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In patients with acute decompensated heart failure (HF), the association of gender and left ventricular ejection fraction (LVEF) with clinical outcomes has not been fully investigated. The aim of this study was to evaluate gender differences in LVEF and adverse outcomes across the full spectrum of LVEF in patients hospitalized for acute decompensated HF. Of the 4,842 patients enrolled in the Acute Decompensated Heart Failure Syndromes registry, 4,231 patients (2,461 men and 1,770 women) discharged alive after hospitalization for acute decompensated HF were investigated to assess the association of gender and LVEF with the primary end point (all-cause death and readmission for HF). Men or women were divided into 5 groups based on the LVEF at hospital discharge (30%, 30% to40%, 40% to50%, 50% to60%, and ≥60%). The median follow-up period after discharge was 523 (384 to 791) days. The frequency of the primary end point did not differ between men and women (36.5% vs 38.1%, p = 0.291). After adjustment for multiple comorbidities, male patients with an LVEF30%, 30% to40%, 40% to50%, or 50% to60% had a significantly higher risk of the primary end point than those with an LVEF ≥60%, indicating an inverse association between LVEF and adverse outcomes. In contrast, the adjusted risk of the primary end point was similar for all 5 LVEF groups of female patients. In conclusions, the association between LVEF and outcomes differs markedly between men and women hospitalized for acute decompensated HF, although event-free survival is similar for both genders.

Background Although an “obesity paradox” exists in patients after myocardial infarction, the association between obesity and the risk of sudden cardiac death (SCD) is limited. The aim of this study was to determine whether obesity is associated with an increased risk of SCD in Japanese survivors of acute myocardial infarction. Methods and Results Pooled data from 2 cohort studies in Japan, JCAD (Japanese Coronary Artery Disease) study and the Heart Institute of Japan Acute Myocardial Infarction‐II (HIJAMI‐II) registry, comprising of 6216 patients (mean age 65±11 years, 75.2% male) with acute myocardial infarction who were discharged alive, were studied. The patients were categorized into the following body mass index (BMI) groups at baseline according to the World Health Organization classification for Asian populations: BMI 2 (n=335), 18.5 to 23 kg/m 2 (n=2371), 23 to 27.5 kg/m 2 (n=2823), and ≥27.5 kg/m 2 (n=687). The main outcomes were all‐cause mortality and SCD. During an average follow‐up period of 3.6±1.4 years, all‐cause mortality was 10.1%, and SCD was 1.2%. Patients with BMI 2 had the highest rate of all‐cause mortality (adjusted hazard ratio, 1.61; 95% confidence interval, 1.20–2.16), but high BMI (≥27.5 kg/m 2 ) was not associated with mortality compared with patients in the group with BMI ≥18.5 and 2 . However, the long‐term risk of SCD was increased in the group with BMI ≥27.5 kg/m 2 (adjusted hazard ratio, 2.97; 95% confidence interval, 1.24–7.15). Multivariate analysis revealed that BMI ≥27.5 kg/m 2 was associated with an increased risk of SCD (hazard ratio, 2.78; 95% confidence interval, 1.35–5.74). Conclusions Obesity (BMI ≥27.5 kg/m 2 ) was associated with the risk of SCD in Japanese patients after myocardial infarction, although an obesity paradox was found for all‐cause mortality.

Rationale & Objective Epidemiologic and clinical studies have suggested that urate-lowering therapy may slow the progression of chronic kidney disease (CKD). However, definitive evidence is lacking. Study Design Randomized, double-blind, placebo-controlled trial. Setting & Participants 467 patients with stage 3 CKD and asymptomatic hyperuricemia at 55 medical institutions in Japan. Intervention Participants were randomly assigned in a 1:1 ratio to receive febuxostat or placebo for 108 weeks. Outcomes The primary end point was the slope (in mL/min/1.73 m2 per year) of estimated glomerular filtration rate (eGFR). Secondary end points included changes in eGFRs and serum uric acid levels at 24, 48, 72, and 108 weeks of follow-up and the event of doubling of serum creatinine level or initiation of dialysis therapy. Results Of 443 patients who were randomly assigned, 219 and 222 assigned to febuxostat and placebo, respectively, were included in the analysis. There was no significant difference in mean eGFR slope between the febuxostat (0.23 ± 5.26 mL/min/1.73 m2 per year) and placebo (−0.47 ± 4.48 mL/min/1.73 m2 per year) groups (difference, 0.70; 95% CI, −0.21 to 1.62; P = 0.1). Subgroup analysis demonstrated a significant benefit from febuxostat in patients without proteinuria (P = 0.005) and for whom serum creatinine concentration was lower than the median (P = 0.009). The incidence of gouty arthritis was significantly lower (P = 0.007) in the febuxostat group (0.91%) than in the placebo group (5.86%). Adverse events specific to febuxostat were not observed. Limitations GFR was estimated rather than measured, and patients with stages 4 and 5 CKD were excluded. Conclusions Compared to placebo, febuxostat did not mitigate the decline in kidney function among patients with stage 3 CKD and asymptomatic hyperuricemia. Funding Funded by Teijin Pharma Limited. Trial Registration Registered at the UMIN (University Hospital Medical Information Network) Clinical Trials Registry with study number UMIN000008343.

In patients with acute decompensated heart failure (HF), the influence of gender on anemia, left ventricular ejection fraction (EF), and outcomes is unclear. We evaluated the association of anemia and left ventricular EF with survival in men or women hospitalized for acute decompensated HF. Of the 4,842 patients enrolled in the Acute Decompensated Heart Failure Syndromes registry, 4,215 patients (2,450 men and 1,765 women) discharged alive after hospitalization for acute decompensated HF were enrolled to evaluate the association of gender, anemia (hemoglobin

Risk stratification of lethal arrhythmias is important for the management of ischemic heart disease. Recently, we developed a novel 187-channel signal-averaged vector-projected high-resolution electrocardiograph (187-ch SAVP-ECG) with a Mason–Likar lead system with 10 electrodes. The purpose of this study was to examine the feasibility of a noninvasive evaluation of the spatial distribution of high-frequency late potentials (HFLPs) in patients with myocardial infarction (MI) by using the 187-ch SAVP-ECG. Sixty-four MI patients (7 women and 57 men), between the age of 39 and 84 years (mean 67.7±9.7 years), with positive ventricular late potentials defined by an X, Y, Z-lead ECG were studied. The integrated ventricular 187-ch SAVP-ECG could identify the area of HFLPs that was projected virtually by mathematically calculated 187 electrograms on the body surface in all patients, and differentiate the locations of MI. The 187-ch SAVP-ECG can be a practical and noninvasive examination tool for identifying the location of infarction areas and possible arrhythmogenic substrates with slow conduction properties in patients with MI.

