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A 76-year-old male who had already been diagnosed with ischemic heart disease and severe aortic stenosis was transferred to our hospital in a state of cardiogenic shock. We finally diagnosed him with severe aortic stenosis. We decided to perform emergency balloon aortic valvuloplasty (BAV) as a bridge treatment to surgical repair. We first performed BAV with a double balloon technique, and next with a triple balloon technique. As a result, the blood pressure recovered, and surgical aortic valve repair could thus be successfully performed.

Pioglitazone (PIO) is widely used as an insulin-sensitizing agent in the treatment of type 2 diabetes, but it also causes an increase in body weight in a dose-dependent manner. Beraprost sodium (BPS), a stable prostaglandin I2 analog, is used clinically for the treatment of peripheral arterial disease and primary pulmonary hypertension. BPS has recently been demonstrated to promote insulin-induced glucose uptake by skeletal muscle. In this study, we examined whether low-dose PIO (PIO-L; 3 mg/kg/day) plus BPS treatment might exert antidiabetic effects without causing body weight gain in obese/diabetic KKAy mice. Treatment with PIO-L plus BPS tended to improve the hepatic insulin resistance and significantly improved the skeletal muscle insulin resistance, yielding a similar degree of hyperglycemia improvement to that obtained with high-dose PIO (PIO-H; 30 mg/kg/day) treatment. Moreover, the increase in body weight observed following PIO-H treatment was not observed following PIO-L plus BPS treatment. An increase in plasma adiponectin levels, which have been shown to be negatively correlated with hepatic glucose production, but not with the glucose disappearance rate during hyperinsulinemic-euglycemic clamp, was observed in the animals treated with PIO-L, PIO-L plus BPS, and PIO-H. This suggests that the improvement in hepatic insulin resistance was associated, at least in part, with an increase in the plasma adiponectin levels observed during PIO treatment. In contrast, treatment with BPS, which failed to increase the plasma adiponectin levels, ameliorated skeletal, but not hepatic insulin resistance. PIO-L plus BPS treatment may represent efficacious treatment for insulin resistance and type 2 diabetes without causing body weight gain.

The association of fibroblast growth factor 23 (FGF-23) with vascular disease in patients with preserved renal function is not well understood. The purpose of this study was to investigate the relationship of serum FGF-23 with coronary calcification in patients without chronic kidney disease and diabetes mellitus (DM).A cross-sectional study was performed in 148 consecutive patients with suspected coronary artery disease who underwent 64-slice computed tomography coronary angiography for diagnosis of coronary artery disease. Patients with eGFR60 mL/min/1.73 m(2), proteinuria, or DM were excluded. Associations of coronary calcification (evaluated by Agatston score) were examined with classical risk factors and with inflammatory markers, adipocytokines and FGF-23.The median creatinine, eGFR and FGF-23 levels were 0.7 mg/dL, 74.6 mL/min/1.73 m(2), and 26 pg/mL respectively. The strongest association was found between age and Agatston score (r = 0.367, p 0.001) in univariate logistic regression analysis. No atherogenic risk factors, including inflammatory markers and adipocytokine levels, were associated with Agatston score. Among calcium/phosphate metabolism markers, FGF-23 showed a weak but significant correlation with Agatston score (r = 0.169, p = 0.039). In multivariate linear regression analysis, age and FGF-23 (r = 0.188, p = 0.016) were independently associated with the Agatston score.Serum FGF-23 levels were associated with coronary calcification independently of classical risk factors and of adipocytokines and inflammatory markers in patients with preserved renal function. FGF-23 may also have a direct effect on progression of coronary calcification and further studies are required to examine this issue.

Objective Electrical cardioversion (EC) is associated with an increased risk of thrombotic events in patients with non-valvular atrial fibrillation (NVAF). Patients who experience AF for a period of >48 hours therefore require adequate anticoagulation therapy for at least 3 weeks before and 4 weeks after EC. While the guidelines address the management of vitamin K antagonists (VKAs), there are limited data on the use of novel oral anticoagulants (NOAC). One NOAC, rivaroxaban, has a rapid onset of action and might therefore shorten the time for which anti-coagulant treatment is required before a patient undergoes EC. Methods This study included 91 patients with NVAF of >48 hours in duration or in whom the time of onset was unknown who were undergoing EC after pretreatment with rivaroxaban. All of the patients were pretreated with rivaroxaban for at least 2 hours before EC and the same dose of rivaroxaban was prescribed for 4 weeks after EC. The primary endpoint was a successful EC without any thrombotic events or bleeding complications within 30 days after EC. The secondary endpoint was the time to EC. Results The mean age was 63±12 years and 70 of the 91 patients were male. The CHADS2 and HAS-BLED scores were 1.0±1.0 and 1.7±1.3, respectively. Although there were no thrombotic events, minor bleeding (gingival hemorrhage) occurred 20 days after the initiation of rivaroxaban treatment in one patient. The average time to EC was 11.9±11.1 days. Conclusion Rivaroxaban is safe and effective drug for NVAF patients who are scheduled for an EC. Furthermore, since VKAs take a substantial amount of time to establish adequate anticoagulation, pretreatment with rivaroxaban could shorten the time to the EC.

