Background The rhythm control treatment strategy for persistent atrial fibrillation (AF) has been shown not to improve quality of life or prognosis any more than rate control. It is unclear whether the prognosis of the patients with paroxysmal AF (PAF) is influenced by the response to antiarrhythmic drug therapy (AAT). Methods and Results The relationship between the response to AAT and long-term prognosis was evaluated in 290 patients with PAF (mean age, 69 years). During a mean follow-up period of 51 months, 114 patients (39%) had no recurrence of AF (Group 1), 113 (39%) had repeated AF recurrence (Group 2), and the remaining 63 (22%) had permanent AF despite AAT (Group 3). The survival rate without any cardiovascular deaths at 60 months was 99% in Group 1, 95% in Group 2 and 94% in Group 3 (p=NS among 3 groups). Survival rate without symptomatic ischemic stroke was 99% in Group 1, 88% in Group 2 and 76% in Group 3 (p<0.05 Group 1 vs Groups 2 and 3). The annual rate of stroke in the patients with warfarin treatment was similar among the 3 groups, whereas that in the patients without warfarin was higher in Groups 2 and 3 than in Group 1. Conclusions Long-term prognosis of patients with PAF varies with the response to AAT: When sinus rhythm is maintained, the prognosis is good even without anticoagulation therapy. (Circ J 2004; 68: 729 - 733)

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Background A fulminant course can be difficult to predict at the onset of acute myocarditis, so the aim of the present study was to identify the predictive clinical symptoms/signs or laboratory findings. Methods and Results Thirty-nine patients with acute lymphocytic myocarditis, excluding 8 who manifested shock at admission, were studied. The fulminant group was defined as 12 patients who developed shock after admission, requiring intraaortic balloon pumping or percutaneous cardiopulmonary support, and the non-fulminant group comprised the 27 patients without shock. Various parameters at admission were compared between the 2 groups, together with multiple logistic regression analysis, excluding 6 patients with partially missing values. In the fulminant group, C-reactive protein (7.0±7.0 vs 2.3±2.2 mg/dl, p<0.01) and creatine kinase (1,147±876 vs 594 ±568 IU/L, p<0.05) concentrations were higher, intraventricular conduction disturbances were more frequent (9/12 vs 7/27 patients, p<0.01) and the left ventricular ejection fraction was lower (40.7±13.9 vs 50.1±10.6%, p<0.05) than in the non-fulminant group. In the multiple logistic regression analysis model with the presence/absence of a fulminant course considered as the independent variable, and C-reactive protein, creatine kinase, intraventricular conduction disturbances, and left ventricular ejection fraction as dependent variables, a high-risk group (expected proportion of fulminant course ≥0.5) and a low-risk group (<0.5) could be differentiated. A fulminant course occurred in 9/13 (69%) patients in the high-risk group, but in only 2/20 (10%) patients in the low risk group (p<0.001). Conclusions The risk of a fulminant course of acute myocarditis was high in patients with elevated C-reactive protein, and creatine kinase concentrations, decreased left ventricular ejection fraction, and intraventricular conduction disturbances at the time of admission. (Circ J 2004; 68: 734 - 739)

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Background Brugada syndrome is a form of idiopathic ventricular fibrillation characterized by right bundle-branch block pattern and ST elevation in the right precordial leads of the ECG. The SCN5A gene encodes the α-subunit of the human heart sodium channel, which plays a critical role in cardiac excitability, and mutations of SCN5A could underlie Brugada syndrome. Methods and Results To detect mutations of SCN5A, DNA samples from 12 Japanese patients with Brugada syndrome were analyzed using direct sequencing. Two patients had novel mutations, G292S and S835L, but no other mutations of SCN5A were detected in the remaining patients. The first mutation, G292S, was identified adjacent to the pore-lining region between the DIS5 and DIS6 transmembrane segments of SCN5A, and the second mutation, S835L, was in the intracellular loop connecting the DIIS4 to DIIS5. Both mutations were not detected in 100 unrelated control subjects. Conclusion Two novel SCN5A mutations have been found in Japanese patients with Brugada syndrome. (Circ J 2004; 68: 740 - 746)

