Background Although there is a close connection between emergency medical services (EMS) system and the outcome of out-of-hospital ventricular fibrillation (VF), few data are available regarding the situation in Japan. Methods and Results A prospective multicenter study of out-of-hospital cardiac arrest was conducted according to the Utstein guidelines. A total of 4,383 patients who were given cardiopulmonary resuscitation (CPR) by EMS personnel for out-of-hospital cardiac arrest were enrolled. The proportion of VF or pulseless ventricular tachycardia (VT) as the first cardiac rhythm after cardiac arrest was 16.2% with a mean call-to-initial-recorded-electrocardiogram (ECG) interval of 11.1 min. In a subgroup of patients with witnessed collapse, the predicted incidence of VF or pulseless VT was 62.7% at the time of cardiac arrest, and the decline accelerated with every minute that the collapse-to-initial ECG interval was delayed. Multivariate analysis showed that the odds ratio for VF or pulseless VT after collapse-to-initial ECG interval was 0.91 (95% confidence interval (CI), 0.89-0.94, p<0.001), and 1.54 (95%CI, 1.24-1.97, p<0.001) after bystander CPR. Conclusions In Japan, VF occurred in 63% of cases at the time of cardiac arrest and the performance of bystander CPR appeared to prolong VF. (Circ J 2005; 69: 1157 - 1162)

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Background The hospital stay after acute myocardial infarction (AMI) is still extremely long in Japan and does not correspond with disease severity. The purpose of the present study was to identify a subgroup of AMI patients suitable for early discharge. Methods and Results A total of 3,739 AMI patients treated with percutaneous coronary intervention (PCI) within 24 h after onset, who enrolled Osaka Acute Coronary Insufficiency Study between April 1998 and March 2004, were studied. Patients showing no complications within the first 7 days (n=1,786) were considered to be eligible for early discharge. In these patients, multivariate logistic regression analysis selected prior myocardial infarction, left anterior descending coronary artery disease and failed PCI as independent predictors of major complications from day 8 to discharge. Patients without any predictor had significant lower rates of major complications from day 8 to 6 months after discharge than those with 1 or more predictors. Furthermore, in the present study there were no deaths in patients without any predictors. Conclusion Patients who either do not have serious complications during the first 7 days or any predictor are at very low risk of major complications from day 8 to 6 months after discharge. These carefully selected patients may be suitable for early (day 8) hospital discharge after AMI. (Circ J 2005; 69: 1163 - 1169)

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Background Data on clinical characteristics, long-term mortality rates, and factors influencing outcome of acute myocardial infarction (AMI) based on an unselected cohort in the percutaneous coronary intervention (PCI) era are still limited in Japan. Methods and Results In the present study 415 consecutive patients with AMI who were admitted to hospital within 24 h of symptom onset between January 1988 and December 2002 were studied. There was a marked seasonal variation of AMI with a minimum in summer and a maximum in winter, as well as a marked circadian variation with a significant morning peak. Overall, 45.8% of patients were treated with primary PCI. Increased age and female sex were negatively associated with the probability of undergoing PCI. During the follow-up period (mean duration, 4.01±3.41 years), the unadjusted long-term all-cause mortality rate was 21.4%. Multivariate Cox regression analysis showed that age, prior cerebrovascular disease, renal failure, Killip ≥2, and ventricular tachycardia/fibrillation were independent predictors of worse long-term mortality after AMI. Furthermore, the use of PCI was independently associated with favorable long-term survival after AMI. Conclusions Although PCI was associated with a favorable long-term mortality, it remains underused in subsets of patients and increased use may further reduce the long-term mortality rate in Japanese AMI patients. (Circ J 2005; 69: 1170 - 1175)

