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Background: Hyogo Prefecture is the 2nd prefecture in Japan, after Kanagawa, to enact a ban with penal code on smoking in public places, although the restriction is partial.Methods and Results:This study included consecutive patients with acute coronary syndrome (ACS) who were admitted to 33 major hospitals in the Hyogo District during the 12 months before implementation of the legislation and during the 24 months thereafter. Consecutive patients with ACS from Gifu Prefecture who were admitted to 20 major hospitals were enrolled as geographical controls. The number of ACS admissions did not change from the years 2012-2015 in both Hyogo District (1,774 in the pre-year, 1,784 in the 1st year, and 1,720 in the 2nd year) and Gifu Prefecture (1,226 in the pre-year, 1,174 in the 1st year, and 1,206 in the 2nd year). However, a clear reduction was observed in the subanalysis for Kobe City (895 in the preceding year, 830 (-7.3%) in the 1st year, and 792 (-11.5%) in the 2nd year), where adherence to the smoking ban was higher than in other Hyogo districts., Conclusions: The primary endpoint did not show a significant change. However, the subanalysis showed a significant decrease in ACS admissions in Kobe City. These results suggest that ACS reduction may depend on the degree of adherence to a smoking ban. (Circ J 2016; 80: 2528-2532).

Background: Chronic kidney disease (CKD) is strongly associated with coronary artery disease (CAD), although the underlying pathophysiological mechanism remains unclear. Epicardial adipose tissue (EAT) has recently been recognized as an important source of various pro-inflammatory cytokines causing coronary atherosclerosis. This study investigated the relationship between CKD and EAT volume in association with high-risk plaque., Methods and Results: The study included 275 patients with an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m(2)who underwent multidetector computed tomography (MDCT) for the evaluation of CAD. Patients were classified, according to eGFR, into a CKD group (30≤eGFR<60 ml/min/1.73 m(2)) or a non-CKD group (eGFR ≥60 ml/min/1.73 m(2)). MDCT was used to assess coronary plaque morphology and EAT volume. One hundred and ten patients with CKD were more likely to be older, have higher prevalence of hypertension, lower serum HDL-C, higher serum CRP, and larger EAT volume, than those without CKD (all P<0.01). On multivariate analysis age, hypertension, and EAT volume were significantly associated with eGFR (all P<0.01). EAT volume was associated with the presence of high-risk plaque, independent of traditional CAD risk factors (P=0.003)., Conclusions: Patients with CKD had significantly increased EAT volume, which could be associated with the presence of high-risk plaque.

Background: Hypertension increases the risk of left ventricular (LV) diastolic dysfunction, and anti-hypertensive therapy may improve LV relaxation. The aim of this study was to investigate whether combining an angiotensin-receptor blocker (ARB) with either hydrochlorothiazide (HCTZ) or a calcium-channel blocker (CCB) improves LV relaxation in patients with hypertension and diastolic dysfunction., Methods and results: Hypertensive patients who had not achieved their target blood pressure with at least 4 weeks of ARB therapy were randomly assigned to receive either a fixed-dose combination of losartan and HCTZ (losartan/HCTZ; n=110) or a combination of amlodipine and a typical ARB dosage (CCB/ARB; n=121) and followed for 24 weeks. The primary endpoint was change in early diastolic mitral annular velocity (e', cm/s). Systolic blood pressure decreased in both groups after switch to the combination therapies. E' velocity increased both in the losartan/HCTZ (0.52 cm/s) and in the CCB/ARB (0.59 cm/s) groups. The mean (95% CI) treatment difference was -0.02 (-0.37 to 0.34) cm/s, indicating that improvement in LV relaxation was similar between the groups. The ratio of early mitral inflow velocity to e' velocity and left atrial volume index were significantly decreased in the losartan/HCTZ group., Conclusions: The combination of losartan and HCTZ is as effective as amlodipine plus ARB in improving LV relaxation in hypertensive patients.

Background: Physical examination as an initial screening tool to diagnose abdominal aortic aneurysm (AAA) has lost favor over the past 20 years. This multicenter cohort study aimed to determine the prevalence of AAA in elderly Japanese patients with hypertension (HT) and to clarify the diagnostic accuracy of physical examination using a pocket-sized ultrasound imaging device (the "pocket-echo"). METHODS AND RESULTS: A total of 1,731 patients with HT aged >60 years from 20 collaborating institutions were enrolled in this study. Abdominal palpation was performed on physical examination, and the pocket-echo was used to confirm the diagnosis of AAA. The abdominal aorta was well visualized in 1,692 patients (98%). AAA was discovered in 69 patients (4.1%), with advanced age and male sex identified as independent risk factors. The prevalence of AAA increased according to age regardless of sex, and reached 9.2% and 5.7%, respectively, in males and females ≥80 years. Overall, 33 cases of AAA were missed on abdominal palpation (sensitivity, 52%), whereas for AAAs >40 mm, the sensitivity was 75%., Conclusions: We assessed the utility of the pocket-echo and physical examination for diagnosing AAA in Japanese patients with HT aged over 60 years. Our findings highlight the importance of AAA screening programs in high-risk Japanese populations, and confirm the ability of physical examination to detect large, but not small, AAAs.

Background: The geographic distribution of cardiovascular (CV) health-care services has not been assessed systematically., Methods and Results: Data of the Japanese Circulation Society (JCS) annual survey were provided to the JCS working group with the permission of the JCS Scientific Committee. The status of CV practice in 2010 was then assessed in 47 prefectures retrospectively, along with national census and gross domestic product (GDP) data. The surveyed indices included resources (hospitals, beds and cardiologists), burden (number of inpatients), and outcome (CV mortality and autopsy) in each prefecture, which correlated well with respective populations or GDP. Inequality of geographic distribution was evident for pediatrics among the 47 prefectures, according to Lorenz curve, Gini coefficient or the maximum/minimum ratio for each index. According to the Gini coefficients, only the number of inpatients (medical or acute myocardial infarction) and beds for the total number of general hospitals or the hospitals surveyed in the present JCS study were lower than expected with regard to GDP., Conclusions: Geographic disparity of CV resources or burden was larger in pediatrics than in CV medicine or surgery. Improvement of equality in CV practice with regard to appropriateness and quality are the coming challenges for the JCS.

Background: Both left atrial spontaneous echo contrast (LASEC) and aortic atherosclerotic plaque (AoP) ≥ 4.0 mm in thickness are predictors of cardiovascular events after stroke. The aim of this study was to investigate impact of AoP ≥ 4.0 mm or LASEC on cardiovascular events in patients with atrial fibrillation (AF)., Methods and Results: One hundred and eight consecutive patients with AF were enrolled and studied. Patients were grouped according to the presence or absence of AoP ≥ 4.0 mm in the proximal aortic arch on transesophageal echocardiography (TEE). Cardiovascular events included death, myocardial infarction, ischemic stroke, systemic embolism and congestive heart failure. During a follow-up period (median, 3.9 years), cardiovascular event-free survival rate was significantly lower in patients with AoP ≥ 4.0 mm than in patients without AoP ≥ 4.0 mm (log-rank, P=0.01). In contrast, patients with LASEC showed a trend toward lower cardiovascular event-free survival than those without LASEC (log-rank, P=0.10). Univariate TEE predictors of cardiovascular events were AoP ≥ 4.0 mm, LASEC and left atrial appendage flow velocity. On multivariate Cox regression analysis, AoP ≥ 4.0 mm was the only TEE predictor of cardiovascular events during follow-up (P=0.02, hazard ratio, 2.6; 95% confidence interval: 1.1-6.0)., Conclusions: In the present unselected patients with AF, AoP predicted long-term cardiovascular events.

