The mid- and long-term outcomes of revascularization procedures in patients with chronic left ventricular (LV) systolic dysfunction due to coronary artery disease (CAD) in the presence or absence of heart failure (HF) symptoms are still uncertain. The identification of dysfunctional myocardial segments with residual viability that can improve after revascularization is pivotal for further patient management. Hibernating myocardium (ie, chronically dysfunctional but still viable tissue) can be identified by positron emission tomography (PET) and cardiac magnetic resonance (CMR) and its presence and extent can predict functional recovery after revascularization. Before β-blockers were introduced as routine care for HF, surgical revascularization appeared to improve survival in these patients. Nowadays, novel medical treatments and devices, such as cardiac-resynchronization therapy and implantable cardioverter-defibrillators, have improved the prognosis of HF patients and their use is supported by a number of clinical trials. To adequately address the unresolved issue of the prognostic benefits of coronary revascularization in CAD patients with chronic LV dysfunction on optimal medical therapy with/without devices a randomized trial is warranted. In such a trial the presence of viability will be assessed by either PET or CMR. This is an overview of the pathophysiological mechanisms, as well as of the main clinical studies and meta-analyses that have addressed this issue in the past 4 decades. (Circ J 2011; 75: 3-10)

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Aortic stenosis (AS) is the most commonly acquired valvular heart disease in the Western world (2-7% of the population aged >65 years) and the mortality for untreated symptomatic severe AS is up to 50-60% at 2 years in high-risk patients. This review summarizes laboratory and recent clinical investigations concerning AS and current best treatment. Particular emphasis will be placed on pathophysiology and on the concept of afterload mismatch and preload reserve in which left ventricular function is proportionately matched to level of left ventricular pressure, mainly because such studies carry important implications for both treatment with transcatheter aortic valve implantation (TAVI) and prognosis. Surgical aortic valve replacement is currently the gold-standard treatment for patients with severe symptomatic AS. Without surgery, the prognosis is extremely poor, with a 3-year survival rate <30%. However, 33% of all patients aged ≥75 years with severe AS are declined for surgery. TAVI was recently introduced as a new therapeutic option for patients with AS, so the current indications, the technical differences between 2 different transcatheter aortic valves and the clinical available data will be also examined in detail. (Circ J 2011; 75: 11-19)

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An autonomic imbalance with a reduction in vagal activity and an increase in sympathetic activity is present in heart failure. The same type of imbalance, when present in patients with a myocardial infarction, is associated with increased risk for cardiac mortality. Experimental studies have demonstrated that vagal stimulation has an antifibrillatory effect and has proven to be beneficial in animal models of heart failure. Given this background, the potential value of chronic vagal stimulation was explored in humans with an implantable neuro-stimulator capable of delivering low current pulses with adjustable parameters to stimulate the right vagus. A small multicenter feasibility and safety study exploring efficacy has recently been completed. A total of 32 patients with left ventricular ejection fraction (LVEF) <35% and a history of chronic heart failure in symptomatic NYHA class II-III were included in the study. The results indicate feasibility and safety. Interestingly, there are also very encouraging results for the efficacy on the NYHA class, quality of life, 6-min walk test, left ventricular end-systolic volume and LVEF. The latter, at the 1-year follow up, had increased from 21±7% to 34±12% (P<0.0001). Finally, vagal stimulation in heart failure patients has a strong rationale and the preliminary data suggests that it is likely to be of value to these patients. It is now appropriate to move toward a randomized controlled clinical trial of adequate size. (Circ J 2011; 75: 20-27)

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Percutaneous septal ablation has emerged as a less invasive treatment of symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM). In the past decade, the availability of this sophisticated technique has revived the interest of cardiologists in left ventricular outflow tract obstruction, which led to the recognition that most patients with HCM have the obstructive type. Follow-up studies have already shown the safety and efficacy of the procedure, which offers symptomatic relief in most patients. Long-term survival is comparable to historical reports after surgical myectomy. Complications are rare and can be further reduced with increased experience of the operators, and the theoretical concern for possible ventricular arrhythmogenicity of the myocardial scar has not been documented by the existing data. Although there are still no randomized trials, percutaneous septal ablation is undeniably a viable alternative for patients with HOCM. (Circ J 2011; 75: 28-37)

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Although heart transplantation is the gold standard for the treatment of advanced stage heart failure, the implantation of mechanical circulatory support devices (MCSDs) has become a well-established therapy for this disease. As the population of patients with severe heart failure has grown, the utilization of MCSDs has increased considerably. That trend is expected to continue, especially in light of dramatic advances in MCSD technology. This review outlines the current status and future directions of mechanical circulatory support therapy in the setting of a constantly evolving field of supportive devices and adjuvant therapies. (Circ J 2011; 75: 38-46)

