Background A multicenter study was conducted to assess the current medical management of unstable angina (UA) and non-ST-elevation acute coronary syndrome in Japan. Methods and Results This study presents the results of a nationwide questionnaire survey of 770 sites and a case report investigation performed at 20 sites. The questionnaire survey revealed that the number of acute myocardial infarction (AMI) patients treated annually was 1.56-fold greater than the number of UA patients. Non-ST-elevation AMI accounted for 17% of all patients with AMI. Analysis of case reports for 885 UA patients showed extensive use of invasive treatment. In the UA patients, the cumulative incidence of a composite endpoint (all-cause mortality, AMI, and urgent coronary revascularization) was 2% at 1 month and 9% at 6 months. Stratified analysis with respect to the composite endpoint through 6 months showed a significantly lower incidence in patients treated with a calcium-channel blocker than in patients not treated with a calcium-channel blocker. Conclusions In Japan, fewer patients are hospitalized annually for treatment of UA than for AMI. The largest percentage of UA patients had Braunwald class III disease. Non-ST-elevation AMI is managed in Japan according to the principle of early invasive treatment, resembling the treatment for ST-elevation AMI. The outcome of treatment is better for Japanese UA patients than for Japanese AMI patients. (Circ J 2007; 71: 1335 - 1347)

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Background Statins are widely used to reduce blood levels of low-density lipoprotein-cholesterol (LDL-C). Each statin has unique pharmacokinetic properties; lipophilicity is one such property and relates to tissue selectivity. Methods and Results The Multicenter Study for Aggressive Lipid-lowering Strategy by HMG-CoA Reductase Inhibitors in Patients with Acute Myocardial Infarction (MUSASHI-AMI) trial evaluated the effect of discretional statin treatment initiated within 96 h after onset of acute myocardial infarction (AMI) in Japanese patients. To clarify whether statin lipophilicity affects prognosis, a post hoc analysis of the MUSASHI-AMI database was performed. Patients who were assigned to receive statin were separated into 2 groups according to the lipophilicity of the statins they were administered: lipophilic statins (atorvastatin, fluvastatin, pitavastatin and simvastatin; LS group; n=131) or hydrophilic statins (pravastatin; HS group; n=110). There was no difference in baseline LDL-C concentrations between the 2 groups. Although LDL-C was decreased more potently in the LS than HS groups (-34% vs -19%; p=0.0069), acute coronary syndrome events tended to occur less frequently (3.6% vs 9.9%; p=0.0530) and the incidence of new Q-wave appearance in electrocardiogram was significantly lower (75% vs 89%; p=0.0056) in the HS than LS groups. Conclusions In normocholesterolemic Japanese patients after AMI, hydrophilic pravastatin could be superior to lipophilic statins at preventing new Q-wave appearance and reducing cardiovascular events. (Circ J 2007; 71: 1348 - 1353)

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Background Data about the long-term mortality of acute myocardial infarction (AMI) patients with renal insufficiency who received sufficient early revascularization are scant, so the present study evaluated the impact of serum creatinine levels on the long-term mortality in patients with AMI undergoing successful primary percutaneous coronary intervention (PCI). Methods and Results The Heart Institute of Japan Acute Myocardial Infarction (HIJAMI) registry has 3,021 consecutive AMI patients. Primary PCI was attempted in 1,451 patients and successful revascularization was obtained in 1,359 patients (93.6%). An elevated serum creatinine level, defined as creatinine ≥1.2 mg/dl, was observed in 216 patients (15.8%). Univariate analyses showed statistical differences between normal and elevated serum creatinine groups in age, gender, hypertension, previous myocardial infarction, number of diseased vessels and Killip class. During a median follow-up period of 39 [32-49] months, the event-free survival rate was lower in elevated creatinine group than normal creatinine group. Multivariate Cox proportional hazards model showed that serum creatinine level was an independent predictor of long-term mortality (adjusted hazard ratio 1.43 [95% confidence interval 1.03-1.99]). Conclusion The serum creatinine level on admission in patients with AMI predicts long-term mortality, even in those with successful primary PCI. (Circ J 2007; 71: 1354 - 1359)

