treated at more than 150 sites in Japan for a 3-year period. (Circ J 2003; 67: 738 - 741)

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The present study was designed to clarify whether osteopontin, an extracellular matrix protein, is released from the heart into the coronary circulation in patients with a previous (>3 months) anterior wall myocardial infarction (MI). Using a commercially available enzyme immunoassay kit, plasma concentrations of osteopontin were measured in 30 patients (26 men, 4 women; mean age, 61±12 years). Blood samples were obtained from the aortic root and coronary sinus. The difference in the plasma concentrations of osteopontin in the aortic root and coronary sinus, which reflects the cardiac production of osteopontin released into the coronary circulation, was compared with the left ventricular ejection fraction (LVEF) and volumes obtained from contrast left ventriculography. Plasma osteopontin concentrations were significantly higher in the coronary sinus than in the aortic root (672±446 vs 610±398 ng/ml, p=0.02). The transcardiac gradient of plasma osteopontin concentration correlated negatively with LVEF (r=-0.55, p=0.0005) and positively with left ventricular (LV) end-diastolic (r=0.63, p=0.0001) and end-systolic volume indexes (r=0.79, p<0.0001). This is the first study to show that in patients with a previous anterior wall MI osteopontin is released from the heart into the coronary circulation in proportion to the LV systolic function and volumes, suggesting that this extramatrix protein is associated with post-MI LV remodeling. (Circ J 2003; 67: 742 - 744)

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It is unknown whether the non-transplanted, denervated human heart is supersensitive to β-adrenergic agonist in terms of inotropism and chronotropism. In the present study, 36 patients with normal left ventricular (LV) wall motion were divided into 3 groups according to the cardiac metaiodobenzylguanidine (MIBG) scintigrams: group I with normal MIBG uptake, group II with regionally reduced MIBG uptake, and group III with globally reduced MIBG uptake (heart-to-mediastinum ratio <1.6). Before isoproterenol (IP) infusion, heart rate (HR), blood pressure (BP) and echocardiographic indices were similar among the groups. There was a trend toward a greater increase in HR with IP (0.01 μg · kg ^-1 · min^-1) in group III (27±18 beats/min) than in groups I (20±8) and II (17±8) despite the lack of a significant difference in BP reduction by IP. During IP infusion, increases in posterior wall motion amplitude and LV fractional shortening were significantly greater in group III (4.5±1.8 mm and 16.4±5.4%, respectively) than in groups I (1.5±2.5 mm and 8.7±6.4%) and II (2.6±1.7 mm and 8.9±7.9%). The present results suggest that the sympathetically denervated human heart is supersensitive to IP and the exaggerated responses may be caused, at least in part, by a postsynaptic mechanism. (Circ J 2003; 67: 745 - 749)

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In the present study, 0.2-0.6 mg/kg (0.4±0.2, mean ± standard deviation) indomethacin was administered intravenously to close a patent ductus arteriosus in 13 infants with co-existing congenital heart defects whose ages ranged from 3 to 48 (14±14) days. All of them were hemodynamically ductus-independent and symptomatic. Echocardiography demonstrated that the ductus had closed in 8 infants, aged 3-33 (12±10) days (responders), but had not closed in 5 infants aged 6-48 (19 ±19) days (non-responders). There was no significant difference between the responders and non-responders in their age, body weight, minimal diameter of the duct, dose of indomethacin, gestational age, birthweight, or Apgar score. One possible major complication might be associated with indomethacin. However, intravenous indomethacin should be considered prior to surgical ligation as one option for infants with a symptomatic patent ductus arteriosus complicated by other congenital heart defects. (Circ J 2003; 67: 750 - 752)

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Electrocardiographic abnormalities, cardiac injury, and autonomic nervous function were investigated in patients with acute-phase subarachnoid hemorrhage (SAH) (42 patients with SAH related to ruptured aneurysm and 42 control subjects). Electrocardiogram and Holter electrocardiogram for spectral analysis of heart rate variability (HRV) were recorded. Concentrations of cardiogenic enzymes (ie, creatine kinase-myocardial fraction [CK-MB], myosin light chain I, and troponin T), plasma concentrations of catecholamine (ie, noradrenaline, adrenaline, 3-methoxy-4-hydroxy-phenylethylene glycol [MHPG]) and HRV were compared in the acute and chronic phase of SAH, and with the values in the controls subjects. As previously reported, patients with acute SAH exhibited electrocardiographic (ECG) abnormalities and increased concentrations of both cardiogenic enzymes and plasma catecholamines, suggesting that acceleration of sympathetic activity is involved. However, HRV analysis showed enhanced parasympathetic activity, probably associated with increased intracranial pressure after the onset of SAH, which may be explained by accentuated antagonism, negative feedback of noradrenaline to the center, and reduction of sympathetic activity after reaching a peak level. The results suggest that not only sympathetic activity but also vagal activity is enhanced during the acute phase of SAH, thus contributing to the ECG abnormalities and the onset of cardiac injury. (Circ J 2003; 67: 753 - 756)

