Since its inception approximately 15 years ago, the ISAResearch group has completed more than 40 randomized controlled trials (RCT) in the field of interventional cardiology, including more than 40,000 patients. Three main principles have characterized the ISAR trials: first, simplicity: 1 question 1 answer; second, a focus on issues that are relevant for practice at the given moment and third, a strong spirit of performing industry-independent studies. The seamless integration of clinical trials into everyday practice and a stringent study discipline allowed inclusion of more than 90% of the patients in 1 of the device or drug trials, the prerequisite for fast recruitment and evaluation of an all-comers population. Moreover, the early setup and maintenance of a comprehensive database with routine follow-up of all patients undergoing percutaneous coronary intervention made it possible to build up a large registry to answer questions beyond clinical trials. Finally, the close collaboration with basic research working groups within the department has triggered new innovations and facilitated translational research from bench to bedside.  (Circ J 2010; 74: 1771 - 1778)

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Recent advances in chemotherapy have substantially improved the prognosis of cancer patients. However, many anticancer drugs, especially newly developed `molecular-target drugs', such as the anti-HER2 blocking antibody and the anti-vascular endothelial growth factor antibody, have serious cardiovascular side-effects such as heart failure, thromboembolism, severe hypertension and lethal arrhythmia, which interrupt cancer treatment and decrease the patient's quality of life. Despite the increasing clinical significance, cardiologists have not been focusing enough of their attention on this issue. The major cardiovascular complications associated with anticancer drugs, and current diagnosis, treatment and prevention strategies are reviewed. Close collaborations between oncologists and cardiologists is necessary to tackle cardiovascular complications and advance cancer treatment.  (Circ J 2010; 74: 1779 - 1786)

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Everyone encounters various stressors (causes of stress), such as psychological pressure, mental fluctuations, and physical burdens, in their everyday life. It is well accepted that the highest levels of perceived stress correlate with early onset of cardiovascular disease. Conversely, appropriate (mild to moderate) stressors, such as physical activity, have been shown to promote health. This bidirectional dose - response relationship of treatments that are beneficial at low levels but noxious at higher levels is referred to as "hormesis". In the fields of toxicology, pharmacology, radiation biology, and medicine, the significance of the biological effects of low-level exposure to various agents has attracted considerable attention. It is very important to understand how biological systems respond to low levels of stress and their implications within society. Aldehydes, the major endproducts of lipid peroxidation, have been implicated in the pathogenesis of oxidative stress-associated diseases. In addition to the pathogenic effect associated with oxidative stress, sublethal levels of aldehydes interact with signaling systems to upregulate the expression of genes to counteract the stressor challenge and to re-establish homeostasis. The present review article discusses current discoveries regarding the hormetic response to aldehyde and its clinical significance in cardioprotection.  (Circ J 2010; 74: 1787 - 1793)

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Background: The aim of the present study was to examine the effect of systemic acidosis on the development of malignant ventricular arrhythmias, including sustained ventricular tachycardia and ventricular fibrillation (VT/VF), after reperfused ST-elevation myocardial infarction (STEMI). Methods and Results: A total of 157 consecutive patients with a reperfused STEMI were examined. Patients were divided into 2 groups according to the presence or absence of systemic acidosis, defined as arterial blood pH <7.40 on admission. Serum creatine kinase and C-reactive protein (CRP) levels were serially measured. Systemic acidosis was observed in 53 patients (34%). There was no significant difference in coronary risk factors and arrival time from onset between the 2 groups. Estimated glomerular filtration rate (eGFR) on admission was lower in patients with acidosis than in those without (P=0.001). Patients with acidosis had a higher incidence of VT/VF (26% vs 4%, P<0.0001), especially within 48 h after STEMI (23% vs 3%, P=0.0002), than those without. The peripheral white blood cell count on admission was higher in patients with than in those without acidosis. Multivariate analysis showed that systemic acidosis was a strong independent predictor of VT/VF (relative risk =8.79, P=0.002) among variables including prior MI and eGFR <60 ml · min^-1 · 1.73 m^-2. Conclusions: Systemic acidosis was a significant determinant of VT/VF after reperfused STEMI and was associated with elevated serum CRP level. Systemic acidosis and subsequent inflammation after ischemia reperfusion may play an important role in the development of VT/VF.  (Circ J 2010; 74: 1808 - 1814)