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Background In the era of drug-eluting stents, percutaneous coronary intervention (PCI) has been considered an established therapeutic modality for patients with coronary artery disease (CAD). However, little is known about the long-term prognosis. Methods and Results Using data obtained from a single-center registry for cases of first-generation bare metallic stent (BMS) implantation, a 10-year follow-up study in patients with CAD was performed. Data for 125 serial patients (aged 62±9 years, 104 males) in whom a BMS was successfully implanted was analyzed. Cardiac death (n=16 [12.8%]), including sudden cardiac death (n=9 [7.2%]), non-cardiac death (n=17 [13.6%]) and non-fatal acute myocardial infarction (n=16 [12.8%]) were documented. At 10 years, cumulative probabilities of target and non-target lesion revascularization were 20.5% and 41.5%, respectively, and only 39.2% of the patients were free from cardiac events (cardiac death/myocardial infarction/unplanned revascularization). Age and left ventricular ejection fraction (LVEF) were significant predictors of total death, and LVEF and the use of diuretics were predictors of cardiac events. Conclusions Stabilization of the initial stented site was relatively good and the majority of cardiac events might have originated in non-target lesions. Prevention of systemic arteriosclerosis progression is important for patients with CAD, even after successful PCI. (Circ J 2007; 71: 1360 - 1365)

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Background Acute myocardial infarction (MI) sometimes occurs without painful symptoms and in such cases, prognosis is worsened by delays in diagnosis and revascularization. Renal insufficiency induces many types of neuropathy, but the relation between renal insufficiency and painless MI remains unclear. Methods and Results Patients with MI and elevated creatine kinase levels were retrospectively analyzed. Renal insufficiency (serum creatinine concentration ≥1.5 mg/dl) and other characteristics (age, sex, body mass index, hypertension, smoking, diabetes mellitus, dyslipidemia, history of stroke, previous MI, hemodialysis, and atrial fibrillation) were compared between patients who had MI with painful symptoms (painful MI, n=131) and patients who had MI without painful symptoms (painless MI, n=18). Other variables compared were the time from symptom onset to admission, peak creatine kinase concentration, Killip class, site of MI, emergency coronary angiography, postprocedural Thrombolysis In Myocardial Infarction grade III flow, and in-hospital death. Univariate analysis identified older age, renal insufficiency, and previous MI as predictors of painless MI. Patients with painless MI showed higher rates of Killip class ≥II and in-hospital death and a longer time from symptom onset to admission. However, multivariate analysis identified only renal insufficiency as an independent predictor of painless MI. Conclusions MI without painful symptoms frequently develops in patients who have renal insufficiency, so the possibility of painless MI should be evaluated in such patients to ensure early diagnosis and treatment. (Circ J 2007; 71: 1366 - 1369)

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Background Stroke associated with percutaneous coronary intervention (PCI) is a tragic complication. Despite advances in the practice of PCI, the incidence of stroke complicating PCI has not changed over the decades. The objective of the present study was to evaluate incidence and correlates of stroke occurring in patients with myocardial infarction (MI) undergoing PCI. Methods and Results Stroke was defined as the presence of any new focal neurological deficit lasting ≥24 h that occurred anytime during or after PCI until discharge. In 2,281 consecutive patients with PCIs for non-ST-elevation MI, or ST-elevation MI (STEMI), 20 strokes were identified (0.88%). Strokes were ischemic in 95%. On multivariate analyses, ejection fraction ≤30% (odds ratio =4.3, p=0.003) was the only independent predictor for stroke. In patients who developed stroke within 24 h of PCI, PCI of vein grafts was more frequent, and use of glycoprotein IIb/IIIa inhibitor was less frequent. Those patients tended to present late in the course of MI. Stroke found more than 24 h after PCI was related to diabetes, higher serum creatinine, lower ejection fraction, anterior wall STEMI and emergency use of intra-aortic balloon pumps. Conclusions Low ejection fraction was the only independent predictor for stroke, but risk factors for periprocedural stroke are different from those of stroke occurring more than 24 h after PCI. Upstream use of glycoprotein IIb/IIIa inhibitor might decrease the risk of periprocedural stroke. (Circ J 2007; 71: 1370 - 1375)

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Background It is not known whether plasma adiponectin levels are associated with the number and function of endothelial progenitor cells (EPCs) in patients with coronary artery disease (CAD). Methods and Results Plasma levels of adiponectin were measured in 70 patients undergoing coronary angiography. The numbers of colony-forming units (CFUs) of EPCs and senescent EPCs, determined by acidic β-galactosidase staining, were counted. The angiogenic growth factors in the culture medium were also measured. There was a significant positive correlation between adiponectin level and CFUs (r=0.257, p<0.05) but not with the occurrence of senescent EPCs. Next, patients were divided into a high adiponectin group (high ADP: ≥6.17 μg/ml, n=36) and low adiponectin group (low ADP: <6.17 μg/ml, n=34). The number of diseased coronary arteries was less in the high ADP group than that in the low ADP patients (1.7±0.8 vs 2.1±0.7, p<0.05). No significant differences between the 2 groups were demonstrated in angiogenic growth factors secreted from EPCs. Conclusions The results suggest that plasma adiponectin levels are associated with the number of EPCs in patients with CAD. (Circ J 2007; 71: 1376 - 1382)

