Early recovery of impaired coronary flow reserve by carvedilol therapy in patients with idiopathic dilated cardiomyopathy: a serial transthoracic Doppler echocardiographic study.
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Publications and source records attributed to Junichi Yoshikawa.
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BACKGROUND: Measurement of left ventricular (LV) volumes and ejection fraction (EF) is important in managing patients with coronary artery disease (CAD). Introduction of free-hand three-dimensional echocardiography (3DE) system which is equipped with small magnetic tracking system and average rotational geometry for LV volumes may provide easy and accurate quantification of LV systolic function in CAD patients. PURPOSE: To evaluate the feasibility and accuracy of LV volumes and EF measurement by free-hand 3DE with rotational geometry in patients with CAD. METHODS AND RESULTS: The study subjects consisted of consecutive 25 patients with CAD who were scheduled for quantitative gated single-photon emission computed tomography (QGS). LV end-diastolic volume (EDV), end-systolic volume (ESV), and EF were determined by conventional two-dimensional echocardiography (2DE), 3DE, and QGS. Three-dimensional echocardiography data acquisition and analysis were possible in 22 of 25 subjects (feasibility 88%). In this 3DE system, image acquisition time was 2 minutes, and 5 minutes were needed for off-line analysis of LV volumes and EF. Correlations and the limits of agreement between 3DE and QGS (r = 0.97, 0.0 +/- 9.1 ml for EDV, r = 0.99, 0.0 +/- 5.0 ml for ESV, and r = 0.97, 0.5 +/- 3.3% for EF, respectively) were superior to those between 2DE and QGS (r = 0.85, 12.6 +/- 26.8 ml for EDV, r = 0.85, 9.7 +/- 26.1 ml for ESV, and r = 0.90, -1.3 +/- 6.9% for EF, respectively). Inter- and intra-observer variabilities of 3DE were smaller than that of 2DE (5% vs 10%, 5% vs 10% for EDV, 6% vs 13%, 5% vs 9% for ESV, and 4% vs 11%, 4% vs 6% for EF, respectively). CONCLUSION: Three-dimensional echocardiography using magnetic tracking system and average rotational geometry offered a feasible and accurate method for quantification of LV volumes and EF in patients with CAD.
BACKGROUND: Transthoracic Doppler echocardiography (TTDE) assessment of coronary flow velocity reserve (CFVR) has been validated in Asian and European centers. This methodology has not gained acceptability in the United States due to the bias that coronary flow velocity (CFV) by TTDE might be difficult in an obese population with relatively poor acoustic windows. METHODS: Baseline CFV in the left anterior descending coronary artery (LAD) by TTDE was obtained in 67 nonselected American patients. A subset of 38/67 received adenosine infusion for measuring CFVR of the LAD. PURPOSE: The aim of this study was twofold: (1) to determine the feasibility of measuring CFV and CFVR in the LAD by TTDE in a relatively obese American population, and (2) to compare CFV and CFVR values in this population with those previously obtained in a group of Japanese patients. RESULTS: The mean body mass index (BMI) of the American population (28 +/- 6 kg/m2, range: 18-46 kg/m2) was significantly higher than that of the Japanese group (23 +/- 4 kg/m2, range: 15-37 kg/m2). Twenty-five American patients were classified as obese (BMI >30 kg/m2). Baseline CFV was obtained in 60/67 patients (feasibility: 90%) with a 10% need for intravenous contrast agent to enhance the delineation of the CFV envelope. The success rate in recording CFVR in American patients (92%) was nearly identical to that of a Japanese group (99%). The time-averaged peak diastolic coronary flow velocity increased from 15.6 +/- 5.5 cm/sec at baseline to 47.1 +/- 17.9 cm/sec during adenosine infusion, and CFVR was calculated to be 3.22 +/- 1.15 (range: 0.94-5.69). Intraobserver and interobserver variability for the CFV recording was 4.7 and 6.2%, respectively. CONCLUSIONS: These results suggest that the noninvasive measurement of CFV and CFVR of the LAD is feasible even in a relatively obese American population. Furthermore, the success rates for recording CFV and CFVR are similar to those measured in a Japanese population. This methodology has the potential to provide useful physiological information on the coronary circulation in American patients.