BACKGROUND To reduce myocardial damage caused by implantable cardioverter defibrillator (ICD) shock, the left axilla was studied as an alternative pulse generator implantation site, and compared with the traditional implantation site, the left anterior chest. METHODS AND RESULTS Computer simulation was used to study the defibrillation conduction pattern and estimate the simulated defibrillation threshold (DFT) and myocardial damage when pulse generators were placed in the left axilla and left anterior chest, respectively; pulse generators were also newly implanted in the left axilla (n=30) and anterior chest (n=40) to compare the corresponding DFT. On simulation, when ICD generators were implanted in the left axilla, compared with the left anterior chest, the whole heart may be defibrillated with a lower defibrillation energy (left axilla 6.4 J vs. left anterior chest 12.0 J) and thus the proportion of cardiac myocardial damage may be reduced (2.1 vs. 4.2%). Clinically, ventricular fibrillation was successfully terminated with a defibrillation output ≤5 J in 86.7% (26/30) of the left axillary group, and in 27.5% (11/40) of the left anterior group (P

Objectives The aim of this study was to characterize coronary plaque in target lesions with vessel remodeling using iMap-intravascular ultrasound (IVUS). Background The relationship between the plaque component and vessel remodeling remains to be elucidated. iMAP-IVUS is an imaging system that can be used to assess the plaque composition by radiofrequency signals from 40 MHz IVUS. Methods IVUS examinations were performed for the de novo target vessels of 146 stable angina pectoris patients (174 vessels). The patients were divided into two groups: including a nonpositive remodeling group (non-PR, remodeling index ≤ 1.0, 125 vessels) and a positive remodeling group (PR, remodeling index > 1.0, 49 vessels). Results The percent plaque burden in the PR group were lager than those in the non-PR group (79.05% vs. 74.36%, P < 0.01). Attenuation plaques were more frequently observed in PR group (40.8% vs. 12.1%, P < 0.0001). The percentages of lipidic and necrotic relative areas at the minimum lumen sites were greater in the PR group than in the non-PR group (7.22% vs. 6.03%, P

Summary Background Circadian variation has been accepted as a factor in acute myocardial infarction (AMI). An increased incidence of cardiac events in the morning has been reported for a long time. Recent reports have indicated that the onset of AMI shows two peaks, which occur in the morning and evening. It has also been demonstrated that circadian pattern of AMI may vary with sex and age. Methods and results We investigated 522 consecutive patients who underwent primary percutaneous coronary intervention (PCI) for ST segment elevation myocardial infarction (STEMI) between 2000 and 2010. The patients were classified into 3 age groups: younger (≤59 years old), intermediate (60–79 years old), and older (≥80 years old). Clinical data were investigated, including the age and sex, angiographic characteristics, and time of onset of STEMI. There were two peaks in the onset of STEMI throughout the day, which were at 7:00–10:00 and 19:00–21:00 h, among all patients (male and female). Stratified analysis showed that older females formed the main part of the second peak. Conclusions There were two peaks in the onset of STEMI in a Japanese population in Tokyo. The second peak was significantly dominated by the older female group. Age and gender influenced the second peak in the circadian variation of AMI in a Japanese population in Tokyo.

Previous epidemiological studies demonstrated plaque vulnerability to be high in diabetic patients. iMap-intravascular ultrasound (IVUS) is a recently developed radiofrequency 40 MHz IVUS imaging system for tissue characterization. This study aimed to characterize coronary plaque in target lesions of diabetic patients using iMap-IVUS.We studied 175 treated vessels in 146 patients with stable angina pectoris and analyzed plaque components of culprit lesions by iMAP-IVUS. Patients were divided into 2 groups: non-diabetic (non-DM: 112 vessels, 93 patients) and diabetic (DM: 63 vessels, 53 patients).In gray-scale IVUS 2D analysis, there were no differences in IVUS parameters. In 3D analysis, the DM group tended to have a larger plaque volume (p=0.07) and plaque burden (p=0.10). At minimum lumen sites, the absolute lipidic and necrotic areas (0.84 ± 0.44 mm(2) vs. 0.58 ± 0.41 mm(2), p0.001, and 2.42 ± 1.65 mm(2) vs. 1.46 ± 1.76 mm(2), p0.001, respectively) and percent lipidic and necrotic areas were significantly greater in the DM than in the non-DM group (8.39 ± 3.38% vs. 5.25 ± 2.30%, p0.0001, and 23.65 ± 11.54% vs. 12.99 ± 10.71%, p0.0001, respectively). In addition, the absolute lipidic and necrotic volumes (11.75 ± 10.59 mm(3) vs. 8.18 ± 6.24 mm(3), p0.01, and 29.99 ± 28.90 mm(3) vs. 19.44 ± 19.35 mm(3), p0.01, respectively) and percent lipidic and necrotic volumes were significantly greater in the DM than in the non-DM group (6.27 ± 1.92% vs. 5.13 ± 1.82%, p0.0001, and 16.54 ± 7.56% vs. 12.08 ± 6.05%, p0.0001, respectively).Characterization of coronary plaque by iMAP-IVUS in diabetic patients showed increased lipidic amount and necrotic plaque volume relative to subjects without DM.

Background: Cardiac resynchronization therapy (CRT) is effective in reducing morbidity and mortality in systolic heart failure patients with cardiac dyssynchrony as demonstrated in studies with primarily Western populations. Although CRT devices with a defibrillator (CRT-D) became available in Japan since 2006, their efficacy remains uncertain in Japanese patients. In this prospective, multicenter study, the efficacy of CRT-D therapy in an all-Japanese population was compared with the study conducted in the US, Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE-ICD). Methods and Results: Ninety-three patients were evaluated according to the subject selection criteria of the MIRACLE-ICD study, and 80 patients were enrolled. Results at baseline and 6-month post-CRT-D implantation were compared in terms of composite clinical response (CCR) and other secondary endpoints. Quality of life (QOL) was assessed with a validated Japanese version of the Minnesota Living with Heart Failure questionnaire. CCR was improved in 55 patients (68.8%), unchanged in 14 (17.5%), and worsened in 11 patients (13.7%) (MIRACLE-ICD general phase: 62.0%, 13.4% and 24.6%, respectively). Non-inferiority was verified by 1-sided test with 10% equivalence margin. QOL score improved significantly (50.0±26.2 vs. 23.6±20.2, P

Intravascular ultrasound studies have shown that patients with unstable angina pectoris (UAP) more frequently had soft plaques in the culprit coronary arteries than patients with stable angina pectoris (SAP). We evaluated coronary plaque characteristics of culprit lesions in patients with UAP by 64-slice computed tomographic coronary angiography (64-slice CTCA). 64-slice CTCA (Aquilion 64, Toshiba Medical Systems, Otawara, Japan) was performed in 30 patients (UAP = 14, SAP = 16) before percutaneous coronary intervention (PCI). Coronary plaque area was measured by manual tracing for the difference between the area within the external elastic membrane and the area of the vessel lumen at the site of maximal luminal narrowing as observed on a cross-sectional 64-slice CTCA image where PCI was performed. Within this plaque area, CT low-density plaque area (< 50 Hounsfield units) was automatically calculated. There were no differences in stenotic rate and whole plaque area of the culprit lesion between patients with UAP and SAP. However, the CT low-density plaque area was significantly greater in patients with UAP than in those with SAP. A greater area of CT low-density plaque in the culprit lesion is associated with UAP rather than SAP. Measuring CT-low density plaque area on 64-slice CTCA images could be useful for understanding the clinical setting of UAP.