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Background: Matrix metalloproteinases (MMPs) play an important role in degradation of the extracellular matrix of injured tissue. MMP-9 expression increases in fibrillating atrial tissue; however, the mechanism for this increase has not been clarified. Methods and Results: Changes in the expression of vascular endothelial growth factor (VEGF), VEGF receptors, and hypoxia-induced transcription factor-1α (HIF-1α) in fibrillating atrial tissue were investigated. Atrial tissue samples were obtained from 13 patients with atrial fibrillation (AF) and 25 patients without a history of AF (regular sinus rhythm, RSR) undergoing cardiac operations. Western blot, real-time polymerase chain reaction, and immunofluorescence analyses of the expression of VEGF, VEGF receptors, and HIF-1α were performed. The VEGF mRNA and protein levels increased significantly in the AF group compared with the RSR group (P<0.05), and the expression of HIF-1α protein was also significantly higher in the AF group. VEGF receptor-1 mRNA, a high-affinity receptor for VEGF, but not VEGF receptor-2 mRNA, was upregulated in the atria of the AF group (P<0.05). Immunofluorescence staining revealed excess production and co-localization of HIF-1α, VEGF and MMP-9 in the endothelium of the atrial arteries in the AF group. Conclusions: It is possible that upregulation of HIF-1/VEGF is involved in the enhancement of MMP-9 expression under hypoxic conditions.  (Circ J 2010; 74: 1815 - 1821)

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Background: Electrical storm (ES) is a serious problem in patients with an implantable cardioverter defibrillator (ICD). However, insufficient reports have indicated the predictors of ES in ICD patients with idiopathic dilated cardiomyopathy (DCM). The purpose of this study was to clarify the predictors of ES for risk stratification in DCM patients with an ICD. Methods and Results: Of 446 ICD patients, 53 DCM patients were included in this study. During a mean follow-up of 55±36 months, ES (≥3 times appropriate ICD therapy within 24 h) occurred in 18/53 (34%) patients. According to multivariate Cox proportional hazard regression analysis, a duration of the terminal low amplitude signals of <40 μV (LAS40) (HR 1.4/10 ms increase, 95% confidence interval (CI) 1.1-2.1; P=0.0049) or root mean square voltage of the last 40 ms of the QRS complex (RMS40) (HR 0.88/1 μV, 95%CI 0.77-0.96; P=0.001) on the signal averaged electrocardiogram, and a history of atrial fibrillation (AF) before ICD implantation (HR 2.3, 95%CI 1.2-5.0; P=0.013) were independently associated with an increased risk of ES. Conclusions: Our data indicated that a longer LAS40, lower RMS40 and history of AF before ICD implantation could strongly predict ES, and the combination of those parameters could effectively stratify the risk of ES in DCM patients.  (Circ J 2010; 74: 1822 - 1829)

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Background: Web-like (W) and membrane-like (M) structures have been observed on coronary stent edges on angioscopy but their incidence and mechanisms remain obscure. Methods and Results: First, 26 patients [acute coronary syndromes (ACS) in 10 and stable angina (SA) in 16] underwent angioscopy of the stented coronary artery immediately after, and 32 patients (ACS in 18 and SA in 14) 6 months after insertion of bare-metal stents. Second, angioscopy of the stented coronary artery was performed in 4 beagles 5 h after, and in 9 beagles 1 month after stenting. W and M were observed in patients with ACS and those with SA (80.0% vs 18.7%; P<0.05) immediately after and 6 months after stenting (55.5% vs 28.5%; NS). They were stained with Evans blue that selectively stains fibrin immediately after stent insertion, but not 6 months later. In beagles, W and M were observed in 75.0% at 5 h and in 66.6% 1 month later. Histologically, W and M were composed of fibrin at 5 h, whereas they were composed of collagen fibers at 1 month. Conclusions: W and M were frequently formed on the edges of coronary stents. They were formed with fibrin in the acute phase, whereas this fibrin was replaced by collagen fibers in the chronic phase.  (Circ J 2010; 74: 1830 - 1836)

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Background: The efficacy of cutting or plain balloon angioplasty (CBA or PBA) has not been analyzed for the treatment of drug-eluting stent (DES) restenosis vs bare metal stent (BMS) restenosis. Methods and Results: The 252 in-stent restenosis (ISR) lesions in 224 consecutive patients treated by CBA (n=167) or PBA (n=85) between July 2002 and December 2007 were analyzed. At 6-month angiographic and 12-month clinical follow-up, CBA and PBA showed similar efficacies: repeat-ISR (37.0% vs 37.8%, P=0.90), late loss (0.62±0.60 vs 0.61±0.47 mm, P=0.92), and target lesion revascularization (18.3% vs 22.4%, P=0.50). This comparable efficacy was maintained for treatment in the DES-ISR and BMS-ISR subgroups. However, target lesion-related myocardial infarction (n=9) occurred more frequently in the CBA than in the PBA arm (6.2% vs 0%, P=0.03), most of which developed early after ISR treatment (n=7; 54±26 days). Independent predictors of repeat-ISR were diffuse ISR and smaller pretreatment minimal lumen diameter, both of which might imply heavier plaque burden in the ISR group. Conclusions: Plain or cutting balloon angioplasty for ISR seems to be comparable, as the angiographic or clinical endpoints were not affected by initial stent type but by parameters related to the plaque burden of the ISR lesion. However, CBA might be associated with higher risk of myocardial infarction than PBA, suggesting more attention to dual-antiplatelet therapy after its use for ISR.  (Circ J 2010; 74: 1837 - 1845)

