Background Renal insufficiency is common in patients with chronic heart failure (CHF), so to improve the prognosis of patients with cardiovascular risks clinical guidelines recommend estimating the glomerular filtration rate (GFR), which detects chronic kidney disease more accurately than does the serum creatinine level alone. However, the clinical usefulness of the estimated GFR (eGFR) in Japanese CHF patients is still unclear. Methods and Results Of 1,278 patients registered in a Japanese CHF registry, termed the Chronic Heart Failure Analysis and Registry in the Tohoku District study, the study population included 920 symptomatic patients with sufficient data. Baseline eGFR (ml ·min^-1 · 1.73 m^-2) was calculated using the Cockcroft-Gault equation. Patients were divided into three groups based on eGFR: ≥60, 30-59, and <30 ml · min^-1 ·1.73 m^-2. Kaplan-Meier analysis revealed that the incidence of the combined event of all-cause death and admission because of CHF was significantly higher in patients with reduced eGFR and such patients were older and more frequently had an ischemic etiology of CHF, a higher prevalence of diabetes, lower hemoglobin level, and higher B-type natriuretic peptide level. Multivariate Cox regression analysis showed that reduced eGFR was significantly associated with the combined endpoint. Conclusions GFR should be evaluated in all Japanese patients with CHF to improve risk stratification and treatment. (Circ J 2008; 72: 173 - 178)

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Background Outcomes after percutaneous coronary intervention (PCI) for patients with acute myocardial infarction (AMI) complicated by renal insufficiency have not been well described. The aims of this study were to evaluate the association of estimated glomerular filtration rate (GFR) and risk of unsuccessful PCI for AMI, and to evaluate the prognostic importance of PCI success in patients with renal insufficiency. Methods and Results From the Heart Institute of Japan Acute Myocardial Infarction (HIJAMI) registry, 1,706 patients undergoing primary PCI were analyzed. The adjusted odds ratios for unsuccessful PCI of GFR 30-60 and <30 ml · min^-1 · 1.73 m^-2 were 1.97 (95% confidence interval (CI): 1.22-3.18) and 2.56 (95%CI: 1.13-5.78), respectively. During the mean follow-up period of 29 months, the adjusted hazard ratios for death of successful compared with unsuccessful PCI were 1.0 (reference) compared with 2.04 (95%CI: 0.87-4.81) in the highest GFR group, 1.51 (95%CI: 1.11-2.06) compared with 2.07 (95%CI: 1.19-3.62) in the intermediate GFR group, and 2.69 (95%CI: 1.72-4.22) compared with 10.07 (95%CI: 4.91-20.5) in the lowest GFR group. Conclusions Decreased GFR was associated with the risk of unsuccessful primary PCI. Moreover, unsuccessful PCI was associated with strikingly poor long-term survival in patients with GFR <30 ml ·min^-1 · 1.73 m^-2. Steady success is essential when using PCI for such a high-risk population. (Circ J 2008; 72: 179 - 185)

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Background It has been recently demonstrated that the hemodynamic consequences of exercise-induced increase in left ventricular (LV) filling pressure can be demonstrated noninvasively with supine bicycle exercise Doppler echocardiography. One of the practical drawbacks of Doppler echocardiography for assessing LV filling during exercise is the technical difficulty obtaining adequate signals for meaningful analysis during the rapid heart rates achieved during exercise. The purpose of this study was to assess LV filling pressures during the recovery period, as well as at rest, in healthy subjects to establish reference values of Doppler LV filling indices during recovery after exercise. Methods and Results Seventy-three healthy subjects (age 38±14 years, 62 males) underwent supine bicycle exercise. Mitral inflow and annular velocities were recorded at baseline and during recovery at 2, 5, and 10 min after cessation of exercise. The ratio of the mitral inflow early diastolic filling velocity (E) to the mitral annular early diastolic velocity (E') was used as an estimation of mean left atrial pressure (E/E'). The mean E/E' ratio at rest was 7.6±1.8 and it was <15 in all patients. Mean exercise duration was 837±184 s (range, 390-1,260). The E/E' ratio during recovery 2, 5, and 10 min after cessation of exercise was 8.8±1.9, 8.2±2.0 and 7.8±1.8, respectively, and none of the patients had an E/E' >15 during the recovery phase. Conclusion In healthy subjects, the E/E' is less than 15 at rest, as well as during the recovery period up to 10 min after cessation of exercise. Because the E/E' is not elevated in healthy subjects, an elevated E/E' during the recovery period may be helpful for detecting exercise-induced diastolic dysfunction in subjects with tachycardia, even with low levels of exercise. (Circ J 2008; 72: 186 - 188)

