Hideki Okino

Early assessment of reperfusion therapy using cardiac troponin T

OBJECTIVES The purpose of this study was to investigate the utility of cardiac troponin T for early assessment of reperfusion therapy. BACKGROUND Several biochemical markers are used for early noninvasive detection of reperfusion during intravenous thrombolytic therapy. However, cardiac troponin T, a new myocardial-specific marker, has not been used previously for this purpose. METHODS We measured troponin T and creatine kinase, MB isoenzyme (CK-MB) levels in 38 patients with acute myocardial infarction whose infarct-related artery was totally occluded before reperfusion therapy. Subjects comprised 14 patients with successful angioplasty (group 1), 12 patients with successful thrombolytic therapy (group 2) and 12 patients with unsuccessful attempted reperfusion (group 3). Blood samples were taken every 15 min, and coronary angiography was performed every 5 to 8 min until 60 min after reperfusion (groups 1 and 2) or after the initiation of treatment (group 3). We calculated the increase in troponin T (delta troponin T) and CK-MB (delta CK-MB) 60 min after treatment was initiated and 60 min after reperfusion in groups 1 and 2. RESULTS Mean (+/- SD) delta troponin T and delta CK-MB levels were 9.35 +/- 7.83 ng/ml and 125 +/- 83 mU/ml in group 1 and 3.23 +/- 3.08 ng/ml and 130 +/- 137 mU/ml in group 2, respectively, 60 min after treatment and were 10.1 +/- 8.35 ng/ml and 131 +/- 84 mU/ml in group 1 and 6.84 +/- 8.30 ng/ml and 158 +/- 146 mU/ml in group 2, respectively, 60 min after reperfusion. These values were significantly higher than those 60 min after treatment in group 3: 0.16 +/- 0.19 ng/ml and 10 +/- 9 mU/ml, respectively. The predictive accuracy for detecting reperfusion using a threshold value of 0.50 ng/ml of delta troponin T and 25 mU/ml of delta CK-MB was 100% in group 1 and 92% in group 2 60 min after treatment, respectively. There was significant correlation between delta troponin T and delta CK-MB. CONCLUSIONS Serial measurements of cardiac troponin T as well as of CK-MB are useful for early assessment of reperfusion therapy.

Marked alternans of the elevated ST segment during occlusion of the left anterior descending coronary artery in percutaneous transluminal coronary angioplasty: clinical background and electrocardiographic features.

To investigate the clinical background and the electrocardiographic features of marked alternans of the elevated ST segment during coronary angioplasty, we examined 12-lead electrocardiograms recorded continuously during occlusion of the left anterior descending coronary artery by balloon inflation in 41 patients. The incidence of marked ST alternans was 27% of 41 patients and 15% of 117 balloon occlusions. The incidence decreased progressively from the first to the third occlusion. The time course of ST alternans was determined. Compared with patients without ST alternans, patients with ST alternans had a shorter history of angina, less severe stenosis of the target lesion before coronary angioplasty, more leads showing ST elevation during occlusion, higher ST elevation during occlusion and lower incidence of previous myocardial infarction in the left anterior descending coronary arterial area. ST alternans recorded on the surface electrocardiogram may thus be considered a marker of acute severe and extensive myocardial ischemia.

Use of the QRS scoring system in the early estimation of myocardial infarct size following reperfusion

While the QRS scoring system has been established as a convenient tool for estimating infarct size in nonreperfused patients during the chronic stage of myocardial infarction, its applicability to reperfused patients in the acute stage has not been established. To investigate whether infarct size could be estimated by the QRS scoring system soon after reperfusion, we evaluated QRS scores obtained serially 6 hours to 1 month after reperfusion, total creatine kinase release, and left ventricular ejection fraction in 126 patients with acute myocardial infarction who underwent successful reperfusion therapy. A significant correlation was observed between the QRS score obtained after 6 hours and that obtained after 1 month (r = .89). The QRS scores obtained after 6 hours and 1 month were significantly correlated with total creatine kinase release (r = -.65 and r = -.75, respectively) and left ventricular ejection fraction (r = .62 and r = .76, respectively). Thus, the QRS scoring system can be used as a simple and economical method for estimation of infarct size soon after reperfusion.