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Background: The purpose of the present study was to assess the preventive effect of preoperative statin treatment on atrial fibrillation (AF) after elective isolated off-pump coronary artery bypass grafting (off-pump CABG) in propensity score-matched Japanese patients. Methods and Results: Among 770 consecutive patients undergoing isolated CABG by the same surgeon (99.2% with off-pump technique without conversion to cardiopulmonary bypass) between 2002 and 2009, after excluding emergency (n=150), chronic AF (n=30), and use of cardiopulmonary bypass (n=6), 584 patients were retrospectively reviewed. Of this cohort, 364 patients received statin at least 5 days before operation and 220 patients received no statin. We identified 195 propensity score-matched pairs. Propensity scores were created based on 8 preoperative factors (C statistics, 0.69). There was no significant difference between the 2 groups in baseline characteristics, perioperative medications, or operative procedures. AF occurred in 14.4% in the statin group and in 24.6% in the no statin group (P=0.01). Multivariate logistic regression including potential univariate predictors identified statin (odds ratio [OR] =0.49; 95% confidence interval [95%CI] =0.22-0.81; P=0.01), age (OR =1.33 per 10-year increase; 95%CI =1.04-1.69; P=0.02), and transfusion (OR =2.21; 95%CI =1.38-3.55; P=0.01) as independent predictors of postoperative AF. Conclusions: Preoperative statin significantly reduces the incidence of AF after elective isolated off-pump CABG in Japanese patients.  (Circ J 2010; 74: 1846 - 1851)

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Background: Despite several studies that evaluated the effects of renin-angiotensin system (RAS) inhibitors on postoperative renal function in cardiac surgery patients, no final conclusions are available. The aim of the present study was to determine the effect of RAS inhibitors on renal function following off-pump coronary artery bypass grafting (OPCAB). Methods and Results: Among patients who underwent OPCAB, perioperative characteristics, postoperative renal function and incidence of acute kidney injury (AKI) were compared between those who received RAS inhibitors for at least 2 weeks (RASI group, n=296) and those not treated with RAS inhibitors (Control group, n=176). AKI was defined as an increase in serum creatinine >0.3 mg/dl or >50% from baseline. Preoperative comorbidities were more frequent in the RASI group. Operative data were similar. Incidence of postoperative AKI (19.9% vs 20.9%, P=0.815) and of postoperative renal function was comparable between groups. In the adjusted multivariate logistic regression model for propensity scores between groups, diabetes mellitus, preoperative creatinine level and perioperative transfusion were significant risk factors for postoperative AKI, whereas preoperative treatment with RAS inhibitors did not increase the risk. Conclusions: Chronic preoperative use of RAS inhibitors did not affect postoperative renal function or increase the risk of postoperative AKI in patients undergoing OPCAB.  (Circ J 2010; 74: 1852 - 1858)

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Background: It has been reported that approximately one-third of patients undergoing cardiovascular surgery experience paroxysmal atrial fibrillation (AF) during the postoperative period. There is, however, little information on the selection of anti-arrhythmic drugs for terminating postoperative paroxysmal AF. Methods and Results: Between April 2007 and March 2009, 118 patients (76 men, 42 women, mean age 68±10 years) who had postoperative paroxysmal AF lasting ≥30 min were randomly assigned to receive either iv cibenzoline (70 mg, n=60) or disopyramide (50 mg, n=58) for terminating postoperative paroxysmal AF. The success rate of iv cibenzoline therapy (47%) was significantly greater than that of iv disopyramide therapy (24%; P<0.05). To identify clinical factors to increase the termination efficacy of iv cibenzoline, multivariate logistic regression was used to adjust for several covariates and to generate adjusted odds ratios (OR). The significant variables for the termination of paroxysmal AF after iv cibenzoline therapy were pretreatment with oral β-adrenergic blockers (OR =8.224, P=0.030) and smaller left atrial dimensions (OR =0.879, P=0.039). Conclusions: The efficacy of iv cibenzoline for the termination of postoperative paroxysmal AF was significantly better than that of disopyramide, especially in patients with pre-administration of oral β-adrenergic blockers and those with smaller left atrium.  (Circ J 2010; 74: 1859 - 1865)