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.
Hepatitis C virus (HCV) has been reported to be associated with cardiomyopathy. However, the mechanism of cardiomyopathy in chronic HCV infection is still unclear. Therefore, we investigate the development of cardiomyopathy in mice transgenic for the HCV-core gene. After the age of 12 months, mice developed cardiomyopathy that appeared as left ventricular dilatation, and systolic and diastolic dysfunction assessed by Doppler echocardiography. Histologically, hypertrophy of cardiomyocytes, cardiac fibrosis, disarray and scarcity of myofibrils, vacuolization and deformity of nuclei, myofibrillar lysis, streaming of Z-bands, and an increased number of bizarre-shaped mitochondria were found in HCV-core transgenic mice. These histological changes are just consistent with cardiomyopathy. In conclusion, the HCV-core protein directly plays an important role in the development of cardiomyopathy.
This study examined the effect of azithromycin therapy on the coronary microcirculation using measurement of coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography in 35 patients with coronary artery disease. CFVR increased significantly after azithromycin therapy (3.0 +/- 0.7 vs 3.5 +/- 0.7, p <0.001). The changes in CFVR were negatively correlated with changes in high-sensitivity C-reactive protein levels in patients receiving azithromycin.
Because the clinical significance of von Willebrand factor (vWF), a marker of endothelial injury, has not been well studied in adult patients with dermatomyositis (DM), we evaluated whether plasma vWF levels are useful as an index of disease activity in these patients. We measured plasma vWF antigen levels in 11 patients with active adult DM, 13 patients with inactive DM, and 18 healthy subjects using an enzyme-linked immunosorbent assay. The association of vWF level with clinical condition and muscle-derived enzyme leakage among DM patients was examined using analysis of covariance and logistic regression analysis. Furthermore, we studied the effects of treatment on the vWF antigen level. The mean vWF antigen level was significantly higher in active DM patients than in inactive DM patients and healthy subjects. Higher vWF levels were associated with clinical symptoms, such as general fatigue, fever, and muscle weakness. They were also associated with the levels of aspartate aminotransferase, alanine aminotransferase, and aldolase, but not with those of lactate dehydrogenase and creatine kinase (CK). vWF antigen was correlated with muscle enzymes except for CK. The plasma vWF levels in six patients with active DM significantly decreased after successful corticosteroid treatment. Plasma vWF level may be considered a useful marker of disease activity in adult DM patients.
BACKGROUND: Calcification is a common finding in human coronary arteries; however, the relationship between calcification patterns, plaque morphology, and patterns of remodeling of culprit lesions in a comparison of patients with acute coronary syndromes (ACS) and those with stable conditions has not been documented. METHODS AND RESULTS: Preinterventional intravascular ultrasound (IVUS) images of 178 patients were studied, 61 with acute myocardial infarction (AMI), 70 with unstable angina pectoris (UAP), and 47 with stable angina pectoris (SAP). The frequency of calcium deposits within an arc of less than 90 degrees for all calcium deposits was significantly different in culprit lesions of patients with AMI, UAP, and SAP (P<0.0001). Moreover, the average number of calcium deposits within an arc of <90 degrees per patient was significantly higher in AMI than in SAP (P<0.0005; mean+/-SD, AMI 1.4+/-1.3, SAP 0.5+/-0.8). Conversely, calcium deposits were significantly longer in SAP patients (P<0.0001; mean+/-SD, AMI 2.2+/-1.6, UAP 1.9+/-1.8, and SAP 4.3+/-3.2 mm). In AMI patients, the typical pattern was spotty calcification, associated with a fibrofatty plaque and positive remodeling. In ACS patients showing negative remodeling, no calcification was the most frequent observation. Conversely, SAP patients had the highest frequency of extensive calcification. CONCLUSIONS: Our observations show that IVUS allows the identification of vulnerable plaques in coronary arteries, not only by identifying a fibrofatty plaque and positive remodeling, but also by identifying a spotty pattern of calcification.