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Background: Acute aortic dissection (AAD) classically presents as sudden, severe chest, back, or abdominal pain. However, there have been several documented cases presenting with atypical features. The clinical characteristics and outcomes of patients with painless AAD were investigated. Methods and Results: The study group comprised 98 patients (53 males, 45 females; 66±12 years) with AAD admitted to hospital from 2002 to 2007: 16 patients (17%) had no pain (Painless group) and 82 patients had pain (Painful group). In 81% of the Painless group and 70% of the Painful group there was a type A dissection. The Painless group more frequently had a persistent disturbance of consciousness (44% vs. 6%, P<0.001), syncope (25% vs. 1%, P<0.001) and a focal neurologic deficit (19% vs. 2%, P=0.006) as presenting symptoms. Imaging study findings were not significantly different. Cerebral ischemia (50% vs. 1%, P<0.001) and cardiac tamponade (38% vs. 13%, P=0.01) were more frequent complications in the Painless group. In-hospital mortality was not significantly different (19% vs. 15%). However, the Painless group had a more unfavorable functional outcome on overall performance category (P<0.001). Conclusions: Painless AAD may be more frequent than previously reported. Painless AAD patients often present with a disturbance of consciousness or a neurologic deficit, and have a higher morbidity than painful AAD patients. (Circ J 2011; 75: 59-66)

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Background: This retrospective cohort study evaluated whether long term outcome of atrial resynchronisation therapy using bi-atrial pacing (BiaP) to treat atrial fibrillation (AF) was effective in patients deemed unfit for left atrial (LA) ablation procedures. Methods and Results: The patient population comprised 2 groups: those deemed suitable for left LA ablation (n=14) and those who were not (n=17). Both groups underwent BiaP and outcomes were evaluated by comparing symptoms, AF duration, admissions and antiarrhythmic drugs (AAD) for an equal period of time pre and post implantation. Median follow-up was 24 months (range 8-66 months) for the unsuitable group and 31 months (range 7-84 months) for the suitable group. Efficacy in reduction of both AF and symptoms was similar (P=0.44) in both groups (unsuitable group: 13/17; suitable group: 8/14). There was significant improvement in median AF episodes/week pre and post BiaP in both groups (unsuitable group AF reduction: 5 days/week, P=0.001; suitable group AF reduction: 4.9 days/week, P=0.03); the improvement was similar in both groups (P=0.33). There was a significant reduction in the median number of admissions for AF in both groups (unsuitable group: P=0.003; suitable group: P=0.01) and this reduction was also similar (P=0.70). The median number of AAD was also reduced to a similar degree (P=0.83) in both groups (suitable group: P=0.004; unsuitable group: P=0.001). Conclusions: Atrial resynchronisation therapy is effective in the long term management of drug-resistant AF in patients unsuitable for LA ablation, leading to significant reductions in symptoms, AF duration, admissions and AAD. (Circ J 2011; 75: 67-72)

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Background: The incidence and clinical implication of dissociated pulmonary vein (PV) electrical activities after circumferential antrum PV ablation for paroxysmal atrial fibrillation (AF) remains unclear. Methods and Results: A total of 196 patients with symptomatic paroxysmal AF who underwent circumferential antrum PV ablation were prospectively studied. Dissociated PV electrical activities were observed in 101 patients (Group 1), but absent in the remaining 95 patients (Group 2). There were no significant differences in the baseline clinical characteristics between them, except that Group 2 had a higher prevalence of hypertension (30 vs. 44%, P=0.04). After 21.8±7.9 months of follow-up, 148 had no recurrence of AF after the initial procedure. AF recurrence rate was significantly higher in Group 2 than in Group 1 (P=0.023). Relapse of PV conduction was the major cause of AF recurrence in both groups (16/16 vs. 19/23, P=0.08), and the overall procedural success rate after the redo ablation procedure was similar in the 2 groups (90 vs. 86%, P=0.44). However, the total number of patients with non-PV foci was significantly higher in Group 2 than in Group 1 (12/95 vs. 2/101, P<0.01). Conclusions: Dissociated PV electrical activities might identify a subgroup of patients with relatively higher initial procedural success with circumferential PV antrum ablation. (Circ J 2011; 75: 73-79)