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Background: The purpose of this study was to compare hospital outcomes and long-term survival in Japanese patients with or without renal dysfunction and to estimate the risk of renal dysfunction for survival after isolated off-pump coronary bypass grafting (CABG). Methods and Results: Among 661 consecutive Japanese patients undergoing isolated CABG (656 by the off-pump technique), after exclusion of 51 patients managed with chronic dialysis and 5 patients being revascularized using cardiopulmonary bypass, data from 605 patients were included in the present study. The 30-day mortality was 2.7%, 2.5%, and 0.7% in patients with a glomerular filtration rate (GFR) <30, 30-60, and >60 ml · min^-1 · 1.73 m^-2 (P=0.173). Mean follow-up period was 3.4±1.8 years. The 5-year survival free from overall death was 77%, 82%, and 93% in patients with a GFR <30, 30-60, and >60 ml · min^-1 · 1.73 m^-2 (P=0.002). Similarly, the 5-year survival free from cardiovascular death was 82%, 86%, and 97%, respectively (P=0.001). Multivariate Cox model identified GFR as a risk factor of overall death (hazard ratio, 0.82 per 10-ml · min^-1 · 1.73 m^-2 increase, 95% confidence interval, 0.70-0.95, P=0.008) and cardiovascular death (hazard ratio, 0.70 per 10-ml · min^-1 · 1.73 m^-2 increase, 95% confidence interval, 0.57-0.85, P=0.001). Conclusions: Off-pump CABG has a relatively low 30-day mortality in patients with renal dysfunction, but preoperative renal dysfunction is an independent risk factor of long-term survival after isolated off-pump CABG in Japanese patients.  (Circ J 2010; 74: 1866 - 1872)

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Background: Atrial fibrillation (AF) after rheumatic valve replacement is the most common arrhythmic complication. Previous studies reported angiotensin-II receptor blocker can prevent AF. This study aimed to assess the effect of a combination of irbesartan and amiodarone on the maintenance of sinus rhythm after cardioversion of AF in patients with post-rheumatic valve replacement in a randomized, controlled trial. Methods and Results: Eighty-five consecutive patients undergoing rheumatic valve surgery were enrolled and randomly assigned to an irbesartan plus amiodarone (irbesartan 150 mg/d, n=43) or an amiodarone group (n=42) starting 10 days before scheduled electrical cardioversion. The primary end-point was recurrence of AF. Pharmacological conversion was documented in 7 patients, and electrical conversion in 68 patients (87.2%). A higher rate of maintenance of sinus rhythm (69.8% vs 40.5%, P=0.01) and a better AF-free survival (χ²=7.466, P=0.006) were observed in the irbesartan plus amiodarone group compared to the amiodarone group during the 1-year follow-up period. Cox regression showed that use of irbesartan was an independent factor associated with the maintenance of sinus rhythm after cardioversion (OR=0.43, P=0.018), whereas increased left atrium diameter was associated with increased risk (OR=1.54, P=0.005). Conclusions: In patients with post-rheumatic valve replacement, the combination of amiodarone and irbesartan demonstrated a lower rate of AF recurrence after cardioversion than amiodarone alone, which might be due to preventing the atrial remodeling.  (Circ J 2010; 74: 1873 - 1879)

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Background: It has been reported that cardiovascular events occur more frequently in the morning than in the evening. The purpose of the present study was to assess the characteristics of out-of-hospital cardiac arrests due to cardiac cause in a 24-h period in Japanese patients. Methods and Results: Of 2,199 consecutive patients with cardiopulmonary resuscitation outside hospital, 1,293 cardiogenic patients were enrolled. The incidence of cardiac arrests was assessed as hourly data (ie, circadian variation), and investigated for differences in age, gender, and the location at onset. Cardiac arrests had an apparent circadian rhythm that was characterized by 2 long zeniths in the morning and evening. The peak was at 17:00-18:00 hours. Younger patients had more cardiac arrests in the morning than in the evening. In contrast, older patients had more events in the evening than in the morning. The circadian rhythm did not differ in gender. Regarding location, the patient's residence was the most common place for cardiac arrest. In the residence, the bathroom was associated with the evening zenith of circadian variation. Conclusions: Out-of-hospital cardiac arrests due to cardiac cause in Japanese patients have an apparent circadian variation with 2 long zeniths, with an evening predominance in older patients. Aging affects the evening zenith, in that elderly patients ≥80 years old have a zenith associated with bath time in the evening.  (Circ J 2010; 74: 1880 - 1887)