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Background The aim of the present multicenter study was to investigate whether there is a seasonal difference in the onset of coronary heart disease (CHD) in young patients compared with older patients living in Nagano Prefecture, Japan. Methods and Results The study group comprised 101 young (aged ≤40 years) and 94 older (aged ≥50 years) patients diagnosed with CHD from 1992 to 2002. In young patients, the prevalence of the onset of CHD events was significantly higher from June to September than from December to March (odds ratio =2.23, p=0.035). Obesity was found in 56%, hypertension in 29%, dyslipidemia in 54%, diabetes in 24%, smoking history in 82%, and habitual physical activity in 13% in young patients. There was a trend for an association between the presence of acute myocardial infarction (p=0.082) and history of smoking and the onset of CHD events during the summer months in young patients (p=0.077). Conclusions There is a seasonal difference in the onset of CHD events, with an increase in the prevalence during the summer months in young patients. The data may provide insights into preventive approaches to CHD in the young population. (Circ J 2005; 69: 1176 - 1179)

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Background Although the elevation of circulating plasma matrix metalloproteinase (MMP)-9 levels in patients with acute myocardial infarction (AMI) has been documented, the origin of MMP-9 remains unclear. Methods and Results Plasma MMP-9 levels in both the peripheral circulation and coronary arteries were measured in patients with AMI (n=23) and with stable angina pectoris (SAP, n=10) during percutaneous coronary intervention (PCI) with a distal protection device. Blood samples were collected from the femoral artery (FA) and the coronary artery before (Initial) and after (Second) dilation of the culprit lesion. Coronary sinus blood samples were obtained immediately after PCI (n=7). Coronary artery plaque fragments were aspirated in patients with AMI (n=20) and compared with those from patients with SAP who underwent directional atherectomy (n=10). MMP-9 levels in Initial and Second were significantly higher in patients with AMI than in patients with SAP (p<0.01). In AMI patients MMP-9 levels were significantly higher in Initial than in the FA (p<0.05), and were further increased in Second (p<0.0001), whereas those in the coronary sinus were similar to the FA. Immunohistochemistry revealed augmented MMP-9 expression in the coronary artery plaque fragments from AMI patients. Conclusions MMP-9 is mainly released into the coronary circulation from the coronary artery plaque in patients with AMI. (Circ J 2005; 69: 1180 - 1185)

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Background The relationship between plasma levels of serum amyloid A protein (SAA) concentrations and clinical course (including mortality) was investigated in patients with acute myocardial infarction (AMI). Methods and Results The study enrolled 280 consecutive AMI patients who were admitted within 10 h of onset and were successfully reperfused by primary percutaneous coronary intervention. Plasma SAA concentrations were evaluated at 24 h after onset. The threshold of the upper quintile (325 μg/dl) was used to divide patients into 2 groups: either a high SAA (H group: ≥325 μg/dl; n=56) or low SAA (L group: <325 μg/dl; n=224). (I) Left ventricular (LV) ejection fraction in the chronic phase was significantly less in the H group than in the L group (52±14% vs 57±13%, p=0.03). (II) There were significantly more major complications in the H group than in the L group (cardiac rupture: p=0.0007, cardiogenic shock: p<0.0001; subacute thrombosis: p=0.0007; cardiac death: p=0.0003). (III) Multivariate analysis identified SAA as an independent predictor of 6-month mortality in AMI patients (risk ratio: 5.8, 95%confidence interval: 1.3-27.7, p=0.03). Conclusions In the setting of AMI, plasma SAA concentrations may be closely related to LV systolic dysfunction and poor patient outcomes, including mortality. (Circ J 2005; 69: 1186 - 1191)

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Background Recently, a mutation in the human MEF2A gene was reported to be responsible for an autosomal dominant form of coronary artery disease, so the purpose of the present study was to assess the significance of MEF2A mutations in Japanese subjects with myocardial infarction (MI). Methods and Results The study population consisted of 589 control subjects recruited from the Suita study and 379 subjects with MI. The promoter, all the exons, and 3'-UTR regions of MEF2A were sequenced in 190 subjects with myocardial infarction. We found 2 amino acid length polymorphisms, a 7-amino acid deletion polymorphism, and a nonsense mutation (R447X) in exon 12. The length and deletion polymorphisms did not confer susceptibility to MI. Although the nonsense mutation was detected in 1 subject with MI, and in none of the control subjects, the impact of this mutation does not appear to be great; the subject had the MI while in his 70 s, had 2 major risk factors, and no family history of ischemic heart disease. Conclusion MEF2A polymorphism does not contribute appreciably to MI in the Japanese population. (Circ J 2005; 69: 1192 - 1195)