In the setting of acute decompensated heart failure (HF), relations among the etiology of HF, left ventricular systolic function, and outcomes are unclear. The aim of this study was to investigate the association of HF etiology with outcomes in patients with acute decompensated HF with a preserved or reduced ejection fraction (EF). Of the 4,842 patients enrolled in the Acute Decompensated Heart Failure Syndromes registry, 3,810 patients (1,601 with a preserved EF and 2,209 with a reduced EF) who had a hypertensive, ischemic, valvular, or idiopathic dilated etiology of HF were investigated to assess the association of etiology with a composite end point (all-cause mortality and readmission for HF). The median follow-up period after admission was 502 (381 to 759) days. The composite end point was reached in 44.6% and 41.7% of the preserved and reduced EF groups, respectively. After adjustment for multiple co-morbidities, the risk of the composite end point was comparable among hypertensive, ischemic, and valvular etiologies in the preserved EF group. In contrast, in the reduced EF group, ischemic etiology was associated with a tendency toward greater risk of the composite end point than hypertensive etiology (but this difference was not significant), whereas valvular etiology was associated with a significantly greater risk of the composite end point relative to hypertensive or idiopathic dilated etiology. In conclusion, this study demonstrated that taking the etiology of HF into account may help to reduce the heterogeneity of acute decompensated HF and assist in identifying patients at risk of adverse outcomes, especially among patients with reduced EF.

Background: For stable patients suspected of having coronary artery disease (CAD), myocardial perfusion imaging (MPI) or computed tomographic angiography (CT) is used for initial evaluation, while coronary angiography (CAG) is used for confirming the diagnosis. The choice of the initial diagnostic test might influence the treatment strategy. Methods and Results: Patients scheduled for MPI, CT, or CAG as the initial diagnostic test were enrolled. The primary and secondary end-points were a major adverse cardiac event (MACE) and revascularization, respectively. Of the 2,878 patients enrolled, 2,825 underwent initial diagnostic tests, and 2,780 were followed up for 1.42±0.49 years. After adjustment for CAD severity, Cox proportional hazard regression analysis showed that the risk of MACE in the MPI and CT groups were similar and significantly less than that in the CAG group (hazard ratio, 0.82 vs. 2.19; 95% confidence interval [CI], 0.43–1.58 vs. 1.40–3.44). Furthermore, the rate of revascularization in the MPI group was less than that of the CT (odds ratio, 1.62; 95% CI, 1.20–2.18) and CAG (odds ratio, 5.36; 95% CI, 4.07–7.05) groups. Conclusions: These data indicate that for stable patients with suspected CAD, the use of MPI or CT as the initial diagnostic test was associated with better prognosis than the use of CAG, and that initial evaluation with MPI was associated with a lower requirement of coronary intervention. (Circ J 2012; 76: 2832–2839)

Background: Recent studies have suggested that esmolol is the first choice for rate control in patients with postoperative atrial fibrillation (AF) after coronary artery bypass surgery, but side-effects of esmolol such as hypotension are problematic. To overcome this problem, landiolol, an ultra-short-acting β1-blocker with a less negative inotropic effect than esmolol, has been developed. The aim of the present study was to investigate whether landiolol was effective for both rate control and conversion to normal sinus rhythm (NSR). Methods and Results: A prospective, randomized, open-label comparison between i.v. landiolol and diltiazem in patients with postoperative AF was undertaken between January 2008 and June 2009 in Japan. Of 335 patients included in the analysis, 71 patients went into AF. Among these 71 patients, conversion to NSR within 8h after onset of AF occurred in 19 of 35 patients (54.3%) in the landiolol group vs. 11 of 36 patients (30.6%) in the diltiazem group (P

It remains unclear whether end-stage hypertrophic cardiomyopathy (HCM) is associated with as high a rate of sudden death as occurs among HCM patients with preserved left ventricular (LV) systolic function. The purpose of this study was to evaluate the incidence of sudden death among patients with end-stage HCM and to identify high-risk end-stage patients.A total of 490 consecutive patients with HCM, who were diagnosed and followed-up at our hospital, were analyzed retrospectively. End-stage HCM was defined by an LV ejection fraction50% on echocardiography during follow-up. Among the 490 HCM patients, 43 patients (8.8%) were diagnosed as having end-stage HCM during a mean follow-up period of 12 ± 7 years after the initial diagnosis. During a mean follow-up period of 5 ± 3 years after progression to end-stage HCM, sudden death occurred in 21 of 43 patients (47%). Cox proportional hazards analysis identified syncope as an independent predictor of sudden death (hazard ratio = 6.15; 95% confidence interval, 2.40-15.75; P.001).This study demonstrated that patients with end-stage HCM have a high incidence of sudden death. Therefore, it is suggested that an aggressive therapeutic strategy to counter sudden death should be considered for patients with end-stage HCM.

Background: It is unclear whether depression persists in patients with implantable cardioverter defibrillators (ICDs). We evaluated the prevalence and persistence of depression in ICD patients over a 2-year period. Methods: The study included 90 consecutively hospitalized patients. Patients underlying heart disease was 24% coronary artery disease, 29% idiopathic dilated cardiomyopathy, 24% hypertrophic cardiomyopathy, 13% idiopathic VF/long QT syndrome and miscellaneous conditions 11%. A secondary indication for ICD implantation was present in 20 patients. All patients completed the Zung Self-Rating Depression Scale (SDS) at study baseline and at the their routine follow-up visit 2 years after the baseline questionnaire. Delivery of ICD therapies was tracked throughout the 2 years. Results: Depression, indicated by a Zung SDS index score exceeding 60, was present in 29 (32%) of patients at study baseline. Depression was present in 11/51 (21%) patients scheduled to undergo ICD implantation, 2/2 (100%) patients whose device was upgraded to a CRT-D, 3/14 (21%) patients who had undergone pulse generator replacement, 7/14 (50%) patients who experienced electrical storm and 6/9 (66%) patients hospitalized with acute decompensated heart failure. NYHA functional class III was significantly associated with depression at baseline (HR 6.7, 95% CI 1.68–27.2, p = 0.0007). No differences were noted for female gender, demographics, β-blocker use, or LVEF ≤35% (p = ns). Depression was present in 25 (28%) of patients at 2 years follow-up, persisting in 21 (72%) of patients whose Zung SDS scores were elevated at baseline. The median time from ICD shock therapy to completion of the 2 year questionnaire was 9 months (range, 1–22). Patients who were depressed (9/25, 36%) experienced more shocks than non-depressed patients (6/65, 9%) after 2 years (p = 0.002). Conclusions: Depression is not uncommon among patients who meet criteria for ICD implantation and persists over time particularly when functional status is impaired. Depression is associated with a higher incidence shock therapy. (PACE 2010; 33:1455–1461)

Combination therapy with calcium channel blockers and angiotensin II receptor blockers is recommended as one of the effective therapies for hypertension. However, it remains unclear whether this combination reduces major adverse cardiovascular events (MACEs) in patients with hypertension with coronary artery disease (CAD). The purpose of the present study was to examine the effects of amlodipine plus candesartan on MACEs in patients with hypertension with CAD. The study population was drawn from The Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Artery Disease (HIJ-CREATE), which was a multicenter, prospective, randomized controlled trial including 2,049 patients with hypertension with angiographically documented CAD. Subgroup analysis was performed in patients treated with amlodipine at baseline (n = 388). The median follow-up period was 4.3 years. Treatment using amlodipine plus candesartan reduced the risk for MACEs by 39% (p = 0.015) compared to that using amlodipine without angiotensin II receptor blockers. Among the individual events constituting MACEs, the incidence of unstable angina pectoris requiring hospitalization was significantly lower, by 52% (p = 0.007). In conclusion, amlodipine plus candesartan demonstrated a more favorable effect on reducing cardiovascular events in patients with hypertension with CAD compared to amlodipine-based therapy without candesartan.