Detection of reperfusion 30 and 60 minutes after coronary recanalization by a rapid new assay of creatine kinase isoforms in acute myocardial infarction.

We measured creatine kinase (CK) isoforms by a new immunoinhibition method to evaluate their usefulness in detecting early coronary reperfusion. Blood samples were collected at 15-minute intervals from 50 patients with acute myocardial infarction. CK isoforms were determined by a 10-minute immunoinhibition method with an autoanalyzer. Values for inhibited isoforms (MM3, MM2/2, and MB2/2) were divided by those of noninhibited isoforms (MM1, MM2/2, MB1, MB2/2, and BB) to calculate the isoform ratio. In the reperfused group the increase in the isoform ratio was 2.69 +/- 1.80 (SD) 30 minutes after reperfusion and 2.41 +/- 2.01 at 60 minutes, which was significantly higher than the corresponding values in the nonreperfused group (0.17 +/- 0.16 and 0.32 +/- 0.26, respectively). When an increase of 0.70 or more in the isoform ratio was used as the criterion for reperfusion, the sensitivity and specificity were 92% and 100% at 30 minutes and 100% and 100% at 60 minutes after recanalization, respectively. We conclude that the isoform ratio obtained by the new 10-minute assay of CK isoforms is useful for the noninvasive detection of reperfusion 30 and 60 minutes after recanalization in acute myocardial infarction.

Early detection of coronary reperfusion by rapid assessment of plasma myoglobin

We assayed plasma myoglobin and creatine kinase to elucidate the usefulness of rapid assessment of myoglobin for detecting coronary reperfusion in 31 patients with acute myocardial infarction. Reperfusion was achieved in 20 patients by thrombolytic therapy or angioplasty, and it was not in 11 patients. Blood sampling was performed before and 43 +/- 15 (+/- SD) min after the start of treatment. In the reperfused group, blood samples were obtained before and 26 +/- 10 min after reperfusion. Myoglobin was assayed by a new quantitative test based on latex agglutination turbidimetry which required an assay time of 10 min. After treatment, the rate of increase of plasma myoglobin was significantly higher than that of plasma creatine kinase in the reperfused group (9.7 +/- 9.5 and 2.8 +/- 1.6-fold), but not in the occluded group (1.8 +/- 0.6 and 1.5 +/- 0.3-fold). When a 3.0-fold or greater increase in myoglobin (1.9-fold or greater increase in creatine kinase) was taken as evidence of coronary reperfusion, the sensitivity and specificity were 95% and 100% (70% and 82% in creatine kinase), respectively. In conclusion, using the rate of increase of myoglobin, as measured by latex agglutination turbidimetry, coronary reperfusion can be diagnosed within 1 h after reperfusion.

Myocardial infarct size can be estimated from serial plasma myoglobin measurements within 4 hours of reperfusion.

BackgroundAn early estimation of infarct size is useful for the appropriate early treatment of patients with acute myocardial infarction. We evaluated how early and how accurately infarct size could be estimated from serial plasma myoglobin (Mb) measurements in patients with successful reperfusion Methods and ResultsWe measured plasma Mb and creatine kinase (CK) in 35 patients in whom reperfusion therapy was successfully performed. Blood samples were collected at 15-minute intervals for 2 hours after reperfusion, at 30-minute intervals for the subsequent 2 hours, and at 3-6-hour intervals until 52 hours after reperfusion. Plasma Mb was measured by a newly developed turbidimetric latex agglutination assay. Total Mb and CK release (IMb, ICK) were calculated with a one-compartment model. The mean chord motion in the most hypokinetic 50% of the infarct-related artery territory was calculated from follow-up ventriculograms as an index of the severity of regional hypokinesis. There were significant correlations between 1Mb and ICK (r=0.89), between log 1Mb and the severity of regional hypokinesis (r= -0.85), and between log ICK and the severity of regional hypokinesis (r= -0.74). The time required for the cumulative Mb release curves to reach a plateau was 64±28 minutes. An additional 53±14 minutes was required to calculate the disappearance rate constant of Mb, and 15 minutes was necessary for the assay. Therefore, the total time required for 1Mb to be available was 132±40 minutes, significantly shorter than the time required for ECK, 24.3±9.1 hours (p<0.001). The infarct size could be estimated from the 1Mb in 34 of 35 patients within 4 hours of reperfusion. ConclusionInfarct size can be estimated accurately 4 hours after reperfusion by calculating the YMb in patients with successful reperfusion.