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Background A pharmacokinetic (PK) study was conducted to evaluate sirolimus-eluting stents (SES) in Japanese people, representing the first clinical trial of the use of drug-eluting stents in Japan. Methods and Results The PK study was conducted in 20 patients with 30 lesions treated with sirolimus-coated BX Velocity stents. All lesions were treated with a single SES (3×18 mm). Angiographic follow-up was performed at 8 months after SES implantation, and the clinical outcomes were evaluated at 1 year in all cases. All procedures were successful, and all patients were discharged without any adverse cardiac events. The total restenosis rate was 10% (3 lesions) and target vessel revascularization was performed in those 3 cases (15%). Restenoses occurred at the proximal and distal stent margins. Intravascular ultrasound examination of restenosis cases revealed abundant plaque burden at the stent edges even though the luminal area was preserved. Conclusions The sirolimus-eluting BX Velocity stent is safe and useful for Japanese patients with coronary artery disease. However, restenosis at proximal stent edge seems to be a problem. (Circ J 2005; 69: 1196 - 1201)

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Background The present study tested the hypothesis that high-sensitivity C-reactive protein (hs-CRP) concentrations might show significant serial changes in patients with unstable angina (UAP), and that elevation of hs-CRP might indicate a progressively obstructive lesion, rather than late restenosis in such patients undergoing coronary stenting. Methods and Results Serum concentrations of hs-CRP in 168 patients with UAP undergoing coronary stenting for a new obstructive lesion were prospectively measured (pre-procedure, and on days 21, 90, and 180 post-procedure). The hs-CRP concentrations were also evaluated in 30 at-risk controls and 50 healthy volunteers. Moderately obstructive lesions of non-culprit vessels (defined as ≥50-69% stenosis) that were not treated by coronary angioplasty were found in 107 (63.7%) patients. The hs-CRP concentration was significantly higher at pre-procedure in the study patients than in the controls and healthy volunteers (all p-values <0.0001) and markedly declined after the procedure (p<0.0001). Pre-procedure (p=0.799) and post-procedure hs-CRP concentrations (all p-values >0.1) did not differ between restenotic and non-restenotic patients. However, at pre-procedure or on day 180, the concentration of hs-CRP was independently associated with progressively obstructive lesions of non-culprit vessels that required coronary angioplasty (both p-values <0.05). Conclusion The hs-CRP concentration was significantly higher at pre-procedure and declined substantially thereafter in patients with UAP following coronary stenting. There was no evidence of a positive association between an elevated hs-CRP concentration and late restenosis. However, both the pre-procedure and day 180 concentrations of hs-CRP were strongly associated with the progression of moderately obstructive lesions in non-culprit vessels. (Circ J 2005; 69: 1202 -1207)

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Background Platelet activation is crucial in the development of acute or subacute stent thrombosis following implantation. This study investigated whether a conventional regimen comprising a loading dose of 300 mg of clopidogrel, followed by daily doses of 75 mg, could significantly suppress platelet activation in patients with unstable angina (UA) undergoing coronary stenting. Methods and Results Platelet activation (expressed by CD62p) was serially examined using flow cytometry in 42 consecutive patients with UA who underwent coronary stenting. CD62p expression was also evaluated in 30 normal control subjects. CD62p expression was markedly higher pre-procedure in the study patients than in the normal control subjects (5.2±4.0% vs 1.4±0.6%, p<0.0001). CD62p expression in the study patients remained significantly higher at 24 h after the procedure than in the control subjects (3.8±2.1% vs 1.4±0.6%, p<0.001). Additionally, only 26% of CD62p expression (5.2% vs 3.8%, p=0.026) in the study patients was suppressed at 24 h after the procedure. However, more than 60% of CD62p expression (5.2% vs 2.0%, p<0.0001) was suppressed on day 7 after the procedure. Conclusion Less than one-third of CD62p expression was suppressed at 24 h by the conventional loading dose (300 mg) of clopidogrel in patients with UA following coronary stenting. This finding indicates the need to evaluate whether an increased loading dose of clopidogrel would be a more efficacious and safe regimen for patients in this clinical setting. (Circ J 2005; 69: 1208 - 1211)