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Background: Ventricular tachyarrhythmia is the leading cause of sudden cardiac death, and scroll wave re-entry is known to underlie this condition. Class III antiarrhythmic drugs are commonly used worldwide to treat ventricular tachyarrhythmias; however, these drugs have a proarrhythmic adverse effect and can cause Torsade de Pointes or ventricular fibrillation. Transmural dispersion of repolarization (TDR) has been suggested to be a strong indicator of ventricular tachyarrhythmia induction. However, the role of TDR during sustained scroll wave re-entry is poorly understood. The purpose of the present study was to investigate how TDR affects scroll wave behavior and to provide a novel analysis of the mechanisms that sustain tachyarrhythmias, using computer simulations. Methods and Results: Computer simulations were carried out to quantify the TDR and QT interval under a variety of I_Ks and I_Kr during transmural conduction. Simulated scroll wave re-entries were done under a variety of I_Ks and I_Kr in a ventricular wall slab model, and the scroll wave behavior and the filament dynamics (3-dimensional organizing center) were analyzed. A slight increase in TDR, but not in the QT interval, reflected antiarrhythmic properties resulting from the restraint of scroll wave breakup, whereas a marked increase in TDR was proarrhythmic, as a result of scroll wave breakup. Conclusions: The TDR determines the sustainment of ventricular tachyarrhythmias, through control of the scroll wave filament dynamics. (Circ J 2011; 75: 80-88)

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Background: Anesthesia sometimes suppresses ventricular tachyarrhythmias (VT) resistant to conventional pharmacological treatment. Methods and Results: To know (1) whether deep anesthesia inhibits abnormal repolarization-related VT and (2) if α2-adrenoreceptor (AR) agonistic action is associated with the antiarrhythmic effect of anesthetics, the incidence of VT in a rabbit model of acquired long QT syndrome using different anesthetic regimen was assessed. In Study 1 (n=30), 15 rabbits were lightly anesthetized with ketamine (123±46mg/kg) and an α2-AR agonist, xylazine (9.4±3.0mg/kg), while combination of these anesthetics at high doses were used in the other 15 rabbits (343±78mg/kg and 38.9±3.0mg/kg). Administration of α1-AR stimulant, methoxamine and nifekalant (Ikr blocker) caused VT in all lightly anesthetized rabbits. In contrast, VT was observed only in 1 of the 15 deeply anesthetized rabbits (P<0.01). In Study 2 (n=15), 10 rabbits were anesthetized with high-dose ketamine and low-dose xylazine. In the other 5 rabbits, low-dose ketamine and high-dose xylazine were used. QTc interval in the latter was longer than that of the former (399±56ms vs. 494±57ms, P<0.01). Although no VT appeared in high/low-rabbits, VT occurred in 3 out of 5 low/high-rabbits (P<0.05). Conclusions: These results suggest that (1) deep anesthesia suppresses abnormal repolarization-related VT and (2) antiarrhythmic effect of anesthesia on this type of VT is not dependent on α2-AR agonistic action. (Circ J 2011; 75: 89-93)

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Background: The objective of this study was to investigate whether a distal protection (DP) device can preserve the index of microcirculatory resistance (IMR) after primary percutaneous coronary intervention (PCI) in patients with anterior ST-segment elevation myocardial infarction (STEMI). Methods and Results: The study group of 36 consecutive patients with anterior STEMI were randomized into 2 groups of primary PCI with or without DP: stenting without DP (non-DP group, n=17) and with DP (DP group, n=19). The DP in all cases was Filtrap (Nipro, Japan). Following final coronary angiography after successful PCI, IMR was measured using PressureWire^TM Certus (St Jude Medical, USA) at maximal hyperemia. The averaged IMR of the 36 patients with STEMI after primary PCI was 31.6U. The IMR in the DP group was significantly lower than that in the non-DP group (26.6±25.8U vs. 37.2±23.2U, P=0.03242). Conclusions: DP as an adjunctive therapy of PCI for acute anterior STEMI may have beneficial effects on myocardial microcirculation because of preservation of IMR. (Circ J 2011; 75: 94-98)