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Background The prevalence of subclinical left ventricular (LV) systolic dysfunction in asymptomatic hypertensive patients was determined using tissue Doppler imaging (TDI). Methods and Results TDI-derived mitral annular velocities were acquired in 35 control subjects, 92 asymptomatic hypertensive patients with no heart failure (HHD), and 15 patients with diastolic heart failure (DHF). No significant intergroup differences in LV ejection fraction were noted. Peak systolic annular velocity was significantly reduced in the DHF group compared with the control and HHD group. Using peak systolic velocity <6.1 cm/s as a cut-off value for abnormal velocity, 10% of HHD patients and 53% of DHF showed impaired LV longitudinal systolic velocity. Peak early diastolic annular velocities were significantly reduced in both the HHD and DHF groups compared with the control group. With multivariable regression analysis, peak early and late diastolic annular velocities, female gender and deceleration time of the E wave velocity were selected as independent predictors for peak systolic annular velocities. Conclusions Systolic long-axis LV function was impaired in 10% of asymptomatic hypertensive patients. Its reduction was closely correlated with impaired diastolic function. Assessment of LV longitudinal function by TDI plays an important role in identifying diastolic dysfunction and subclinical LV systolic dysfunction in asymptomatic hypertensive patients. (Circ J 2008; 72: 189 - 194)

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Background The prediction of perioperative cardiovascular complications is important in the medical management of patients undergoing noncardiac surgery. Several indices have been developed, but a simpler, more practical and accurate method is needed. The purpose of this study was to determine whether the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration before operation can be used to predict perioperative cardiovascular complications in elderly patients undergoing noncardiac surgery. Methods and Results The study group comprised 279 patients older than 60 years who were scheduled for elective surgery. The plasma NT-proBNP concentration, clinical cardiac indices and left ventricular ejection fraction were measured prior to operation. The postoperative cardiac outcomes were followed and predictors for postoperative cardiac risk were identified. Cardiovascular complications occurred in 25 patients (9.0%). Age, the incidence of prior ischemic heart disease or congestive heart failure, and the plasma NT-proBNP concentration were significantly higher in patients with perioperative cardiovascular complications than in those without. Using receiver operating characteristic analysis to predict perioperative cardiovascular events, a cut-off value of 201 pg/ml was identified as the optimal predictor of perioperative complications, showing a sensitivity of 80.0% and specificity of 81.1%. Multivariate analysis revealed that NT-proBNP >201 pg/ml (odds ratio (OR) 7.6, 95% confidence interval (CI) 2.2-26.6, p=0.003) and revised cardiac index ≥2 (OR 6.3, 95% CI 1.7-23.8, p=0.007) were independent predictors for perioperative cardiovascular complications. Conclusions Elevated NT-proBNP levels are independently associated with an increase in the risk of perioperative cardiovascular complications in elderly patients undergoing noncardiac and nonvascular operations. (Circ J 2008; 72: 195 - 199)

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Background The aim of the present study was to investigate the clinical importance of microvascular obstruction (MO) on contrast-enhanced magnetic resonance imaging (MRI), comparing it with the myocardial perfusion index (MPI) assessed using first-pass MRI. Methods and Results Cardiac MRI was performed in 33 patients within 7 days after reperfusion of a myocardial infarction (MI). Using a bolus injection of Gd-DPTA, first-pass images were obtained with the Turbo-FLASH sequence. Time-intensity curves in the left ventricular cavity and in myocardial sections were generated and then the MPI was assessed by the maximum slope method. Late enhancement (LE) was assessed using the true-FISP sequence. According to the transmurality of LE, the patients were classified into 3 groups: Group 1 included patients with localized endocardial enhancement; Group 2, patients with transmural enhancement; Group 3, patients having LE with MO. In cases of anterior infarction, the MPI for the anterior wall and parts of the inferior wall in Group 3 was significantly lower than that for Group 1 and 2. For inferior infarction, the MPI for parts of the inferior wall in Group 3 was significantly lower than that for Group 1 and 2. Conclusion MO is related to lower MPI, indicating severe microvascular damage. LE with or without MO is an important marker of perfusion status after reperfused MI. (Circ J 2008; 72: 200 - 204)

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Background The association of inflammatory markers with mortality in ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) remains controversial, so in the present study the relationships of high-sensitivity C-reactive protein (hs-CRP), total white blood cell (WBC) count, neutrophil (N) and lymphocyte (L) counts and the N/L ratio with occurrence of in-hospital mortality were assessed in patients with STEMI treated with primary PCI. Methods and Results Inflammatory parameters were assessed on admission in 1,078 consecutive, unselected patients with STEMI admitted for primary PCI. In-hospital death occurred in 6.3% of the patients. Of the inflammatory parameters, only hs-CRP (p<0.001), and the WBC (p=0.004) and N (p=0.020) counts were predictors of death in the univariate analyses. After adjustment for other baseline clinical variables both hs-CRP and WBC count retained their independent association with mortality when analyzed both in 2 separate and in 1 multivariable models. Conclusions Both hs-CRP and the WBC count may independently of each other predict early outcomes in STEMI patients treated with primary PCI, which suggests different pathological significance of these 2 non-specific inflammatory markers in STEMI. (Circ J 2008; 72: 205 - 211)