This study evaluated the effects of the temporary occlusion and aspiration device GuardWire on percutaneous coronary intervention for acute myocardial infarction. This device brought about a significant reduction in the no-reflow phenomenon and improvement in ST resolution compared with conventional percutaneous coronary intervention.
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.
OBJECTIVES: The aim of this study was to evaluate how decreased plaque volume during percutaneous coronary intervention (PCI) affects coronary flow in patients with acute myocardial infarction (AMI). BACKGROUND: Coronary flow after reperfusion therapy is a major determinant of clinical outcomes in patients with AMI. However, little is still known about the changes in coronary flow that appear after PCI in response to the decreased plaque during the procedure. METHODS: The study group comprised 60 patients with AMI who underwent pre- and post-PCI intravascular ultrasound (IVUS). Qualitative and quantitative analyses were performed on all IVUS procedures. External elastic membrane volume (EEMV), lumen volume (LV), and plaque volume (PV) were measured every 1.0 mm to include the lesion and reference segments 3.0 mm proximal and distal to the lesion. The difference between pre- and post-PCI PV was defined as the index of the decrease in plaque volume (DeltaPV). The corrected TIMI frame count (CTFC) was used to evaluate coronary flow after PCI. RESULTS: Plaque volume was decreased at post-PCI IVUS in all 60 patients. Inadequate reflow (CTFC >40) was observed in 13 patients (21.7%). The decrease in PV was significantly larger in patients with inadequate reflow than in those with reflow (49.4 +/- 18.9 vs. 31.7 +/- 15.5 mm(3), p = 0.0010). Also, DeltaPV was significantly correlated with CTFC after PCI (r = 0.415, p = 0.0012). CONCLUSIONS: The decrease in PV during PCI has a negative impact on coronary flow after PCI in patients with AMI. Embolization induced by PCI may occur in all patients with AMI.
OBJECTIVES: To compare the effects of the angiotensin receptor blocker (ARB) valsartan versus the calcium channel blocker amlodipine, reactive oxygen species (ROS) formation by monocytes, C-reactive protein (CRP), and left ventricular (LV) mass were studied in 104 hypertensive patients with left ventricular hypertrophy (LVH). BACKGROUND: There is evidence that ARBs have blood pressure (BP)-independent effects on LV mass. Whether regression of LV mass by ARBs is correlated to ROS formation by monocytes and CRP is not fully understood yet. METHODS: A cross-sectional and prospective study was performed. Participants were randomly assigned to either the 80-mg valsartan (n = 52) or 5-mg amlodipine (n = 52) group and were treated for eight months. The left ventricular mass index (LVMI) was calculated from two-dimensional M-mode echocardiography. Formation of ROS by monocytes was measured by gated flow cytometry. In addition, CRP, plasma renin activity, plasma aldosterone, and traditional risk factors were assessed. RESULTS: Multiple regression analysis showed a significant correlation between LVMI and ROS formation by monocytes and between LVMI and CRP. Treatment reduced BP to a similar extent in both groups. Valsartan significantly reduced LVMI after eight months, but amlodipine had less effect (16% vs. 1.2%, n = 50, p < 0.01). Formation of ROS by monocytes was reduced to a greater extent with valsartan than with amlodipine (28% vs. 2%, n = 50, p < 0.01). Valsartan but not amlodipine reduced CRP levels. A significant correlation between changes in ROS formation by monocytes and LVMI or between CRP and LVMI was observed. CONCLUSIONS: The ARB valsartan has BP-independent effects on LVH, ROS formation by monocytes, and CRP in hypertensive patients with LVH.