The aim of this study was to assess the effects of angiotensin receptor blocker (ARB)-based therapy on cardiovascular events in high-risk hypertensive patients with coronary artery disease (CAD) and impaired renal function in post hoc analysis of HIJ-CREATE (Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Artery Disease). Patients (n=2049) were randomly assigned to candesartan-based or non-ARB treatment arms; 1022 patients (age 70 ± 6 years, 28% female) with impaired renal function, defined as creatinine clearance

Previous studies indicated that women were less likely to experience ventricular arrhythmia recurrence than men among patients with coronary artery disease and implantable cardioverter defibrillator (ICD). However, it is not clear whether the risk for ventricular tachyarrhythmia is gender-dependent in patients with nonischemic dilated cardiomyopathy. This study included 173 consecutive nonischemic dilated cardiomyopathy patients with a left ventricular ejection fraction of45% (122 men and 51 women), who received ICD therapy between 1990 and 2008. The average follow-up period was 33 +/- 28 months. There was no significant difference in event-free rates of appropriate ICD therapy between genders for all patients (P = 0.15) and by indication of ICD (primary prevention: P = 0.43, secondary prevention: P = 0.24). There was also no significant difference in event-free rates of electrical storm between genders (P = 0.17). In high-risk patients with nonischemic dilated cardiomyopathy who received ICD, there was no gender difference in the incidence of appropriate ICD therapy or electrical storm.

Objective To compare the efficacy and safety of nifekalant, a pure class III anti-arrhythmic drug, and lidocaine in patients with shock-resistant in-hospital ventricular fibrillation (VF) or ventricular tachycardia (VT). Patients and methods Between August 2005 and March 2008, we conducted a prospective, two-arm, cluster observational study, in which participating hospitals were pre-registered either to the nifekalant arm or the lidocaine arm. Patients were enrolled if they had in-hospital VF or VT resistant to at least two defibrillation shocks. Congenital or drug-induced long QT syndrome was excluded. The primary end-point was termination of VF or VT with/without additional shock. The secondary end-points were return of spontaneous circulation (ROSC), 1-month survival and survival to hospital discharge. We also assessed the frequency of adverse events, including asystole, pulseless electrical activity and torsade de pointes. Results In total, 55 patients were enrolled. After nifekalant, 22 of 27 patients showed termination of VF or VT, as compared with 15 of 28 patients treated with lidocaine with/without additional shock (odds ratio (OR): 3.8; 95% confidence interval (CI): 1.1–13.0; P = 0.03). Twenty-three of 27 patients given nifekalant showed ROSC, as compared with 15 of 28 patients given lidocaine (OR: 5.0; 95% CI: 1.4–18.2; P = 0.01). There was no difference in 1-month survival or survival to hospital discharge between the nifekalant and lidocaine arms. There was a higher incidence of asystole with lidocaine (7 of 28 patients) than with nifekalant (0 of 27 patients) ( P = 0.005). Torsade de pointes was not observed. Conclusion Nifekalant was more effective than lidocaine for termination of arrhythmia and for ROSC in patients with shock-resistant in-hospital VF or VT (umin-CTR No. UMIN 000001781).

In patients with acute decompensated heart failure (ADHF) and left ventricular systolic dysfunction (LVSD), the role of initial vasodilator therapy remains uncertain. The present study aimed to evaluate the acute efficacy of initial carperitide therapy and to predict its response in ADHF patients with LVSD.Twenty-four consecutive patients with ADHF and LVSD were enrolled. Inclusion criteria were a left ventricular ejection fraction40%, systolic blood pressure (BP)90 mm Hg, and pulmonary capillary wedge pressureor=18 mm Hg at baseline. Hemodynamic parameters were evaluated by right heart catheterization before and after carperitide infusion. Responders were defined as aor=30% reduction of pulmonary capillary wedge pressure (PCWP) or a decrease to16 mm Hg within 6 h after carperitide infusion.Seventeen (71%) of the 24 patients were responders for initial carperitide therapy. The responders had significantly higher systolic BP and cardiac index at baseline compared with nonresponders. The area under the curve (AUC) for systolic BP was 0.93 and a cut-off value of 120 mm Hg had a sensitivity of 94% and specificity of 86% for predicting the efficacy of carperitide. The AUC for the cardiac index was 0.88 and a cut-off value of 2.30 L/min/m(2) had a sensitivity of 65% and a specificity of 100% for predicting the response to carperitide.The initial use of carperitide therapy safely reduces PCWP in ADHF patients with LVSD and baseline systolic BP may be useful for predicting the response to initial carperitide therapy for ADHF with LVSD.

Objectives and background Recent evidence has revealed that aldosterone (ALDO) is produced in the vasculature, and acts directly in the cardiovascular system. This study was designed to examine the role of ALDO in the process of long-term renin–angiotensin system (RAS) induced vascular remodeling. Material and method Hypertensive transgenic mice that overproduce angiotensin II (AngII), i.e., Tsukuba-Hypertensive-Mice (THM), were given tap water or 1% salt water and treated with or without Spironolactone (SPRL: 20 mg/kg/day) for 4 weeks. We also employed A7r5 cells and investigated the effect of SPRL on the AngII mediated signal transduction in the vascular smooth muscle cells. Results Intimal hyperplasia, medial hypertrophy and degradation of medial elastic laminae were observed in the abdominal aorta, independent of blood pressure. Taking 1% salt water markedly enhanced these changes. In contrast, SPRL-treated THM showed almost complete disappearance of these intimal hyperplasia and medial hypertrophy. Osteopontin (OPN) was markedly up-regulated in the intima and media. However, it was inhibited by SPRL treatment in spite of high level of AngII. In A7r5 cells, AngII (10 −7 μM) induced OPN expression and pretreatment with MEK, PI3K, and EGFR inhibitor suppressed it. SPRL pretreatment also inhibited AngII-induced ERK and AKT phosphorylation, and resulted in the suppression of AngII-induced OPN expression. Conclusions ALDO blockade by SPRL restores the vascular remodeling caused by the long-term RAS enhancement even in the high level of AngII, independent of blood pressure. Blocking AngII alone may not be sufficient, and direct ALDO blockade is also important to prevent vascular disease.