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Background It is unknown whether the association of anemia with elevated plasma levels of B-type and atrial natriuretic peptides (BNP and ANP) is mediated by the hemodynamic effects of anemia. Methods and Results The study group comprised 237 consecutive patients (BNP, median [interquartile range], 28.3 [9.5-77.1] pg/ml; ANP, 17.8 [8.5-39.0] pg/ml) undergoing determination of hemoglobin (Hb) and natriuretic peptide levels and cardiac catheterization for evaluation of coronary artery disease (CAD). Hb correlated with BNP (r=-0.36, p<0.001) and ANP (r=-0.35, p<0.001). Patients with anemia (Hb <12 g/dl for females; <13 g/dl for males, n=63) were more likely to be older with reduced body mass index and renal function, greater severity of CAD and to have higher heart rate, mean pulmonary capillary wedge pressure, and cardiac output. Anemia was a significant predictor for elevated (>third quartile value) natriuretic peptide levels and the predictive value remained significant after adjustment for other predictors, including increased left ventricular end-diastolic pressure and differences in clinical and hemodynamic variables between patients with and without anemia (adjusted odds ratio [95% confidence interval] for elevated BNP and ANP levels, 7.39 [2.76-19.8] and 2.56 [1.08-6.07], respectively). Conclusion Anemia is an independent predictor for elevated natriuretic peptide levels in patients with known or suspected CAD. (Circ J 2008; 72: 212 - 217)

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Background The respective incidences of ischemic heart and cerebrovascular disease (IHD, CVD) are high in diabetic individuals. Complications of dyslipidemia increase the risk, but direct evidence is limited, so a cohort prospective study (Japan-CDM) was conducted. Methods and Results The study group comprised 4,014 subjects with type 2 diabetes (1,936 women, 2,078 men; mean age 67.4±9.5 years) who were divided into dyslipidemic patients (79.1%) with or without medication (medicated, 50.9%; not medicated, 28.2%) and normo-lipidemic patients (20.9%). The incidence of IHD, CVD, arteriosclerosis obliterans (ASO), congestive heart failure (CHF) and death was assessed. IHD and CVD occurred in 0.82 and 0.67%, respectively, during the first year following registration. CHF, ASO and sudden death occurred in 0.27%, 0.12% and 0.12%, respectively. There was a significant statistical difference in the relation of elevated levels of high-density lipoprotein-cholesterol to lower rates of IHD and CVD. IHD and CVD in males were dependent on the level of low-density lipoprotein-cholesterol (LDL-C): 0.45%, 1.56%, 1.78%, 1.91% and 2.34% were observed in less than 2.11, 2.11-2.62, 2.63-3.15, 3.16-3.67, and more than 3.68 mol/L of LDL-C. In the lowest LDL-C group, death other than from vascular diseases was increased. Age, sex (male) and complicated hypertension increased the risk of events. Patients who were prescribed antihyperlipidemic agents suffered less events than patients who were not being treated, which suggests direct effects of therapy. Conclusion Strict lipid control may be effective for reducing the incidence of vascular events in Japanese diabetic individuals. (Circ J 2008; 72: 218 - 225)

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Background The scintigraphic perfusion defect size (DS) at 1 week after acute myocardial infarction (AMI) predicts remote left ventricular (LV) volumes and LV ejection fraction (LVEF). The present study examined whether LV volumes and LVEF 6 months after AMI may be better predicted by the combination of LV volumes and LVEF just after reperfusion, and DS at 1 week, after AMI in patients with Thrombolysis In Myocardial Infarction (TIMI) grade III reperfusion by percutaneous coronary intervention. Methods and Results In 48 patients with AMI and TIMI grade III reperfusion, quantitative gated SPECT (QGS) was performed just after reperfusion, and at 1 week and 6 months after AMI. LV end-diastolic volume index decreased (108±8 to 93±6 ml/m², p<0.05) and LVEF increased (44±3 to 50±2%, p<0.05) 6 months after AMI. In addition, they were better predicted by a combination of LV volumes and LVEF just after reperfusion and DS at 1 week after AMI. Conclusions In AMI with TIMI grade III reperfusion, LV volumes and LVEF at 6 months after MI correlate with the values obtained just after reperfusion. Myocardial perfusion imaging combined with QGS at reperfusion may predict these late-phase parameters. (Circ J 2008; 72: 226 - 231)