Sixty-four-slice multidetector row computed tomography is a noninvasive method of assessing coronary artery stenosis and plaque composition. The aim of this study was to clarify the relation between plaque composition and coronary heart disease. Three hundred sixty consecutive patients and 1,085 plaques were evaluated using 64-slice multidetector row computed tomography. On axial or cross-sectional multiplanar reconstruction images, 3 regions of interest were randomly selected within each plaque. Soft plaques and calcified plaques were defined as having computed tomographic densities 130 Hounsfield units, respectively. The association between coronary risk factors and plaque composition was analyzed. The number of plaques and the mean computed tomographic density of plaques were significantly higher in men than in women (p = 0.002 and p = 0.04, respectively). Coronary plaques were more frequent in patients with stroke, diabetes, hypertension, and dyslipidemia than in patients without these conditions (all p values

Background Identification of coronary plaque composition is important for selecting the treatment strategy, and 64-slice computed tomography (CT) is a noninvasive method of characterizing atherosclerotic plaques. However, the correlation between plaque characteristics detected by CT and intravascular ultrasound (IVUS) is not clear. A 40 MHz IVUS imaging system (iMap-IVUS) has recently been developed to evaluate plaque composition. The aim of this study was to compare iMap-IVUS with 64-slice CT angiography for the characterization of non-calcified coronary plaques. Methods and results Both 64-slice CT angiography and iMap-IVUS were performed in 19 patients (38 plaques). CT values were measured as Hounsfield units (HU) in circular regions of interest (ROI) drawn on the plaques. The iMap-IVUS system analyzed coronary plaques as fibrotic, lipidic, necrotic, or calcified tissue based on the radiofrequency spectrum. A positive correlation was found between CT values and the percentage of fibrotic plaque ( r = 0.34, p = 0.036) or calcified plaque ( r = 0.40, p = 0.011). Conversely, a negative correlation was found between CT values and the percentage of lipidic plaque ( r = −0.41, p = 0.01), or necrotic plaque ( r = −0.41, p = 0.01). Conclusions Good correlations were observed between the characteristics of non-calcified plaque determined by iMap-IVUS and the CT values of plaque detected by 64-slice CT scanning.

Objectives: Cilostazol, a type III phosphodiesterase inhibitor, is an antiplatelet agent with vasodilating properties. Positive inotropic and chronotropic effects are frequently observed with cilostazol, but there are few reports on the influence of cilostazol on left ventricular function. The aim of this study was to assess this effect using tissue Doppler imaging (TDI) and two-dimensional speckle-tracking echocardiography (2D-STE). Methods: Thirty-five patients with normal left ventricular ejection fraction were enrolled in the study. Left ventricular cardiac function was assessed by TDI and 2D-STE before and after oral administration of cilostazol. Peak strain was defined using the peak radial strain (PRS), peak circumferential strain (PCS) and peak longitudinal strain (PLS). Time to peak strain was defined based on the times to PRS, PCS, and PLS, as T-PRS, T-PCS, and T-PLS, respectively. Results: After cilostazol administration, there were significant decreases in the left ventricular end-diastolic and end-systolic diameters (47.3 ± 5.2 vs. 43.3 ± 4.9 mm, P < 0.0001; 29.3 ± 6.4 vs. 26.0 ± 5.5 mm, P < 0.0001, respectively), and significant increases in the left ventricular ejection fraction (70.6 ± 9.5 vs. 72.7 ± 7.8%, P = 0.0381) and peak systolic annular velocity (7.9 ± 1.7 vs. 9.5 ± 3.1 cm/sec, P < 0.0001). PRS, PCS, and PLS all increased significantly and T-PRS, T-PCS, and T-PLS all decreased significantly after cilostazol administration. Conclusion: Positive inotropic and chronotropic effects of cilostazol were found based on assessment by TDI and 2D-STE. We suggest that periodic echocardiographic assessment should be performed before and after oral administration of cilostazol. (Echocardiography 2011;28:431-437)

Background: Radiofrequency catheter ablation (RF) has recently become widely available for the treatment of atrial fibrillation (AF) and has broadened treatment options while confusing the selection of medication therapy or RF. Methods and Results: Two drugs for the maintenance of sinus rhythm (Ry) and 2 drugs for control of the pulse rate (Ra) were selected and the costs of medication therapy were calculated. RF procedures were grouped into 2 groups each for persistent or paroxysmal AF (RF) and for chronic AF (RFChr), according to the cost of the devices used. The calculated cost of medication therapy was 5,270-23,560 yen per month. The calculated cost of RF procedures was 1,063,200-2,029,640 yen. The costs of RF corresponded to those of Ry for 3.8-14.3 years. The costs of RFChr corresponded to those of Ra for 16.6-63.9 years. The treatment of complications ranged from 360,000 to 1,241,500 yen. Conclusions: From the aspect of medical costs and complications, RF should be considered for the treatment of patients with AF detected early or early-stage AF, whereas treatment for its complications should be given priority in patients with chronic AF associated with reduced cardiac function. (Circ J 2011; 75: 1860-1866)

A 29-year-old man presented with complaints of fever and pain and itching of his left neck with atopic dermatitis and abrasion. These symptoms had persisted for two days and dullness and fever developed, but the patient did not consult a physician. On the following day, he had a fever of 40°C and redness and swelling of the left neck. He visited a local clinic and was hospitalized with suspected cellulitis. A thrombus was detected in the internal jugular vein on MRI, and he was referred to our hospital. Neck ultrasonography showed the presence of an immovable thrombus in the area from the left internal jugular vein to the left brachiocephalic peripheral vein. Blood analysis indicated a major inflammatory response and juvenile idiopathic thrombophlebitis was suspected. A filter was carefully inserted into the superior vena cava, and anticoagulant therapy and medication with antibiotics led to remission. We present this case as a rare example of a condition mimicking Lemierre syndrome that was caused by dermal infection, and we include a review of the literature.