Aims To test whether angiotensin II receptor blockers (ARBs) therapy can reduce the incidence of cardiovascular events compared with non-ARB-based standard pharmacotherapy in coronary artery disease (CAD) patients with hypertension. Methods and results Angiographically documented CAD patients with hypertension were randomly assigned to receive either candesartan-based ( n = 1024) or non-ARB-based pharmacotherapy including angiotensin-converting enzyme-inhibitors ( n = 1025). The primary endpoint was the occurrence of a first major adverse cardiovascular event (MACE). There were 552 primary events during a median follow-up of 4.2 years: 264 (25.8%) in the candesartan group and 288 (28.1%) in the non-ARB group (hazard ratio, 0.89; 95% confidence interval, 0.76–1.06). No significant differences existed between groups in terms of cardiovascular death (2.7 vs. 2.4%, 1.14; 0.66–1.95), non-fatal myocardial infarction (2.8 vs. 2.5%, 1.12; 0.66–1.88), or heart failure (3.9 vs. 4.3%, 0.91; 0.59–1.40). New-onset diabetes was diagnosed significantly less frequently with candesartan than with non-ARBs (0.37; 0.16–0.89). Incidence of study drug discontinuation due to adverse events was lower with candesartan than with non-ARBs (5.7 vs. 12.2%, P < 0.001). Conclusion Although candesartan showed no significant differences in MACE compared with the non-ARB treatment group, the drug significantly reduced the incidence of new-onset diabetes and was better tolerated. This study is registered as International Standard Randomised Controlled Trial No. UMIN000000790.

The aims of the present study are to: (1) clarify the angiographic follow-up (AFU) rate after discharge; (2) elucidate the characteristics of those undergoing it; and (3) determine the impact of AFU on subsequent revascularization procedures among patients with acute myocardial infarction (AMI). Three thousand and twenty-one consecutive patients presenting within 48 h of AMI onset were enrolled from 17 centers in Japan between January 1999 and June 2001. To clarify the frequency of AFU and their characteristics, 2736 patients who survived at discharge were analyzed. Among 1160 patients matched by propensity score, the impact of AFU on subsequent revascularization was analyzed. Of 2736 patients, 1367 (50%) underwent AFU and constituted the lower-risk population. Of the 580 matched patient pairs, 120 (21%) in the clinical follow-up group and 198 (34%) in the AFU group underwent subsequent revascularization (hazard ratio 7.54; 95% confidence interval 5.74-9.91). Of the 198 patients in the AFU group, 157 (79%) underwent revascularization at the discretion of the responsible physician based on angiographic findings. Angiographic follow-up led to more subsequent revascularization. More evidence would be necessary to determine the effectiveness and the methods by which patients are selected.

We conducted a prospective multicenter case-control study to confirm the clinical efficacy and safety of Waon therapy on chronic heart failure (CHF).Patients (n=188) with CHF were treated with standard therapy for at least 1 week, and then were randomized to Waon therapy (n=112) or a control group (n=76). All patients continued conventional treatment for an additional 2 weeks. The Waon therapy group was treated daily with a far infrared-ray dry sauna at 60 degrees C for 15 min and then kept on bed rest with a blanket for 30 min for 2 weeks. Chest radiography, echocardiography, and plasma levels of brain natriuretic peptide (BNP) were measured before and 2 weeks after treatment.NYHA functional class significantly decreased after 2 weeks of treatment in both groups. Chest radiography also showed a significant decrease of the cardiothoracic ratio in both groups (Waon therapy: 57.2+/-8.0% to 55.2+/-8.0%, p0.0001; control: 57.0+/-7.7% to 56.0+/-7.1%, p0.05). Echocardiography demonstrated that left ventricular diastolic dimension (LVDd), left atrial dimension (LAD), and ejection fraction (EF) significantly improved in the Waon therapy group (LVDd: 60.6+/-7.6 to 59.1+/-8.4 mm, p0.0001; LAD: 45.4+/-9.3 mm to 44.1+/-9.4 mm, p0.05; EF: 31.6+/-10.4% to 34.6+/-10.6%, p0.0001), but not in the control group (LVDd: 58.4+/-10.3 mm to 57.9+/-10.4 mm; LAD: 46.3+/-9.7 mm to 46.2+/-10.1 mm; EF: 36.6+/-14.1% to 37.3+/-14.0%). The plasma concentration of BNP significantly decreased with Waon therapy, but not in the control group (Waon: 542+/-508 pg/ml to 394+/-410 pg/ml, p0.001; control: 440+/-377 pg/ml to 358+/-382 pg/ml).Waon therapy is safe, improves clinical symptoms and cardiac function, and decreases cardiac size in CHF patients. Waon therapy is an innovative and promising therapy for patients with CHF.

Risk stratification among patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) has been made by clinical scoring. Recently, multiple-detector computed tomography (MDCT) appeared to provide noninvasive coronary angiography (CAG). To clarify the prognostic significance of MDCT, we aimed to evaluate the clinical utility of MDCT in the early management and in predicting the long-term prognosis of NSTE-ACS with low to intermediate risk. Among 84 consecutive patients with NSTEACS, risk stratification using a TIMI risk score was done. A total of 48 patients were categorized as low to intermediate risk. Multiple-detector CT was performed in 30 patients using 16-slice MDCT. MDCT detected coronary stenoses in 18 patients. Compared to invasive CAG, MDCT successfully depicted the coronary stenosis (P < 0.005), with sensitivity of 100% and specificity of 86%. The incidence of in-hospital major adverse clinical events (death, subsequent myocardial infarction, revascularization) was significantly higher in patients with a positive MDCT than in those with a negative MDCT test (44% vs 0%, P < 0.005). Moreover, a Kaplan-Meier analysis showed a significant difference in the event — free survival between MDCT positive and negative groups (33% vs 100%, respectively, P < 0.0001) during the mean follow-up period of 9.9 ± 7.5 months. Sixteen-slice MDCT in conjunction with a TIMI risk score appeared to demonstrate prognostic significance in patients with NSTE-ACS.

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

We report the treatment of four thyrotoxic patients. Two were cases of type I amiodarone-induced thyrotoxicosis (AIT) treated with methimazole. The third Graves' disease patient, who became hypothyroid 25 years after subtotal thyroidectomy, developed type II AIT. Furthermore, one case with heart failure and ventricular tachycardia, who developed an adverse reaction to antithyroid agents and was prescribed amiodarone, underwent total thyroidectomy. The clinical course was uneventful, and the patient is doing well. Since amiodarone contains a large amount of iodine, it is frequently difficult to make a differential diagnosis. Surgical treatment of Graves' disease patients is recommended when immediate control of hyperthyroidism and heart failure is required.

Background Because there is insufficient evidence to support primary percutaneous coronary intervention (PPCI) as the treatment of acute myocardial infarction (AMI), this study elucidated the efficacy of PPCI according to disease severity. Methods and Results Between January 1999 and June 2001, 3,021 AMI patients were registered at Tokyo Women's Medical University and 17 affiliated institutions. Of these, 1,994 patients with ST-elevation AMI were admitted within 12 h of onset. PPCI was performed in 1,143 and 294 were treated conservatively. The 1,437 patients were grouped according to Thrombolysis In Myocardial Infarction-risk score: PPCI was performed in 59.5% of the low-risk group, 61.8% of the moderate-risk group, and 56.2% of the high-risk group. Cardiac death was the primary outcome. In the low-risk group, no significant differences were observed between PPCI and conservative therapy for 30-day and long-term cardiac mortality rates. In the moderate-risk group, the 30-day cardiac mortality rate for PPCI was significantly lower; however, no significant intergroup differences were observed for long-term cardiac mortality. In the high-risk group, 30-day and long-term cardiac mortality for PPCI were significantly more favourable than for conservative therapy (p