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Background It has been reported that stent deployment results in acute inflammation and platelet deposition as an acute phase reaction and smooth muscle cell (SMC) proliferation as a chronic phase reaction. Other studies have shown that statin therapy can reduce thrombosis as a pleiotropic effect. The present study was undertaken to examine whether preprocedural statin therapy can reduce the thrombotic reaction after stent implantation by using in-stent restenosis (ISR) tissue. Methods and Results The study group consisted of 45 consecutive patients (stable angina) with ISR who underwent directional coronary atherectomy (DCA). According to the histological findings, the patients were divided into 2 groups: those whose ISR tissue included thrombus and SMC (T group), and those whose ISR tissue included only SMC (S group). Just before DCA, serum markers were evaluated, including high-sensitivity C-reactive protein (hs-CRP), lipoprotein (a), plasminogen activator inhibitor-1 (PAI-1), fibrinogen, total cholesterol, triglyceride, high-density lipoprotein cholesterol, fasting blood glucose, and hemoglobin A_1c. Preprocedural medications, including statins, were also evaluated. The values for hs-CRP and PAI-1 in the T group were significantly higher than those in the S group, and the rate of statin use in the T group was significantly lower than that in the S group. There were no significant differences in any of the other factors. Multivariate analysis revealed that preprocedural statin use and the PAI-1 level were significant independent variables affecting the histological findings. Conclusion Preprocedural statins, associated with the involvement of PAI-1, can reduce the thrombotic reaction after stent implantation. (Circ J 2008; 72: 232 - 237)

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Background Differentiation between ischemic (ICM) and dilated cardiomyopathy (DCM) has important therapeutic implications because the former may benefit from coronary revascularization. The aim of this study was to investigate right ventricular (RV) function using tissue Doppler echocardiography (TDE) and compare the TDE parameters of the RV among patients with ICM and DCM. Methods and Results Forty-two patients with ICM and 40 patients with DCM were studied with conventional echocardiography and TDE. The 2 groups did not differ in terms of New York Heart Association class, left ventricular ejection fraction and pharmacological treatment. Patients with ICM had higher pulmonary artery systolic pressure (44.4 mmHg vs 34.7 mmHg, p=0.006) and lower tricuspid annular motion systolic (RV Sa 0.06 m/s vs 0.09 m/s, p<0.0001), and diastolic velocities (RV Ea 0.05 m/s vs 0.07 m/s, p=0.0003, RV Aa 0.075 m/s vs 0.11 m/s, p=0.0016). They also exhibited a higher ratio of early transtricuspid filling velocity to early diastolic velocity of the tricuspid annulus (RV E/Ea 8.2 vs 5.7, p=0.0008). Age, pulmonary artery systolic pressure and tricuspid Sa were significant independent predictors of the diagnosis of ICM. Conclusions RV dysfunction is more pronounced in patients with ICM than in patients with DCM. The RV TDE parameters can be used to complement clinical and conventional echocardiographic findings in the assessment of patients with ICM and DCM. (Circ J 2008; 72: 238 - 244)

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Background In calcific aortic valve disease, the early lesion is similar to atherosclerotic plaque, but later calcification prevails. Parathyroid hormone (PTH) and vitamin D are the principal calcium pool regulators, so the present study was designed to assess their association with aortic stenosis (AS) in patients with significant coronary artery disease (CAD), and preserved renal function. Methods and Results The 122 consecutive patients with AS (mean gradient ≥30 mmHg) plus CAD, and 101 patients with nonobstructive aortic sclerosis (mean gradient ≤10 mmHg) plus CAD, as controls, were prospectively enrolled. The AS patients were older (71±7 vs 66±7 years; p<0.001), had higher serum intact (i)PTH (51.4 [39-70] vs 37.4 [27-50] pg/ml; p<0.001), and lower plasma vitamin D (32.0 [25-40] vs 35.8 [27-55] nmol/L; p=0.003) levels than those with aortic sclerosis. The groups did not differ significantly in creatinine level (93 [82-105] vs 96 [85-107] μmol/L, p=0.19), calcium - phosphate product, occurrence of hypertension, smoking, diabetes, dyslipidemia, or body mass index. The iPTH (odds ratio (OR) 1.04, 95% confidence interval (CI) 1.02-1.05; p<0.001) and vitamin D levels (OR 0.97, 95% CI 0.95-0.99; p=0.003) were independently associated with AS. Conclusion Higher serum iPTH with lower vitamin D levels were independently associated with calcific AS in CAD patients. (Circ J 2008; 72: 245 - 250)

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Background Afterload is expected to increase with pneumatic compression of the lower extremities. There are left ventricular (LV) wall stress, which is the most important factor determining myocardial oxygen demand, will also increase, leading to an increase in the sensitivity of dobutamine stress echocardiography (DSE) or a shortened time to a positive response. Methods and Results In 40 patients who underwent DSE and were anticipating undergoing coronary angiography (CAG), the imaging was repeated with pneumatic compression (100 mmHg) of the lower extremities (DSEcomp) prior to CAG. The sensitivity and specificity of DSE and DSEcomp were determined based on the CAG findings. All patients tolerated pneumatic compression of the lower extremities during the tests. LV end-systolic volume (p=0.042) and end-systolic wall stress (p=0.036) were significantly greater with DSEcomp than with DSE. In 3 patients with false-negative results for DSE, DSEcomp gave a positive response, demonstrating a significant increase in sensitivity from 75% to 94% (p=0.045). Only 1 patient with a true negative result for DSE was interpreted as showing a positive response for DSEcomp, resulting in a decrease in specificity from 88% to 83% (p=NS). In 10 of 12 patients with true positive results for both DSE and DSEcomp, positive responses were seen at least 1 stage earlier with DSEcomp than with DSE. Conclusions Pneumatic compression of the lower extremities increases the sensitivity of DSE and shortens the time to a positive response. (Circ J 2008; 72: 251 - 255)