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Background Cardiac syndrome X, also known as microvascular angina, is characterized by exercise-induced chest pain occurring despite a normal coronary angiogram. Several causes and mechanisms have been proposed to explain both the chest pain and ST segment depression. In this study, the association, if any, between cardiac syndrome X and several factors, including blood total antioxidant status, C-reactive protein (CRP), and monocyte chemotactic protein-1 (MCP-1) levels, was investigated. Methods and Results The study group comprised 36 patients who had been diagnosed as cardiac syndrome X on the basis of a positive treadmill test and a normal coronary angiogram, and 24 control patients. Total serum antioxidant status and CRP were assessed, and the levels of P-selectin, MCP-1, and interleukins 6 and 10 were also measured. Total serum antioxidant levels were determined to be significantly lower in the cardiac syndrome X patients than in the controls. CRP and serum MCP-1 levels, however, were found to be significantly higher in the cardiac syndrome X group. The total serum antioxidant levels and serum MCP-1 levels were comparable with the levels observed in a group of chronic stable angina patients. Conclusions In the present study, patients who had been diagnosed as cardiac syndrome X demonstrated increased systemic oxidative and enhanced inflammatory status. (Circ J 2005; 69: 1212 - 1217)

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Background The aim of the present study was to assess the feasibility and usefulness of the arterial stiffness index (ASI) measured non-invasively by computerized oscillometry and by comparing it with the pulse wave velocity (PWV). Methods and Results The study group comprised 60 consutive patients who underwent coronary angiography and whose aorto-femoral PWV were obtained with a Judkins catheter. The ASI was obtained using Cardio Vision ^® MS-2000 (IMDP, Las Vegas, NV, USA): (i) baseline (ASI-B); (ii) hyperemia induced by compression of the arm with cuff pressure for 5 min (ASI-H); and (iii) sublingual nitroglycerin (ASI-N). In total, 34 patients had significant coronary artery disease (CAD). The PWV and all ASI were higher in patients with CAD than in those without CAD (ASI-B, 85.9±57.8 vs 48.2±24.5, p=0.001; ASI-H, 98.1±49.8 vs 48.1±21.3, p<0.01; ASI-N, 66.7±55.7 vs 33.2±27.9, p=0.002). However, only ASI-B and ASI-H were positively correlated to the PWV (ASI-B, r=0.27, p=0.03; ASI-H, r=0.49, p=0.001; ASI-N, r=0.19, p=0.16). The ASI was increased after hyperemia in patients with CAD (ASI-H, 85.9±57.8 to 98.1±49.8, p=0.01), but not in patients without CAD (ASI-H, 48.2±24.5 to 48.1±21.3, p>0.01). After adjusting their age, only ASI-H was correlated to the presence of CAD (r=0.33, p<0.01). Conclusions It is feasible and useful to use the ASI for detection of atherosclerotic coronary disease. The findings of ASI-H suggests that in addition to stiffening of the arterial wall itself, the impairment of flow mediated vasodilation, because of endothelial dysfunction, further increases the arterial stiffness. (Circ J 2005; 69: 1218 - 1222)

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Background The purpose of this study was to investigate cardiac events in patients with transient left ventricle (LV) dilation on stress myocardial perfusion single-photon emission computed tomography images (MPI). Methods and Results Consecutive patients (n=53, 31 males, mean age 71 years) with transient LV dilation on thallium-201 stress MPI (treadmill: 21, pharmacologic: 32) were followed for 17 months. Follow-up time was censored at the occurrence of cardiac death, congestive heart failure, acute coronary syndrome, or revascularization. Images were scored and then the summed stress score (SSS), summed rest score, and summed difference score were calculated. Cardiac death occurred in 3 patients, hospitalization occurred in 8 patients, and revascularization occurred in 20 patients. The combined cardiac event rate was 59% (76% for exercise stress vs 47% for pharmacologic stress, p=0.034). Cox regression analysis demonstrated that a combination of higher SSS and slow washout rate was the best predictor of cardiac events (hazard ratio =3.3, p=0.029). Conclusions A high cardiac event rate is associated with transient LV dilation on thallium-201 stress MPI. The event rate is particularly high for exercise stress MPI. Furthermore, a combination of the SSS and thallium-201 slow washout is the best predictor of cardiac events in patients with transient LV dilation. (Circ J 2005; 69: 1223 - 1229)