Background: In the absence of obstructive coronary narrowing, impaired coronary flow reserve (CFR) represents coronary microvascular dysfunction. Transthoracic Doppler echocardiography (TTDE) allows non-invasive measurement of CFR in the left anterior descending (LAD) artery. This study aimed to assess the prognostic value of TTDE-derived CFR (as a marker of microvascular function) in predicting long-term cardiovascular events, acute coronary syndrome (ACS) events, and the development of heart failure (HF)., Methods and Results: This study consisted of 272 patients with coronary artery disease not involving obstructive narrowing (≥50%) in the LAD. Patients underwent TTDE examination for CFR measurement in the LAD. During the follow-up period of 4.0±1.9 years, 32 patients (12%) had cardiovascular events. Cox proportional hazard analysis identified lower CFR as an independent risk factor of cardiovascular events (P<0.001), ACS events (P=0.008), and HF development (P=0.003). A CFR less than 2.4 was the best cut-off value for predicting all events (area under the curve=0.82). CFR excellently predicted the development of HF (area under the curve=0.95), but not ACS events (area under the curve=0.67)., Conclusions: This TTDE study demonstrated that CFR was a significant and independent determinant of long-term cardiovascular events, ACS events and HF in patients with coronary artery disease. A CFR greater than 2.0 was not suitable to predict a favorable long-term outcome, even in the absence of obstructive coronary narrowing.

Background: Atrial fibrillation (AF) is associated with considerable morbidity and mortality in patients with coronary artery disease (CAD). Epicardial adipose tissue (EAT) is recognized as an important inflammatory tissue that may exert deleterious effects on the adjacent left atrial (LA) wall. Multidetector computed tomography (MDCT) can accurately assess EAT's volume and distribution. This study used MDCT to investigate the effect of peri-atrial EAT on new-onset nonvalvular AF., Methods and Results: The study group consisted of 279 patients (176 men; age, 65±10 years) with no history of AF who underwent MDCT examination for evaluation of CAD. EAT was automatically identified on the basis of threshold attenuation values of -30 to -250 Hounsfield units. EAT volume was calculated as the sum of EAT area and subsequently divided into peri-atrial and peri-ventricular EAT. During follow-up of 3.3±1.0 years, AF occurred in 17 (6.1%) patients. Cox proportional hazards regression analysis indicated that male sex, and the LA and peri-atrial EAT volumes (P=0.03, P<0.001, and P<0.001, respectively) were independent predictors for future AF. The sensitivity and specificity for the prediction of AF using a peri-atrial EAT volume index of ≥27 ml/m(2) were 88% and 92%, respectively., Conclusions: This is the first study demonstrating that peri-atrial EAT volume estimated by MDCT excellently predicted the development of new-onset AF in patients with CAD, independent of LA enlargement.

Background: The recently developed real-time 3-dimensional echocardiography (RT3DE) is a promising imaging method to quantify cardiac chamber volumes and their functions in clinical practice. However, normal reference values of RT3DE parameters have not been fully investigated in a large, healthy Japanese population., Methods and Results: This study consisted of 410 healthy subjects aged from 20 to 69 years who had a RT3DE at one of the 23 collaborating institutions. All subjects had no history of cardiac disease and no risk factors. The mean values in men and women were as follows: 50 ± 12 ml/m(2) and 46 ± 9 ml/m(2) for left ventricular (LV) end-diastolic volume index, 19 ± 5 ml/m(2) and 17 ± 4 ml/m(2) for end-systolic volume index, 61 ± 4% and 63 ± 4% for ejection fraction, 64 ± 1 2 g/m(2) and 56 ± 11 g/m(2) for mass index, 23 ± 6 ml/m(2) and 24 ± 6 ml/m(2) for left atrial (LA) maximum volume index, 10 ± 3 ml/m(2) and 10 ± 3 ml/m(2) for minimum volume index, and 58 ± 6% and 58 ± 6% for percent volume change. LV sizes decreased with age, whereas LV mass index did not change. LA sizes slightly increased with age., Conclusions: This multicenter investigation determined normal reference values for LV and LA sizes, and their functional parameters on RT3DE in a large, healthy Japanese population. The results of the present study support the use of RT3DE for the diagnosis and management of cardiovascular disease.

Background: Although echo Doppler machines have consistently advanced within a quarter of a century, age related prevalence of valvular regurgitation detected by currently available echo machines remains uncertain. The aim of this study was to investigate the prevalence and correlates of valvular regurgitation in healthy individuals., Methods and Results: A total of 1,333 apparently healthy individuals were enrolled in this study. Echocardiographic examinations were performed using a currently available echo machine. Aortic regurgitation (AR) was detected less frequently (<10%) in younger subjects. Prevalence of aortic regurgitation increased with advancing age and reached 46% in their 9th decade. Mitral regurgitation (MR) was detected in two-thirds of the subjects >30 years old. Tricuspid regurgitation (TR) was frequently (>80%) detected in all age groups. In general, prevalence of valvular regurgitation was higher than those reported previously, except for a relatively lower prevalence of AR in the elderly population. Age was an independent correlate of AR and MR, but not of TR. The presence of AR and MR were independent correlates of TR., Conclusions: In healthy subjects, AR, MR or TR are commonly detected by using a current echo machine. These "physiological" valvular regurgitations should not be considered as a "pathological" valvular heart disease.

Background: The purpose of the present study was to investigate gender differences in age-related changes of left ventricular (LV) and right ventricular (RV) geometries and functions throughout the entire adult age range using the Japanese Normal Values for Echocardiographic Measurements Project (JAMP) study database., Methods and Results: Seven hundred healthy volunteers (aged 20-79 years) underwent 2-dimensional and Doppler echocardiography. The subjects were stratified into 6 different age groups and then stratified by gender in each age group. LV diastolic function was assessed from pulsed wave Doppler measurements of mitral early (E) and late (A) inflow velocities and tissue Doppler measurements of mitral early (e') and late (a') annular velocities. LV volume decreased and LV mass increased with age to a similar extent in both men and women. Furthermore, for subjects <50 years, women had significantly greater E, E/A ratio and e' than men, but these parameters were similar between genders in subjects >50 years. In addition, there was a significant interaction between age and gender that affected the differences in E, e' and E/e' among the groups (P<0.03, P<0.01, and P<0.03, respectively; ANOVA). There were no gender differences in age-related changes in RV parameters., Conclusions: Gender differences were found in age-related changes in LV diastolic function in a healthy population. Gender differences should be considered for optimal diagnosis and management of cardiovascular disease.