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Background This study aimed to demonstrate the long-term prognostic implication of left atrial appendage (LAA) mechanical reserve determined after electrical cardioversion (CV) of atrial fibrillation (AF). Methods and Results 53 successfully cardioverted chronic AF patients were studied (M/F =40/13, mean age =59±3). LAA emptying velocity (LAAEV) and filling velocity (LAAFV) were measured using transesophageal echocardiography (TEE) before cardioversion, immediately after CV, and with isoproterenol infusion. TEE was done at baseline, 1 month, 3-6 months, and 1 year after CV. At 1-year follow-up, 27 patients remained in sinus rhythm (SR, Group 1) and 26 patients showed AF recurrence (Group 2). Baseline clinical and echocardiographic findings were similar between the 2 groups. Immediately after CV, LAAEV and LAAFV decreased similarly in both groups. With isoproterenol infusion, the increase of LAAEV was greater in group 1 than in group 2. Multivariate analysis revealed that the peak increase of LAAEV after isoproterenol infusion was an independent predictor for SR maintenance (odds ratio 1.044, 95% confidence interval 1.014 to 1.075; p=0.0033). Prediction model consisting of the peak increase of LAAEV (>34.4 cm/s) and E/A ratio immediately after CV (<2.5) showed a good predictability for SR maintenance (correct ratio 69.8%). Conclusion This study presents a valid evaluation method for LAA mechanical reserve and demonstrated that LAA mechanical reserve is responsible for the maintenance of SR. (Circ J 2008; 72: 256 - 261)

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Background Pacing at the right atrial septum (RAS) appears to be superior to that performed at the right atrial appendage for preventing paroxysmal atrial fibrillation and for reducing complications. However, atrial lead insertion at the RAS is difficult and time-consuming. Although a few useful devices have been reported, handling of the atrial lead around the RAS is sometimes difficult even with those devices. Therefore, in the present study a long-straight sheath (LSS) was used in an attempt to secure sufficient space for handling the atrial lead around the RAS. Methods and Results Seventy-six consecutive patients who underwent insertion of an atrial lead at the RAS from a left-sided approach were examined. The non-LSS group comprised 24 patients and the LSS group had 52. The success rate of atrial lead insertion was significantly higher in the LSS group than in the non-LSS group [50/52 (96.1%) vs 13/24 (54.2%); p<0.01]. The operation time was significantly shorter in the LSS group (13.6±9.1 min vs 32.7±11.1 min, p<0.01). P wave duration was significantly shorter during RAS pacing than during normal sinus rhythm. Conclusion The LSS technique is useful for atrial lead insertion at the RAS because it enables sufficient space to be secured for lead handling. (Circ J 2008; 72: 262 - 267)

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Background Ventricular tachyarrhythmias (VT/VF) are 1 of the most important factors determining the prognosis of patients with heart failure (HF). Although priority is given to implantable cardioverter defibrillator (ICD) therapy for the prevention of sudden cardiac death, electrophysiologic-study (EPS)-guided preventive therapy could be important for reducing the number of cardiac events. Methods and Results Of 864 patients with a history of HF, an EPS was performed in 168 and 121 had inducible VT/VF. Under the basic therapy of an ICD, additional catheter ablation was attempted for 95 of 124 monomorphic VT foci in 74 patients, and 78 of the VT were successfully ablated. The prognoses were compared among 5 patient groups with different results for the EPS and catheter ablation: (1) success group (n=43), (2) failure group (n=15), (3) not attempted group (n=16), (4) VF group (n=47), and (5) no inducible VT/VF group. During a follow-up period of 31±22 months, the incidence of VT/VF was lower in the success and no inducible VT/VF groups than in the other groups (p=0.0018), although a significant difference was not observed for the total deaths. Conclusion EPS-guided preventive therapy using an ICD and catheter ablation can be useful, at least for the reduction of arrhythmic events in patients with HF. (Circ J 2008; 72: 268 - 273)