Atrial fibrillation (AF) is the most common cardiac rhythm disorder and a major risk factor for stroke. For more than 60 years, warfarin has been the only approved anticoagulant for prevention of stroke in patients with AF. Although highly effective, it has many limitations that make its use difficult. Therefore, several novel anticoagulants are under development to overcome the limitations of warfarin, and some of these have entered phase III clinical trials. Dabigatran is an oral, reversible direct thrombin inhibitor approved in Europe and in several other countries for the prevention of venous thromboembolism after elective knee and hip replacement surgery. It has also been approved in the United States and Japan for the prevention of stroke and systemic embolism in patients with nonvalvular AF. In this review, the mechanism of action and pharmacological properties of new anticoagulants are described in detail, and the correct use of dabigatran in clinical practice is discussed.

The prognostic and diagnostic values of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in ischemic heart disease have already been investigated in many previous studies. Although NT-pro-BNP is affected by many factors, these previous studies did not strictly exclude them. This study included 110 patients who received coronary arteriography between November 2007 and September 2009. Excluded from the study were those patients who had clinical symptoms of heart failure, asynergy by echocardiography or left ventriculography (LVG), atrial fibrillation, prior myocardial infarction, valvular disease, lung disease, anemia or renal dysfunction. We compared the laboratory data, LVG and early transmitral-to-early diastolic annular velocity ratio (E/E (a)) in echocardiography between the group with coronary stenosis and the group without it. NT-pro-BNP and the low-density lipoprotein/high-density lipoprotein ratio (LDL/HDL) independently associated with the presence of coronary artery stenosis (odds ratio of NT-pro-BNP, each 50 pg/ml 2.367, 95% confidence interval 1.302-4.303, p = 0.005). The area under the curve of the receiver-operating characteristic (ROC) curve of NT-pro-BNP, used to predict coronary artery stenosis, was 0.801 (0.719-0.883, p 0.001). According to the ROC curve, the optimal cut-off level for predicting coronary stenosis was 64.3 pg/ml (sensitivity 82.5%, false-positive 34%). NT-pro-BNP is an attractive supplemental marker to predict the presence of coronary artery stenosis in a population that strictly excluded any affecting factors. In the population without factors affecting NT-pro-BNP, a slight increase suggests the presence of ischemic heart disease. The normal criteria for NT-pro-BNP in the patients undergoing coronary angiography may be much lower than the one currently used.

Summary Background The best way to treat in-stent restenosis (ISR) after drug-eluting stent (DES) implantation remains unclear. The aim of this study was to evaluate angiographic restenosis and target lesion revascularization (TLR) at 8 months after intervention in patients with DES-ISR, and to identify predictive factors of subsequent TLR after treatment of DES-ISR. Methods and results A total of 100 patients with 105 lesions underwent subsequent intervention for DES-ISR between April 2004 and January 2009. At baseline, focal and diffuse ISR were observed in 76.2% and 23.8%. DES-ISR was treated by five modalities: sirolimus-eluting stent (n = 42); paclitaxel-eluting stent (n = 24); balloon angioplasty (n = 23); cutting balloon angioplasty (n = 14); and bare-metal stent (n = 2). Angiographic follow-up data were available for 95 lesions (91%). The rates of angiographic restenosis and TLR were 37.9% and 33.3%. Late loss of sirolimus-eluting stent, paclitaxel-eluting stent, cutting balloon, and balloon angioplasty were 0.50 mm, 0.49 mm, 0.93 mm, and 1.10 mm. By multivariate analysis, totally occluded ISR (OR 15.43, p = 0.0005), diabetes mellitus (OR 3.45, p = 0.02), and re-stenting with DES (OR 0.14, p = 0.0002) were identified as independent predictors of TLR. Conclusions The restenosis rate was significant in this cohort of patients with DES-ISR. Angiographic pattern of DES-ISR and diabetes mellitus are the most important predictors of TLR, whereas re-stenting with DES is protective.

The purpose of this study is to determine the normative Doppler values and gender differences in left ventricular (LV) diastolic function in healthy subjects at each decade of life. Four hundred sixty-seven male and 455 female healthy subjects, aged 20–90 years, underwent standard echocardiography and tissue Doppler imaging. We divided the subjects into seven groups, based on the decade of their age (i.e., 20s, 30s, 40s, 50s, 60s, 70s, and 80s), and measured standard echocardiographic parameters and Doppler indices. Females younger than 50 years had significantly higher mitral E velocity, and females older than 40 years had significantly higher mitral A velocity, compared with their male counterparts. There was no difference in mitral E to A velocity ratio (E/A) at any age. The tissue Doppler method showed significantly lower early diastole velocity of the mitral annulus (E a) in females—especially females older than 50 years—than in males (10.7 ± 3.7 versus 11.2 ± 3.7 cm/s, p

SummaryBackgroundThe disadvantageous effect of kidney dysfunction on left ventricular (LV) diastolic function is still unknown.MethodsForty non-chronic kidney disease (CKD) patients and 202 CKD patients, aged 40–89, were examined by standard echocardiography and the new modality of tissue Doppler imaging. All subjects were divided into 5 groups depending on their estimated glomerular filtration rate (GFR: ml/min/BSA). Classifications by GFR were defined as follows: group 1 (more than 90: normal subjects), group 2 (60–89), group 3 (30–59), group 4 (15–29) and group 5 (less than 15).ResultsThere were no significant differences in LV systolic function among the groups. Mitral E velocity was significantly lower in groups 1–4 (p