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Background When using 16-slice multidetector-row computed tomography (MDCT) to detect coronary artery stenosis, coronary arteries measuring 1.5 mm or larger in lumen diameter are usually evaluated. The purpose of this study was to investigate the frequency of the visualized lumen in each coronary artery segment measuring more than 1.5 mm in diameter. Methods and Results Electrocardiographic-gated 16-slice MDCT was used to scan 20 patients after administration of nitroglycerin. The luminal diameter of each coronary artery segment was measured on cross-sectional images using a caliper method. The frequency of the visualized lumen of each coronary artery segment measuring larger than 1.5 mm in diameter was as follows: #1: 100%, #2: 100%, #3: 100%, #4PD: 85%, #4AV: 80%, #5: 100%, #6: 100%, #7: 100%, #8: 90%, #9: 85%, #10: 40%, #11: 100%, #12: 65%, #13: 100%, #14: 80%. Averaged lumen diameter±standard deviation (mm) larger than 1.5 mm in all patients was calculated as follows: #1: 3.8±0.70, #2: 3.5±0.69, #3: 3.2±0.82, #5: 4.2±1.04, #6: 3.4 ±0.79, #7: 2.9±0.62, #11: 2.9±0.69, #13: 2.6±0.57. Conclusion Luminal diameter larger than 1.5 mm of each coronary artery segment can be assessed in most cases by 16-slice MDCT. (Circ J 2005; 69: 1230 -1232)

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Background The goal of the present study was to test if ambulatory Holter recordings can predict the electrophysiologic study (EPS) findings in patients with supraventricular tachycardia (SVT). Methods and Results The study involved 110 patients with SVT who underwent Holter recording, and then EPS. The hypotheses were that (1) a P'R interval of premature atrial complexes (PACs) between 280 and 400 ms in the Holter recordings predicted dual atrioventricular nodal (AVN) pathways, (2) P'R interval >400 ms predicted triple or more AVN pathways, and (3) SVT initiated by a single PAC suggested easy SVT induction during the EPS. The EPS revealed dual AVN pathways in 14 (93%) of 15 patients with P'R intervals between 280 and 400 ms on the Holter recordings, and triple or more AVN pathways in 18 (90%) of 20 patients with P'R intervals >400 ms. In addition, a single extrastimulus easily induced SVT during the EPS in 11 (85%) of 13 patients in whom SVT was initiated by a single PAC during Holter recording. Conclusion The ambulatory Holter recording criteria specifically predicted the EPS findings, thereby providing useful advance information. (Circ J 2005; 69: 1233 - 1236)

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Background Because class I anti-arrhythmic drugs sometimes suppress cardiac function caused by their negative inotropic effects, they are not adequate for use in patients with severe heart failure, even as emergency treatment for life-threatening ventricular tachyarrhythmias (ventricular tachycardia (VT)/ventricular fibrillation (VF)). Methods and Results An objective evaluation committee re-evaluated the effect of nifekalant in 191 patients with refractory VT/VF. The attack termination was achieved in 45 out of 93 patients (48.4%). Nifekalant was administered to 39 patients with direct-current (DC) shock-resistant VT/VF and directly terminated VT/VF in 9 patients. In 15 of the remaining 29 patients (51.7%), VT/VF was successfully cardioverted by additional DC shock after nifekalant administration. Prevention of recurrence was achieved in 60 out of 99 patients (60.6%). Corrected QT interval (QTc) was significantly prolonged after initial administration of nifekalant (0.463±0.056 to 0.504 ±0.072), and during maintenance infusion (0.470 ±0.056 to 0.547±0.070). As an adverse reaction, excess prolongation of QTc was noted in 11 patients including 3 patients with torsades de pointes. Hemodynamic parameters tended to improve after maintenance infusion of nifekalant. Conclusion Nifekalant is effective and useful for life-threatening refractory ventricular tachyarrhythmias, although careful observation of the QT interval is required. (Circ J 2005; 69: 1237 - 1243)