Background Heart failure (HF) represents a major public health issue in an aging population. Although HF is a leading cause of morbidity and mortality in developed countries, the clinical features of HF in Japan remain unclear. Methods and Results This observational cohort study analyzed data from the Heart Institute of Japan - Department of Cardiology (HIJC)-HF Registry, which is based on a nationwide survey by the HIJC, Tokyo Women's Medical University and its affiliated hospitals. Of 3,578 consecutive patients (average age, 69.8 years; females 40.7%) hospitalized for HF between January 2001 and December 2002, 95.0% were followed up until the end of 2005 (median, 2.8 years). The 1- and 3-year mortality rates were 11.3% and 29.2%, respectively. Multivariate analysis revealed that advanced age (hazard ratio 1.71 [95% confidence interval 1.38-2.12]; p

It has been reported that (123)I-metaiodobenzylguanidine (MIBG) scintigraphy can predict the poor prognosis in patients with dilated cardiomyopathy (DCM). However, the prognostic significance of MIBG is still unknown in patients with other heart diseases. In this study, we compared the prognosis and MIBG findings in various heart diseases.Consecutive 565 patients undergoing MIBG scintigraphy were enrolled (392 men, 52 +/- 16 years). Indications were that 127 had ischemic heart disease (IHD), 120 DCM, 101 hypertrophic cardiomyopathy (HCM), 21 hypertensive heart disease (HHD), 58 volume-load valvular disease (VVD), 38 pressure-load valvular disease (PVD), and 101 ventricular tachycardia or fibrillation (VTF). Heart-to-mediastinum ratio (H/M) and washout rate (WR) of MIBG were evaluated. Cardiac events were defined as sudden cardiac death, heart failure, and acute ischemic event (follow-up, 22.7 +/- 17.0 months).A total of 106 cardiac events including 40 cardiac deaths occurred. Cox hazard model analysis showed that in the IHD, HCM, and DCM groups, H/M and WR were associated with cardiac death, but not in the HHD, PVD, VVD, or VTF groups. Only death and congestive heart failure (CHF) episodes were related to H/M and WR. On the other hand, fatal arrhythmia, myocardial infarction, or angina pectoris were not related to H/M and WR. The data indicated that WR or H/M may predict death and CHF but does not predict fatal arrhythmia or acute ischemic event.MIBG WR and H/M were associated with heart failure, sudden death, and cardiac death events, and were useful to predict the prognosis in DCM, HCM, and IHD. In contrast, fatal arrhythmia events were not associated with MIBG indices, and thus it does not appear to be useful in predicting cardiac events in patients with VTF.

Junctophilin subtypes, designated as JPH1 approximately 4, are protein components of junctional complexes and play essential roles in cellular Ca2+ signaling in excitable cells. Knockout mice lacking the cardiac-type Jph2 die of embryonic cardiac arrest, and the mutant cardiac myocytes exhibit impaired formation of peripheral couplings and arrhythmic Ca2+ signaling caused by functional uncoupling between dihydropyridine and ryanodine receptor channels. Based on these observations, we hypothesized that mutations of JPH2 could cause human genetic cardiac diseases. Among 195 Japanese patients (148 index cases and 47 affected family members) with hypertrophic cardiomyopathy (HCM), two heterozygous nonsynonymous nucleotide transitions, G505S and R436C, were newly found in JPH2. When Fisher's exact test was used to compare index cases with HCM to unrelated Japanese healthy controls in the frequencies of mutant alleles, only the G505S mutation showed statistical significance (4/296 HCM patients and 0/472 control individuals, P=0.022). This result was still significant after Bonferroni's correction for multiple comparisons (P=0.044). To the best of our knowledge, this is the first report on JPH2 mutation associated with HCM.

The purpose of this study was to evaluate delayed enhancement (DE) of the aortic wall of atherosclerotic aneurysms using computed tomography and to evaluate the relationships between DE and wall thickness of abdominal aortic aneurysm (AAA), diameter of AAA, serum levels of C-reactive protein (CRP) which indicate inflammation status, and pathological findings. Computed tomographic images of atherosclerotic AAA in 110 patients were studied between July 2001 and March 2003. Computed tomography (CT) scanning included unenhanced, enhanced early, and enhanced delayed phases. Pathological findings were obtained from 19 of the 110 patients. We determined DE of the AAA wall and assessed the association between DE and AAA wall thickness, AAA diameter, serum levels of CRP, and pathological findings. Delayed enhancement on CT was demonstrated in 66 of 110 patients with atherosclerotic AAA (60.0%). Patients with DE demonstrated significantly larger AAA diameter (4.8 +/- 0.9 versus 3.9 +/- 0.6 cm, P0.0001) and significantly higher levels of CRP (5.0 +/- 6.0 versus 2.3 +/- 2.9 mg/l, P = 0.033) than those patients without DE. Patients with DE also had significantly thicker and more severe atheroma and a tendency toward more prominent inflammation and vascularity in pathologic findings. There was no significant difference in wall thickness between AAA with and without DE (1.44 +/- 0.7 versus 1.24 +/- 0.22 mm, P = 0.352). Delayed enhancement on CT demonstrated in over half of atherosclerotic AAA may be associated with chronic inflammation by atherosclerosis.

Background Several reports have suggested a possible link between bronchial asthma and coronary spasm, but the possibility of a relationship in coronary spastic angina (CSA) has not been clarified. Methods and Results Airway responsiveness to methacholine and coronary spasticity to acetylcholine were examined in 42 patients with CSA and 36 patients with chest pain syndrome (CP). Furthermore, 18 control subjects were examined and their airway responsiveness compared with that of the CSA and CP patients. The incidence of airway hyperresponsiveness was significantly higher in the CSA group (74%) than in the CP (19%) and control (17%) groups (p

Noninvasive risk stratification is important for screening for lethal arrhythmia. We developed a 187-channel signal-averaged vector-projected high-resolution electrocardiograph (187-ch SAVP-ECG) for detecting abnormalities in the spatial location of ventricular high-frequency late potentials (HFLPs) and ventricular repolarization. The subjects consisted of 30 normal controls (CONTROL) and 13 patients with HFLPs (6 with myocardial infarction [MI], 6 with cardiomyopathy, and 1 with Brugada syndrome). The modified X, Y, Z-lead ECG and the synthesized signals from vector-projected 187-channel ECGs were amplified and passed through a digital filter. We calculated the integration of the HFLPs area between QRS(end) and 30 ms before QRS(end). The integrated HFLPs map was superimposed on the corrected recovery time (RTc) and Tpeak-end dispersion maps composed by 187-ch SAVP-ECG. All patients received an examination by 64-channel magnetocardiography (64-ch MCG) on the same day. The spatial distribution of HFLPs by the 187-ch SAVP-ECG map was in agreement with the location of increased RT dispersion in MI. The spatial distribution of HFLPs in DCM demonstrated a wide variety of patterns. Interestingly, the spatial distribution of HFLPs in cases with ARVC was located at around a right ventricular outflow region. The spatial distribution of HFLPs by 187-ch SAVP-ECG was in agreement with those determined by 64-ch MCG. The 187-ch SAVP-ECG might be useful for evaluating the spatial distribution of nonuniform conduction and ventricular repolarization heterogeneity.