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Background Vasospastic angina (VA) can occasionally cause acute myocardial infarction (AMI). Methods and Results From January 2003 to June 2005, coronary spastic angina was diagnosed in 292 patients by performing spasm provocation tests. Among the 292 patients, 21 (7.2% of all the VA patients) had an AMI. There were 20 patients who initially visited the emergency room for AMI without suffering prior VA. One patient with a history of VA had an AMI when he discontinued his medication. Among the 21 VA patients with AMI, 14 had experienced severe emotional stress before they visited the emergency room. The spasm provocation test showed that the VA patients with AMI had more multivessel and diffuse spasm than the VA patients without AMI (p<0.001). Conclusion Clinically, the VA patients with AMI usually had their first symptom of VA as the severe chest pain of AMI. Two-thirds of the VA patients with AMI had experienced emotional stress before their AMI. Angiographically, the spasm provocation test for VA patients with AMI showed more multivessel and diffuse spasm than in VA patients without AMI. (Circ J 2007; 71: 1383 - 1386)

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Background Cardiopulmonary bypass may exacerbate myocardial damage in compromised left ventricles. Early and mid-term outcomes of off-pump coronary artery bypass grafting (OPCAB) vs on-pump coronary artery bypass grafting (On-pump CABG) were compared in patients with poor left ventricular dysfunction, using an analysis of a propensity score matching. Methods and Results Between December 2000 and November 2005, 1,473 patients underwent isolated coronary artery bypass grafting in our institute and 153 patients who had a left ventricular ejection fraction (LVEF) lower than 35% were enrolled. The OPCAB group contained 100 patients and the On-pump CABG group contained 53 patients. Preoperative risk factors were compared and 50 patients in each group were matched. The mean follow-up time was 35.5±17.3 months. Three deaths (3.0%) occurred in the matched cohort, with no significant difference between 2 groups. The operation time, ventilation time, intensive care unit admission time and occurrence of respiratory failure were significantly lower in the OPCAB group. The mean LVEF of the 2 groups improved significantly. The overall 6-year actuarial survival rates of the OPCAB and On-pump CABG group were 88.2% and 72.4% (p=0.2), respectively, and there were no significant differences in 6-year rates of freedom from major adverse cardiac and cerebrovascular events (p=0.97). Conclusions Coronary artery bypass grafting in patients with poor left ventricular dysfunction improved myocardial function. Postoperative respiratory failure was significantly related to the cardiopulmonary bypass for surgical myocardial revascularization. Off-pump and On-pump surgical revascularization resulted in equivalent mid-term outcomes. (Circ J 2007; 71: 1387 - 1394)

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Background Perioperative cardiac risk in high risk surgery is often stratified with myocardial perfusion single-photon emission computed tomography (SPECT). However, little and no data are available about intermediate and low-risk surgery, respectively. Methods and Results A total of 1,220 consecutive patients underwent electrocardiography-gated dipyridamole stress SPECT to evaluate myocardial perfusion and cardiac function before intermediate or low risk non-cardiac surgery. Variables predictive of perioperative cardiac events were determined and the usefulness of combining pretest information and the incremental prognostic value of SPECT was estimated. The frequency of all cardiac events depended on clinical risk factors and type of surgical procedures. After sorting the patients with clinical risk factors and surgical risk, assessment of myocardial perfusion or cardiac function yielded significant risk stratification in intermediate, but not in low-risk surgery. Adding functional data to perfusion variables offered an incremental prognostic value for patients with an intermediate clinical risk and scheduled intermediate risk surgery. Conclusions Integrating information about clinical risk factors, type of surgery, myocardial perfusion and cardiac function allows detailed preoperative risk stratification. Preoperative SPECT provides an incremental prognostic value in intermediate, but not in low-risk surgery. (Circ J 2007; 71: 1395 - 1400)