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Background Elevated concentrations of cardiac troponin T and heart-type fatty acid-binding protein (H-FABP) identify patients with chronic heart failure (CHF) and ongoing myocardial damage (OMD) who are at increased risk for future cardiac events. Cardiomyocyte necrosis and/or apoptosis via activated tumor necrosis factor (TNF) and the Fas/Fas ligand (FasL) system may be related to the development of OMD. Methods and Results The serum concentrations of H-FABP, a sensitive marker of membrane damage of cardiomyocytes, soluble Fas (sFas) and TNF-α were measured in 38 patients with CHF. The concentrations of H-FABP, TNF-α and s-Fas in patients with New York Heart Association (NYHA) III + IV were all significantly higher than in those patients in NYHA II (H-FABP; III + IV 9.3±5.9 vs II 5.1±1.8 ng/ml, p=0.003, TNF-α; III + IV 10.5±3.8 vs II 8.0±2.7 pg/ml, p=0.02, sFas; III + IV 3.36±1.37 vs II 2.58 ±0.84 ng/ml, p=0.03). Increased concentrations of H-FABP significantly correlated with the concentrations of TNF- α (r=0.57, p=0.0001) and sFas (r=0.69, p<0.0001), independent of renal function. Conclusion OMD detected by H-FABP, a marker of membrane damage, is related to activated TNF and the Fas/FasL system, which suggests a pathophysiological role of cardiomyocyte necrosis and/or apoptosis in patients with worsening heart failure. (Circ J 2004; 68: 747 - 750)

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Background A new system of synthesizing a 12-lead electrocardiogram (Syn-ECG) with practically identical waveforms to the standard 12-lead ECG (Stn-ECG) from 3-channel ECGs recorded by Holter monitoring has been developed. Methods and Results The study group comprised 16 healthy individuals and 13 patients with abnormal ECGs. The bipolar _eV₁, _eV₅ and _eV_F leads were recorded using digital Holter monitoring and nine Syn-ECGs, corresponding to each lead of the Stn-ECG, were synthesized. The 9 ECGs consisted of a theoretical Syn-ECG and 8 Syn-ECGs positioned around the theoretical Syn-ECG at 3 cm intervals on the Frank's image surface. Of the 9 ECGs, the Syn-ECG with the maximum product of the cross-correlation coefficient of the QRS wave and that of the T wave, was automatically selected as the optimal Syn-ECG. The amplitude data from the QRS wave, R wave, T wave, and ST level, and also the amplitude ratio of the R wave, T wave to the QRS wave, were significantly well correlated between the Syn-ECG and Stn-ECG. Conclusions A practically identical ECG morphology, comparable with a Stn-ECG, was successfully created using this system. (Circ J 2004; 68: 751 - 756)

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Background Sudden cardiac death commonly occurs in young patients with hypertrophic cardiomyopathy (HCM); however, their heart rate variability (HRV) and blood pressure (BP) response to daily life activities is not well known. Methods and Results HRV and ambulatory BP monitoring were performed in 20 patients (age range: 7-21 years) and 57 age-matched healthy volunteers (age range: 10-22 years). Time domain variables and spectral data were obtained at hourly intervals throughout the day. To determine the BP response to daily life activities, the ratios of the mean BP and pulse pressure in the morning, afternoon, and night to those during sleeping were calculated. The association between the BP level and HRV was also evaluated. The HCM patients showed significantly increased sympathovagal imbalance and decreased parasympathetic activity in the early morning, around noon, and in the early evening. This abnormality was independent of cardiac symptoms. Symptomatic patients showed a significantly lower systolic BP response in the morning, and a higher incidence of dissociation between sympathetic activity and BP response than asymptomatic patients. Conclusion An abnormal BP response in the presence of impaired HRV appears to be predictive for cardiac events in young patients with HCM. (Circ J 2004; 68: 757 - 762)