Epidemiologic studies suggest that tea consumption decreases the risk for cardiovascular events. However, there has been no clinical report examining the effects of tea consumption on coronary circulation. The purpose of this study was to evaluate the effects of black tea on coronary flow velocity reserve (CFVR) using transthoracic Doppler echocardiography (TTDE). This was a double-blind crossover study of 10 healthy male volunteers conducted to compare the effects of black tea and caffeine on coronary circulation. The coronary flow velocity of the left anterior descending coronary artery was measured at baseline and at hyperemia during adenosine triphosphate infusion by TTDE to determine CFVR. The CFVR ratio was defined as the ratio of CFVR after beverage consumption to CFVR before beverage consumption. All data were divided into 2 groups according to beverage type: group T (black tea) and group C (caffeine). Two-way analysis of variance showed a significant group effect and interaction in CFVR before and after beverage consumption (p = 0.001). CFVR significantly increased after tea consumption in group T (4.5 +/- 0.9 vs 5.2 +/- 0.9, p <0.0001). The CFVR ratio of group T was larger than that of group C (1.18 +/- 0.07 vs 1.04 +/- 0.08, p = 0.002). Acute black tea consumption improves coronary vessel function, as determined by CFVR.
Coronary flow reserve was evaluated using transthoracic Doppler echocardiography before and after 3 months of fluvastatin therapy in patients with hypercholesterolemia. Coronary flow reserve increased significantly after lipid-lowering therapy, and coronary microcirculation was improved in patients with hypercholesterolemia.
PURPOSE: Chronic hepatitis C virus (HCV) infection may have adverse effects on pulmonary function in patients with chronic obstructive pulmonary disease. This prospective study was designed to determine whether chronic HCV infection affects decline in lung function and airway responses to salbutamol in asthmatic patients. METHODS: Interferon alpha (6 MIU three times a week for 6 months) was given to 55 HCV-positive asthmatic patients, 18 of whom had a virologic response to interferon. Pre- and postbronchodilator forced expiratory volume in 1 second (FEV(1)) and reversibility with salbutamol or oxitropium at years 1, 3, and 6 after interferon therapy were examined. RESULTS: We found a significant decrease in pre- and postbronchodilator FEV(1) from year 1 to years 3 and 6 only in interferon nonresponders. Reversibility with salbutamol at years 3 and 6 was significantly lower in interferon nonresponders than in HCV-negative patients (P <0.0001) and interferon responders (P <0.0001). Moreover, there was a steep decline in reversibility with salbutamol during the follow-up period only in interferon nonresponders. In contrast, reversibility with oxitropium at years 3 and 6 was significantly higher in interferon nonresponders than in HCV-negative patients and interferon responders, and there was a steep increase in reversibility with oxitropium only in interferon nonresponders. In addition, declines in the diffusing capacity of the lung for carbon monoxide during follow-up were significantly greater in interferon nonresponders than in HCV-negative patients and interferon responders. CONCLUSION: Chronic HCV infection is associated with an accelerated decline in lung function and impaired reversibility with salbutamol among asthmatic patients who do not respond to interferon therapy.
BACKGROUND: Because nicorandil, a potassium channel opener, has a cardioprotective effect and attenuates reperfusion injury in patients with acute myocardial infarction (AMI), intravenous nicorandil should reduce arrhythmic mortality and QT dispersion in patients with AMI. OBJECTIVES: The purpose of this study was to evaluate whether intravenous nicorandil reduces the occurrence of ventricular fibrillation and QT dispersion in patients with successful coronary angioplasty in AMI. METHODS: A historical cohort study on the effect of nicorandil on ventricular fibrillation and QT dispersion was conducted. Eighty-three patients with AMI who underwent successful percutaneous transluminal coronary angioplasty (PTCA) were enrolled. The patients were divided into two groups: nicorandil (n=46) and control group (n=37). Nicorandil was injected at 4 mg/h continuously from admission to 48 h after PTCA in the nicorandil group. QT dispersion was measured before, immediately after, 24 h after and 48 h after PTCA. RESULTS: Ventricular fibrillation was observed in three patients in the control group, but none was observed in the nicorandil group. QT dispersion in the nicorandil group was shorter than that in the control group 48 h after PTCA (QT dispersion was 23.2+/-16.1 ms and 33.4+/-24.0 ms, respectively, P<0.05). There was a significant difference between the two groups in time course after the onset of AMI (P<0.05). CONCLUSIONS: Because intravenous nicorandil reduces the occurrence of ventricular fibrillation and QT dispersion in patients with successful coronary angioplasty in AMI, it would prevent the occurrence of cardiac events after successful PTCA for AMI.