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Background: The cytochrome P450 (CYP) 2C19*2 polymorphism is associated with reduced responsiveness to clopidogrel and poor clinical outcome after stent implantation. Despite the high frequency of this polymorphism in Japanese patients, its contribution to cardiac events and stent thrombi after drug-eluting stent (DES) implantation is not clear in this population. Methods and Results: One hundred Japanese patients received clopidogrel and underwent follow-up optical coherence tomography (OCT) after DES implantation. The patients were divided into 2 groups: those with at least one CYP2C19*2 allele (*2 carriers) and non-carriers. The incidence of stent thrombosis and major adverse cardiac events (MACE; ie, death, myocardial infarction, and target vessel revascularization) was compared between the 2 groups. In addition, OCT was used to evaluate the incidence of intra-stent thrombus, defined as a mass protruding into the lumen with significant attenuation. Of the 100 patients, 42 were *2 carriers. No remarkable differences in the baseline characteristics were noted. Although MACE did not differ significantly between the 2 groups, a subclinical intra-stent thrombus was detected more frequently in *2 carriers than in non-carriers (52.3% vs. 15.5%, P=0.0002). Multivariate logistic regression analysis showed that the presence of the CYP2C19*2 polymorphism was the only independent predictive factor for intra-stent thrombus (P=0.00006). Conclusions: From these results it is suggested that CYP2C19*2 polymorphism is associated with subclinical thrombus formation among Japanese patients receiving clopidogrel. (Circ J 2011; 75: 99-105)

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Background: Late stent thrombosis (LST) after drug-eluting stent (DES) implantation is a major clinical problem that has not been fully explained. Incomplete neointimal coverage of stent struts is an important morphometric predictor of LST, which may be associated with impaired healing and the absence of full coverage of struts at branch-point ostia. Optical coherence tomography (OCT) was performed to compare 3 types of stents placed across side branches. Methods and Results: At 9-month follow-up, the neointimal coverage of the struts of 58 stents across a side branch was measured by OCT (bare metal (BMS), n=20; sirolimus-eluting (SES), n=23; paclitaxel-eluting (PES), n=15). According to the diameter ratio of side branch to main vessel, the side branches were classified as either large (ratio >0.33) or small (ratio ≤0.33). BMS had the lowest frequency of uncovered struts (29.4%) and the greatest neointimal thickness on the struts (123±33μm). Neointimal thickness on the struts was less for SES than for PES (72±16 vs. 91±22μm, P=0.009), but there was no difference in the frequency of uncovered struts (66.1% vs. 58.6%, P=0.493). For large side branches, the frequency of uncovered struts was greater than in the small group for SES (87.5% vs. 40.7%, P=0.0002) and PES (83.3% vs. 18.2%; P=0.0013); there was no significant difference for BMS (43.8% vs. 16.7%, P=0.138). Conclusions: Neointimal coverage on struts across a side branch was less frequently observed in DES than in BMS, particularly in large side branches. (Circ J 2011; 75: 106-112)

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Background: Long-term follow-up studies revealed a significant decline in the benefits of intracoronary radiation for in-stent restenosis. Methods and Results: A total of 25 study and 25 contemporaneous control patients with diffuse in-stent restenosis who underwent cutting balloon angioplasty (CBA) transradially, followed by subsequent intracoronary irradiation with a liquid β-emitter Rhenium-188 (¹⁸⁸Re)-filled balloon were enrolled in the study. The mean clinical follow-up durations were 64.9±13.0 and 66.3±13.8 months for the irradiated and control patients, respectively. Six-month angiographic restenosis was observed in 16% (4 of 25) of the patients in the irradiated group and 48% (12 of 25) of the patients in the control groups (P=0.03). The 6-month major adverse cardiac events (MACE) rate was 12% and 44%, respectively (P=0.025). The 3-year follow-up angiography was performed in 16 of 21 (76%) irradiated patients and in 4 of 13 (31%) control patients who had no significant restenosis at the 6-month angiographic follow-up. Restenosis occurred in 1 of 16 (7%) irradiated patients and 2 of 4 (50%) control patients. Late target lesion revascularization was performed in 1 irradiated and 2 control patients. The MACE rate within 6 years was significantly reduced in the irradiated group (20% vs. 56%, P=0.019). Conclusions: Brachytherapy using ¹⁸⁸Re-filled balloon following CBA for diffuse in-stent restenotic native coronary arteries is effective in reducing target lesion restenosis and improving long-term outcomes. (Circ J 2011; 75: 113-120)

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Background: In Japan, the TOYOBO left ventricular assist device (LVAD) has been commercially available for heart failure patients as of 2010, but clinical risk stratification before implantation has not been widely performed. Methods and Results: In the present study data from 47 patients (age 38.6±14.6 [SD] years, male 74.5%, non-ischemic 74.5%) implanted with a TOYOBO LVAD between November 2002 and February 2010 were analyzed. Kaplan-Meier survival analysis showed significantly higher mortality in the patients who had cardiogenic shock preoperatively (P=0.031). Multivariate analysis revealed that the preoperative total bilirubin level (odds ratio [OR] 1.312, P<0.001) and age (OR 1.076, P=0.013) were independent risk factors for death. Perioperative necessity of a right ventricular assist device was also an independent risk factor for poor prognosis. Conclusions: LVAD implantation is preferable before the patient experiences hemodynamic collapse. The preoperative total bilirubin level can be used to predict prognosis after device implantation in end-stage heart failure patients. (Circ J 2011; 75: 121-128)