Background— The prognosis of patients with saddleback or noncoved type (non–type 1) ST-elevation in Brugada syndrome is unknown. The purpose of this study was to clarify the long-term prognosis of probands with non–type 1 ECG and those with coved (type 1) Brugada-pattern ECG. Methods and Results— A total of 330 (123 symptomatic, 207 asymptomatic) probands with a coved or saddleback ST-elevation ≥1 mm in leads V 1 –V 3 were divided into 2 ECG groups—type 1 (245 probands) and non–type 1 (85 probands)—and were prospectively followed for 48.7�15.0 months. The absence of type 1 ECG was confirmed by drug provocation test and multiple recordings. The ratio of individuals with a family history of sudden cardiac death (14%) was lower than previous studies. Clinical profiles and outcomes were not notably different between the 2 groups (annual arrhythmic event rate of probands with ventricular fibrillation; type 1: 10.2%, non–type 1: 10.6%, probands with syncope; type 1: 0.6%, non–type 1: 1.2%, and asymptomatic probands; type 1: 0.5%, non–type 1: 0%). Family history of sudden cardiac death at age P =0.005; hazard ratio, 2.66; 95% confidence interval, 1.06 to 6.71; P =0.03, respectively, by multivariate analysis), although spontaneous type 1 ECG and ventricular fibrillation inducibility by electrophysiological study were not reliable parameters. Conclusions— The long-term prognosis of probands in non–type 1 group was similar to that of type 1 group. Family history of sudden cardiac death and the presence of early repolarization were predictors of poor outcome in this study, which included only probands with Brugada-pattern ST-elevation.

Background: While preprocedural statin treatment for acute coronary syndrome (ACS) is widely regarded as beneficial, there has been no prospective randomized multicenter trial of patients with non-ST elevation ACS in the Japanese population to examine the efficacy of preprocedural aggressive statin use. The aim of this study was to confirm this effect by prospective randomized multicenter design. Methods: Fifty patients who presented with non-ST elevation ACS were enrolled, and randomly assigned to aggressive statin administration before percutaneous coronary intervention (PCI). Troponin-T (TnT), creatine phosphokinase (CK), CK-myocardial band (CK-MB), high-sense C-reactive protein (hs-CRP), and brain natriuretic peptide (BNP) were measured at baseline and/ or after procedure. Results: Three days after PCI, the statin group had significantly less CK elevation compared with the nonstatin group (84±17 IU/l versus 180±68 IU/l, respectively, p = 0.02). CK-MB elevation also tended to be lower in the statin group than in the nonstatin group (3.2±1.9 versus. 7.0±3.0, respectively, p = 0.07), as was BNP level (3.2±1.9 versus 7.0±3.0 pg/ml, respectively, p = 0.07). The change of serum LDL cholesterol was significantly correlated with CK ( p = 0.01) and TnT ( p = 0.02) at 1 day after PCI. Conclusions: Aggressive statin usage before PCI to Japanese patients with non-ST elevation ACS appears to reduce myocardial damage after procedure. The degree of serum lipid level reduction may reflect the vulnerability of atheromatous plaques that could cause cardiac damage after PCI.

Introduction: This is a rare case of antidromic reciprocating tachycardia developing 8 years after successful catheter ablation. Result: A 15-year-old girl had recurrence of palpitations 8 years after the ablation of manifest right posteroseptal accessory pathway. Atrial burst pacing revealed Wenckebach atrioventricular conduction with preexcitation. Wide QRS tachycardia with identical morphology to sinus rhythm associated with retrograde His potential recorded immediately after the V-wave was induced by isoproterenol infusion. Atrial premature stimulus applied at the identical timing of His potential advanced the subsequent ventricular beat and His potential. Conclusion: Catheter ablation may produce decremental accessory pathway conduction and rarely cause antidromic atrioventricular reciprocating tachycardia. This may be explained by a presence of “de novo” accessory pathway with decremental conduction properties that became manifest after the first ablation.

Objectives To investigate stent deformation by torsional stress after implantation at the ostium of a model coronary artery. Background Little is known about coronary stent deformation, especially the association between stent design and deformation at the coronary ostium. Recent reports have suggested that mechanical factors are important for stent restenosis. Methods A coronary ostium model was constructed and three different stents (Express 2 , Cypher, and Tsunami, n =5 each) were implanted at the aorto-ostial junction. Differences of stent deformation were assessed after exposure to torsional stress. Intravascular ultrasound was used to measure the luminal area along each stent. Then the extent and pattern of plastic deformation were compared between the three stent types. Results The Express 2 stents and Cypher stents both showed significant deformation ( P P =.045, respectively) adjacent to the ostium, whereas only a minimal decrease of luminal area was observed with the Tsunami stent. In the central and distal parts of each stent, the decrease of luminal area was minimal and no differences were noted among the three types. Sudden fracture of a Cypher stent strut occurred during the experiment. Conclusion Differences of structural characteristics influence permanent plastic deformation at sites where continuous stress occurs, such as the coronary ostium. A more elastic design may show better resistance to such stress.

【背景】胸背部痛や重要臓器の虚血症状といった典型的な臨床症状を伴う急性大動脈解離（acute aortic dissection：以下AADと略す）は，近年の画像診断の普及によって診断すること自体は比較的容易な疾患である．一方で，その臨床症状の多彩さから非典型例で診断が遅れることはまれではない．【症例】70歳，男性．高血圧性腎硬化症を原因とするCKDステージ5（Cr 9.8 mg/dL）の患者．すでに内シャント造設を終え，待機的に血液透析導入予定であった．定期外来受診時，白血球上昇を伴わないC反応性蛋白（C-reactive protein以下CRP）の上昇（19.0 mg/dL）を認めたが，自覚症状は全くなかった．高CRP血症の精査を目的として入院となった．入院時の胸部単純X線検査でごくわずかに左肋横隔膜角が鈍であったため，原因精査目的に胸部造影CTを施行したところ，stanford B型（DeBakeyIIIa型）大動脈解離を認めた．入院後，自然経過でCRPは低下した．その他，各種培養など高CRP血症の原因精査を行ったが，有意なものはなく，CRPの上昇はAADに伴うものと考えられた．【まとめ】AADや大動脈瘤破裂に代表される大血管の疾患では炎症反応の上昇がみられる．腎不全患者は心血管イベントのハイリスク患者群であり，原因不明のCRP上昇を認めた場合，常に重篤な血管病変を意識して診療にあたる必要があるとの教訓を得た．