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Background: Natriuretic peptides exert vasodilatory, natriuretic, and diuretic effects and inhibit renin and aldosterone secretion. Carperitide, a recombinant α-human atrial natriuretic peptide (hANP), is used for the treatment of cardiac failure. Patients with renal failure often require renal replacement therapy, and little is known about the pharmacokinetics of carperitide when used for renal replacement therapy. Methods and Results: Eleven patients who received continuous carperitide infusion and needed continuous venovenous hemofiltration (CVVHF) for acute renal failure were observed. The plasma hANP concentration was noted and the hANP clearance during CVVHF was calculated. The results indicated that infused hANP was removed by CVVHF. Although the clearance of hANP by CVVHF was relatively lower than the expected whole body clearance, CVVHF slightly reduced plasma hANP and cyclic guanosine monophosphate concentrations and increased arterial pressure. Conclusions: CVVHF affects the pharmacology of infused hANP in critically ill patients. Some caution with respect to blood pressure may be necessary when carrying out CVVHF for critically ill patients receiving continuous infusion of natriuretic peptides.  (Circ J 2010; 74: 1888 - 1894)

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Background: The lifesavers responsible for lifesaving at the waterside routinely undergo cardiopulmonary resuscitation (CPR) training, but in Japan, they are considered as lay persons. Lifesavers are likely to have better basic life support skills than lay persons. The objective of this study is to demonstrate that the accuracy of carotid pulse checks by lifesavers is not inferior to that of paramedics and is superior to that of lay persons by using CPR training mannequins. Methods and Results: This was an observational study in which the subjects included 48 lifesavers certified by the Japan Lifesaving Association, as well as 16 paramedics and 15 lay persons. The accuracy of the examinees' answers and the time taken to answer in the 3 groups were compared. The accuracy rate was 93% in lifesavers, 94% in paramedics, and the difference was not significant (P=1). The accuracy rate of the lay persons' answers was 63%, with significant differences between this group and the lifesavers (P<0.001) and the paramedics (P<0.001). The average time taken to answer the questions was 6.6 s for the lifesavers and 7.0 s for the paramedics, and the difference was not significant (P=0.44). The average time taken to answer the questions from the lay persons group was 20.5 s, with significant differences between this group and the lifesavers (P<0.001) and the paramedics (P<0.001). Conclusions: The results of this evaluation, using CPR-training mannequins, to test the accuracy of carotid pulse checks by lifesavers were equivalent to those of paramedics and superior to those of lay persons.  (Circ J 2010; 74: 1895 - 1899)

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Background: Although left ventricular (LV) diastolic dysfunction is associated with increased risk for incident heart failure in patients with coronary artery disease (CAD), no specific treatment for diastolic abnormalities has been established. Animal and small human studies have shown that an acute increase in LV afterload adversely impacts on LV early diastolic relaxation, but little is known about its chronic effect on diastolic function. Methods and Results: The relationships of various components of arterial load (arterial compliance, total vascular resistance index, and augmentation index [AI] in the ascending aorta) with LV diastolic function indices determined on cardiac catheterization (relaxation time constant [Tau] and end-diastolic pressure [EDP]) and those on tissue Doppler echocardiography (early diastolic mitral annular velocity [E'] and the ratio of early diastolic mitral inflow to annular velocities [E/E']) were investigated in 303 consecutive patients undergoing cardiac catheterization for CAD. All components of arterial load correlated with diastolic function indices, with AI, an index reflecting late-systolic load, having the strongest correlations with diastolic function indices. After adjustment for potential confounders, AI correlated with Tau (standardized β=0.25, P<0.001), EDP (β=0.25, P<0.001), E' (β=-0.21, P<0.001), and E/E' (β=0.23, P<0.001). Conclusions: Increased AI is independently associated with LV diastolic function in patients with known or suspected CAD. Late-systolic load may be a therapeutic target to improve LV diastolic abnormalities in this population.  (Circ J 2010; 74: 1900 - 1905)

