Yoshimasa Yabe

A Prospective, Randomized, Double-Blind Multicenter Trial of a Single Bolus Injection of the Novel Modified t-PA E6010 in the Treatment of Acute Myocardial Infarction: Comparison With Native t-PA

Abstract Objectives. This prospective, randomized, double-blind multicenter trial evaluated the efficacy and safety of a single bolus injection of the novel modified tissue-type plasminogen activator (t-PA) E6010 in the treatment of acute myocardial infarction compared with that of native t-PA. Background. E6010 is a novel modified t-PA with a prolonged half-life (t1/2alpha ≥23 min) compared with native t-PA (t1/2alpha = 4 min). E6010 can be administered in patients as a single intravenous bolus injection, and early recanalization can be expected. Methods. The efficacy of E6010 was compared with that of native t-PA in 199 patients with acute myocardial infarction who were treated within 6 h of onset in a prospective, randomized, double-blind multicenter trial. Patients were given either 0.22 mg/kg body weight of E6010 intravenously over 2 min or native t-PA (tisokinase) 28.8 mg or 14.4 million IU (10% of the total dose over 1 to 2 min, the remainder infused over 60 min). Results. The primary end point was the recanalization rate of the infarct-related coronary artery at 60 min after the start of treatment. Time to reperfusion was shorter in the E6010 group than in the native t-PA group. Thrombolysis in Myocardial Infarction flow grade 2 or 3 recanalization at 15, 30, 45 and 60 min after administration was observed in 37%, 62%, 74% and 79% (95% confidence interval [CI] 70% to 87%) of the E6010-treated patients and in 14%, 32%, 50% and 65% (95% CI 55% to 74%) of native t-PA-treated patients, respectively (p = 0.032 at 60 min). Conclusions. The present study indicates that, compared with native t-PA, a single bolus injection of E6010 over 2 min produces a higher rate of early recanalization of the infarct-related coronary artery without fatal bleeding complications. (J Am Coll Cardiol 1997;29:1447–53)

Percutaneous transluminal coronary angioplasty for culprit lesions in patients with post myocardial infarction angina based on dextrocardia and anomalous coronary arteries. Case reports and methods.

Four cases of successful coronary angioplasty for anomalous coronary arteries, including dextrocardia associated with three-vessel disease, single left coronary artery with proximal left anterior descending lesion, anomalous right coronary artery (RCA) from adjacent left coronary sinus of Valsalva associated with proximal RCA lesion, and anomalous left circumflex angulated lesion bifurcated from the RCA, were encountered. Four cases with 8 target lesions who had a mean age of 63.5 ±11.5 years old are presented. All the targets lesions were completely dilated through balloon angioplasty, including use of a newly developed support device for cases with large jeopardized myocardium. The factors for complete revascularization were appropriate selection of catheters and originality and ingenuity of procedural technique based on the anatomic characteristics.

Study of the efficacy of nicorandil in patients with ischaemic heart disease using Exercise-Tl-201 myocardial tomography

SummaryThe effect of nicorandil on myocardial perfusion in ischaemic heart disease has been studied using exercise-load Tl-201 myocardial SPECT (Ex-SPECT). Ex-SPECT was carried out in 12 patients with previous myocardial infarction (OMI) and 9 with angina pectoris (AP) before and after administration of nicorandil 15 mg/day, for three or more weeks; % Tl uptake and the washout rate in infarcted or ischaemic areas were calculated from short axial images using the Bulls eye method.In the OMI group, % Tl uptake and washout rates in the infarction areas improved significantly from 52.4% and 0.25 before nicorandil to 60.4% and 0.38 after it. In the AP group, too, % Tl uptake and washout rates showed a significant improvement from 56.9% and 0.10 before to 69.1% and 0.33 after administration. Six subjects who had not received the drug, and who showed negative washout rates, had high improvement rates when nicorandil was administered, suggesting that the drug could increase myocardial perfusion during exercise loading as well as suppressing coronary spasm.Ex-SPECT was done in 4 subjects before and after nicorandil and after subsequent surgical treatment (PTCA or CABG) and the effects of the two therapies were compared. The washout rate was improved from 0.01 to 0.34 by administration of nicorandil, and a notable increase in coronary artery blood flow was achieved compared to the level after surgical treatment, i.e. 0.50.It was concluded that, normal dosages of nicorandil have a powerful direct effect of dilating the coronary arteries without any influence on preload or afterload.