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Background Fibrosis, as well as myocyte hypertrophy, is the major determinant of prognosis in hypertrophic cardiomyopathy (HCM). Valsartan, an angiotensin II type 1 receptor blocker, may improve myocardial fibrosis in patients with HCM. Methods and Results Twenty-three patients with HCM were randomly divided into 2 groups: 11 patients had valsartan added to conventional treatment (V group) and 12 patients received the conventional therapy (C group). Plasma concentrations of brain natriuretic peptide (BNP), troponin T (TnT), aldosterone (ALDO), procollagen type I (PIP) and procollagen type III aminoterminal peptide (PIIINP) were measured before and 12 months after this study. Left ventricular wall thickness (LVWT) and ejection fraction (LVEF) were measured by echocardiography. PIP was decreased in the V group (123.2±63.1 ng/ml to 102.8±37.6, p<0.05), but unchanged in C group (110±40.5 ng/ml to 119.9±47.4, p=0.22). ALDO concentration was unchanged in the V group (88.5±26.2 pg/ml to 91.2±26.8, p=0.27), and increased in C group (92.6±36.6 ng/ml to 116.0±33.3, p<0.05). BNP, PIIINP, and TnT were unchanged by the treatment. There was no significant difference between the 2 groups in either LVWT or LVEF. Conclusion Valsartan suppresses the synthesis of type I collagen in patients with HCM and this was associated with suppression of the increase in ALDO. (Circ J 2005; 69: 1244 - 1248)

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Background It has been suggested that chronobiology can provide new insights into the evaluation and treatment of cardiovascular disease. In the present study the hyperbaric index (hyperBI) and hypobaric index (hypoBI) were compared with the mean blood pressure (BP) over 24 h to evaluate the antihypertensive effect of long-acting nifedipine on essential hypertension. Methods and Results Fourteen patients were treated with nifedipine CR (20-40 mg/day) for 6 months. Ambulatory BP monitoring was performed before and after treatment. The hyperBI (mmHg · h/day) was calculated as the integrated BP area above the conventional upper limit (140/90 mmHg for the daytime and 120/80 mmHg at night), and the hypoBI was calculated as the integrated BP area below the conventional lower limit (110/60 mmHg for the daytime and 100/50 mmHg at night). At baseline, both the systolic and diastolic 24-h hyperBI values closely correlated with the 24-h mean BP (r=0.994 and 0.935, p<0.0001). Treatment with nifedipine significantly lowered both the 24-h mean systolic and diastolic BP (143±14/89 ±12 to 124±16/80±8 mmHg, p<0.001/p=0.001), as well as the casual BP (167±11/101 ±8 to 140±13/86±10 mmHg, p<0.001/p<0.01). Reduction of both the systolic and diastolic hyperBI values was statistically significant over the 24-h period (274±266 to 90±155, p=0.009; 145±187 to 41±63, p=0.024), as well as during the daytime (200±181 to 66±116, p=0.014; 105±120 to 24±38, p=0.017) and at night (systolic, 74±106 to 24±52, p=0.021). The 24-h mean BP was normalized, but a small excess BP load persisted despite treatment. There was no significant increase of systolic hypoBI during the 24-h period (1±2 to 25±30, p=0.065), the daytime (0±0 to 14±38, p=0.20), or at night (1±3 to 11±19, p=0,052). Similar findings were obtained for diastolic hypoBI. Conclusions Nifedipine CR improved the 24-h hyperBI and mean BP without causing excessive hypotension. These 2 parameters have a close relationship when assessment is done by 24-h BP monitoring. The hyperBI and hypoBI may assist in providing adequate antihypertensive therapy for individual patients by detecting an excessive BP load or hypotension, respectively. (Circ J 2005; 69: 1249 - 1255)