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Background: No reliable precursor of sudden cardiac death is known. Methods and Results: Holter electrocardiograms of 34 patients experiencing a cardiac event (event group, 20 deaths) were compared with 191 controls (no event group). The event group included 25 patients with ventricular fibrillation or acute myocardial infarction (AMI), and 9 with cardiac arrest due to complete atrioventricular block. The logarithms were calculated of the moving average of 5 successive values for the low-frequency component (LF), the high-frequency component (HF), and the ratio LF/HF of heart rate variability: ln(LF), ln(HF) and ln(LF/HF). A V-shaped trough appeared in the curve of ln(LF/HF) [sV-trough] or ln(HF) [pV-trough] before such an event in 31 patients in the event group. The V-trough was marked by a small variation lasting 2 h, an abrupt descent lasting 30 min, and a sharp ascent for 40 min. An sV-trough was observed in 22 patients before the onset of ventricular fibrillation or AMI. A pV-trough was observed in all 9 patients before the onset of complete atrioventricular block. In the no event group, an sV-trough and a pV-trough were observed in 10 subjects (5%) and 20 subjects (10%), respectively. The positive predictive accuracy of an sV-trough for ventricular fibrillation or AMI and that of a pV-trough for complete atrioventricular block was 88% and 100%, respectively. Conclusions: A previously unidentified V-trough of autonomic activity is a potential precursor of lethal events.  (Circ J 2010; 74: 1906 - 1915)

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Background: This study was designed to determine the clinical risk for hard events after normal single-photon emission computed tomography (SPECT) and to identify the predictors of increased risk in asymptomatic patients with diabetes mellitus, based on a Japanese Assessment of Cardiac Events and Survival Studies by quantitative gated SPECT (J-ACCESS)-2 study. Methods and Results: A total of 513 consecutive asymptomatic patients who underwent stress ^99mTc-tetrofosmin SPECT in Japan were included in this study. Based on SPECT image and QGS data, 319 had a summed stress score ≤3, a summed difference score <2 and normal cardiac function (end-systolic volume ≤60 ml, males, ≤40 ml, females; left ventricular ejection fraction ≥49%, males, ≥50%, females). Myocardial perfusion was normal in 62% of this study population. During a 3-year follow-up, there were a total of 8 cardiac major events (2.5%): 2 cases of sudden death, 5 of acute coronary syndrome, and 1 of hospitalization because of congestive heart failure. The annual major event rate was 0.8%. Subjects undergoing coronary angiography had significantly more major events than those who did not among normal SPECT subjects (P=0.01). Kaplan-Meier analysis showed that the cardiac major events rate was very low, and subjects with normal SPECT can be considered as low risk among asymptomatic patients with diabetes. Conclusions: An excellent prognosis was associated with a normal SPECT in asymptomatic patients with diabetes, so these patients can be exempted from further invasive procedure.  (Circ J 2010; 74: 1916 - 1921)

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Background: Few studies have serially monitored the change of coronary plaque after statin therapy using multiple plaque imaging modalities. Methods and Results: A prospective open-label trial was performed to assess coronary plaque regression and stabilization following 52 weeks of pitavastatin treatment (2 mg/day). Coronary segments that included the most diseased plaque of 90 patients determined on angioscopy were analyzed using intravascular ultrasound (IVUS). The yellow grade of each plaque of 46 patients who had matched angioscopy and IVUS data was evaluated on angioscopy. Low-density lipoprotein-cholesterol (LDL-C) was reduced 34.5% (145.0±24.0 mg/dl to 93.6±22.6 mg/dl, P<0.001), and high-density lipoprotein cholesterol increased 17.8% (44.9±11.1 mg/dl to 51.9±11.7 mg/dl, P<0.001). Yellow grade decreased (2.9±0.8 to 2.6±0.7, P=0.040) during 52 weeks. The reduction of yellow grade was not correlated with the LDL-C level at 52 weeks or its change. The change of yellow grade was inversely correlated with maximum yellow grade at baseline. Percent atheroma volume on IVUS did not change during 52 weeks, but its change for 52 weeks was significantly correlated with LDL-C level at 52 weeks (Spearman's rank correlation coefficient 0.312, P=0.035). Conclusions: Fixed dose pitavastatin stabilized vulnerable coronary plaques by the reduction of yellow grade without significant reduction of plaque volume. The stabilization and regression of atherosclerotic plaques by statin may differ, but both nonetheless contribute to the reduction of cardiovascular events (UMIN Clinical Trials Registry UMIN000001107).  (Circ J 2010; 74: 1922 - 1928)

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Background: This study explored the clinical significance of CD34⁺/133⁺ circulating progenitor cell (CPC) counts in patients with stable angina pectoris (AP) who underwent percutaneous coronary intervention (PCI). Methods and Results: Subjects comprised 52 patients with stable AP requiring PCI and 50 control patients without AP. In the AP group, blood samples were taken before and 20 min and 24 h after PCI to measure CPC counts by fluorescence-activated cell sorter analysis. The baseline number of CPCs was smaller in the AP group than in controls. In the AP group, body mass index (BMI) correlated positively with the baseline number of CPCs and was an independent predictor of CPC count in multivariate regression analysis. Other conventional risk factors, daily exercise activity and statin administration showed no association with CPC count. CPC counts remained unchanged within 24 h after PCI. Conclusions: CPC counts in patients with AP are influenced by BMI, but not by other coronary risk factors. CPC counts remain unchanged within 24 h after PCI.  (Circ J 2010; 74: 1929 - 1935)