Background: Electrocardiographic (ECG) left ventricular hypertrophy (LVH) is a risk factor for cardiovascular events and the incidence of LVH increases with age. However, few studies have assessed risks associated with LVH in elderly hypertensive patients., Methods and Results: The Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive Patients (JATOS) was conducted to determine optimal blood pressure in elderly patients. At study entry, the sum of the S-wave in lead V(1) and the R-wave in lead V(5) (SV1+ RV5) could be determined in 3,230 patients, among whom 164 (5.1%) had cardiovascular events. On univariate analysis, the hazard ratio for cardiovascular events was 1.51 for each 10 mm (=1 mV) (95% confidence interval (CI): 1.34-1.69, P<0.0001) when SV1+ RV5 was considered a continuous variable, and 2.17 (95%CI: 1.54-3.05, P<0.0001) and 2.83 (95%CI: 1.91-4.19, P<0.0001) when SV1+ RV5 was classified into 2 groups at threshold values of either 35 mm or 40 mm, respectively. Multivariate Cox analysis showed that gender, age, current smoking, diabetes mellitus, history of renal disease, history of stroke, and SV1+ RV5 were significantly related to the occurrence of cardiovascular events. Kaplan - Meier curves showed that increasing SV1+ RV5 values were associated with higher incidences of cardiovascular events., Conclusions: ECG LVH is strongly related to cardiovascular events in elderly hypertensive patients.

Background: A pocket-sized portable transthoracic echocardiographic (pTTE) imaging device is commercially available, but its feasibility and accuracy in the assessment of cardiac chamber size and function has not been fully compared with the results of standard TTE (sTTE) examination., Methods and Results: The target population comprised 125 unselected patients who underwent sTTE and pTTE examinations. The left ventricular (LV) diastolic and systolic dimensions, fractional shortening (FS), the thickness of the interventricular septum (IVS) and of the LV posterior wall (PWT), left atrial (LA) dimension, and ascending aorta diameter were measured. Echocardiographic measurements were completed for both pTTE and sTTE in all patients (feasibility 100%). LV dimensions, FS, IVS, PWT, LA dimension, and aorta diameter obtained by pTTE showed excellent correlation and agreement with sTTE (r=0.87-0.98, all P<0.001). Observer variabilities for these measurements were similar between pTTE and sTTE., Conclusions: In the present study, pTTE with the Acuson P10 was feasible and accurate for assessing cardiac chamber size and function.

Background: Although multidetector computed tomography (MDCT) allows non-invasive assessment of coronary artery stenosis, the presence of calcified lesions often lead to an overestimation of the stenosis. The present study was an evaluation of whether enhancement of first-pass myocardial data can improve the diagnostic accuracy of 64-MDCT., Methods and Results: Data from 70 patients with single-vessel disease who underwent 64-MDCT followed by catheter-based coronary angiography (CAG) were analyzed. Myocardial enhancement was quantified by exaimining the signal densities at diastole. Among a total of 83 plaque segments, 35 calcified plaque segments were detected and 46 segments were found to have more than 50% coronary stenosis on catheter-based CAG. The average diameter stenosis was 75.2+/-12.8%. Diagnosis by 64-MDCT of significant stenosis (segment-based analysis) had a sensitivity, specificity and accuracy for segments without calcified lesions of 92%, 100% and 99.7%, respectively, and 95.2%, 50%, and 77.1%, respectively, for calcified lesions. Taking into account the myocardial enhancement by calculating the decrease of the standardized signal densities in percent, these parameters could be improved to 95.2%, 85.7% and 91.4%, respectively, for segments with calcified lesions., Conclusions: The diagnostic accuracy of 64-MDCT for stenosis with calcified lesions in particular can be improved by taking into account the myocardial enhancement data.

Background: Although approximately 50% of heart failure patients are reported as heart failure with preserved left ventricular systolic function (HFPSF), echocardiographic prognostic predictors have not been well investigated. Recently, the tissue Doppler-derived index, the ratio of the early transmitral flow velocity and the early mitral annular velocity (E/E'), was reported as useful in predicting prognosis of patients with heart diseases. The purpose of this study was to investigate whether E/E' predicts prognosis in HFPSF., Methods and Results: A total of 50 patients with HFPSF (ejection fraction >50%) were consecutively enrolled and studied. Echocardiographic examination was performed on admission and repeated after optimized medical therapy. Cardiac events were defined as death and unplanned hospitalization because of congestive heart failure. Cardiac event-free survival curves from patients with E/E' >15 and E/E' 15 after medical therapy showed significantly lower cardiac event-free survival than patients with E/E' 15 after medical therapy was the only independent predictor of cardiac events (P=0.037, risk ratio=6.1, 95% confidence interval: 1.12-33.3) in patients with HFPSF., Conclusions: Elevated E/E' after optimized medical therapy may be useful in predicting cardiac events in patients with HFPSF.

Background: Accumulating evidence indicates that C-reactive protein (CRP) is an independent predictive factor for atherosclerotic vascular disease in Caucasians. Accordingly, this study sought to investigate the relationship between the serum level of CRP and cardiovascular events of Japanese patients with coronary artery disease (CAD)., Methods and Results: The Japanese CAD (JCAD) study enrolled 15,628 patients who had significant diameter stenosis (>or=75%) in at least 1 coronary artery. Of these, 6,802 patients had their baseline serum CRP data available. Patients were followed up for a mean of 2.7 years (follow-up rate 88.3%). The primary endpoint of the JCAD study was all events. Baseline covariates possibly influencing the event rate were adjusted between the 2 groups with and without elevated serum CRP level. Kaplan-Meier analysis demonstrated a 30% higher all-events rate in patients with a serum level of CRP >or=0.1 mg/dl (P=0.0002). Cox proportional hazard analysis also showed that a serum level of CRP >or=0.1 mg/dl was an independent predictor of all events (P=0.0001), and of cardiac events and cardiac death (P=0.0005)., Conclusions: Elevated serum level of CRP is an independent predictor of cardiovascular events in JCAD patients.

Background: With multislice computed tomography (MSCT) it is possible to visualize the coronary arteries, as well as the aorta, in a single computed tomography scan. Using MSCT, atherosis and sclerosis of the descending thoracic aorta (DTA) were quantified and differences between patients with and without coronary artery disease (CAD) were analyzed., Methods and Results: The population comprised 89 patients who underwent ECG-gated MSCT: 40 patients with suspected CAD by MSCT underwent invasive coronary angiography, and had documented significant stenoses (CAD group), 49 patients did not have significant stenoses (control group). Twenty cross-sectional images of DTA were reconstructed every 5% (0-95%) of the RR interval, and the largest and smallest luminal areas were traced. Atheromatous score and stiffness beta of DTA were quantified; both were significantly higher in the CAD group than in the controls. Multivariate analysis revealed that the average atheromatous score was an independent factor associated with CAD (p<0.005)., Conclusion: This study demonstrates that atherosis and sclerosis of DTA are associated with CAD. In cases with image quality that is unsatisfactory for interpretation of coronary stenoses, additional assessment of atherosclerosis of the DTA will be useful for identifying patients with CAD.