Background Although previous clinical trials demonstrated the non-inferiority of a rate control to rhythm control strategy for management of atrial fibrillation (AF), the optimal treatment strategy for paroxysmal AF (PAF) remains unclear. Methods and Results A randomized, multicenter comparison of rate control vs rhythm control in Japanese patients with PAF (the Japanese Rhythm Management Trial for Atrial Fibrillation (J-RHYTHM) study) was conducted. The primary endpoint was a composite of total mortality, symptomatic cerebral infarction, systemic embolism, major bleeding, hospitalization for heart failure, or physical/psychological disability requiring alteration of treatment strategy. In the study, 823 patients with PAF were followed for a mean period of 578 days. The primary endpoint occurred in 64 patients (15.3%) assigned to rhythm control and in 89 patients (22.0%) to rate control (P=0.0128). No significant differences between the treatment strategies were observed in the incidences of death, stroke, bleeding and heart failure. Meanwhile, significantly fewer patients requested changes of assigned treatment strategy in the rhythm control vs the rate control group, which was accompanied by improvement in AF-specific quality of life scores. Conclusion The J-RHYTHM study showed that rhythm control was associated with fewer primary endpoints than rate control. However, mortality and cardiovascular morbidity were not affected by the treatment strategy (umin-CTR No. C000000106).

Rimonabant has been shown to not only decrease the food intake and body weight but also to increase serum adiponectin levels. This increase of the serum adiponectin levels has been hypothesized to be related to the rimonabant-induced amelioration of insulin resistance linked to obesity, although experimental evidence to support this hypothesis is lacking. To test this hypothesis experimentally, we generated adiponectin knock-out (adipo(-/-))ob/ob mice. After 21 days of 30 mg/kg rimonabant, the body weight and food intake decreased to similar degrees in the ob/ob and adipo(-/-)ob/ob mice. Significant improvement of insulin resistance was observed in the ob/ob mice following rimonabant treatment, associated with significant up-regulation of the plasma adiponectin levels, in particular, of high molecular weight adiponectin. Amelioration of insulin resistance in the ob/ob mice was attributed to the decrease of glucose production and activation of AMP-activated protein kinase (AMPK) in the liver induced by rimonabant but not to increased glucose uptake by the skeletal muscle. Interestingly, the rimonabant-treated adipo(-/-)ob/ob mice also exhibited significant amelioration of insulin resistance, although the degree of improvement was significantly lower as compared with that in the ob/ob mice. The effects of rimonabant on the liver metabolism, namely decrease of glucose production and activation of AMPK, were also less pronounced in the adipo(-/-)ob/ob mice. Thus, it was concluded that rimonabant ameliorates insulin resistance via both adiponectin-dependent and adiponectin-independent pathways.

SummaryInsulin receptor substrate (Irs) mediates metabolic actions of insulin. Here, we show that hepatic Irs1 and Irs2 function in a distinct manner in the regulation of glucose homeostasis. The PI3K activity associated with Irs2 began to increase during fasting, reached its peak immediately after refeeding, and decreased rapidly thereafter. By contrast, the PI3K activity associated with Irs1 began to increase a few hours after refeeding and reached its peak thereafter. The data indicate that Irs2 mainly functions during fasting and immediately after refeeding, and Irs1 functions primarily after refeeding. In fact, liver-specific Irs1-knockout mice failed to exhibit insulin resistance during fasting, but showed insulin resistance after refeeding; conversely, liver-specific Irs2-knockout mice displayed insulin resistance during fasting but not after refeeding. We propose the concept of the existence of a dynamic relay between Irs1 and Irs2 in hepatic insulin signaling during fasting and feeding.

ベプリジル継続投与中の有効血中濃度は明確にされておらず, 同様に有効性との関連も明確にされていない.そこで頻脈性不整脈治療を目的にベプリジル継続投与中の101例で血中濃度を測定し, 血中濃度とべプリジル摂取後の時間経過との関連を検討した.ベプリジルは100～200mg/日を朝, 夕の2回あるいは朝, 昼夕の3回服用し, 全例が服用開始後30日以上経過した継続例であった.服用後1時間での最高値は0, 7μg/mL, 最低値は0.27μg/mL, 2時間の最高値は1.37μg/mL, 最低値は0.20μg/mL, 3時間では1.83μg/mLと0.17μg/mL, 4時間は1.69μg/mLと0.05μg/mL, 5時間は1.59μg/mLと0.26μg/mLであった.また, ベプリジルが有効であった症例の血中濃度と服用後の時間経過をみると2時間後も10時間後も血中濃度は0、6μg/mL以上であった.一方, ベプリジルが有効でない症例の血中濃度と服用後の時間経過をみると, 2時間後および4, 5時間後の血中濃度は0.3μ9/mL前後であった.ベプリジルの血中濃度は用量依存性を示した、また, 慢性腎不全で血液透析を受けている3症例に心房細動予防の目的で投与されたべプリジルの血中濃度を透析前後で比較してみると, ベプリジルは透析で除去されることなく, 透析前後でほぼ同様の値を示した.

Background Subcutaneous implantable cardiac defibrillator (S-ICD) systems have a lower invasiveness than traditional ICD systems, and expand the indications of ICD implantations. The S-ICD standard defibrillation shock output energy, however, is approximately 4 times that of the traditional ICD system. This raises concern about the efficacy of the defibrillation and myocardial injury. In this study, we investigated the defibrillation efficacy and myocardial injury with S-ICD systems based on computer simulations. Methods and results First, computer simulations were performed based on the S-ICD system configurations proposed in a previous study. Furthermore, simulations were performed by placing the lead at the left or right parasternal margin and the pulse generator in the superior and inferior positions (0-10 cm) of the recommended site. The simulated defibrillation threshold (DFT) for the 4 S-ICD system configurations were 30.1, 41.6, 40.6, and 32.8 J, which were generally similar to the corresponding clinical results of 33.5, 40.4, 40.1, and 34.3 J. Conclusions The simulated DFT were generally similar to their clinical counterparts. In the simulation, the S-ICD system had a higher DFT but relatively less severe myocardial injury compared with the traditional ICD system. Further, the lead at the right parasternal margin may correspond to a lower DFT and cause less myocardial injury.