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Background: Previous studies have demonstrated that intrathoracic impedance monitoring (IIM) is associated with fluid overload. However, it remains unclear whether this new technology can predict heart failure (HF) before deterioration. Whether fluid status based on IIM predicts HF in patients with left ventricular (LV) systolic dysfunction was investigated. Methods and Results: A prospective clinical observational study of 123 patients implanted with IIM-capable cardiac devices was carried out. The primary endpoint was the positive predictive value (PPV) at 12 months. Secondary endpoints were a correlation between onset of HF and IIM, optimal threshold of fluid index and duration between the alert and HF. Complete follow-up clinical data were obtained from 111 patients. During the observational period, 168 alerts were confirmed from 68 patients. In patient-based analysis (alert-based analysis), PPV was 33.8% (33.9%). Sensitivity, specificity and false positive was 67.6% (83.8%), 49.4% (28.4%) and 50.6% (71.6%), respectively. Mean duration between the alert and HF event was 21.4±6.1 days. On multivariate logistic analysis, maximum fluid index, LV ejection fraction and atrial fibrillation were independent predictors of HF events. The optimal cut-off value determined by receiver operating characteristic curve was 114-ohm·day with sensitivity and specificity of 89.5% and 73.0%, respectively. Conclusions: IIM-based fluid index in patients with HF due to LV systolic dysfunction was effective in predicting worsening HF. (Circ J 2011; 75: 129-134)

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Background: There are limited studies conducted in Asia to investigate the progression rate to hypertension (HTN). This study was done to estimate the progression rate of new-onset pre-HTN (PreHTN) to HTN during an 8-year follow-up period, and to compare the impact of PreHTN on progression to HTN. Methods and Results: A total of 49,228 participants, aged 30 to 54 years with new-onset PreHTN at baseline (1994-1996) from a biennial national medical exam were enrolled and followed up every 2 years until 2004. The incidence rate recorded at each interval and the cumulative incidence rate of HTN were analyzed. Hazard ratio of high-normal and high blood pressure (BP) in men and women was calculated. The cumulative incidence rate for high-normal BP was 27.6% and 26.4% at 2-year follow-up, increased to respectively 64.1% and 55.8% in men and women at the 8-year follow-up. Compared to optimal BP, hazard ratios for men with high-normal BP across all age groups were 3- to 4-fold higher at 2-year, and 2- to 3-fold higher at 8-year follow-up. Hazard ratios for women were about 6-fold higher at 2-year and around 4-fold higher at 8-year follow-up. Conclusions: New PreHTN was a significant predisposing factor for future HTN, in young adults and the effect is more prominent in women. (Circ J 2011; 75: 135-140)

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Background: Automated function imaging (AFI) is a recently developed method of calculating the longitudinal peak systolic strains (LS) of the regional left ventricular (LV) wall using speckle tracking echocardiography and displaying them on a single bull's-eye map. The feasibility of AFI in patients with regional LV wall motion abnormalities caused by myocardial infarction (MI) was evaluated by comparison with visual assessment and myocardial perfusion single-photon emission computed tomography (SPECT). Methods and Results: Segmental LS was measured by AFI in 60 patients with MI (67±11 years) and 58 controls (71±9 years). Wall thickening (WT) was measured by SPECT in 20 patients with MI. There was a strong positive linear relationship between the wall motion score index by expert visual assessment and global LS. The receiver-operating characteristic analysis revealed the best cutoff value of 11% <LS to identify hypokinetic segments. The overall accuracy of wall motion scoring by LS in the 2,006 segments was 96.8% (κ=0.90) compared with visual assessment. The correlation coefficient between LS and WT was R²=0.65 in the 340 segments. Conclusions: Assessment of LV regional asynergy by AFI showed good agreement with visual and SPECT assessments. AFI is clinically useful for quantitative assessment of LV regional wall motion abnormalities. (Circ J 2011; 75: 141-147)