Background: Normal values for echocardiographic measurements and the relationship between these parameters and age in a large Japanese population are still unknown., Methods and Results: A total of 700 healthy Japanese aged 20-79 years underwent 2-dimensional and Doppler echocardiography at collaborating institutions. The respective mean values obtained in men and women were as follows: septal wall thickness, 0.9+/-0.1 and 0.8+/-0.1 cm; posterior wall thickness, 0.9+/-0.1 and 0.8+/-0.1 cm; left ventricular (LV) diastolic diameter, 4.8+/-0.4 and 4.4+/-0.3 cm; LV systolic diameter, 3.0+/-0.4 and 2.8+/-0.3 cm; LV diastolic volume, 93+/-20 and 74+/-17 ml; LV systolic volume, 33+/-20 and 25+/-7 ml; LV ejection fraction, 64+/-5 and 66+/-5%; maximum left atrial (LA) volume, 42+/-14 and 38+/-12 ml. Aortic root diameter, LV wall thickness, and LV mass slightly increased with age, whereas indexed LA volume did not vary with age. Diastolic parameters assessed by mitral inflow and mitral annular velocities declined with age, as previously reported., Conclusions: Normal values of echocardiographic measurements in a large Japanese population are reported for the first time; several systolic and diastolic parameters varied with age. These results provide important reference values that should be useful in routine clinical practice as well as in clinical trials.

Background: Plaque rupture and secondary thrombus formation play key roles in the onset of acute coronary syndrome (ACS). Multidetector computed tomography (MDCT) allows the non-invasive assessment of coronary artery stenosis and plaque properties. In this study, we investigated whether 64-slice MDCT could non-invasively detect a plaque rupture in patients with de novo angina., Methods and Results: The study population comprised 67 patients with de novo angina. All patients underwent contrast-enhanced 64-slice MDCT and intravascular ultrasound (IVUS). Patients were divided into a plaque rupture group (n=27) and a non-rupture group (n=40) based on the IVUS. The 64-slice MDCT revealed that the prevalence of an ulcer-like enhancement space (37% vs 5%, p<0.01), a ring-like sign (41% vs 18%, p=0.04), in the plaque rupture group was higher than those in the non-rupture group. Maximum plaque thickness (2.1+/-0.9 mm vs 1.6+/-1.0 mm, p=0.04), outer vessel area (17.6+/-4.9 mm2 vs 13.4+/-5.0 mm2, p<0.01), percentage plaque area (82.3+/-9.1% vs 73.4+/-15.7%, p=0.01), and remodeling index (1.11+/-0.18 vs 1.01+/-0.15, p=0.04) of the plaque rupture group were all significantly larger than those of the non-rupture group., Conclusions: The 64-slice MDCT can identify differences in lesion morphologies between ruptured plaques and non-ruptured plaques. From our results, the 64-slice MDCT might provide a useful tool for the non-invasive detection of plaque rupture.

Background: Recent advancements in 16-slice multidetector-row computed tomography (16-slice MDCT) provide for non-invasive assessment of not only coronary artery disease (CAD), but also myocardial properties and the anatomy of the whole heart. The purpose of the present study was to investigate whether the aortic valve area (AVA) in patients with aortic stenosis (AS) assessed by 16-slice MDCT corresponds to echocardiographic assessment and to evaluate simultaneously the clinical accuracy in detecting CAD with 16-slice MDCT., Methods and Results: The AVA of 29 consecutive AS patients with transthoracic echocardiography (TTE) and 16-slice MDCT were analyzed. The AVA was estimated by means of the continuity equation method in 2-dimensional echocardiography (DE) and the quantitative planimetric method after multi-planar reformation in 16-slice MDCT. Concomitantly, the severity of the coronary artery stenosis was assessed by 16-slice MDCT. In the present study, the AVA assessed by TTE and 16-slice MDCT was 1.34+/-0.32 cm(2) and 1.38+/-0.32 cm(2), respectively. Regression analysis showed that the AVA in patients with AS determined by 16-slice MDCT correlated well with those determined by 2-DE (r=0.96, p<0.001). Significant coronary artery stenosis of more than 50% diameter reduction was present in 48% of the study population., Conclusions: In patients with AS, the analysis of the severity of the AVA by 16-slice MDCT provides a feasible and accurate estimation with the concomitant evaluation of CAD.

Background: Gender differences in the predictors of outcome among patients with known or suspected coronary artery disease (CAD) undergoing contrast-enhanced dobutamine stress echocardiography (CE-DSE) have not been completely determined., Methods and Results: Follow-up (30+/-17 months) data for 581 men and 309 women with known or suspected CAD who underwent CE-DSE (mean age: 66 years) were obtained. Hard cardiac events included cardiac death and nonfatal myocardial infarction. Total cardiac events included hard cardiac events, unstable angina, congestive heart failure, and late revascularization (>3 months). Cardiac events occurred in 123 male and 50 female patients. Positive results for CE-DSE were associated with worse prognosis in both men and women (2-year total event free rate: 73.5% vs 88.2% in men, p<0.0001, 80.3% vs 91.3% in women, p<0.01). Addition of CE-DSE results, including abnormal left ventricular end-systolic volume response and left ventricular ejection fraction at peak stress <50%, to the clinical and rest echocardiography model provided incremental information for predicting total cardiac events (increase in chi-square value for the model from 60 to 72, p<0.001) in men and (increase in chi-square value for the model from 17 to 32, p<0.001) in women., Conclusions: CE-DSE provides incremental information for predicting future cardiac events in both men and women.

Background: No reflow following percutaneous coronary intervention (PCI) is a major concern in patients with acute coronary syndrome (ACS) and it may be influenced by the preexisting plaque type., Methods and Results: To evaluate the impact of plaque characteristics on coronary reflow following PCI in patients with ACS, a total of 110 patients (89 acute myocardial infarction, 21 unstable angina) were assessed by intravascular ultrasound. Plaque type was categorized as either atherosclerotic plaque without ultrasonic attenuation (group 1) or atherosclerotic plaque with attenuation (group 2). External elastic membrane, plaque plus media, and lumen area were measured. Coronary flow was assessed by Thrombolysis in Myocardial Infarction (TIMI) grade and TIMI frame count. Although the final TIMI frame count was similar between the 2 groups, TIMI frame count immediately after the first balloon inflation was significantly higher in group 2 (p=0.03). Despite the similar final TIMI grade and TIMI frame count, peak creatine kinase level was significantly higher (3,035+/-2,553 vs 1,950+/-1,958 IU/L, p=0.04) and fatal arrhythmia more frequently observed (16.4% vs 2.7%, p=0.04) in group 2 than in group 1., Conclusions: Atherosclerotic plaque with ultrasonic attenuation may be related to a transient deterioration in coronary flow and as a result larger infarct size and higher incidence of fatal arrhythmia following PCI in patients with ACS. These results may help in selecting lesions suitable for distal protection devices.