Background More efficacious and/or safer decongestive therapy is clearly needed in acute heart failure (AHF) patients complicated by renal dysfunction. We tested the hypothesis that adding tolvaptan, an oral vasopressin-2 receptor antagonist, to conventional therapy with loop diuretics would be more effective treatment in this population. Methods and Results A multicenter, open-label, randomized control trial was performed, and 217 AHF patients with renal dysfunction (estimated glomerular filtration rate 15–60 mL • min −1 • 1.73 m −2 ) were randomized 1:1 to treatment with tolvaptan (n = 108) or conventional treatment (n = 109). The primary end point was 48-hour urine volume. The tolvaptan group showed more diuresis than the conventional treatment group (6464.4 vs 4999.2 mL; P .001) despite significantly lower amounts of loop diuretic use (80 mg vs 120 mg; P .001). Dyspnea relief was achieved significantly more frequently in the tolvaptan group at all time points within 48 hours except 6 hours after enrollment. The rate of worsening of renal function (≥0.3 mg/dL increase from baseline) was similar between the tolvaptan and conventional treatment groups (24.1% vs 27.8%, respectively; P = .642). Conclusions Adding tolvaptan to conventional treatment achieved more diuresis and relieved dyspnea symptoms in AHF patients with renal dysfunction. Clinical Trial Registration URL: http://www.umin.ac.jp/ctr/index/htm/ Unique identifier: UMIN000007109

Hemodialysis (HD) patients with critical limb ischemia (CLI) suffer chronic inflammation and repeated infection, require intervention, and may have a protracted hospital stay. Therefore, early prediction is particularly important for management of CLI in patients with suspected peripheral artery disease. The purpose of this study is to develop a simple score for predicting the incidence of CLI in HD patients with suspected peripheral artery disease. The subjects were 139 asymptomatic patients receiving maintenance HD and with ABI1.0. Multivariate logistic regression analysis was used to identify factors associated with development of CLI. These factors were subsequently weighted and integrated into a scoring system for the prediction of onset of CLI. Twenty-five patients had onset of CLI. Five factors selected from the multivariate model were weighted proportionally using their respective odds ratio (OR) for incidence of CLI (history of cerebral vascular disease, OR 6.42 [3 points]; diabetes, OR 3.92 [2 points]; hypoesthesia, OR 4.21 [2 points]; left ventricular ejection fraction50%, OR 3.89 [2 points]; serum albumin3.5 g/dL, OR 4.39 [2 points]). Three strata of risk were defined (low risk, 0 to 3 points; intermediate risk, 4 to 6 points; and high risk 7 to 11 points) with excellent prognostic accuracy for progression to CLI using the Kaplan-Meier method. Five factors were identified that increased the risk of progression to CLI in HD patients with suspected peripheral artery disease. A combination of those factors permitted establishment of three risk strata for accurate prediction of onset of CLI.

It is not unusual to perform coronary angiography (CAG) for elderly adults in aging society. However, there is few data about angiographic characteristics in oldest-old patients (age ≥85 years old). The aim of this study is to evaluate the prevalence and severity of coronary artery disease (CAD)

Background: While some therapies implemented for newly diagnosed Diabetes Mellitus (DM) or impaired Glucose Tolerance (IGT) are effective in preventing cardiovascular events, investigations of coronary plaque in patients with newly diagnosed DM or IGT are lacking. Methods: We evaluated 96 patients with acute coronary syndrome. The External Elastic Membrane (EEM), Lumen Cross-Sectional Area (CSA), plaque CSA, and plaque burden in the Left Anterior Descending (LAD) artery proximal to the lesion, diagnosed as normal by Coronary Angiography (CAG), were measured using Intravascular Ultrasound (IVUS). Patients were divided according to DM status (DM=35, non-DM=61). Non-DM patients underwent a 75g Oral Glucose Tolerance Test (OGTT) and were further divided into abnormal glucose tolerance (AGT; n=29) and Normal Glucose Tolerance (NGT) groups (n=32). Results: Quantitative Coronary Angiography (QCA) showed no significant differences in EEM or vessel diameter between groups. However, the lumen CSA was significantly smaller in the DM group than in the NGT group. The plaque CSA and plaque burden were significantly greater in the DM and AGT groups than in the NGT group. Total insulin and glucose values and insulin and glucose values at 120 min after the OGTT correlated with plaque CSA; insulin values at 120 min after the OGTT showed the strongest correlation (R=0.505, P

Objectives We conducted a collaborative cohort study to evaluate the predictive power of microvolt T-wave alternans (TWA) in patients with preserved left ventricular ejection fraction (LVEF) after myocardial infarction (MI). Background There is little information available about the prognostic value of risk stratification markers in this population. Although these patients have a relatively good prognosis, identifying high-risk patients is important in clinical practice. Methods This study enrolled 1,041 post-MI patients with an LVEF ≥40% (average 55 ± 10%). Microvolt TWA testing was performed 48 ± 66 days after acute MI, and 10 other risk variables were also evaluated. The end points were prospectively defined as sudden cardiac death or life-threatening arrhythmic events. Results During a follow-up of 32 ± 14 months, 38 patients (3.7%) died of nonarrhythmic causes and were not considered for analysis. Of the 1,003 evaluable patients, 18 (1.8%) reached an end point. Microvolt TWA was positive in 169 patients (17%), negative in 747 (74%), and indeterminate in 87 (9%). A positive microvolt TWA test, nonsustained ventricular tachycardia, and ventricular late potentials were predictors of events, and percutaneous coronary intervention decreased the risk rate. On multivariate analysis, a positive microvolt TWA test was the most significant predictor, with a hazard ratio of 19.7 (p Conclusions In patients with preserved cardiac function, the incidence of indeterminate results of microvolt TWA is low, and a positive test result is associated with arrhythmic events. Microvolt TWA could be used for risk stratification in this low-risk population.