Evaluation of left ventricular wall motion and function in patients with previous myocardial infarction by three-dimensional99mTc-HSAD multigated cardiac pool imaging

To evaluate left ventricular (LV) wall motion stereoscopically from all directions and to calculate the LV volume by three-dimensional (3D) imaging,99mTc-DTPA human serum albumin-multigated cardiac pool-single photon emission computed tomography (99mTc-MUGA-SPECT) was performed. A new data processing program was developed with the Application Visualization System-Medical Viewer (AVS-MV) based on images obtained from99mTc-MUGA-SPECT. In patients with previous myocardial infarction, LV function and LV wall motion were evaluated by 3D-99mTc-MUGA imaging. The LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) were obtained from 3D-99mTc-MUGA images by the surface rendering method, and the left ventricular ejection fraction (LVEF) was calculated at thresholds of 35% (T1), 40% (T2), 45% (T3), and 50% (T4). There was a strong correlation between the LV volume calculated by 3D-99mTc-MUGA imaging at a threshold of 40% and that determined by contrast left ventriculography (LVEDV: 194.7 ± 36.0ml vs. 198.7 ± 39.1ml, r = 0.791, p < 0.001; LVESV: 91.6 ± 44.5ml vs. 93.3 ± 41.3ml, r = 0.953, p < 0.001), respectively. When compared with the LVEF data obtained by left ventriculography, significant correlations were found for 3D images reconstructed at each threshold (T1: r = 0.966; T2: r = 0.962; T3: r = 0.958; and T4: r = 0.955). In addition, when LV wall motion obtained by 3D-99mTc-MUGA imaging (LAT and LAO views) was compared with the results obtained by left ventriculography (RAO and LAO views), there was good agreement.3D-99mTc-MUGA imaging was superior in allowing evaluation of LV wall motion in all directions and in assessment of LV function, since data acquisition and image reconstruction could be done within a short time with the three-detector imaging system and AVS-MV. This method appears to be very useful for the observation of both LV wall motion and LV function in patients with ischemic heart disease, because it is a noninvasive examination.

Efficacy and issues of emergent percutaneous transluminal coronary angioplasty : comparison of clinical results in younger and elderly patients

The authors investigated the efficacy and prognosis of emergency percutaneous trans luminal coronary angioplasty (PTCA) in elderly patients. A study was conducted on the early and late prognosis of the study group composed of 66 younger patients < sixty-five years in Group A and 46 elderly patients ≥ seventy years in Group B who underwent reperfusion therapy, including PTCA, for acute myocardial infarction (AMI). No difference was seen in the initial success rate of 82% for Group A and 85% for Group B, or in the vessel patency in the predischarge coronary arteriogram (CAG) with 84% for Group A and 87% for Group B. However, in-hospital mortality was 3% for Group A and 11% for Group B. The patient restenosis rate in the 4.2 months follow-up CAG was 28% for Group A and 50% for Group B. The lesion restenosis rate was 30% for Group A and 53% for Group B (P < 0.05), and the late period mortality rate was 3% for Group A and 11% for Group B. Although there was no difference in the initial success rate of reperfusion through PTCA for AMI in the elderly as compared with the younger patient group, poorer results were seen in the restenosis rate and mortality rate.

Evaluation of viral myocarditis in children by radionuclide method.

Evaluation of viral myocarditis is essential for the clinician to assess the prognosis. In this study, Tl-201 myocardial scintigraphy and Tc-99m gated cardiac blood pool scan were performed in 16 patients with myocarditis diagnosed by clinical symptoms and laboratory findings and these nuclear medicine techniques were followed up for 5 years.Exercise Tl-201 scintigraphy using a bicycle ergometer was performed in 8 patients by SPECT imaging. There were mild to severe persistent defects found in all cases (100%), but pressure rate products showed normal response. The Tl-201 defect ratio improved gradually, but did not change significantly. In the resting Tl-201 image one of 16 patients showed severe multifocal defects.LVEF increased significantly from 1 year to 5 years after onset, while RVEF measured by gated blood pool scans showed slight increases 3 years to 5 years after diagnosis. It was concluded that myocardial perfusion improved only incompletely. Cardiac function (LVEF and RVEF) improved gradually, and pressure rate products were normal. Myocarditis should therefore be followed up in order to assess the prognosis; moreover, the relationship of myocarditis to dilated cardiomyopathy needs to be further studied.