PURPOSE: To compare the effects of carvedilol and propranolol on oxidative stress in leukocytes and C-reactive protein levels in patients with hypertension. METHODS: Sixty hypertensive patients were randomly assigned to carvedilol (20 mg; n = 30) or propranolol (60 mg; n = 30) for 6 months. Thirty normotensive subjects who were given placebo served as controls. Oxidative stress in polymorphonuclear cells and mononuclear cells were measured by gated flow cytometry. C-reactive protein levels were measured by immunonephelometric assay. RESULTS: Oxidative stress in polymorphonuclear cells and mononuclear cells was increased significantly in hypertensive patients compared with in normotensive controls. After 6 months of treatment, carvedilol decreased oxidative stress significantly in polymorphonuclear cells by a mean of 45 arbitrary units (95% confidence interval [CI]: 32 to 59 arbitrary units; P <0.001) and propranolol decreased oxidative stress significantly by 20 arbitrary units (95% CI: 7 to 33 arbitrary units; P <0.003; P = 0.001 for difference between treatments). Carvedilol also decreased oxidative stress significantly in mononuclear cells by 23 arbitrary units (95% CI: 15 to 31 arbitrary units; P <0.001), whereas propranolol decreased oxidative stress by 2 arbitrary units (95% CI: 7 to 12 arbitrary units; P = 0.62; P = 0.002 for difference between treatments). Carvedilol decreased C-reactive protein levels significantly by a median of 0.073 mg/dL (interquartile range, 0.034 to 0.112 mg/dL; P <0.001), whereas propranolol decreased levels by 0.012 mg/dL (interquartile range, 0.009 to 0.032 mg/dL; P = 0.26; P = 0.003 for difference between treatments). CONCLUSION: These findings suggest that carvedilol inhibits oxidative stress in polymorphonuclear and mononuclear cells, as well as lowers C-reactive protein levels, to a greater extent than does propranolol in hypertensive patients.
Asthma and eosinophilic bronchitis are characterized by a similar type of eosinophilic inflammation. However, eosinophilic bronchitis differs from asthma in that there is no variable airflow obstruction or airway hyperresponsiveness. We evaluated the roles of vascular endothelial growth factor (VEGF) and microvascular permeability in causing these differences between the two diseases. Inflammatory indexes in induced sputum, exhaled nitric oxide levels, and vascular permeability index were examined in 11 normal control subjects, 19 beclomethasone dipropionate (BDP)-treated subjects with asthma, 20 non-BDP-treated subjects with asthma, and 17 patients with eosinophilic bronchitis. The percentage of eosinophils in sputum and exhaled nitric oxide levels were significantly higher in non-BDP-treated subjects with asthma and patients with eosinophilic bronchitis than in other two groups; however, VEGF levels and vascular permeability index were significantly higher in non-BDP-treated (VEGF: mean; 4,710 [SD; 1,150] pg/ml, p < 0.0001; vascular permeability index: 0.028 [0.009], p < 0.0001) and BDP-treated (2,560 [1,070] pg/ml, p = 0.0002; 0.016 [0.006], p = 0.004) subjects with asthma than in patients with eosinophilic bronchitis (1,120 [800] pg/ml; 0.01 [0.005]) and normal control subjects (1,390 [1,280] pg/ml; 0.008 [0.003]). We found significant correlations between the VEGF level and the airway vascular permeability index in all patient groups. Thus, interaction between airway microcirculation and VEGF may be a key element in differences in airway function between asthma and eosinophilic bronchitis.