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Background: Acute coronary syndrome (ACS) commonly results from vulnerable plaque rupture, and occasionally results from thrombus formation in lesions without plaque rupture. The aim of the present study was to clarify the clinical features of different etiology of ACS and clinical predictors of culprit plaque rupture assessed on intravascular ultrasound (IVUS). Methods and Results: One hundred and ten ACS patients with emergent coronary angiography were classified into 2 groups based on the presence or absence of culprit plaque rupture assessed on IVUS. Clinical characteristics were compared between the 2 groups. Culprit coronary plaque rupture was observed in 60 patients (55%). Patients with plaque rupture were younger and were more likely to be male (P<0.03 and P<0.02, respectively). In the rupture group, the prevalence of metabolic syndrome was higher (P<0.002), and among the components of metabolic syndrome, waist circumference was greater and serum high-density lipoprotein cholesterol level was lower (P<0.0001 and P=0.0004, respectively). IVUS-assessed lesion remodeling index was greater in the rupture group (P<0.0001). On multivariate analysis metabolic syndrome was an independent predictor of culprit plaque rupture (odds ratio =5.26, 95% confidence interval =1.49-21.40, P<0.02). Conclusions: Abdominal obesity and low high-density lipoprotein-cholesterol level are the characteristics of metabolic syndrome that seem to be the key factors for vulnerable plaque rupture with coronary compensatory enlargement.  (Circ J 2010; 74: 1936 - 1942)

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Background: Although calcium channel blockers (CCB) are highly effective for suppression of vasospastic angina (VSA) attacks, their prognostic effects in VSA patients remain to be examined in a large number of patients. Methods and Results: Databases for related papers were searched and then a meta-analysis regarding the effects of CCB on major adverse cardiovascular events (MACE) in Japanese VSA patients with the 4 previous studies was performed. A total of 1,997 patients with positive coronary spasm provocation tests were evaluated. They were treated with either alone or combination of benidipine (n=320), amlodipine (n=308), nifedipine (n=182) or diltiazem (n=960). MACE were observed in 143 patients (cardiac death: 36, myocardial infarction: 51, heart failure: 26, stroke: 65, and aortic aneurysm: 11). The hazard ratio for the occurrence of MACE was significantly lower in patients treated with benidipine than in those with diltiazem. There was no significant difference in the clinical characteristics affecting the occurrence of MACE among the 4 CCB groups. Furthermore, the hazard ratio for the occurrence of MACE was significantly lower in those treated with benidipine, even after correction for patient characteristics that could have affected the occurrence of MACE (hazard ratio 0.41, P=0.016). Conclusions: These results suggest that among the 4 major CCB that effectively suppress VSA attacks in general, benidipine showed significantly more beneficial prognostic effects than others.  (Circ J 2010; 74: 1943 - 1950)

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Background: There have been no studies on the clinical characteristics and prognostic factors of pediatric ventricular tachycardia (VT). Methods and Results: Eighty-one patients with pediatric VT were studied retrospectively at a single center. The median follow-up period was 6.0 years (0.7-23.5 years). Patients were categorized into 6 groups: idiopathic VT (IVT, n=37), catecholaminergic polymorphic VT (CPVT, n=10), congenital heart disease-associated VT (n=15), myocarditis-associated VT (n=8), cardiomyopathy-associated VT (CMP-VT, n=5) and miscellaneous. The age distribution of VT had 2 peaks (infant and teenager). VT with left bundle branch block configuration was more frequently nonsustained than VT with right bundle branch block configuration (61% vs 8%). Although 22% were asymptomatic, 38% experienced syncope or seizure and 16% had cardiac arrest. The overall mortality rate was 7.4%. The expected life span without cardiac arrest was <4 years in the CMP-VT group and the 10-year survival rate in CPVT patients was approximately 55%. Onset at infancy, monomorphic type and transcatheter/surgical ablation were related to the successful resolution of VT. Logistic regression analysis revealed that CPVT, CMP-VT, polymorphic VT and sustained VT were significantly correlated with death or cardiac arrest. Conclusions: The clinical features and prognosis of pediatric VT differed with the VT type, clinical categories and onset age. Accurate diagnosis and proper treatment according to the clinical categories may improve the outcome.  (Circ J 2010; 74: 1951 - 1958)