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

Introduction: Amiodarone infusion has been recommended for life-threatening ventricular arrhythmias. However its effectiveness in Japanese patients has not yet been determined. Methods: This was an uncontrolled, open-label trial involving patients with hemodynamically unstable ventricular tachycardia (VT) or ventricular fibrillation (VF). Intravenous amiodarone was delivered as a 125 mg bolus followed by infusion of 50 mg/h for 6 hours, then 25 mg/h for 42 hours. The primary endpoint for efficacy was the proportion of patients free from hemodynamically unstable VT/VF at 48-hour. Secondary endpoints included: event frequency; proportion of patients event-free, treatment outcome, and safety. Results: Forty-seven patients were enrolled. Forty-one patients were evaluated for efficacy and safety parameters were assessed for all 47 patients. The proportion of patients free from hemodynamically unstable VT/VF was 53.9%; the proportion of patients free from hemodynamically unstable VT/VF relapse or whose treatment was discontinued was 48.8%. Eight patients died; all deaths were judged, by the investigator, as being unrelated to amiodarone. No cases of torsades de pointes were reported. Mild abnormal thyroid function was noted in one patient. No cases of interstitial lung disease or pulmonary fibrosis were observed. Conclusion: Amiodarone infusion provides a useful tool in preventing acute relapse of lifethreatening ventricular arrhythmias in Japanese patients.

There has been growing evidence associating obstructive sleep apnea (OSA) with cardiovascular pathogenesis. We hypothesized that OSA may affect outcomes after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). We performed a sleep study in 89 consecutive patients with ACS who were successfully treated with PCI. Patients with an apnea hypopnea indexor =10/hour were considered to have OSA. Co-morbidity of OSA with ACS was found in 51 patients (57%). There were no differences in baseline demographics between patients with and without OSA, except for significantly higher high-sensitivity C-reactive protein levels (0.59 +/- 0.75 vs 0.29 +/- 0.20 mg/dl, p = 0.019) in patients with OSA. Patients were followed for a mean period of 227 days. The incidence of major adverse cardiac events (cardiac death, reinfarction, and target vessel revascularization) was significantly higher in patients with OSA (23.5% vs 5.3%, p = 0.022). By multivariate analysis, the presence of OSA was an independent predictor for major adverse cardiac events (hazard ratio 11.61, 95% confidence interval 2.17 to 62.24, p = 0.004). In addition, quantitative coronary angiography at 6-month follow-up depicted significantly greater late loss (1.28 +/- 0.84 vs 0.69 +/- 0.81 mm, p = 0.003) and a higher binary restenosis rate (36.5% vs 15.4%, p = 0.026) in patients with OSA compared with those without OSA. In conclusion, the present study showed a high prevalence of OSA among patients with ACS. Moreover, OSA appeared to be an independent predictor for clinical and angiographic outcomes after PCI.

The efficacy of long-term drug therapy for patients with hypertrophic obstructive cardiomyopathy (HOCM) remains unclear. This study was performed to characterize the echocardiographic findings of patients responsive to drug therapy.Left ventricular outflow tract (LVOT) gradient and morphologic characteristics of the septum, posterior wall, and mitral valve were measured echocardiographically in 35 Japanese patients. The mean follow-up time was 41+/-22 months.Long-term drug therapy was effective in 14 patients and ineffective in 21 patients. Five of the refractory patients required mitral valve replacement to become free of symptoms. Only 5 of 21 patients whose LVOT gradient was 100 mm Hg were responsive to drug therapy, whereas 9 of 14 patients whose LVOT gradient was100 mm Hg were responsive to drug therapy. Seven of eight patients with an asymmetric septal hypertrophy (ASH) ratio==1.3 and LVOT gradient100 mm Hg were responsive to drug therapy. Only 3 of 16 patients with an ASH ratio1.3 were responsive to drug therapy. There was no correlation between the efficacy of drug therapy and the morphology of the mitral valve or the width of the LVOT.Our results demonstrate that drug therapy effectively reduces the LVOT gradient in patients with asymmetric septal hypertrophy and a less severe LVOT gradient.

Background Many clinicians have seen the reperfusion phenomenon, a paradoxical response that includes a transient increase of chest pain, additional ST-segment elevation or ventricular arrhythmias immediately after coronary reperfusion, in patients with acute myocardial infarction (AMI). The aim of the present study was to investigate the impact of this phenomenon during coronary reperfusion on left ventricular (LV) remodeling in patients with AMI. Methods and Results One hundred and thirty-eight consecutive patients with a first anterior-wall AMI, undergoing coronary reperfusion treatment within 24 h of onset were prospectively evaluated for reperfusion phenomenon and followed up with scheduled evaluations of LV function and morphology with left ventriculography for 1 year. Of the 138 enrolled patients, 77 underwent serial left ventriculography at the acute, subacute and 1-year phases. Of these 77 patients, 39 demonstrated the reperfusion phenomenon. The LV end-diastolic volume index significantly increased from the acute to subacute phase and to the 1-year phase, but was unchanged in the 38 patients without reperfusion phenomenon. In multivariate analysis, reperfusion phenomenon was the only determinant of LV dilatation after AMI. Conclusions Reperfusion phenomenon was a strong predictor of LV remodeling after reperfusion therapy for AMI. (Circ J 2005; 69: 884 - 889)

Background Because class I anti-arrhythmic drugs sometimes suppress cardiac function caused by their negative inotropic effects, they are not adequate for use in patients with severe heart failure, even as emergency treatment for life-threatening ventricular tachyarrhythmias (ventricular tachycardia (VT)/ventricular fibrillation (VF)). Methods and Results An objective evaluation committee re-evaluated the effect of nifekalant in 191 patients with refractory VT/VF. The attack termination was achieved in 45 out of 93 patients (48.4%). Nifekalant was administered to 39 patients with direct-current (DC) shock-resistant VT/VF and directly terminated VT/VF in 9 patients. In 15 of the remaining 29 patients (51.7%), VT/VF was successfully cardioverted by additional DC shock after nifekalant administration. Prevention of recurrence was achieved in 60 out of 99 patients (60.6%). Corrected QT interval (QTc) was significantly prolonged after initial administration of nifekalant (0.463±0.056 to 0.504 ±0.072), and during maintenance infusion (0.470 ±0.056 to 0.547±0.070). As an adverse reaction, excess prolongation of QTc was noted in 11 patients including 3 patients with torsades de pointes. Hemodynamic parameters tended to improve after maintenance infusion of nifekalant. Conclusion Nifekalant is effective and useful for life-threatening refractory ventricular tachyarrhythmias, although careful observation of the QT interval is required. (Circ J 2005; 69: 1237 - 1243)

重症虚血性心疾患の急性期に認められる致死性不整脈に対し, 塩酸ニフエカラントの投与を行った5症例を経験した.有効例は3症例であり, 2症例は無効であった, 無効例はいずれもカテコラミン併用症例であった.心電図波形の比較を行ったところ, T波の波形の違いも認められ, 無効例ではTpeak-T end時間の延長が認められていた.これは, カテコラミンの作用による細胞間活動電位のばらつきによるものではないかと推測された.ニフエカラントを使用する際には, カテコラミンとの併用は行わず, 血行動態が不安定な場合には大動脈内バルーンパンピング (IABP) , 経皮的心肺補助装置 (PCPS) などの機械的サポートが有効であると考えられた.また, ニフエカラントの有効性の評価として, QT時間のみでなく陽性T波の形態 (Tpeak-Tend時間) も有効であると考えられた.