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Background: Treatment of heart failure by surgical procedures such as mitral annuloplasty and left ventricular (LV) restoration is increasingly applied to patients with ischemic mitral regurgitation (IMR) and LV dysfunction. The clinical efficacy of delayed enhancement magnetic resonance imaging (DE-MRI) was studied to predict LV functional recovery and adverse outcomes after these therapies. Methods and Results: In 26 patients with IMR and a LV ejection fraction <40%, DE-MRI was performed before the operation and the percentage of regional myocardial scarring was quantified at the basal, mid, and apical LV. Calculated percentage of fibrosis was 12±12% at the base, 24±15% at the mid, and 35±31% at the apical LV. The degree of basal fibrosis was a significant predictor of less improvement of LV ejection fraction and postoperative restrictive diastolic filling. A linear correlation was noted between basal fibrosis and postoperative ejection fraction (P=0.001, R=-0.61), the early to late mitral valve flow ratio (P=0.0005, R=0.66), and deceleration time (P=0.01, R=-0.51). Logistic regression analysis demonstrated that the percentage of basal fibrosis was the independent predictor of postoperative adverse clinical outcomes (odds ratio, 1.26; P=0.04). Conclusions: In patients undergoing surgical heart failure therapy for IMR, the extent of basal fibrosis characterized by DE-MRI might be a useful predictor of postoperative LV systolic and diastolic functional recovery and postoperative adverse outcomes. (Circ J 2011; 75: 148-156)

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Background: Despite growing interest in non-target lesion events in patients undergoing percutaneous coronary intervention (PCI), there has been little discussion of predictors. Methods and Results: A total of 155 consecutive patients who underwent PCI were enrolled. Conventional and integrated backscatter intravascular ultrasound (IB-IVUS) parameters were measured in non-target lesions utilizing a 40-MHz intravascular catheter. Lipid-rich plaques (LRP) were defined as lesions with an increased lipid volume (>median) and greater lipid content. Non-target ischemic events were defined as death, non-fatal myocardial infarction, any repeat revascularization and rehospitalization for angina involving the non-target vessel or the target vessel outside the index lesion. During the follow-up period (median: 1,265 days), non-target events were observed in 16 patients (11%). Using the Cox proportional hazard model, LRP (odds ratio [OR], 6.06; 95% confidence interval [CI]: 1.81-20.4, P=0.0035), elevated serum C-reactive protein (CRP) levels (OR, 6.83; 95%CI: 2.19-21.3, P=0.0009) and acute coronary syndrome present at baseline (OR, 4.08; 95%CI: 1.21-13.8, P=0.024) were significantly and independently associated with non-target events. Synergistic effects of LRP and elevated serum CRP levels for prediction of non-target events (OR, 14.8; 95%CI: 4.57-48.0, P<0.0001) were found even after adjusting for confounders. Conclusions: LRP measured using IB-IVUS proved to be an independent morphologic predictor of non-target ischemic events after PCI, particularly enhancing the risk in patients with elevated serum CRP levels. (Circ J 2011; 75: 157-166)

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Background: A limited number of studies comparing the main risk scores (RS) for acute coronary syndromes (ACS) have been conducted and there is a limited number of long-term observations of unselected patient cohorts evaluated with the various RS. The aim of this study was to validate 5 RS (TIMI STEMI RS, TIMI NSTEMI/UA RS, GRACE RS, SIMPLE RS and ZWOLLE RS) in a Polish population and to develop a new RS that would specifically predict 1-year mortality in the unselected ACS patient cohort. Methods and Results: Single-center ACS registry analysis with 1-year follow-up of 931 patients and prospective comparison of 5 RS was conducted. Creation of an RS was attempted. Risk factors were evaluated in a multivariate logistic regression model. The predictive value of the model was assessed with evaluation of the area under curve (AUC) in receiver-operating characteristic analysis. Twelve independent factors influencing 1-year mortality were identified and of them, clerking, physical findings on admission, first ECG and myocardial necrosis markers demonstrated sufficiently high predictive value. All 5 RS were successfully validated in the target registry and although they all displayed high predictive value, the TIMI RS STEMI (AUC=0.84) and GRACE RS (AUC=0.84) proved superior. Conclusions: The developed Banach score offers both high goodness-of-fit and predictive value and may be used irrespective of ACS type. (Circ J 2011; 75: 167-173)