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Background Low-dose continuous human atrial natriuretic peptide (hANP) administration during cardiac surgery has been reported on previously. In the present study, the efficacy of the therapy during emergent coronary artery bypass grafting (CABG) for acute coronary syndrome (ACS) is investigated. Methods and Results One hundred and twenty-four patients patients undergoing emergent CABG for ACS were divided into 2 groups; a group receiving administration of hANP (hANP group) and a group not receiving hANP infusion (non-hANP group). The postoperative peak levels of creatine kinase-MB were significantly lower in the hANP group as compared with those in the non-hANP group. The incidence of postoperative arrhythmias was also significantly lower in the hANP group as compared with that in the non-hANP group. The postoperative brain natriuretic peptide was significantly lower in the hANP group as compared with that in the non-hANP group until 1 year after the operation. The free-rate of cardiac events after the operation was also significantly higher in the hANP group as compared with that in the non-hANP group. Conclusions It is therefore considered that hANP might not only be effective for overcoming some major shortcomings of cardiopulmonary bypass, but also might be effective to attenuate ischemia-reperfusion injury, protect the myocardium, have an anti-arrhythmic effect, and suppress left ventricular remodeling. (Circ J 2007; 71: 1401 - 1407)

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Background This study evaluated the right ventricular end-diastolic volume index (RVEDVI) as a marker of the hemodynamic response to a fluid challenge in the postoperative care of cardiac surgery patients. Methods and Results Continuous RVEDVI and other hemodynamic parameters were analyzed during and after 17 fluid challenges with 480-500 ml colloids (5% albumin, fresh frozen plasma or 6% hydroxyethyl starch) given over 30-60 min following cardiac surgery. Changes in stroke volume index (SVI) were assessed to indicate fluid responsiveness. Responders were defined as those who experienced a 10% or greater increase in SVI. Fluid challenges with simultaneous changing of vasoactive agents were excluded. Linear regression analysis between the percentage change in SVI and baseline RVEDVI revealed a statistically significant but weak correlation (r²=0.249; p=0.041). Although the baseline RVEDVI was higher in non-responders than in responders (112.4±6.1 vs 104.4±5.8 ml/m²; p=0.05), there was a marked overlap of baseline RVEDVI values, which did not allow identification of the threshold value of RVEDVI discriminating responders. Conclusions After cardiac surgery, RVEDVI reflected fluid responsiveness only to a limited degree. Patients should not be resuscitated to an absolute RVEDVI alone and empirical fluid challenge should still be required. (Circ J 2007; 71: 1408 - 1411)

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Background Although Doppler left ventricular (LV) filling abnormalities have been extensively analyzed in patients with systolic heart failure (SHF), they have not yet been well characterized in patients with acute to chronic diastolic heart failure (DHF) in the light of plasma brain natriuretic peptide (BNP) levels. Methods and Results In 25 patients presenting with acute DHF and 25 with acute SHF, echo Doppler parameters and plasma BNP levels were obtained on admission and in the chronic stage. The mitral E/A ratio was lower in DHF patients than in SHF patients in the acute stage (1.3 ±0.4 vs 1.8±0.9, p<0.05), and in the chronic stage of DHF the ratio decreased with plasma BNP level, but plasma BNP level was still greater than 100 pg/ml in 15 patients (60%). Among patients with DHF the plasma BNP level did not correlate with the mitral E/A ratio or deceleration time (r=0,25, p=NS; r=0,23, p=NS), but did with estimated pulmonary artery systolic pressure (r=0.64, p<0.01). Conclusions A restrictive mitral flow velocity pattern is observed in only 25% of patients with DHF, so it is particularly important to recognize pseudonormalization in those with possible DHF. Persistently elevated plasma BNP level is not primarily caused by LV diastolic dysfunction, but by secondary alteration for hemodynamic adjustment (elevated LV end-diastolic pressure) in patients with DHF. (Circ J 2007; 71: 1412 - 1417)

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Background It has been recently reported that cerebral oxyhemoglobin (O₂Hb) decreases during exercise in nearly 50% of patients with dilated cardiomyopathy. The present study evaluated whether the inhalation of supplemental O₂ diminishes the decrease in cerebral O₂Hb during exercise. Methods and Results Ten patients with a left ventricular ejection fraction <50% and a clearly observable decrease in cerebral O₂Hb during preliminary exercise testing underwent 2 additional symptom-limited incremental exercise tests: 1 while breathing room air (control) and the other while breathing 50% O₂. In the latter test, the switch from room air to 50% O₂