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Background This study was performed to investigate the incidence of arrhythmias in patients with Kawasaki disease (KD). Methods and Results Electrophysiologic studies (EPS) were performed in 40 patients (mean age: 10.3±5.1 years; 30 males, 10 females) with KD who had severe to moderate coronary artery disease. Clinical arrhythmias were documented in 4 patients (premature ventricular contractions, ventricular tachycardia, atrioventricular block, and ventricular fibrillation). Dual atrioventricular nodal pathways were demonstrated in 3 patients. Nonsustained atrial fibrillation was induced in 1 patient. The AH interval was prolonged in 2 patients. The Wenckebach rate was 164±37 beats/min, and 4 of the patients had a decreased Wenckebach rate. The maximum and corrected sinus node recovery times were 997±257 ms and 281±130 ms, respectively, and 7 patients were thought to be abnormal. The sino-atrial conduction time was 108±64 ms, and 2 patients had prolonged conduction times. Conclusions Although there was no relationship between coronary stenosis or obstruction and the EPS parameters, the incidence of abnormal sinus node and atrioventricular node function is apparently higher in KD patients than in the normal population. These functional abnormalities may possibly be caused by myocarditis or an abnormal microcirculation in the sinus node and atrioventricular node artery. In some patients, myocardial ischemia may provoke malignant ventricular arrhythmia. (Circ J 2008; 72: 274 - 280)

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Background Medical therapy of atrial fibrillation (AF) can be challenging in patients with Brugada electrocardiograms (ECGs). The purpose of this study was to investigate the efficacy of pulmonary vein (PV) isolation (PVI) in AF patients with Brugada ECGs. Methods and Results PVI was performed in 6 consecutive patients exhibiting Brugada ECGs (type I in 1, type II in 4, and type III in 1) at baseline. In all patients exhibiting type II or III Brugada ECGs but 1, the administration of sodium-channel blockers converted those ECG patterns to a type I. Five of 6 (83%) patients were free of symptomatic AF without any antiarrhythmic drugs after the first procedure. In the 1 remaining patient with AF recurrence and newly developed atrial tachycardia (AT), the residual conduction gaps of the 3 previously isolated PVs and a focal AT originating from the mitral isthmus were eliminated in the 2^nd session. Finally, during the follow-up period (11±6 months) after the last procedure, all patients were free of any symptomatic atrial arrhythmias without any antiarrhythmic drugs. No other complications occurred. Conclusions Because of the concerns of proarrhythmias with antiarrhythmic drugs, PVI may be an effective strategy for highly symptomatic patients with AF who have a Brugada ECG pattern. (Circ J 2008; 72: 281 - 286)

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Background The purpose of this study was to assess the use of the Günther Tulip Filter (GTF) for the management of venous thromboembolism (VTE). Methods and Results Between December 2000 and April 2005, 118 patients (42 males, 76 females; mean age 60.5 years) diagnosed with VTE, underwent treatment with a GTF. The filter was left permanently in 52 patients. In the other 66 patients, attempts were made to retrieve it, with success in 60 cases (90.9%). No major complication was found throughout the filter's use. Of the 58 patients with the permanent filters, 41 underwent enhanced computed tomography at follow-up in the chronic phase. Thirty-eight filters (92.7%) remained patent, and under low-intensity anticoagulation therapy (international normalized ratio 1.8±0.4), the patency rate was 97.1%. Penetration of the inferior vena cava (IVC) wall by the filter's struts beyond a distance of 3 mm occurred in 23 patients (56.1%), but there was no observable leakage from the IVC or injury to adjacent organs. Conclusions The GTF is feasible and safe for treating VTE. When used permanently, GTFs have a high patency rate, and there is neither leakage from the IVC nor injury to adjacent organs in the event of penetration by the struts. (Circ J 2008; 72: 287 - 292)

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Background Blood pressure (BP) variability has been reported to be associated with hypertensive target organ damage and cardiovascular events. However, the exact mechanism linking BP variability and organ damage is uncertain. This study was designed to investigate the association between BP variability and inflammatory marker in hypertensive patients. Methods and Results Fifty-two hypertensive patients (28 men, 55.9±1.5 years) completed 24-h ambulatory BP monitoring. Inflammatory markers were evaluated by measuring plasma levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α by enzyme-linked immunosorbent assay and high sensitive C-reactive protein (hs-CRP) by particle-enhanced light-scattering immunoassay. BP variability was obtained by calculating within-subject standard deviation (SD) and coefficient of variation of BP. Subjects were grouped into tertiles according to IL-6, TNF-α, and hs-CRP levels. A significant association between ambulatory BP and TNF-α level was identified (P for trend =0.011). In contrast, no association was observed between BP and IL-6 level; however, BP variability index was linked to IL-6 level (P for trend =0.046). The association between inflammatory marker and pattern of diurnal variation was investigated. The hs-CRP concentration was significantly higher in the riser group compared with the dipper group. However, IL-6 and TNF-α levels did not differ among the different diurnal variation groups. Correlation analysis showed varying associations between IL-6 and TNF-α. TNF-α level correlated with the BP index; however, IL-6 level correlated with the BP variability index. Multiple linear regression models revealed that the SD of daytime systolic BP (β=0.065, p=0.001) and age (β=0.024, p=0.016) were all positively and significantly related to IL-6. In contrast, only daytime diastolic BP (β=0.029, p=0.002) was independently related to TNF-α. Conclusion Inflammatory markers are associated with BP variability in hypertensive patients. This finding implies that inflammation may be a mediator for the link between BP variability and target organ damage. (Circ J 2008; 72: 293 - 298)