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Background Although percutaneous transluminal angioplasty (PTA) is being widely used for the treatment of stenosis of peripheral arteries, the high in-stent restenosis rate (50-60%) in the femoropopliteal artery still remains an unsolved issue. Cilostazol is a unique antiplatelet drug that has vasodilatory effects and inhibits smooth muscle cell proliferation. Methods and Results A total of 141 consecutive patients scheduled for PTA in the femoropopliteal artery between September 1999 and April 2004 were retrospectively analyzed for the use of cilostazol. Target lesion revascularization (TLR) was defined as repeated PTA in patients who had a recurrence of symptoms with diameter stenosis >50% by angiography. Patient and lesion characteristics were similar between the cilostazol (+) and cilostazol (-) groups. Use of other medications was similar between the groups, except for ticlopidine, which was more frequently used in the cilostazol (-) than in the cilostazol (+) group (15% vs 61%, p<0.01). TLR was significantly reduced in the cilostazol (+) group (12% [8/68] vs 32% [23/73], p<0.01). Conclusions Although this study was retrospective and nonrandomized, the results suggest that cilostazol reduces TLR after PTA in the femoropopliteal artery. (Circ J 2005; 69: 1256 - 1259)

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Background Implantation of bone marrow mononuclear cells, including endothelial progenitor cells, into ischemic limbs has been shown to improve collateral vessel formation. In the present study the safety and feasibility of autologous peripheral blood mononuclear cells (PBMNCs) implantation after granulocyte-colony stimulating factor (G-CSF)-induced mobilization was investigated in patients with severe peripheral arterial disease. Methods and Results Six cases were enrolled: 5 of thromboangitis obliterans and 1 of arteriosclerosis obliterans. Following administration of G-CSF (10 μg · kg^-1 · day^-1), PBMNCs were harvested and injected intramuscularly (5 legs and 1 arm) for 2 days for the patients with ischemia of the legs. No serious adverse events related to G-CSF administration, harvest or implantation were observed during this study period. Improvement in the ankle - brachial pressure index (ABI: >0.1) was seen in 4 patients at 4 weeks and ischemic ulcers improved in 3 of 3 patients. The mean maximum walking distance significantly increased from 203 m to 559 m (p=0.031) at 4 weeks and was sustained for 24 weeks. Significant improvement was seen in physiological functioning subscale of Short Form-36. Conclusion Implantation of PBMNCs collected after G-CSF administration could be an alternative to therapeutic angioplasty in patients with severe peripheral arterial disease. (Circ J 2005; 69: 1260 - 1265)

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Background Studies on microorganisms in a large cohort of patients with congenital heart disease (CHD) and infective endocarditis (IE) are rare. Using a nationwide survey, the relationship between causative microorganisms and clinical profiles in patients with CHD and IE was investigated. Methods and Results Data from 188 patients with CHD (pediatric patients (n=113), mean age, 6.2±4.9 years; adult patients (n=75), mean age 28.4±13.4 years) and IE from 60 institutions were analyzed. Causative microorganisms were Streptococcus species (94:50.0%), Staphylococcus species (68:36.2%), Haemophilus species (9:4.8%), Candida (5:2.7%), Pseudomonas species (4:2.1%) and other unclassified microorganisms (8:4.3%). Staphylococcal IE was observed significantly higher in perioperative IE (11/16), in cyanotic patients (32/73) and patients younger than 1 year old (11/16). Streptococcal IE was observed significantly higher in acyanotic patients (64/109) and patients aged 16 years or older (48/75). Total mortality was 20/188 (10.6%) and was high for candidial (2/5; 40%) and pseudomonal IE (2/4; 50%). Mortality was highly associated with younger age, especially infants (5/16), and methicillin-resistant staphylococcal IE (6/15). Conclusions The causative microorganisms are significantly related to the clinical profile and outcome in patients with IE and CHD. These results form the basis for selecting appropriate antibiotics for prevention and management. (Circ J 2005; 69: 1266 - 1270)

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Background Coil occlusion of patent ductus arteriosus (PDA) is now widely accepted as the first-line treatment, but there are few reports of age-dependent differences in the complications associated with this technique. Methods and Results Sixteen patients (11 adults, 5 children) with a PDA larger than 3 mm, who underwent coil occlusion at Sapporo Medical University Hospital between September 1995 and August 2004, were enrolled. Immediate and intermediate outcomes and complications were analyzed. Procedural success rate was 72.7% (8/11) in the children and 100% (5/5) in the adults. Coil migration occurred in 4 children and 1 adult, and 3 adult patients had hemolysis. Conclusion Hemolysis was more frequent in adults than in children even though the residual shunt was trivial. (Circ J 2005; 69: 1271 - 1274)