Background Mega trials of rhythm vs rate control could not demonstrate the usefulness of available antiarrhythmic drugs, so a more effective and safer therapy for atrial fibrillation (AF) is now required. One candidate is the so-called "upstream therapy", which refers to the blockade of upstream modifying elements (renin - angiotensin system, cathecholamines, oxidative stress etc) that contribute to the arrhythmogenic substrate. Methods and Results The Japanese Rhythm Management Trial II for Atrial Fibrillation (J-RHYTHM II study) is a randomized comparative evaluation of an angiotensin II type 1 blocker (candesartan) and a dihydropiridine calcium blocker (amlodipine), both combined with antithrombotic therapy, as an antiarrhythmic therapy for the treatment of paroxysmal AF (PAF) associated with hypertension. To test the usefulness of this therapy, this study will reveal the recurrence rate of asymptomatic as well as symptomatic PAF during 1-year of treatment with candesartan or amlodipine, using daily transtelephonic monitoring. Conclusions The J-RHYTHM II study will follow 400 patients with PAF and hypertension who were treated at approximately 50 sites throughout Japan, and will provide clinically important information. (Circ J 2006; 70: 1318 - 1321)

Pharmacological treatment for atrial fibrillation has a variety of purposes, such as pharmacological defibrillation, maintenance of sinus rhythm, heart rate control to prevent congestive heart failure and prevention of both cerebral infarction and atrial remodeling. Sodium channel blockers are superior to potassium channel blockers for atrial defibrillation, while both sodium and potassium channel blockers are effective in the maintenance of sinus rhythm. In general, digitalis or Ca antagonists are used to control heart rate during atrial fibrillation to prevent congestive heart failure, while amiodarone or bepridil also reduce heart rates during atrial fibrillation. Anticoagulant therapy with warfarin is recommended to prevent cerebral infarction and angiotensin converting enzyme antagonists or angiotensin II receptor blockers are also used to prevent atrial remodeling. One should select appropriate drugs for treatment of atrial fibrillation according to the patient's condition.

The Japanese Rhythm Management Trial for Atrial Fibrillation (J-RHYTHM study) is a randomized comparative evaluation of rate control and rhythm control, both combined with antithrombotic therapy, as therapeutic strategies for the treatment of atrial fibrillation (AF). This study differs from the earlier AFFIRM and RACE studies in that it has a composite primary end-point representing mortality and also physical/psychological disablement (total mortality, symptomatic cerebral infarction, systemic embolism, major bleeding, hospitalization for heart failure requiring intravenous administration of diuretics, and patient disablement). Patients' will to change the therapeutic strategy to the other is also considered as an end-point representing disablement under the assigned strategy. The secondary end-point includes quality of life scores and the efficacy and safety of drugs used in treating AF. The J-RHYTHM study emphasizes patient-reported experience and perception of AF-specific disablement, and the safety of antiarrhythmics available in Japan; it will follow 2600 patients treated at more than 150 sites in Japan for a 3-year period.

Brugada症候群におけるrisk stratificationを明らかにするため, 脱分極 (伝導) 異常を反映するfate potentials (LP) , 再分極異常を反映するQT dispersion (QTD) およびT-wave alternans (TWA) と不整脈事故との関連性を, 電気生理学的誘発性 (EPS) やH-V時間と絡めて評価した, 対象は, Brugada型心電波形を示した44例である.LP, QTD, TWAの測定はすべて自動計測で行われ, V1～V3誘導の最大ST上昇値も自動計測された, EPSによる誘発には, 抗不整脈薬も使用された.検査時に典型的Brugada波形を示した33例における各指標の陽1生率は, LP: 24例 (73%) , TWA: 5例 (15%) , QTD: 9例 (27%) であった.LPの陽1生率は健常者40例と比較して有意に高値であった (P

The case of a 58-year-old man with a previous anterior wall myocardial infarction and direct stenting who underwent multislice spiral computed tomographic (MSCT) coronary angiography with a row of 16 detectors before and after nine months of treatment with a statin is presented. MSCT coronary angiogram showed no significant stenosis in the left anterior descending (LAD) coronary artery, including the stented portion, and stress myocardial perfusion imaging showed that there was no ischemia. However, MSCT coronary images showed a lipid-rich plaque in the proximal portion of the stent implantation site in the LAD with a density of 17 Hounsfield units (HU) and with a size of 1.5 × 1.5 × 2.0 mm. MSCT coronary images obtained after nine months of treatment with pitavastatin showed that the plaque was smaller and had a density of 114 HU. MSCT coronary angiography allowed us to evaluate coronary artery plaque morphology before and after treatment with pitavastatin.

High levels of high-sensitivity cardiac troponin T (hs-cTnT) are associated with coronary artery disease (CAD). The SYNTAX score (SXscore) is an angiographic tool used to grade the complexity and extent of CAD. We investigated the relationship between hs-cTnT levels and SXscore. We conducted a cross-sectional analysis of 408 patients who underwent first diagnostic coronary angiography between December 2011 and December 2012. SXscore was recorded, and serum hs-cTnT levels were measured in all patients. The median hs-cTnT level was 0.009 μg/L. Elevated hs-cTnT levels (≥0.014 μg/L) were observed in 136 patients (33 %). Twenty-seven patients (7 %) had complex CAD as defined by intermediate or high SXscores. The levels of hs-cTnT were significantly higher in patients with high or intermediate SXscores than in those with low SXscores (0.044 ± 0.055 vs. 0.018 ± 0.058 μg/L, p = 0.03). Multivariate analysis identified hs-cTnT level, and diabetes mellitus as independent predictors for complex CAD. The adjusted odds ratio of hs-cTnT level for predicting complex CAD was 2.86 (95 % confidence interval 1.90-4.45, p