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Background Obtaining an accurate measure of physical activity energy expenditure (PAEE) can be difficult, so the simple measurement of steps per day has become widely promoted and accepted in the general population. However, the relationship between PAEE and steps per day has not been evaluated in patients with cardiovascular disease. Methods and Results A total of 77 (53 men, 24 women) cardiac rehabilitation program participants aged between 46 and 88 years were enrolled. By means of an accelerometer the step count per day, amount of PAEE, as well as time per day spent in physical activity at light (<3 metabolic equivalents (METs)), moderate (3-6 METs) and vigorous (>6 METs) intensity were evaluated for each subject. The number of daily step counts strongly correlated with total PAEE (r=0.92, p<0.001) and time spent in moderate to vigorous intensity physical activity (r=0.85, p<0.001). The mean (95% confidence intervals) step counts associated with 214 and 314 kcal/day (ie, 1,500 and 2,200 kcal/week) were 6,470 and 8,496 steps/day, respectively. Conclusion To achieve the total amount of PAEE generally recommended for the secondary prevention of cardiovascular disease, patients should be encouraged to accumulate 6,500-8,500 steps/day. (Circ J 2008; 72: 299 - 303)

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Background A novel index, the cardio-ankle vascular index (CAVI), which reflects the stiffness of the aorta, femoral artery, and tibial artery, was recently developed by measuring brachial - ankle pulse wave velocity and blood pressure. Methods and Results In the present study 1,014 Japanese adults from the general population were screened to clarify the correlation between CAVI and other existing markers related to atherosclerosis, including carotid intima - media thickness (CIMT) and homocysteine (HCY). CAVI was strongly associated with age in both men and women. After adjustment for age and sex, CAVI was correlated with systolic and diastolic blood pressures. In addition, CAVI was significantly correlated with total cholesterol hemoglobin A_1c and total HCY, as well as CIMT. Conclusion CAVI is an appropriate screening tool for atherosclerosis, but further studies are needed to establish a convenient and effective screening system using it. (Circ J 2008; 72: 304 - 308)

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Background The Gαq protein-coupled receptor (GPCR) signaling pathway, which includes diacylglycerol (DAG) and protein kinase C (PKC), plays a critical role in the development of cardiac hypertrophy and heart failure (HF). It has been reported that the expression of a constitutively active mutant of the G protein αq subunit in the hearts of transgenic mice (Gαq-TG) induces cardiac hypertrophy and lethal HF. DAG kinase (DGK) catalyzes DAG and controls its cellular levels, thus acting as a regulator of GPCR signaling. It has been found that transgenic mice with cardiac-specific overexpression of DGKζ (DGKζ-TG) inhibit GPCR agonist-induced activation of the DAG-PKC signaling and subsequent cardiac hypertrophy, so this study tested the hypothesis that DGKζcould rescue Gαq-TG mice from developing HF. Methods and Results Double transgenic mice (Gαq/DGKζ-TG) with cardiac-specific overexpression of both DGKζand Gαq were generated by crossing Gαq-TG with DGKζ-TG mice, and the pathophysiological consequences were analyzed. DGKζ prevented cardiac dysfunction, determined by dilatation of left ventricular (LV) dimensions, reduction of LV fractional shortening, and marked increases in LV end-diastolic pressure in Gαq-TG mice. Translocation of PKC isoforms, phosphorylation activity of c-jun N-terminal kinase and p38 mitogen-activated protein kinase in Gαq-TG mice were attenuated by DGKζ. DGKζ improved the survival rate of Gαq-TG mice. Conclusions These results demonstrate the first evidence that DGKζ blocks cardiac dysfunction and progression to lethal HF by activated Gαq protein without detectable adverse effects in the in-vivo heart and suggest that DGKζis a novel therapeutic target for HF. (Circ J 2008; 72: 309 - 317)