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Background The angiographic no-reflow phenomenon is an adverse prognostic factor in patients with acute myocardial infarction (AMI). The aim of the present study was to evaluate the effects of an occlusive balloon type distal protection device (PercuSurge GuardWire: GW) during primary stenting in patients with anterior AMI. Methods and Results The GW group included 42 patients treated by primary stenting with GW protection and the control group included 30 patients treated by primary stenting after thrombectomy without distal protection. Left ventricular (LV) function was measured and compared by left ventriculography obtained soon after percutaneous coronary intervention (PCI) and 3 weeks after onset. The corrected TIMI frame count values were lower in the GW group than in the control group (27.5±2.3 vs 35.1 ±2.5, p=0.030). The number of patients with myocardial blush grade 3 after PCI was higher in the GW group than in the control group (45.7 vs 20.0%, p=0.029). Peak concentration of creatine kinase myocardial fraction was lower in the GW group than in the control group (326.6±41.5 vs 454.9±46.2 mg/dl, p=0.043). GW patients showed greater improvement at 3 weeks after PCI in terms of LV ejection fraction (+4.6±1.2 vs -1.1±1.5, p=0.004), LV end-systolic volume index (+0.5±2.4 vs +9.0±2.7, p=0.023), and regional wall motion abnormalities (-2.03±0.14 vs -2.51±0.14, p=0.018). Conclusion Primary stenting with GW protection can restore epicardial coronary flow and myocardial perfusion, and also preserve LV function in anterior AMI. (Circ J 2004; 68: 763 - 768)

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Background In a previous study the adjusted thresholds at which the diameters of coronary arteries determined by enhanced electron-beam computed tomography (CT) scans are equal to the corresponding quantitative coronary angiography measurements were analyzed, and their correlation with maximum CT values for the vessel short axes was determined. A rapid accurate method for such measurements was sought by substituting maximum CT values for the descending aorta in the corresponding axial images for those for the short axes. Methods and Results In 8 patients, 179 sites were measured. Means (± SD) of adjusted thresholds and the maximum CT values for vessel short axes and the descending aorta in the corresponding axial images for all vessels were 108 ±66, 227±80, and 363±75 Hounsfield Unit (HU), respectively. Adjusted thresholds correlated with the maximum CT values for the corresponding vessel short axes and the descending aorta in the corresponding axial images, with R²=0.55, 0.33, p<0.01, respectively. An abbreviated formula for use of maximum CT values for the descending aorta in the corresponding axial images was y=0.5x-75 (HU) (y= adjusted threshold, x= maximum CT value for the descending aorta in the corresponding axial image). Conclusions The abbreviated formula provided a rapid, accurate method for measurements independent of arterial enhancement. (Circ J 2004; 68: 769 - 777)

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Background End-tidal CO₂ partial pressure (PETCO₂) has been suggested as a noninvasive index reflecting cardiac output under constant ventilation. The aim of this study was to examine whether PETCO₂ does reflect cardiac output, even during exercise, in patients with acute myocardial infarction (AMI) undergoing exercise training early after onset. Method and Results Patients aged 47-73 years were randomly assigned to either a training group (n=18) or a control group (n=18) 1 week after the onset of AMI. Those in the training group performed exercise training under supervision at the anaerobic threshold level for 2 weeks, while patients in the control group followed a conventional walking regimen. In the training group, but not in the control group, PETCO₂ at the respiratory compensation point increased significantly from 39.1±3.5 to 41.1±3.7 mmHg (p<0.01). Similarly, the cardiac index at peak exercise increased only in the training group (from 6.04±0.98 to 7.31±0.97 L/min per m², p<0.01). These 2 measurements correlated well both before and after the study period. Peak oxygen uptake and anaerobic threshold were increased only in the training group. Conclusions Aerobic exercise training early after the onset of AMI significantly increased PETCO₂ during exercise, which may reflect an improvement in cardiac output during exercise in response to physical training via a decreased ventilation - perfusion mismatch. (Circ J 2004; 68: 778 - 783)

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Background Currently, there are various types of statins used in the treatment of hyperlipidemia and coronary artery disease. The purpose of this study was to compare the effects of a lipophilic statin (cerivastatin) with those of a hydrophilic statin (pravastatin) on the carotid arterial media using integrated backscatter (IB) ultrasound. Cerivastatin (C) has a strong anti-proliferative effect (APE) on smooth muscle cells (SMCs), whereas pravastatin (P) has a weak effect. Methods and Results The IB values in the media of 72 segments of carotid arteries were measured in 36 patients with hyperlipidemia before and after statin therapy or diet for 6 months (C, n=13: P, n=12: diet, n=11). In addition, IB values of 34 segments of carotid arteries were measured in 34 patients without coronary risk factors. Intima - media thickness (IMT) and arterial stiffness (stiffness β) were measured by conventional echo at the same time. IB values did not significantly change in the P group (12.8±3.5 vs 12.7±2.7 dB), but decreased in the C group (12.1 ±2.9 vs 10.0±2.7 dB, p<0.01). Also, stiffness β did not significantly change in the P group (8.3±3.1 vs 7.6±2.5), but decreased in the C group (10.1±4.3 vs 7.9±3.3, p<0.05). IB values correlated with age (r=0.70, p<0.01) and stiffness β (r=0.67, p<0.01) in the 34 patients without coronary risk factors. Conclusions Statin therapy with cerivastatin, but not pravastatin, decreased the IB values of the carotid media and arterial stiffness. The difference between these 2 statins may be related to their effective dose range. (Circ J 2004; 68: 784 - 790)