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Background: Cardiac angina is the hallmark of myocardial ischemia, but the role of the cardiac sensory nerve has received relatively little attention. Recently, both acid-sensing ion channel 3 (ASIC3) and capsaicin receptor (TRPV1) have been suggested as important mediators in sensing cardiac ischemia. However, studies comparing the physiological roles of ASIC3 and TRPV1 in the neuronal-cardiac sensing circuits in vivo are lacking. Methods and Results: Isoproterenol (1.5mg/kg, intraperitoneally) was used to induce transient cardiac ischemia in Asic3^+/+ and Asic3^-/- mice and a radio-telemetry system was used for electrocardiography with mice in a conscious state. Isoproterenol-induced cardiac ischemia was first demonstrated with ST-segment depression and further confirmed by hypoxia-mediated chemical reactions in cardiac tissue. Mice lacking Asic3 showed prolonged duration of ST-segment depression compared with Asic3^+/+ mice (44.3±3.1 vs. 31.7±2.9min; P<0.05). Although ischemia was transient, severe cardiac fibrosis was found in Asic3^-/- but not in Asic3^+/+ mice littermates. In contrast, isoproterenol-injected Trpv1^+/+ and Trpv1^-/- mice showed no difference in duration of ST-segment depression and, surprisingly, deletion of Trpv1 did not aggravate cardiac fibrosis. Conclusions: An isoproterenol-induced cardiac ischemia model mimicking clinical conditions of early cardiac angina was used to demonstrate that ASIC3 but not TRPV1 plays a protective role in sensing cardiac ischemia. (Circ J 2011; 75: 174-178)

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Background: Generally, both the preprocedural evaluation and endovascular therapy (EVT) for lower limb arteries require contrast media that is harmful for patients with chronic renal insufficiency. In the present study these procedures were performed without using nephrotoxic contrast media in patients with preexisting renal insufficiency and iliofemoral artery disease. Methods and Results: The 36 consecutive patients with chronic renal insufficiency underwent preprocedural evaluation with duplex examination, magnetic resonance angiography (MRA) without contrast media, and plain computed tomography (CT). A total of 51 lesions were treated using intravascular ultrasound (IVUS) without contrast media. The overall technical success was 100% without any complications. Pre- and postprocedural ankle-brachial indices changed from 0.59±0.23 to 0.92±0.14. The mean serum creatinine concentration before and after treatment, and 3 months after treatment did not change (2.1±1.4, 2.0±1.4, and 2.1±1.6mg/dl, respectively). The overall 3-month survival rate and limb salvage rate was 100%. Conclusions: EVT comprising duplex, MRA, and CT for preprocedural evaluation and IVUS-guided procedure is feasible and may avoid intra-arterial contrast injection in selected patients deemed at high risk for renal failure from nephrotoxic contrast material. (Circ J 2011; 75: 179-184)

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Background: Cigarette smoking is an independent risk factor for cardiovascular events such as myocardial infarction and stroke. To date, a useful and convenient method of predicting such events in smokers has not been established. The rheological properties of blood assessed by the microchannel method reflect the blood's viscosity and the state of microthrombus formation, which may predict cardiovascular thrombotic events. Methods and Results: Blood fluidity was assessed in 74 smoking patients (54 men, 20 women, mean age 57.9 years) by measuring the blood passage time (BPT) in an aliquot (100μl) of blood using the Micro Channel Array Flow Analyzer. BPT was significantly related with smoking variables such as daily consumption of tobacco (r=0.236, P=0.044), Brinkman's index (r=0.252, P=0.033), the Fagerstrom Test for Nicotine Dependence (r=0.257, P=0.029), and the score of a self-rating depression scale (r=0.236, P<0.05). Multivariate regression analysis revealed that an independent BPT determinant was daily consumption of tobacco (r=0.326, P=0.045). Furthermore, smoking cessation markedly decreased BPT from 63.0s to 49.7s (P=0.002) at 3 months after the start of therapy. Conclusions: Unfavorable blood rheology is closely associated with cigarette smoking and may reflect increased cardiovascular risk in smokers. The study results also suggest that such risk can be reduced after only 3 months of smoking cessation. (Circ J 2011; 75: 185-189)

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Background: Serum total bilirubin (TB) is a potent antioxidant and may be a negative risk factor of cardiovascular disease. In non-diabetic adults, hemoglobin A_1c (HbA_1c), but not fasting plasma glucose, is an independent risk factor of cardiovascular disease. Methods and Results: Linear regression using TB as a dependent variable and cardiovascular risk factors, including HbA_1c, as independent variables, linear regression using HbA_1c as a dependent variable and other cardiovascular risk factors, including TB, as independent variables, and logistic regression using the highest decile (≥5.4%) of HbA_1c as a dependent variable and TB and other cardiovascular risk factors as independent variables were performed for 893 apparently healthy male smokers, 1,607 male nonsmokers, and 1,680 women. The standardized regression coefficient of HbA_1c for TB and that of TB for HbA_1c was -0.12 (P=0.007) and -0.06 (P=0.02), respectively, in the smokers, -0.20 (P<0.0001) and -0.07 (P<0.0001), respectively, in the nonsmokers, and -0.21 (P<0.0001) and -0.14 (P<0.0001), respectively, in the women. The odds ratio of 1 SD increment in TB for HbA_1c ≥5.4% was not significant in the smokers, 0.67 (P=0.002) in the nonsmokers, and 0.55 (P<0.0001) in the women. Conclusions: Bilirubin was negatively associated with HbA_1c independently of other cardiovascular risk factors in apparently healthy Japanese men and women. The association was weak in male smokers. (Circ J 2011; 75: 190-195)