Background: Increased levels of oxidized low-density lipoprotein (ox-LDL) are related to plaque instability, so the aim of the present study was to investigate whether there is a relationship between angiographic coronary plaque morphology in patients with unstable angina pectoris (UAP) and the level of ox-LDL., Methods and Results: Plasma ox-LDL levels were measured in 149 patients with UAP and in 88 control subjects, using a highly sensitive enzyme-linked immunosorbent assay method. Angiographic morphology of the culprit lesion was classified as either simple or complex based on the Ambrose classification. Plasma ox-LDL levels in patients with Braunwald class III were significantly higher than in patients with class I (p<0.0001) or in control subjects (p<0.0001). In each of the 3 Braunwald classes, plasma ox-LDL levels in patients with a complex lesion were significantly higher than in patients with a simple lesion. Multivariate logistic regression analysis revealed that ox-LDL level and Braunwald class III were independent factors associated with angiographically detected complex lesions., Conclusion: In each Braunwald class of UAP, elevated plasma levels of ox-LDL closely relate to the presence of angiographically detected complex and thrombotic lesion morphology.

Background: Previous intravascular ultrasound (IVUS) studies have shown that calcification can be quantified by the determination of the arc on one cross-section. However, because calcium levels change along the length of lesions, it is important to assess the length of calcium using serial cross-sectional images. The correlation between the largest arc and length of each calcium deposit in patients with coronary artery disease (CAD) has not been determined. The present study was performed to determine this correlation., Methods and Results: Pre-interventional IVUS images of 194 patients with CAD were studied. The largest arc and length of all calcium within the 10-mm-long culprit lesion segment were quantified using serial cross-sectional images. One hundred and ninety-four patients had 277 calcium deposits. In all patients, the length of each calcium exhibited a strong correlation with the largest arc of calcium (R=0.750, p<0.0001)., Conclusions: Our findings revealed the quantitative characteristics of each calcium within the culprit lesion segment. They will be useful in interpreting results of previous and future IVUS studies, which deal only with the arc of calcium, as well as studies using new modalities such as computed tomography that assess calcium mainly along the long axis of the coronary artery.

Background: Non-invasive diagnosis and risk stratification of coronary artery disease are important for the selection and optimization of therapeutic interventions in diabetic patients, which may improve survival. The aim of this study was to determine the incremental value of contrast-enhanced dobutamine stress echocardiography (CE-DSE) for risk stratification., Methods and Results: CE-DSE was performed in 326 patients with diabetes mellitus (mean age; 66 +/- 10 years, 223 men). All patients were followed up for a mean of 29 months (1-61 months). Dobutamine was infused in a standard protocol with an intravenous contrast agent. The primary endpoints for hard cardiac events included cardiac death and nonfatal myocardial infarction. The primary endpoints for total cardiac events included hard cardiac events, unstable angina pectoris, congestive heart failure, and late coronary revascularization (> 3 months). Cardiac events occurred in 74 patients. The addition of the CE-DSE results, including abnormal left ventricular end-systolic volume response and left ventricular ejection fraction at peak stress < 50%, to the clinical and rest echocardiography model provided incremental information in predicting total cardiac events (increase in chi-square value for the model from 17 to 24, p < 0.05) and hard cardiac events (increase in chi-square value for the model from 18 to 24, p < 0.05)., Conclusions: Quantitative assessment of left ventricular function during CE-DSE provides incremental prognostic information in predicting cardiac events in diabetic patients.

Background: Both beta-adrenergic blockers and angiotensin-II receptor blockers were reported to improve the prognosis of patients with heart failure, but the efficacy of combination therapy with these agents has not been fully elucidated. Also the efficacy of celiprolol, a beta1-selective adrenoceptor antagonist with partial beta2-agonist properties, for heart failure treatment is still controversial. We examined the cardioprotective effects and mechanisms of the therapy with celiprolol or candesartan, an angiotensin-II receptor blockers and their combination in heart failure induced by isoproterenol (ISO)., Methods and Results: ISO 300 mg/kg was injected in rats to produce heart failure. Two months after the injection, the ISO-injected rats were divided into 4 groups (8 rats each) and treated for 4 weeks as follows: (a) vehicle; (b) celiprolol 10 mg/kg per day (BB); (c) candesartan 0.2 mg/kg per day (ARB); and (d) their combination BB+ARB. ISO significantly elevated left ventricular (LV) end-diastolic pressure, decreased peak-negative dP/dt and LV ejection fraction. BB and ARB similarly ameliorated cardiac dysfunction due to ISO, but BB+ARB were more potent than the individual therapies. Separately, ARB preserved the histological structure in LV myocardium. In contrast, BB ameliorated calcium handling, as shown by the increased ratio of SERCA2 to phospholamban protein, despite having little effect on the histology., Conclusion: Both celiprolol and candesartan showed cardioprotective effects in this heart failure model. The potential use of the combination treatment in heart failure might result in a synergistic effect through the different cardioprotective mechanisms of celiprolol and candesartan.

Background: Endothelin-1 (ET-1) receptor antagonist is expected to improve the prognosis of patients with heart failure, but the role of the ET(B) receptor in cardiac function and structure is complicated. In the present study the NADPH diaphorase activity and ET-1 content in the failing heart treated with ET(A) or ET(B) receptor antagonist were evaluated in a model of dilated cardiomyopathy., Methods and Results: Selective ET(A) receptor antagonist, ABT-627 (10 mg/kg per day), or selective ET(B) antagonist, A-192621 (30 mg/kg per day), was given to 22-week-old J2N-k cardiomyopathic hamsters for 8 weeks. The effects of ABT-627 and A-192621 on cardiac function, left ventricular (LV) histology, ET-1 content and NADPH diaphorase activity in the LV were evaluated. Treatment with ABT-627, but not A-192621, significantly decreased ET-1 content and NADPH diaphorase activity. Although the improvement of LV function was modest, ABT-627 prevented tissue damage in J2N-k hamsters. In contrast, A-192621 worsened the degeneration of cardiomyocytes despite improving hemodynamic parameters., Conclusions: Selective ET(A) antagonist, but not ET(B) antagonist, reduced the ET-1 content as well as the NADPH diaphorase activity, and preserved the fine structure of LV myocardium in cardiomyopathic hamsters. Long-term blockade of ET(B) receptor might worsen the degeneration of cardiomyocytes through the ET-1/ET(A) system even if LV function could be improved.