Estimating Myocardial Damage and the Need for Surgery in Patients With Valvular Heart Disease by Tl-201 SPECT

Left ventricular myocardial disorders due to volume overload were investigated by Tl-201 myocardial SPECT (Tl-201 SPECT) in patients with aortic or mitral regurgitation, and its utility for timing cardiac valve replacement was studied. There were significant correlations between Tl-201 scores and electrocardiographic changes and the New York Heart Association classification. There also were favorable correlations between Tl-201 scores and the left ventricular end-diastolic dimension and between Tl-201 scores and left ventricular ejection fraction, and a close relationship between the presence of a left ventricular myocardial disorder and left ventricular diameter. These results suggest that myocardial perfusion abnormalities and left ventricular myocardial disorders may accompany left ventricular dilatation owing to volume overload. After valve replacement, left ventricular end-diastolic dimension normalized, and Tl-201 scores improved slightly, suggesting normalization of myocardial perfusion. When moderate or more severe Tl-201 defects are present on Tl-201 SPECT images, in addition to inverted Tl-201 waves on the electrocardiogram or a left ventricular end-diastolic dimension of 65 mm or more, cardiac valve replacement should be considered.

Myocardial Energy Metabolism of Congestive and Hypertrophic Cardiomyopathy in Man

A key enzyme of glycolysis (pyruvate kinase) and main enzymes of the electron transport system (NADH cytochrome c reductase, succinic cytochrome c reductase, and cytochrome c oxidase) were measured in left ventricular biopsy specimens from six hypertrophic (HCM) and six congestive (CCM) cardiomyopathy. Pyruvate kinase was 104.0 and 45.0 mU/mg protein in HCM and CCM, respectively. NADH cytochrome c reductase, succinic cytochrome c reductase, and cytochrome c oxidase were 146.0, 9.9, and 775.0 mU/mg protein in HCM and 87.4, 5.2, and 502.0 mU/mg protein in CCM, respectively. From these data, it is evident that glycolysis and enzyme activities of the electron transport system are increased in HCM and decreased in CCM. Cardiac function reflects the state of these energy metabolism pathways in the myocardium. The changing energy metabolism in the right ventricle of the emphysema hamster seems to support this concept.

DNA Synthetic Activity of Right and Left Ventricular Biopsy Specimens in Patients with Cardiomyopathy

This investigation was designed to evaluate the difference in DNA activity between biopsy specimens obtained from right and left ventricles. Nucleic DNA in the myocardial cells of hypertrophied and congestive forms of cardiomyopathy was analyzed to investigate the relationship between cell function and clinical manifestations. Endomyocardial biopsy specimens were obtained simultaneously from right ventricular septal wall and left ventricular inferolateral wall by a transcatheter biotome. Measurement of DNA was based on the Feulgen reaction and dual wavelength cytophotometry. In this series, 12 patients with hypertrophic cardiomyopathy and four patients with congestive cardiomyopathy were studied. In the normal heart, the DNA value (arbitrary units) of the right ventricle was 138.6, whereas that of the left ventricle was 144.4. In the hypertrophic group, the mean DNA value in the right ventricle was 279.9, whereas that of the left ventricle was 317.5. In the congestive group, the DNA mean value in the right ventricle was 108.8, whereas that of left ventricle was 144.8. The linear relationship (r = 0.67) between right and left ventricular DNA values suggests that cellular function of one ventricle is affected by that of the other side. Higher DNA values of the left ventricle may indicate the difference in work load between the ventricles. The relationships among DNA values, LV wall thickness, LV mass, and parameters of contractility were statistically high.

Evaluation of the visualized left atrium by 201Tl myocardial scintigraphy

201Tl myocardial scintigraphy was evaluated in patients with 18 mitral stenosis cases. Left atrium was to be seen in ANT (16.7%), LAO (16.7%), MLAO (16.7%) and L-LAT (11.1%), respectively. Furthermore, 201Tl uptake ratio of left atrium, right ventricle, pulmonary area tended significantly to increase in visible group compared with invisible group. PCW pressure was correlated with left atrial Tl uptake (r = 0.51, p less than 0.005), and it indicated some correlation between left atrial pressure and 201Tl uptake.