Increased heparin-releasable platelet factor 4 and D dimer in patients one month after the onset of acute myocardial infarction: persistent activation of platelets and the coagulation/fibrinolytic system.

To evaluate the activity of platelets and the coagulation/fibrinolytic system 1 month after the onset of acute myocardial infarction, we measured the plasma levels of molecular markers, i.e. beta-thromboglobulin, platelet factor 4, thrombin-antithrombin III complex and D dimer, in 16 patients with acute myocardial infarction and in 11 normal subjects. Blood was drawn through a catheter placed in the pulmonary artery before heparin injection. The heparin-releasable platelet factor 4 was calculated by subtracting the level before the injection of 5000 U of heparin, from the level 5 min after injection. The plasma beta-thromboglobulin, thrombin-antithrombin III complex and the D dimer levels in the acute phase of myocardial infarction were 134.9 +/- 121.2, 11.2 +/- 7.1 and 164.4 +/- 115.3 ng/ml, respectively. These values were significantly higher than those in the normal subjects. The plasma levels of beta-thromboglobulin and thrombin-antithrombin III complex, 1 month after the onset (36.6 +/- 16.4 and 4.6 +/- 2.3 ng/ml, respectively) were not significantly different from those of the normal subjects. In contrast, D dimer and heparin-releasable platelet factor 4 were 216.9 +/- 176.9 and 80.5 +/- 29.3 ng/ml, respectively, and significantly higher than in the normal subjects. These findings suggest a latent but persistent activation of the platelets and the coagulation/fibrinolytic system 1 month after the onset of acute myocardial infarction.

Right Ventricular Stiffness Measured by a New Method Without Volume Estimation in Coronary Artery Disease

This study was designed to measure the right ventricular (RV) stiffness (delta P/ delta V) with a new method without estimating the RV volume itself. RV stiffness has rarely been measured due to the difficulty in estimating the RV volume. Without measuring RV volume itself, stiffness can be determined by measuring its volume change (delta V). Tricuspid filling flow volume, which is the diastolic RV delta V, is measurable by using Doppler echocardiography. Thus, RV stiffness may possibly be obtained from Doppler echocardiography combined with high-fidelity RV pressure. Subjects consisted of 8 controls, 8 patients with angina pectoris, 8 with anterior, 8 with posterior, and 8 with inferior prior myocardial infarction. Tricuspid annular dimension was measured by 2-dimensional echocardiography and the tricuspid annular area was calculated. Velocity-time integral of the tricuspid filling flow during the late diastole was measured by pulsed Doppler echocardiography. Then, the late diastolic RV delta V was obtained as the product of the tricuspid annular area and the integral. The late diastolic RV pressure rise (delta P) was also measured with a micromanometer catheter. The RV elastic chamber stiffness constant ([delta P/ delta V]/P) was obtained by dividing simple stiffness by the mean RV pressure during late diastole. The RV elastic chamber stiffness constant did not significantly differ among controls, patients with angina pectoris, and those with anterior and posterior myocardial infarction (0.0054 +/- 0.0009 vs 0.0057 +/- 0.0018 vs 0.0064 +/- 0.002 vs 0.0052 +/- 0.0019 ml-1). However, it was significantly increased in patients with inferior myocardial infarction (0.010 +/- 0.004 ml-1, p < 0.01 or 0.05) compared with those in the other 4 groups. These results suggest (1) that RV stiffness can be measured with a new method without RV volume estimation, and (2) that this new method is useful in evaluating RV diastolic pathophysiology in patients with coronary artery disease.

Mitral regurgitation during B bump of the mitral valve studied by Doppler echocardiography

Abstract B-bump formation of the mitral valve, a plateau between the A and C points on the mitral valve M-mode echocardiogram, suggests a high left ventricular end-diastolic pressure. 1 However, what kind of mitral flow occurs during the B bump is not clear. We used Doppler echocardiography to assess whether mitral regurgitation (MR) occurs during the mitral valve B bump.