Background: Several studies have demonstrated the benefit of the patency of infarct-related artery (IRA) in acute myocardial infarction (AMI). However those studies have not been concerned with myocardial viability in the region-at-risk. In the present study the effect of the patency of IRA was investigated in the setting of anterior AMI with poor viable myocardium in the risk region., Methods and Results: From 1993 to 1996 patients with a first time anterior AMI and poor viable myocardium in the region-at-risk at 1 month after onset were identified and enrolled. Patients with a totally occluded IRA were included in the Non-Open group (n=44), and patients with a reperfused IRA were included in the Open group (n=49). At 5 years after onset, left ventricular function was better preserved in the Open group than in the Non-Open group (p<0.05). Kaplan-Meier survival curves for cardiac mortality and event-free survival curves revealed poor prognoses in the Non-Open group over a 5-year period (p<0.05, respectively). The advantages of a patent IRA were further seen in health-related quality-of-life outcomes (p<0.05)., Conclusions: Even in patients with poor myocardial viability after an anterior AMI, the patency of the IRA is strongly associated with improved long-term survival, independent of residual myocardium viability.

Background: Low-dose dobutamine stress echocardiography (LDDE) has become a useful and safe method for identifying hibernating or stunned myocardium and for predicting improvement in wall motion after coronary revascularization., Methods and Results: In the present study, fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET), rest-redistribution thallium-201 ((201)Tl) single-photon emission computed tomography (RR-Tl SPECT), (123)I-15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid (BMIPP) and LDDE were performed in 30 patients with acute myocardial infarction (AMI) at 10+/-3 days after the onset of AMI. Also, exercise (201)Tl reinjection SPECT (RI-Tl SPECT) was performed at 14+/-2 days. Follow-up echocardiography was performed 5+/-3 months later in all patients after interventional therapy for the assessment of functional recovery. Of the 390 segments analyzed by echocardiography, 110 (28%) had abnormal wall motion. There were no significant differences between RR-Tl SPECT and LDDE in sensitivity, specificity, positive predictive value and negative predictive value using the chi(2)-test; however, in akinetic segments, there was a significant difference in sensitivity. Among FDG-PET, RI-Tl SPECT, BMIPP and LDDE, there were significant differences in 3 variables. In akinetic segments, LDDE is superior to RR-Tl SPECT in sensitivity and to FDG-PET in specificity. In hypokinetic segments, LDDE is superior to RI-Tl SPECT and BMIPP in sensitivity, and to FDG-PET and BMIPP in specificity., Conclusions: LDDE could detect functional recovery of viable myocardium in the early period of AMI and can be performed easily and safely.

Background: Myocardial infarction (MI) promotes deleterious remodeling of the myocardium, resulting in ventricular dilation and pump dysfunction. Supplementing infarcted myocardium with neonatal myocyte would attenuate deleterious remodeling and so the present study used Doppler echocardiography and histology to analyze the cardiac function and histological regeneration of the damaged myocardium after cellular cardiomyoplasty., Methods and Results: Experimental MI was induced by 24-h coronary ligation followed by reperfusion in adult male Lewis rats and neonatal myocytes were injected directly into the infarct and peri-infarct regions. Three groups of animals were studied at 4 weeks after cellular cardiomyoplasty: noninfarcted control (control), MI plus sham injection (MI), and MI plus cell injection (MI + cell). Ventricular remodeling and cardiac performance were assessed by Doppler echocardiography or contrast echocardiography. At 4 weeks after cellular cardiomyoplasty, MI + cell hearts exhibited attenuation of global ventricular dilation and cardiac function compared with MI hearts not receiving cellular cardiomyoplasty. Immunohistochemically, connexin-43-positive small cells were observed in the vicinity of the infarction in MI + cell heart. By electron microscopy, these cells contained myofilaments with Z-bands and poorly developed intercalated disks, suggesting neonatal myocardial cells. Furthermore, the myocardial cells were often making close contact with interstitial cells., Conclusions: Implanted neonatal myocytes form viable grafts after MI, resulting in attenuated ventricular dilation and enhanced contractile function. Echocardiography, electron microscopy, and immunohistochemistry are useful methods for assessing the functional and histological regeneration of the damaged myocardium.

Background: Because the effects of an aldosterone receptor antagonist on transcriptional factors and mRNA expression have not been fully examined in myocardial infarction (MI), the present study examined the effects of spironolactone (SPIRO) and candesartan cilexitil (CAN) on activation of activator protein-1 (AP-1), nuclear factor-kappaB (NF-kappaB) and mRNA expression in the non-ischemic myocardium after MI., Methods and Results: MI was induced by ligation of the coronary artery in Wistar rats, which were separated into (1) vehicle-treated group, (2) CAN-treated group (10 mg/kg per day), (3) SPIRO-treated group (100 mg/kg per day) and (4) CAN + SPIRO-treated group. The activity of both AP-1 and NF-kappaB was significantly increased at 4 weeks after MI. CAN or SPIRO significantly prevented the cardiac remodeling and activity of AP-1 and NF-kappaB. Furthermore, CAN + SPIRO prevented the cardiac remodeling and activation of AP-1 and NF-kappaB, compared with CAN or SPIRO alone. Myocardial atrial natriuretic peptide, brain natriuretic peptide, collagen I and III mRNAs were enhanced by MI, and CAN or SPIRO alone significantly reduced the mRNAs. CAN + SPIRO significantly prevented these mRNAs, compared with CAN or SPIRO alone., Conclusions: Both aldosterone and angiotensin II are involved in the myocardial transcriptional activation of AP-1, NF-kappaB and the cardiac remodeling-related mRNAs. The combination of CAN and SPIRO may be a potent therapeutic strategy for preventing cardiac remodeling after MI.

Background: Microvascular damage immediately after reperfusion therapy is an independent predictor of left ventricular function in patients with acute myocardial infarction (AMI). However, its recovery may vary among individuals and the relationship between convalescent stage microvasculature and late myocardial morphologic change is unclear., Methods and Results: Patients treated with coronary angioplasty within 12 h of their first anterior AMI were enrolled in this study. Coronary flow reserve (CFR) was measured 3 weeks post AMI, in both branches of the left coronary artery: culprit (left anterior descending artery: LAD) and non-culprit (left circumflex artery: LCX). Left ventriculography was performed at 3 weeks and 6 months post AMI and compared. Seventeen patients showed abnormal CFR in the LAD (Group 1: CFR<2), whereas 20 patients showed normal CFR (Group 2: CFR >/=2). Percent changes of end-diastolic volume tended to be higher in Group 1 than in Group 2 (11.8+/-21.6% vs -1.3+/-14.4%, p=0.056), and %changes of end-systolic volume was significantly smaller in Group 2 (11.8+/-22.1% vs -8.7+/-25.1%, p<0.05). A statistically significant correlation was found between absolute and relative CFR in the LAD and %change of end-systolic volume (r=-0.58: p<0.001, and r=0.40: p<0.05, respectively)., Conclusions: Microvascular function in the convalescent stage may be related to these favorable changes.