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Background: Transforming growth factor-β (TGFβ) and its receptors have been detected by immunohistochemistry in the normal vessel wall and in atherosclerotic lesions of human coronary arteries. However, TGFβ is normally secreted as an inactive complex associated with a latent TGFβ-binding protein (LTBP). Therefore, detection of TGFβ antigen only in the arterial wall does not imply the activated form of the growth factor. Methods and Results: In situ hybridization and immunohistochemistry demonstrated LTBP1 mRNA and protein expression throughout the media and intima of early coronary artery lesions, with the highest levels of protein at the luminal surface. In advanced lesions, LTBP1 mRNA and protein were detected mainly in regions of high cell density, such as the fibrous cap. Conclusions: Assays of the TGFβ signalling pathway will be required to determine the activity associated with TGFβ antigen in the vessel wall. (Circ J 2011; 75: 196-200)

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Background: Bucolome, a nonsteroidal antiinflammatory drug, enhances the effects of warfarin. In the present study, the effects of combination therapy (bucolome+warfarin) vs. warfarin alone on atrial fibrillation were investigated. Methods and Results: Combined therapy resulted in a decrease in the warfarin dose to approximately one-third. The fluctuations of the international normalized ratio and the time in therapeutic range were similar in both groups. There was no adverse effect in either group. Interestingly, uric acid was lower in the bucolome group. Conclusions: Bucolome enhanced the effects of warfarin, resulting in a decreased dose of warfarin without adverse effects and it showed similar anticoagulant stability to warfarin alone. (Circ J 2011; 75: 201-203)

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The indications for percutaneous coronary intervention (PCI) have expanded, especially after the approval of drug-eluting stents, for both complex lesions and those with intermediate stenosis. Because recent randomized trials have demonstrated the non-inferiority of optimal medical treatment for stable angina compared with coronary revascularization, and the benefits of PCI guided by coronary pressure measurement have been shown in another trial, the appropriateness of current indications for PCI has been called into question. In the evaluation of coronary artery stenosis, inter- and intraobserver variabilities can be problematic. Therefore, the use of PCI for intermediate coronary stenosis based on angiographic evaluation alone without documentation of myocardial ischemia could be questionable. Guidelines mention that physiological assessment of myocardial ischemia is most useful in patients with intermediate coronary artery stenosis, while interobserver differences in the assessment of severe stenosis are usually small. Accordingly, routine provocation testing for myocardial ischemia before PCI may be less than ideal for real-world practice, and the indications for PCI should be multifactorial. (Circ J 2011; 75: 204-210)

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Compared with coronary artery bypass graft surgery (CABG), similar safety and efficacy have been demonstrated for percutaneous coronary intervention (PCI) with bare metal stents (BMS), except for the inferiority of PCI to CABG for repeat revascularization. Drug-eluting stents (DES) have dramatically reduced in-stent restenosis compared with BMS, and comparable prognoses could be expected in PCI with DES compared with CABG. Nevertheless, the long-term prognostic effect of PCI on major adverse cardiovascular events (MACE) in patients with stable coronary artery disease (CAD) remains uncertain, so the spotlight has been focused on the comparative long-term results of DES and CABG. At the moment, we should know that previous studies have reported only that PCI decreases angina frequency and improves short-term exercise performance in chronic CAD patients, and it effectively reduces the incidence of both death and myocardial infarction (MI) only in patients with acute coronary syndromes. Furthermore, a recent study also describes no advantage in improvement of prognosis including death, MI and other MACE for PCI compared with aggressive medical therapy in stable CAD patients, and for stenotic lesions without evidence of ischemia, the benefit of revascularization is less clear; medical therapy alone is likely to be equally effective. In conclusion, based on these data we should restrain ourselves from lesion treatment by simple PCI for angiographically significant CAD without any objective evidence of myocardial ischemia. (Circ J 2011; 75: 211-217)

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