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The effect of insulin resistance (IR) on the fatty acid metabolism of myocardium, and therefore on the recovery of left ventricular (LV) wall motion, has not been established in patients with acute myocardial infarction (AMI). A total of consecutive 58 non-diabetic AMI patients who had successfully undergone emergency coronary angioplasty were analyzed retrospectively. They were categorized into 2 groups, normal glucose tolerance (NGT) and impaired glucose tolerance (IGT), based on a 75-g oral glucose tolerance test (OGTT). The parameters of OGTT, myocardial scintigraphy (n=58) (thallium-201 (Tl) and iodine-123-β-methyl-iodophenylpentadecanoic acid (BMIPP)) and left ventriculography (n=24) were compared in the 2 groups after reperfusion (acute phase) and 3-4 weeks after the AMI (chronic phase). The insulin resistance (IR), estimated by the serum concentration of insulin at 120 min (IRI 120') of the OGTT and by the HOMA (the homeostasis model assessment) index, was higher in the IGT group than in NGT group. An inverse correlation was found between the recovery of regional LV wall motion in the ischemic lesion and the IRI 120' and HOMA index. Although the recovery of BMIPP uptake from the acute to the chronic phase was higher in the IGT group, it was only correlated with the degree of IRI 120', not with the HOMA. IR accompanied by IGT can negatively influence the recovery of regional LV wall motion. (Circ J 2003; 67: 757 - 762)

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Percutaneous transluminal septal myocardial ablation (PTSMA) is a new therapeutic option for patients with hypertrophic obstructive cardiomyopathy (HOCM). In the present study, the acute and follow-up results of PTSMA were evaluated. From August 1997 to March 2003 27 medically refractory patients (New York Heart Association (NYHA) functional class 2.9±0.6) with HOCM underwent PTSMA. The target septal branch was determined by probationary ballooning in 3 and by myocardial contrast echocardiography in 24 patients. The mean resting left ventricular outflow tract pressure gradient (PG) was reduced from 70±44 to 24±22 mmHg (p<0.0001); the peak concentration of creatine kinase was 1,545±686 IU/L. Although transient trifascicular block was observed in 14 patients, permanent pacemaker implantation was not required. There were no major adverse cardiac events during the hospital stay; the mean clinical follow-up was 2.2±1.7 years. Repeated PTSMA was needed in 1 patient; however, symptomatic improvement had been well preserved in all patients (NYHA class 1.2±0.4). Follow-up echocardiographic examination showed sustained improvement in PG, septal and left ventricular posterior wall thicknesses, and the grade of systolic anterior movement and regurgitation of the mitral valve. In conclusion, PTSMA is a safe and effective therapeutic option for medically refractory patients with HOCM. (Circ J 2003; 67: 763 - 767)

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In acute myocardial infarction (AMI), slow flow (<TIMI 3) after reperfusion remains a problem. Removing the thrombus from culprit lesions should reduce this phenomenon and improve clinical outcome, so to evaluate the advantages of the Rescue percutaneous thrombectomy system (Rescue PT), 65 cases of AMI in which Rescue PT (RT group) was carried out were compared with 66 cases of AMI that were treated before Rescue PT became available (non-RT group). The study compared angiographic results, in-hospital clinical outcomes and the cost estimation during hospitalization. In the RT group, direct stenting was chosen more frequently (57% vs 5%, p=0.002) and the number of balloon catheters used was less (0.7±0.8 vs 1.4±0.6, p<0.0001). The incidence of slow flow and the maximum serum creatine kinase value over 24 h were lower in the RT group (3.1% vs 19.7%, p=0.01 and 3,444±2,218 IU vs 4,182±3,010 IU, p<0.05 respectively); however, in-hospital clinical outcomes were identical. No major complication related to the Rescue PT procedure was found. The cost for the initial procedure and the total cost during hospitalization were similar between the groups. Thrombectomy with Rescue PT before mechanical dilatation of the culprit lesions is safe and feasible, even in the emergency clinical setting, and results in better angiographic coronary flow. This therapy facilitates direct stenting and does not increase the cost of treatment. (Circ J 2003; 67: 768 - 774)

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The diagnostic accuracy of using electrocardiographic findings to identify affected vessels in cases of myocardial infarction and angina pectoris treated by percutaneous transluminal coronary angioplasty was assessed. From the anterior wall leads, ST segment elevation in leads I and aV_L showed diagnostic accuracy (sensitivity, specificity and positive predictive value) in identifying proximal lesions of the left anterior descending coronary artery of 89%, 58% and 62%, and the diagnostic accuracy of the QS wave in V₁ was 62%, 83% and 72%, respectively. For the posterior wall leads, the corresponding values for the diagnosis of affected vessels based on R/S>1 in V₁ for the left circumflex coronary artery were 50%, 89% and 60%, respectively. The inferior wall leads with ST segment elevation in leads II, III and aV_F, and ST segment depression in aV_L, showed diagnostic accuracy for the right coronary artery of 90%, 90% and 92%, respectively. Bifurcation of the first diagonal branch, dominance of the posterior descending branch, the normal subtypes of the coronary artery and the occurrence of spontaneous recanalization may have influenced the accuracy of diagnosis. Adding a high lateral wall lead one intercostal space above V₄ and a posterior wall lead located one intercostal space below V₆ appeared to increase the diagnostic accuracy of detecting the coronary artery lesions responsible for myocardial ischemia. (Circ J 2003; 67: 775 - 780)