Three-dimensional echocardiography is an ideal tool for the measurement of left ventricular (LV) volume because no geometric assumptions about LV shape are needed. The introduction of new real-time 3-dimensional echocardiography (RT3DE) has allowed rapid acquisition of a 3-dimensional dataset with good image quality. The purpose of this study was to examine the accuracy of RT3DE for the measurement of LV volume and ejection fraction in patients with wall motion abnormalities by using quantitative gated single-photon emission computed tomography (QGSPECT) as a reference standard. The study population consisted of 25 consecutive patients with wall motion abnormalities who underwent LV volume measurement by 2-dimensional echocardiography and by QGSPECT. LV volume and ejection fraction by RT3DE were measured offline by using the average rotation method. In 23 of 25 patients (92%), it was possible to measure 3-dimensional volume with RT3DE. RT3DE correlated well with QGSPECT in the measurement of end-diastolic volume and end-systolic volume (r = 0.97, mean difference 3.4 ml; r = 0.98, mean difference 2.0 ml, respectively), 2-dimensional echocardiography also correlated with QGSPECT but underestimated LV volume (r = 0.98, mean difference 21.1 ml; r = 0.98, mean difference 15.6 ml, respectively). Ejection fraction obtained by RT3DE had better agreement with that obtained by QGSPECT than that obtained by 2-dimensional echocardiography (r = 0.92, mean difference -0.2%; r = 0.89, mean difference -2.7%, respectively). RT3DE allows convenient and accurate estimation of LV volume and ejection fraction in patients with wall motion abnormalities.

A patient with infective endocarditis (IE) due to methicillin-resistant staphylococcus aureus (MRSA) was found to have conversion of the hypoechoic region of the posterior mitral valve ring apparatus into a clearly delineated echolucent space by repeating transthoracic echocardiography at an interval of 1 week. Color Doppler showed features of blood entry into this space. Abscess formation in IE due to MRSA may be quick and repeated echocardiography may help detect the complications of IE. Semiurgent mitral valve plasty was performed for the associated prolapse of the posterior mitral leaflet using a hand-made, rolled, twisted autologous pericardial ring.

Background: Takayasu arteritis is associated with a low incidence of coronary artery involvement, such as stenosis, obstruction, aneurysm, and coronary steal syndrome, but coronary ischemia can be fatal. Methods: Between 1972 and April 2001, 81 of 130 patients given a diagnosis of Takayasu arteritis underwent selective coronary angiography, and among them, 31 patients (4 male and 27 female patients; mean age, 41.1 ± 13.2 years) had abnormal coronary angiographic findings and were recruited for this study. Results: Abnormal coronary findings consisted of 24 coronary artery stenoses of greater than 75%, 3 coronary artery-bronchial artery anastomoses, 3 aneurysmal coronary ectasias, and 1 combined coronary ectasia and anastomosis. Among 24 patients with coronary stenosis, the ostium was most frequently involved (87.5%). Twenty-three of 24 patients with coronary artery stenoses were treated surgically. The mean follow-up duration was 9.65 ± 6.9 years, with a 100% follow-up rate. Four fistulas and 4 aneurysms in 7 patients were not treated surgically. Coronary steal phenomenon was always associated with occluded pulmonary arteries and pulmonary hypertension. Aneurysmal coronary ectasia was related to severe aortic hypertension with or without aortic regurgitation and atypical coarctation. There were 2 (8.7%) in-hospital deaths and 3 (13%) late deaths. The actuarial survival rate, including in-hospital deaths, was 86.5% ± 7.3% at 5 years and 81.4% ± 8.4% at 10 years. Conclusion: The incidence of coronary abnormalities is relatively low in patients with Takayasu arteritis; however, surgical treatment is recommended for patients with coronary ostial stenoses because coronary ischemia can be one of the major causes of death. J Thorac Cardiovasc Surg 2003;125:570-7

Apical hypertrophic cardiomyopathy has been divided into two entities: apical asymmetric septal hypertrophy (apical ASH) and apical symmetric hypertrophy (AH). The latter differs clinically from hypertrophic cardiomyopathy (HCM) with ASH, and it is unclear whether AH represents a distinct subtype of HCM. In the present study, the presence or absence and the extent of cardiac muscle cell disorganization, a histologic characteristic of HCM, were compared in patients with AH (n = 10) and ASH (n = 29) in whom cardiac biopsy specimens were obtained from the left ventricular apex and interventricular septum. Disorganization was graded as (1+) in only 1 patient in the AH group and (−) in the remaining 9. In contrast, in the ASH group disorganization was graded as (1+) in 15 patients, (2+) in 7, (3+) in 3, and (−) in only 4 (P < 0.0001). Thus, it was observed that in AH disorganization is virtually absent or at most limited to a very narrow area. It is concluded from a histological stand point as well that the type of apical hypertrophic cardiomyopathy showing apical symmetric hypertrophy differs from usual HCM.

Pimobendan, an oral inotropic drug with phosphodiesterase III-inhibitory activity, induces cAMP-dependent relaxation of vascular smooth muscle in the pulmonary artery, as well as in the systemic cardiovascular system. We report here a patient with severe primary pulmonary hypertension (PPH), who had developed right heart failure (New York Heart Association functional class IV) despite uptitrated intravenous epoprostenol, and who was treated with extremely low-dose (0.625–1.25 mg daily) pimobendan as an adjunct to prostacyclin therapy. The combination therapy of low-dose pimobendan, prostacyclin, intravenous epoprostenol and oral beraprost has been continued for over 2 years without occurrence of fatal arrhythmia, and her six-minute walk test has exceeded 400 m. We suggest that low-dose pimobendan may enhance the hemodynamic effect of prostacyclin in severe PPH.

The present study investigated both the clinical significance of atrial fibrillation (AF) before right atrial appendage (RAA) pacing and the influence of prolonged P wave on AF occurrence in RAA-paced patients with sick sinus syndrome (SSS). Fifty-seven patients (age 68+/-10 years; 19 men, 38 women) with SSS who underwent RAA pacing were divided into 2 groups: 23 patients without AF before pacing (I + II; Rubenstein I or II) and 34 patients with AF before pacing (III; Rubenstein III). The P wave duration in intrinsic rhythm and with RAA pacing were measured on the standard electrocardiography in leads II and V(1) with the use of a digitizing tablet. Group III was further subdivided into 2 groups: 20 patients (IIIb) with a paced P wave >130 ms in both leads II and V(1) and the other 14 patients (IIIa). The duration of the intrinsic P wave in leads II and V(1) was significantly greater in group III than in group I + II (119+/-20 vs 108+/-21 ms, p=0.0417, 106+/-16 vs 95+/-21 ms, p=0.0258, respectively). During the follow-up of 40+/-21 months, AF recurrence was significantly higher in group IIIb than in groups IIIa and I + II (17/20 vs 5/14 vs 2/23 p