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Background The antiarrhythmic or reverse remodeling effects of bepridil, a multi-ion channel blocker, have been recently reported, but inhomogeneity of the electrical remodeling and effects of bepridil have been observed in previous reports. In this study, the effect of long-term administration of bepridil on atrial electrical remodeling was evaluated in a comparison of the right and left atrium (RA and LA) in a canine rapid atrial stimulation model. Methods and Results In 10 beagle dogs, rapid atrial pacing (400 beats/min) was delivered for 6 weeks and the atrial effective refractory period (AERP), conduction velocity (CV) and inducibility of atrial fibrillation (AF) were evaluated every week. In 5 of the pacing dogs, bepridil (10 mg · kg^-1 · day^-1) was administered orally, starting 2 weeks after the initiation of the rapid pacing. At the end of the protocol, the hemodynamic parameters and extent of tissue fibrosis were evaluated and the mRNA of SCN5A, Kv4.3, the L-type Ca²⁺ channel (LCC) and connexin (Cx) 40, 43, and 45 in both atria were examined by quantitative real-time reverse transcriptase-polymerase chain reaction. In the pacing control group, AERP shortening, decreased CV, increased AF inducibility and downregulation of the expression of SCN5A and LCC were observed. In the bepridil group, the AERP exhibited a relatively quick recovery after bepridil was started in the first week and continued to recover gradually until the end of the protocol, but that recovery was smaller in the LA than in the RA. The CV was not affected by bepridil administration. AF inducibility was well suppressed in the RA in the bepridil group, but the induction of short-duration AF could not be suppressed in the LA. The mRNA downregulation of the LCC and SCN5A was negated by bepridil administration in the RA; but not in the LA; however, the data showed similar tendencies. There were no significant differences in the hemodynamic parameters or tissue fibrosis and the mRNA expression of Kv4.3, Cx40, 43, and 45 between the pacing control and bepridil groups. Conclusion Bepridil exhibited an anti-electrical remodeling effect in this study as previously reported, but the effect was inhomogeneous between the RA and LA, with the LA appearing to be more resistant to the effect of bepridil. (Circ J 2008; 72: 318 - 326)

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A 49-year-old woman was referred to hospital because of chest discomfort. Coronary angiography revealed subtotal occlusion of the left coronary artery and the right coronary artery, but subsequent hemodynamic collapse occurred. Based on the results of intravascular ultrasound the occlusion was suspected to be caused by coronary vasospasm, which was not relieved by intracoronary injection of isosorbide dinitrate (1 mg), but was alleviated by nicorandil (2 mg), a potassium-channel opener. After discharge from hospital, the patient stopped taking her medication and returned complaining of chest discomfort again. Intravenous verapamil (5 mg) did not improve it, but direct intracoronary administration of nicorandil (2 mg) did bring relief. This case suggests that nicorandil is effective for coronary vasospasm. (Circ J 2008; 72: 327 - 330)

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A patient had multiple myeloma and associated cardiac amyloidosis, which caused diastolic dysfunction and recurrent ventricular fibrillation. After implantation of a cardioverter-defibrillator (ICD), the patient underwent autologous peripheral blood stem cell transplantation (PBSCT). The life-threatening arrhythmias, such as ventricular fibrillation, disappeared, and diastolic dysfunction assessed by quantitative gated single photon emission computed tomography and Doppler echocardiography improved 7 months later. This may be the first report to document improvement of both a lethal rhythm disorder and diastolic dysfunction by PBSCT following ICD implantation in a case of cardiac amyloidosis associated with multiple myeloma. (Circ J 2008; 72: 331 - 334)

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Transvenous endocardial pacemaker implantation is contraindicated in patients after prosthetic tricuspid valve replacement. A 65-year-old woman underwent both replacement of the mitral and tricuspid valves and pacemaker implantation with epicardial lead for bradycardia with chronic atrial fibrillation. At 2 years after this operation, the pacemaker's battery became low, and she was admitted for a battery exchange. To avoid frequent battery exchanges because of high stimulation thresholds, a left ventricular pacing lead was implanted via a coronary vein. There were no complications and the stimulation thresholds were stable. Coronary vein leads enable a minimally invasive approach, improve safety, and give effective stimulation for patients with a prosthetic tricuspid valve. This is the first case report in Japan of left ventricular pacing in such a patient. (Circ J 2008; 72: 335 - 336)

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Primary pericardial sarcomas are very rare. A 62-year-old Japanese man presented with cardiac tamponade. Echocardiography, computed tomography and magnetic resonance imaging revealed massive pericardial effusion and a large tumor in the pericardial cavity, attached to the pericardium of the left ventricular posterolateral free wall. Surgical excision of the tumor was performed and histopathological and immunohistochemical examinations identified high-grade myofibroblastic sarcoma. Because of local recurrence soon after surgery, the patient received adjuvant chemotherapy, including doxorubicin and ifosfamide, and subsequent radiotherapy. As of 6 months after completing radiotherapy, the patient was alive and no disease progression or distant metastases were evident. This may be the first report of primary high-grade myofibroblastic sarcoma arising from the pericardium. (Circ J 2008; 72: 337 - 339)

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Background Antiplatelet therapy in patients with sirolimus-eluting stents (SES) may be stopped because of bleeding or an invasive procedure. Methods and Results In 254 patients with SES, the incidence of discontinuation of antiplatelet therapy and subsequent adverse cardiac events was evaluated. Follow-up was complete for 97.2% of the population and mean follow-up was 15.6±8.9 months. Discontinuation of antiplatelet therapy occurred for 46 patients (18.1%): 1 case of late stent thrombosis (2.2%) occurred 10 days after cessation of therapy because of pulmonary hemorrhage 7 months after SES deployment. Conclusion Discontinuation of antiplatelet therapy in patients with SES is not infrequent. (Circ J 2008; 72: 340 - 341)

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