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It has been reported that the xanthine oxidase inhibitor, allopurinol, has a protective effect on ischemia - reperfusion injury, but the precise mechanism of its action is still unclear. Therefore, in the present study the mechanisms of the myocardial protection of allopurinol were evaluated in isolated perfused rat hearts. Allopurinol significantly inhibited myocardial xanthine oxidase activity, and improved left ventricular dysfunction after ischemia - reperfusion. In addition, the lactate dehydrogenase content in the coronary effluent obtained after reperfusion was significantly decreased. ATP, ADP, AMP and IMP significantly decreased, whereas inosine, hypoxanthine and xanthine significantly increased after ischemia in both the control and allopurinol groups. The concentration of xanthine was significantly decreased after ischemia - reperfusion in the allopurinol group; however, allopurinol did not affect the other purine metabolites. To evaluate the accumulation of oxidative stress, thiobarbituric acid reactive substances (TBARS) production in myocardial tissue was measured and allopurinol significantly decreased TBARS formation after ischemia - reperfusion. Finally, myocardial hydroxyl radicals were directly measured by electron spin resonance spectroscopy with the nitroxide radical 4-hydroxy-2, 2,6,6-tetramethyl-piperidine-N-oxyl. Hydroxyl radicals significantly increased immediately after reperfusion, but were significantly decreased in the allopurinol group. In conclusion, allopurinol reduced myocardial injury after ischemia-reperfusion by suppressing oxidative stress, but not by salvage of ATP. These findings may lead to the development of new therapeutic strategies for myocardial ischemia - reperfusion injury. (Circ J 2003; 67: 781 - 787)

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The combining of molecular biology and physiology is essential for the further development of cardiovascular medicine, and DNA microarray is a useful tool for assessing multiple gene expressions. A canine DNA microarray has been designed and tested. Approximately 60 cardiovascular-related genes were cloned from newly developed canine cDNA libraries and spotted on slides. Using the arrays, the gene expression profiles of canine myocardium in were analyzed 2 protocols: (1) ischemic myocardium by 50% reduction of the coronary blood flow, and (2) necrotic myocardium caused by coronary artery ligation. Three hours after 50% flow reduction, cardiovascular-related genes, including ecto-5'-nucleotidase, endothelin-1, PAI-1, and AT receptors, exhibited rapid alteration and there were many more altered genes than with the complete coronary occlusion. Irreversible ischemic damage without necrosis more strongly affected gene expressions in surviving myocardium than in fatally damaged myocardium. The canine DNA microarray is a useful tool for assessing the precise molecular events following changes in the pathophysiological conditions of the heart. (Circ J 2003; 67: 788 - 792)

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Pulmonary capillary hemangiomatosis (PCH) is a rare idiopathic lung disorder that occurs in young patients and leads to pulmonary hypertension (PH). It is difficult to diagnosis in the early stage and is often mistaken for primary PH; in almost all cases of PCH, the correct diagnosis is not made until autopsy. In the present case of PCH, the patient had severe pulmonary hypertension and died of respiratory failure. Pathologically, PCH is characterized by proliferation of benign thin-walled capillary sized blood vessels in the lung parenchyma. (Circ J 2003; 67: 793 - 795)

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Pulmonary vein varix is a rare abnormality, often resembling a pulmonary or mediastinal mass on chest radiographs, and pulmonary angiography has been the mainstay of diagnosis. An unusual case of pulmonary vein varix was clearly defined by echocardiography performed in a 47-year-old woman with chest discomfort who had been found to have an abnormal structure behind the cardiac silhouette on a chest radiograph. The diagnosis of left lower pulmonary vein varix was noninvasively confirmed by transthoracic echocardiography and transesophageal echocardiography. (Circ J 2003; 67: 796 - 798)

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Hemolytic anemia following mitral valve repair and annular ring placement is uncommon compared with mitral valve replacement. A 60-year-old man, who had undergone mitral valve repair with a Duran ring, developed hemolytic anemia and needed a blood transfusion. Transesophageal echocardiography revealed a paravalvular mitral regurgitation jet colliding with the Duran ring. Most cases of severe hemolysis after mitral valve repair have undergone reoperation, but in the present case study, the hemolysis after mitral valve repair reduced without the need for reoperation, although the paravalvular mitral regurgitation jet continued to collide with the Duran ring. (Circ J 2003; 67: 799 - 801)

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A 69-year-old woman had acute cholecystitis that mimicked right bundle branch block with coved-type ST-segment elevation in the precordial electrocardiogram leads (Brugada-type ST shift). The patient did not have obvious heart disease, syncope, or a family history of sudden death. The coved-type ST-segment elevation disappeared as the acute inflammation subsided. Intravenous administration of pilsicainide, a pure sodium channel blocker, could reproduce the Brugada-type ST shift. This is the first report of the Brugada-type ST shift occurring in association with acute cholecystitis. (Circ J 2003; 67: 802 - 804)

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