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A 63 year-old female presented with dyspnea on exertion. Her chest X-ray showed cardiomegaly, and right ventricular overload and tricuspid regurgitation were detected. Her pulmonary ventilation and blood flow scintigraphy findings were suspicious of pulmonary vascular disease; the diagnosis was pulmonary hypertension and bilateral branch pulmonary artery stenosis. After the inflammation settled, the stenotic bilateral branch pulmonary artery was reconstructed with a prosthetic vessel and the pulmonary pressure normalized immediately. A resected specimen revealed that the stenotic changes were from Takayasu's disease. The patient's postoperative course was uneventful, and pulmonary ventilation and blood scintigraphy returned to an almost normal range. At follow-up 5 years and 6 months after the operation, there was no evidence of pulmonary artery disease (eg, stenosis and/or ischemia) or of any change in the central vessels of the retina, the so-called Takayasu's retinopathy. (Circ J 2004; 68: 791 - 794)

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A 48-year-old Japanese man was admitted to hospital for acute myocardial infarction associated with a giant organized thrombus occupying the left sinus of Valsalva. Cardiac catheterization revealed no organic stenosis in either coronary artery, but left ventriculography and aortography showed a filling defect above the left coronary cusp. Transesophageal echocardiography was immediately performed and showed a round mass filling the left sinus of Valsalva. A solid, round mass approximately 2.5 cm in diameter was removed during emergency surgery and determined to be a thrombus on the basis of microscopic findings. This is the second report of a giant organized thrombus occupying the entire left sinus of Valsalva, obstructing the ostium of the left coronary artery intermittently, and leading to acute myocardial infarction. (Circ J 2004; 68: 795 - 798)

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A 64-year-old female, admitted because of severe dyspnea on exertion and facial edema, showed echocardiographic findings of a large tumor in the right ventricle (RV). Echocardiography revealed a cardiac mass extending from the RV across the tricuspid valve into the right atrium, synchronized with the cardiac cycle, and severe tricuspid regurgitation was apparent. The mass was removed under cardiopulmonary bypass. It measured 7×5×5 cm with diffuse superficial calcification and arose from the posterior wall of the RV, just under the tricuspid valve ring, with a short pedicle. During the same procedure, after the successful excision of the tumor, small atrial and ventricular septal defects were found that had been caused by the tumor and these were closed directly. The tricuspid valve was repaired with valvuloplasty, chordoplasty and annuloplasty. The microscopic findings were of typical myxoma; however, a right ventricular myxoma protruding into the right atrium is exceedingly rare. (Circ J 2004; 68: 799 - 801)

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Although gallium-67-citrate (⁶⁷Ga) scanning and single-photon emission computed tomography (SPECT) are useful in the assessment of disease activity in cardiac sarcoidosis, a patient with cardiac sarcoidosis in whom SPECT imaging with ⁶⁷Ga failed to predict the deterioration in the clinical course is presented. A 53-year-old woman diagnosed with cardiac sarcidosis had ⁶⁷Ga scanning and ⁶⁷Ga SPECT, both of which showed abnormal high uptake. After treatment with corticosteroid, there was an apparent improvement in the ⁶⁷Ga SPECT findings, and the dose of the corticosteroid was reduced. Subsequently, the disease activity of the cardiac sarcoidosis was thought to be well controlled, because abnormal uptake was not found on repeat ⁶⁷Ga SPECT. However, 4 years after initial diagnosis, thinning at the basal ventricular septal wall and complete atrioventricular block were noted. Despite repeating the evaluation with ⁶⁷Ga SPECT and additional fluorine-18-fluorodeoxyglucose positron emission tomography (¹⁸FDG PET) after discovering this progression, neither of these examinations showed any abnormality. Unfortunately, in this patient, the disease activity of cardiac sarcoidosis was underestimated by the diagnostic imaging modalities. (Circ J 2004; 68: 802 - 805)

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