The purpose of this study was to determine whether the elimination or the alleviation of hyperglycemia would improve coronary flow velocity reserve (CFVR) using transthoracic Doppler echocardiography (TTDE). CFVR was measured by TTDE in the left anterior descending coronary artery in 49 poorly controlled diabetic patients before and after antidiabetic treatment and 15 well controlled diabetic patients also underwent the same measurements. The fasting blood glucose level in the poorly controlled patients reduced from 270 +/-106 mg/dl to 116+/-39 mg/dl at 20+/-15 days after the intensive treatment. Although baseline coronary flow velocity (CFV) did not change between the 2 measurements (19.9+/-6.9 cm/s vs 19.0+/-5.4 cm/s, p=NS), the hyperemic CFV increased significantly after the treatment (47.3+/-13.4 cm/s vs 55.4+/-13.2 cm/s, p<0.001). Thus, the CFVR improved significantly after the treatment (2.47+/-0.55 vs 2.98+/-0.56, p<0.001). Although there was minimal improvement in the control group (2.37+/-0.38 vs 2.50+/-0.37, p<0.05), the improvement in CFVR was significantly greater in the poorly controlled patients with intensive treatment (0.51+/-0.33 vs 0.12+/-0.19, p<0.001) than that in the control group. These results suggest that optimal hypoglycemic therapy is important to improve the CFVR in poorly controlled diabetic patients.

The Japanese Circulation Society appointed a committee to develop guidelines for the prevention, diagnosis and management of infective endocarditis in Japan. In making such guidelines, the committee required information on the current clinical characteristics of infective endocarditis and therefore performed a nationwide questionnaire survey of cases from 2000 and 2001. In total, data were received for 848 cases from 277 of the 817 hospitals surveyed. Mean age was 55+/-18 years and most patients were aged in their 50 s or 60 s; 53.9% of the patients had infective endocarditis of unknown origin (without any prior predisposing conditions or procedures) and the second most common etiology was post dental procedures. The most common microorganism was Gram-positive cocci (345 streptococci and 221 staphylococci) and methicillin resistant Staphylococcus aureus (MRSA) was found in 7.3%. Although more than 90% of cases with Streptococcus viridans were sensitive to penicillin G, 6.6% were resistant. All MRSAs were sensitive to vancomycin. The information obtained from the survey assisted in the making of the guidelines, which should become an indispensable tool for all clinicians.

It remains uncertain whether factors other than the severity of coronary artery disease (CAD) are associated with the worsening of the left ventricular ejection fraction (LVEF) by exercise. In the present study the impact of coronary risk factors on the worsening of LVEF by exercise was investigated in 391 patients with known or suspected CAD using exercise-gated (201)Tl scanning to calculate the LVEF. Significant worsening of the LVEF by exercise was defined as >4.7% (mean plus 1 SD of the value in 116 patients without CAD). Multivariate analysis revealed that diabetes mellitus (DM) was an independent risk factor for the worsening of LVEF by exercise in patients with multivessel (2- or 3-vessel) CAD with an odds ratio (95% confidence interval) of 2.2 (1.1-4.5, p=0.037). In 157 patients with 2- or 3-vessel CAD, 20 (23.5%) of 85 nondiabetic patients and 31 (43.1%, p=0.009 vs nondiabetic patients) of 72 diabetic patients showed significant worsening of LVEF by exercise. In patients with 2- or 3-vessel CAD, there was no significant difference in Gensini score or reversibility of perfusion defects between nondiabetic and diabetic patients. Thus, DM is a risk factor for worsening LVEF by exercise in addition to the severity of CAD.

Experimental studies have postulated the ischemic cascade and the present study was designed to elucidate whether it can be observed in the clinical setting. Fifty-three patients suspected of having coronary artery disease were studied. Myocardial perfusion abnormalities (MPA) and wall motion abnormalities (WMA) were assessed simultaneously by infusion of Levovist during dobutamine stress echocardiography. Time - intensity data of myocardial opacification were fitted for Y=A (1-e(-)(beta) (t)) from which the rate of increase (beta) of intensity were derived both at rest and during stress. Wall motion was also given a score. Bright opacification was observed in 50 patients: 25 showed significant stenosis (>50%) in the left anterior descending artery (group II) on coronary angiography and 25 did not (group I). Significant differences were found in the beta ratio (stress/rest) between the 2 groups at a low-dose (2.0+/-0.3 vs 1.5+/-0.5, p<0.05) and at a high-dose of dobutamine (2.7+/-1.0 vs 1.1+/-0.5, p<0.001), whereas the wall motion score differed only at a high-dose. Of the 25 patients in group II, MPA preceded WMA in 12, both occurred at the same stage in 12, and neither MPA nor WMA was seen in 1. These data prove the ischemic cascade clinically, using contrast echocardiography, by demonstrating that MPA precede WMA during dobutamine stress in patients with coronary stenosis.

Accurate interpretation of dobutamine stress echocardiography (DSE) needs expertise. Color kinesis (CK) allows objective assessment of wall motion (WM), and its feasibility and accuracy are enhanced under harmonic imaging with contrast agents. To explore its utility, CK was performed in 41 unselected patients during contrast-enhanced DSE. After bolus injection of Levovist, the CK image was acquired in the apical 4- and 2-chamber views at baseline and peak stress using the ultraharmonic mode. Quad screen format with second harmonic imaging after another injection of Levovist was also obtained as a reference. Regional WM (12 segments in the apical view) was independently assessed by both methods. Heart rate increased from 67 beats/min at baseline to 135 beats/min (88% of age predicted maximal heart rate) at peak stress. The CK image was successfully obtained in all patients at baseline and in 38/41 patients at peak stress. CK tracked endocardial motion accurately in 93% (456/492) of left ventricular segments at baseline and 87% (427/492) at peak stress. The concordance rate of normal and abnormal WM between the 2 methods was 86% (392/456, Kappa 0.61) at baseline and 85% (362/427, kappa 0.53) at peak stress. Among the 38 patients in whom both methods were completed, the standard quad screen display showed abnormal DSE results in 17 patients and 28/114 vascular territories. The sensitivity, specificity and diagnostic accuracy of CK for detecting abnormal findings were, respectively, 71% (12/17), 90% (19/21) and 82% (31/38) in patients and 57% (16/28), 97% (83/86) and 87% (99/114) in vascular territories. The application of CK was highly feasible during contrast-enhanced DSE and gave an objective assessment of WM. This method can be a valuable adjunct to the conventional interpretation of DSE.

Recent developments in tissue harmonic imaging and intravenous contrast agents have enhanced left ventricular endocardial border delineation (EBD). In a total of 48 patients with poor quality images, apical 4- and 2-chamber views were obtained with fundamental, tissue harmonic and contrast harmonic imaging with or without intravenous Levovist, an air-filled contrast agent. The left ventricle (LV) was divided into 12 segments, and the EBD of each segment was scored: (1) not visible, (2) barely visible, (3) well delineated. The EBD index (EBDI), defined as the sum of the endocardial scores divided by 12 was obtained for each patient. Of a total of 576 LV segments, 231 were scored as 1 by fundamental imaging and that number decreased to 125 segments by tissue harmonic imaging and 116 segments by fundamental imaging with Levovist. The number of segments scored as 1 decreased to 38 segments by tissue harmonic imaging with Levovist, and to 29 segments by contrast harmonic imaging with Levovist. The EBDI by fundamental imaging was 1.85+/-0.29, which improved significantly with the addition of Levovist (2.10+/-0.36, p<0.001) and was nearly identical to that by tissue harmonic imaging (2.15+/-0.32, p=NS). Tissue and contrast harmonic imaging with Levovist further enhanced the EBDI (2.43+/-0.26, 2.51+/-0.27, respectively). Levovist enhances EBD, even in the fundamental mode, to the level obtained with tissue harmonic imaging. Tissue harmonic and contrast harmonic imaging are the best modalities for enhancing EBD after Levovist injection.