Brain natriuretic peptide (BNP) is a powerful neurohormonal marker of left ventricular function and prognosis. Amiodarone either has no effect or improves the haemodynamics in patients with left ventricular dysfunction, but its effect on BNP is unknown. This study evaluated the effect of amiodarone on plasma BNP level in patients with heart failure and ventricular tachyarrhythmia. Plasma BNP level was studied in 46 patients with heart failure ventricular tachyarrhythmia, before (baseline) and at week 2 and months 1, 3 and 6 of amiodarone treatment. In addition, 21 patients with heart failure and ventricular tachyarrhythmia, who received an implantable cardioverter defibrillator, but not amiodarone, were studied on the same schedule. All patients had previously received potent vasodilator and beta-blocker therapy. Echocardiography and Holter monitoring were also performed. Amiodarone significantly decreased plasma BNP levels at week 2 to month 6 during therapy. Heart rates and frequencies of premature ventricular complexes were markedly reduced by amiodarone. Echocardiographic findings did not show a change in left ventricular end-diastolic dimensions, despite a slight increase in fraction shortening at month 6 during amiodarone therapy. The above parameters showed no change in patients without amiodarone. The effect of heart rate, premature ventricular complexes, fraction shortening, serum creatinine or thyroid stimulating hormone level was not significantly associated with decrease in BNP level during amiodarone therapy by a multivariate analysis. Among amiodarone-treated patients, mortality was higher in 24 with BNP levels ≥100 pg/ml at month 6 than in 22 with BNP levels

Objective: Cystic medial degeneration (CMD) is a histologic abnormality that is common in aortic diseases such as aortic dilation, aneurysm, or dissection. Although little is known about the mechanism underlying CMD, we have previously demonstrated that angiotensin II signaling via angiotensin II type 2 receptor (AT2R) plays a central role in apoptosis of vascular smooth muscle cells (VSMCs) occurring in CMD associated with Marfan syndrome. The aim of this study is to elucidate the role of angiotensin II signaling in THE pathogenesis of aortic diseases associated with CMD. Method: We investigated the effects of angiotensin-converting enzyme inhibitor (ACEI), temocapril (n = 15), angiotensin II receptor type-1 (AT1R) blocker, CS-866 (n = 15), and vehicle control (n = 17) on 0.25% β-aminopropionitrile monofumarate (BAPN)-induced aortic dissection and histopathologic findings in a rat model. Results: Temocapril significantly prevented aortic dissection (P < .05), CMD (P < .01), and VSMC apoptosis (P < .01) compared with vehicle control in BAPN-fed rats. However, CS-866 did not show any preventive effect. Reversed transcriptase-polymerase chain reaction demonstrated that expression of both AT1R and AT2R was detected in control rat aortas, and that AT2R expression was significantly upregulated in the aortas of BAPN-fed rats (P < .01). Blood pressure was significantly and equally lowered in both temocapril and CS-866 groups compared with control. Conclusions: Differential expression of angiotensin II receptors and AT2R signaling are involved in the pathogenesis of CMD and aortic dissection in BAPN-fed rats. ACEIs might be of clinical value for the prevention and treatment of aortic diseases related to CMD. (J Vasc Surg 2002;36:818-23.)

Aim: Abdominal aortic aneurysm (AAA) is a common vascular degenerative disease. AAA wall contains inflammatory cells that produce matrix metalloproteinases (MMPs) that probably contribute to elastolysis and remodeling of the aneurysm. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown to reduce the expression of various molecules (including MMPs) independently of their cholesterol-lowering effect. The aims of this study are to investigate whether statins could modulate the biology of AAA wall and have a potential therapeutic value against AAAs. Methods: We performed immunohistochemical analysis, evaluated MMP-9 production in the aortic wall from patients with infrarenal AAA (n = 10) and control patients with aortoiliac occlusive disease (n = 8), and examined the effect of cerivastatin on MMP-9 production in the AAA wall with organ culture. Results: Neutrophils and macrophages were the cellular sources of MMP-9 in the AAA wall. The tissue concentrations of both total and active MMP-9 were significantly higher in tissues from AAA walls than in control aortic walls. Cerivastatin (0.001 to 0.1 μmol/L) significantly reduced the tissue levels of both total and active MMP-9 in a concentration-dependent manner (P < .001), and the production of tissue inhibitor of MMP-1 was unaffected. Cerivastatin neither reduced the number of infiltrating neutrophils and macrophages nor enhanced apoptosis of those cells, as evaluated with terminal transferase-mediated deoxyurisine triphosphate nick end labeling. Conclusion: These results suggest that cerivastatin can directly modulate the biology of the AAA wall and suppress MMP-9 production in the AAA wall by inhibiting the activation of neutrophils and macrophages, indicating that statin therapy could be useful for the prevention or treatment of AAA. (J Vasc Surg 2002;36:158-63.)

Pimobendan is an inotropic and vasodilating drug with phosphodiesterase (PDE) III-inhibiting and calcium-sensitizing effects. It may also have a bronchodilatory effect by inhibiting PDE III in airway smooth muscle. We tried a beta-blocker combined with low-dose pimobendan in 2 patients who had refractory heart failure of NYHA functional class III or IV with idiopathic dilated cardiomyopathy (DCM) and chronic obstructive pulmonary disease (COPD). Both of them had previously failed to tolerate beta-blocking drugs because of the exacerbation of bronchospasm. After pimobendan was administered at 1.25 to 2.5 mg daily, metoprolol could be successfully introduced from a low dose of 1.25 mg daily without decreasing the peak expiratory flow rate. Over the next 1 to 2 years, they have continued beta-blocker therapy. One is currently receiving 10 mg daily of bisoprolol and another is taking 15 mg daily of metoprolol, and both are in NYHA functional class II without worsening heart failure or COPD. The combination of beta-blocker with low-dose pimobendan may be helpful for patients with DCM and COPD, but further clinical investigation is required.

A 41-year-old man was admitted because of syncope. The electrocardiogram showed torsade de pointes (Tdp) with no long QT interval and the coupling interval of the initial beat of Tdp was 240 ms. Heterogeneity of ventricular refractoriness was observed together with shortness of the effective refractory period measured at the right ventricular inflow site where the paced QRS morphology was the same as that of the initial beat of Tdp. Verapamil could suppress frequent ventricular premature complexes with a short coupling interval, which lead to Tdp. Polymorphic ventricular tachycardia was induced by triple ventricular extrastimuli. A pure potassium channel blocker was successful in inhibiting polymorphic ventricular tachycardia inducibility by prolongation of refractoriness. These results suggested that triggered ventricular premature complexes may be represent the initiating mechanism, whereas the shortness of local refractory period and heterogeneity of ventricular refractoriness may play a role in the development and the maintenance of the Tdp.

A 58-year-old patient is presented who had a pulmonary adenoid cystic carcinoma which recurred 10 years after sleeve left pneumonectomy. The patient developed acute heart failure because the lesion obstructed blood flow by compressing the left atrium. Transesophageal echocardiography and magnetic resonance imaging demonstrated a solid mass arising from the pericardium which displaced the posterior wall of the left atrium. The mass was resected. Postoperative radiation was not performed.