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Background Myocardial fibrosis is a major component of ventricular remodeling after myocardial infarction (MI). The aim of the present study was to determine the outcome of transplantation into ischemic myocardium of bone marrow derived stem cell (MSC) on left ventricular (LV) function and remodeling, and to look closely at extracellular matrix gene expression. Methods and Results MI was induced by direct ligation of the left anterior descending coronary artery in rats, followed by MSC transplantation into the ischemic myocardium. Hemodynamic evaluations were performed at 7 and 28 days after coronary ligation. Changes in the mRNA expressions of collagen type I and type III, matrix metalloproteinase-1, tissue inhibitor of matrix metalloproteinase (TIMP)-1 and transforming growth factor (TGF)-β₁ were investigated using reverse transcription polymerase chain reaction and in situ hybridization after MI. Heart/body weight ratio in the MI + MSC group decreased after coronary ligation. However, LV systolic pressure and LV peak velocities of contraction and relaxation significantly increased compared with the MI group (p<0.01). There was marked up-regulation of the mRNA expressions of collagen types I and III, TIMP-1 and TGF-β₁ in the MI rats, all of which were significantly attenuated by MSC transplantation. Conclusions MSC transplantation could inhibit LV remodeling, improve heart function and reduce the expression of extracellular matrix genes. (Circ J 2005; 69: 1275 - 1283)

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Background The developmental changes of Ni²⁺-sensitivity to automaticity of Nkx2.5-positive cells derived from mouse embryonic stem cell have been identified, suggesting developmental regulation of expressing Ni²⁺-sensitive T-type Ca²⁺ channel, although the mechanism of the change has not been fully studied. Methods and Results Transcripts of Cav3.2, Cav3.1 and Cav1.2 genes of beating Nkx2.5-positive cells, which encode the Ni²⁺-sensitive T-type Ca²⁺ channel, Ni²⁺-insensitive T-type Ca²⁺ channel, and L-type Ca²⁺ channel, respectively, were investigated by real-time reverse-transcriptase-polymerase chain reaction, and the current density of each channel was measured by patch-clamp techniques at the early and late stages of differentiation. The expression of the Cav3.2 transcript predominated in the early stage whereas those of Cav3.1 and Cav1.2 transcripts were upregulated in the late stage, which was consistent with the change in each current density, suggesting the expression of channel proteins is largely determined at the transcriptional level. Conclusion The results indicate that the mechanism of change of Ni²⁺-sensitivity is partly, if not completely, the subtype switch of T-type Ca²⁺ channel from Cav3.2 to Cav3.1 at the transcriptional level, and that the expression of the L-type Ca²⁺ channel might have an attenuating effect on Ni²⁺-sensitivity to automaticity in the late stage of differentiation. (Circ J 2005; 69: 1284 - 1289)

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The presence of antiphospholipid antibodies is associated with arterial and venous thrombosis. A young female with initial presentation of dyspnea and cough that lasted for days is reported. A computed tomographic scan of her chest and echocardiography showed features of thrombus formation over the right atrium, complicated with pulmonary thromboembolism. Antiphospholipid syndrome was diagnosed according to elevated activated partial thromboplastin time, high serum titers of anticardiolipin antibody, and the presence of intracardiac thrombus with pulmonary embolism. This thrombus was subsequently removed successfully with surgical intervention, and the patient's recovery was uneventful. (Circ J 2005; 69: 1290 -1292)

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Cystic tumor of the atrioventricular nodal region is a rare cardiac primary tumor that can cause heart blockage and sudden death. Antemortem diagnosis and successful excision of the atrioventricular nodal region are extremely rare. A 45-year-old woman who presented with palpitations is reported. Electrocardiography revealed first-degree atrioventricular block. Echocardiography, computed tomography, and magnetic resonance imaging scans revealed a cystic mass attached to the interatrial septum. Complete surgical excision of the mass was achieved, although placement of a permanent pacemaker was required for complete heart blockage. Histopathological examination revealed the mass to be a cystic tumor of the atrioventricular nodal region. A 5-year follow-up has revealed no sign of recurrence. (Circ J 2005; 69: 1293 - 1294)

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