The purpose of this study was to examine the effects of nipradilol on the cardiac function and mRNA expression in Wistar rats with a myocardial infarction (MI) that was created by ligation of the anterior descending coronary. Ten mg x kg(-1) x day(-1) of nipradilol were administrated to the rats in random order, and hemodynamic and Doppler-echocardiographic findings and myocardial mRNA expression were analyzed at 4 weeks after MI. Although left ventricular end-diastolic pressure (LVEDP) and central venous pressure (CVP) were increased in the MI rats, nipradilol significantly reduced the degree of the increase in both parameters. MI also significantly increased the weight of the left and right ventricles, and increased the left ventricular end-diastolic dimension (LVDd), effects that were attenuated by nipradilol. The MI rats showed decreased fractional shortening as systolic dysfunction and decreased E wave deceleration rate as diastolic dysfunction, and nipradilol significantly prevented these. Nipradilol significantly suppressed the increase in the non-infarcted myocardial mRNA expression of atrial natriuretic peptide, brain natriuretic peptide and collagen I and III. In conclusions, nipradilol prevents the cardiac remodeling that is accompanied by systolic and diastolic dysfunction, and inhibits abnormal myocardial gene expression after MI.

Hepatocyte growth factor (HGF) is a well-known powerful proliferative factor of vascular endothelial cells and it has been reported that plasma HGF concentrations are increased in acute myocardial infarction (AMI), although the mechanisms are not yet well delineated. Serum HGF levels and C-reactive protein (CRP) were measured in 22 patients with unstable angina pectoris (UAP) (15 males, 7 females; class IIb or IIIb of the Braunwald classification), 60 patients with AMI (37 males, 23 females; average time from the onset of symptoms to admission 4.6+/-0.7h, range, 0.5-12h), and 20 normal subjects. Immediate angioplasties were performed in 51 patients with AMI, and the time course of the HGF levels were measured in 31 patients among them. Heparin dramatically increased the HGF level and it declined to the normal range 18h after heparin injection. Blood samples were taken before heparin treatment, or at least 24h after. Serum HGF levels on admission was significantly increased in UAP (mean+/-SE: 0.30+/-0.03ng/ml, p<0.01), and AMI (0.27+/-0.02ng/ml, p<0.01) compared with the normal subjects (0.19+/-0.01 ng/ml). Even in the early stage (within 3 h of onset of symptoms to admission, average time was 1.8+/-0.1 h), serum HGF levels were already elevated (0.25+/-0.02 ng/ml, p<0.05). There was no significant difference between the HGF levels in UAP and AMI. Fifty-one of the 60 patients with AMI underwent immediate percutaneous transluminal coronary angioplasty and blood samples were obtained from 31 of them on days 7, 14, and 21 after MI. Serum HGF levels peaked on day 7 (0.34+/-0.04ng/ml, p<0.01) and there was a weak relationship between peak creatine kinase and serum HGF levels at that time. A statistically significant correlation was found between peak CRP and serum HGF levels on day 7 (r=0.62: p<0.001). Serum HGF levels decreased to nearly normal by day 21 (0.22+/-0.01 ng/ml). The study shows that serum HGF levels during the early stage of AMI increased significantly and peaked by day 7 after the onset, at which time there was a strong correlation with peak CRP levels. These data suggest that HGF production may be related to the inflammatory response in AMI.

To clarify whether the myocardial perfusion abnormalities observed on harmonic power Doppler imaging (HPDI) during hyperemia are related to a decrease in coronary flow velocity reserve (CFVR), HPDI and CFVR were measured in the left anterior descending coronary artery (LAD) territory of 75 patients. During continuous infusion of Levovist, dual-frame triggered apical 4-chamber views were obtained at rest and during adenosine triphosphate (ATP) infusion. The persistence of perfusion defects during ATP infusion or stress-induced defects in the LAD territory was defined as abnormal. Both HPDI and coronary flow velocity recordings of adequate quality were successfully obtained in 73 patients, and 37 patients showed abnormal myocardial perfusion. CFVR was significantly lower in patients with abnormal perfusion than in patients who had normal findings (1.38+/-0.38 vs 2.60+/-0.76, p<0.001). A CFVR less than 1.9 had a sensitivity of 89% (33/37) and a specificity of 89% (32/36) for predicting the presence of abnormal myocardial perfusion. This study demonstrates that myocardial perfusion abnormalities observed during HPDI using ATP stress are closely correlated to a decrease in CFVR and may reflect significant stenosis or microvascular damage in the LAD territory.

Many studies have suggested that the renin-angiotensin system plays an important role in the left ventricular (LV) remodeling and cardiac dysfunction that occurs after myocardial infarction (MI). Although angiotensin II type IA (AT1A) receptor knockout (KO) mice are reported to display less LV remodeling after MI, diastolic dysfunction has not been fully evaluated, so the present study measured transmitral inflow pattern in both AT1A receptor KO mice with MI (KO-MI) and wild type mice with MI (WT-MI). Cardiac geometry and function were examined by Doppler echocardiography and myocardial mRNA expression was determined by Northern blot analysis at 4 weeks after MI. The LV internal diastolic dimension of WT-MI was larger than that of the KO-MI (p<0.05). Marked increases in the E wave velocity and the ratio of the peak velocity of the E wave to the A wave were observed in the WT-MI (p<0.01). The deceleration rate of the E wave in KO-MI was lower than in WT-MI (p<0.05). mRNA expressions of ANP, BNP, collagen I and collagen III in the non-infarcted LV and RV of KO-MI were significantly lower than WT-MI. In conclusion, transmitral inflow abnormalities in KO-MI were attenuated compared with WT-MI.

A 52-year-old Japanese man who had suffered from Behçet's disease since the age of 45 years was admitted to hospital for evaluation of syncope and heart murmur. Echocardiography and aortography revealed severe aortic regurgitation and cystic masses under the right coronary cusp and the left ventricular outflow tract, but no shunt jet. He was diagnosed with unruptured aneurysm of the sinus of Valsalva, and surgical closure of the orifice of the aneurysm was performed. The diameter of the orifice was 11 mm and the aneurysm was 15 mm in depth, and consisted of 2 chambers. Because the aortic regurgitation was reduced after patch closure of the orifice, aortic valve replacement was not performed. Unruptured aneurysm of the sinus of Valsalva is a rare clinical lesion, but patients with active inflammatory disease of the aorta, such as in Behçet's disease, should have periodic echocardiography for early detection of an aneurysm or valvular involvement, even if there are not any symptoms.