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Background: Subintimal percutaneous transluminal angioplasty (SIA) is a treatment option for long segment occlusions in the lower limb arteries. In the present study the factors influencing success and patency following SIA in patients with TransAtlantic Inter-Society Consensus (TASC) C and D peripheral arterial disease (PAD) were investigated. Methods and Results: The 63 consecutive SIAs were performed in 54 consecutive patients suffering from limb ischemia with TASC C and D lesions. Follow-up consisted of routine office visits with pulse examination, ankle-brachial index (ABI), and serial surveillance by color duplex ultrasound and scanning at 3- to 6-month intervals for 1 year. The morphology of lesions in all patients were type C (n=13, 20.6%) or type D (n=50, 79.4%). SIA was technically successful in 59 of 63 arterial occlusive lesions (93.6%). Post-procedural ABI was 0.89±0.16. The mean increase in ABI after SIA was 0.45 (range, 015-0.87). The primary patency rate at 12 months was 51.7%. Occlusion length, lesions involving the distal superficial femoral artery (SFA), and post-procedural distal run-off vessels (P=0.04, 0.006, 0.018, respectively) were independent patency determinants by multivariate analysis. Conclusions: The length of the occlusion, lesions involving the distal SFA, and post-procedural distal run-off vessels were strong independent predictors for 1-year patency in TASC C/D severe occlusive femoropopliteal artery disease treated by SIA.  (Circ J 2010; 74: 1959 - 1964)

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Background: Pulmonary hypertension (PH) still remains a serious disease, for which the plasma level of brain natriuretic peptide (BNP) and hemodynamic variables (eg, cardiac index: CI) are established prognostic factors. The aim of the present study was to identify new additional prognostic factors of the disorder to improve the management of PH. Methods and Results: The study cohort comprised 136 consecutive PH patients admitted to hospital from 1974 to 2008, all of whom were closely followed every 6-12 months. During the follow-up period of 53.5±4.5 [SEM] months, 47 patients died of cardiopulmonary causes. The patients who were initially treated with monotherapy showed improved pulmonary hemodynamics when subsequently treated with combination therapy. Multivariate analysis showed that BNP and CI were significant and independent prognostic factors in all PH patients. However, in PH patients with low CI at diagnosis, only CI improvement by PH therapy was a significant and independent prognostic factor. Indeed, the patients with low CI at diagnosis (CI <2.5) followed by subsequent normalization in response to therapy (CI ≥2.5) showed a significantly better survival compared with those without such normalization. Conclusions: CI normalization in response to treatment is an independent new prognostic factor of PH in patients with low CI at diagnosis, suggesting the importance of intensive therapy to achieve CI normalization.  (Circ J 2010; 74: 1965 - 1971)

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Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and it has a significant impact on morbidity and mortality. Large randomized trials have failed to demonstrate a benefit for mortality of the pharmacological rhythm control strategy as compared with the rate control strategy, indicating that rate control may be an adequate treatment for AF. However, further study determined that the presence of AF at the time of study termination was a more potent predictor of mortality than the treatment strategy, suggesting the importance of sinus rhythm. On the other hand, catheter ablation recently has emerged as an alternative treatment option to pharmacological therapy for AF. Although AF ablation is an invasive strategy, over the past decade its efficacy has increased and the complication rate has decreased with the growing experience of operators and evolving technology. Moreover, the ablation methodology, such as pulmonary vein isolation based ablation, is consistent worldwide and the success rate of AF ablation, especially in paroxysmal AF, is similar. Therefore, catheter ablation is established as a treatment option for AF.  (Circ J 2010; 74: 1972 - 1977)

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In recent years, catheter ablation for atrial fibrillation (AF) has evolved in tandem with the results from many large-scale randomized clinical studies with antiarrhythmic drugs. The current situations seem to be a concerted move from pharmacological to non-pharmacological treatment. However, the clinical studies with medications have revealed an important viewpoint for the management of AF: the importance of the core aim of AF treatment and the position of electrographic findings as a surrogate marker. Catheter ablation is under challenge as the answers to these issues are awaited. Moreover, many problems with this invasive therapy are to be solved, most of them deriving from the vague definition of success of ablation and no standardization of the technique. For these reasons, catheter ablation is still on the way to maturation and multicenter studies in Japan are required to set a fair benchmark for Japanese patients, drawing a lesson from randomized clinical studies with medications.  (Circ J 2010; 74: 1978 - 1982)

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(Circ J 2010; 74: 1625 - 1634)

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