Hirofumi Kambara

Serum Soluble Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Levels Are Elevated in Acute Coronary Syndrome A Novel Marker for Early Diagnosis

Background—Markers of cardiac injury, including troponin-T (TnT), are used to diagnose acute coronary syndrome (ACS); however, markers for plaque instability may be more useful for diagnosing ACS at the earliest stage. Lectin-like oxidized LDL receptor-1 (LOX-1) appears to play crucial roles in the pathogenesis of atherosclerotic plaque rupture and ACS onset. LOX-1 is released in part as soluble LOX-1 (sLOX-1) by proteolytic cleavage. Methods and Results—We examined serum sLOX-1 levels in 521 patients, consisting of 427 consecutive patients undergoing coronary angiography, including 80 ACS patients, 173 symptomatic coronary heart disease patients, 122 patients with significant coronary stenosis without ischemia, and 52 patients without apparent coronary atherosclerosis plus 34 patients with noncardiac acute illness and 60 patients with noncardiac chronic illness. Time-dependent changes in sLOX-1 and TnT levels were analyzed in an additional 40 ACS patients. Serum sLOX-1 levels were significantly higher in ACS than the other groups and were associated with ACS as shown by multivariable logistic regression analyses. Given a cutoff value of 1.0 ng/mL, sLOX-1 can discriminate ACS from other groups with 81% and 75% of sensitivity and specificity, respectively. sLOX-1 can also discriminate ACS without ST elevation or abnormal Q waves and ACS without TnT elevation from non-ACS with 91% and 83% of sensitivity, respectively. Peak values of sLOX-1 in ACS were observed earlier than those of TnT. Conclusions—sLOX-1 appears to be a useful marker for early diagnosis of ACS.

Prognostic value of an increased in flourine-18 deoxyglucose uptake in patients with myocardial infarction: Comparision with stress thallium imaging

OBJECTIVES This study was undertaken to evaluate the prognostic value of an increase in fluorine (F)-18 deoxyglucose uptake compared with clinical, angiographic and stress thallium findings in patients with myocardial infarction. BACKGROUND Positron emission tomography (PET) imaging using F-18 deoxyglucose has been applied to assess tissue viability in patients with coronary artery disease. We hypothesized that patients with a myocardial segment with augmented F-18 deoxyglucose uptake are at high risk for a future cardiac event. METHODS One hundred fifty-eight consecutive patients with myocardial infarction referred for F-18 deoxyglucose PET and stress thallium scans were studied. Follow-up was obtained in 84 patients at a mean interval of 23 months to investigate prognostic implications of radionuclide studies. RESULTS Seventeen patients had a cardiac event during the follow-up interval. Univariate analysis showed that an increase in F-18 deoxyglucose uptake was the best predictor of a future cardiac event (p = 0.0006), followed by the number of stenosed vessels (p = 0.008). In the multivariate analysis, when an increase in F-18 deoxyglucose uptake was entered into the model, only angiographic variables had an independent prognostic value, whereas no other radionuclide variables showed significant prognostic value. Among patients who did not show redistribution, a future cardiac event was observed more often in patients with than in those without an increase in F-18 deoxyglucose uptake (p < 0.05). CONCLUSIONS Thus, an increase in F-18 deoxyglucose uptake seemed to be the best predictor of a future cardiac event among all clinical, angiographic and radionuclide variables in this study of stable patients with myocardial infarction. Even when a stress thallium-201 scan does not show redistribution, those patients who have an increase in F-18 deoxyglucose uptake in a PET study may be at risk for a future cardiac event, and these patients may need aggressive treatment to prevent a future cardiac event.

Regional myocardial perfusion and glucose metabolism in experimental left bundle branch block.

BackgroundSeveral authors have reported cases in which 201TI scintigraphy demonstrated perfusion abnormality in the septum of patients with left bundle branch block (LBBB) and normal coronary arteriogram. The mechanism of this abnormality, however, remains to be clarified. Methods and ResultsTo determine whether LBBB itself induces abnormal myocardial perfusion and ischemia and to elucidate its mechanism, we used an in vivo animal model. LBBB was induced by right ventricular pacing in 17 open-chest dogs. We examined myocardial perfusion and glucose uptake using 201T1 and 18F-labeled 2-fluoro-2-deoxy-D-glucose. 201T1 activity in the septum was reduced to 74.7±14.5% of its maximal activity, and mean activity was 86.5±5.3% in the free wall (p<0.05). 18F activity in the septum was also reduced compared with that in the free wall (67.4±12.1% versus 88.0plusmn;5.2%, p<0.05). Regional myocardial blood flow was significantly reduced in the septum compared with the free wall, averaging 0.53±0.18 ml/min/g versus 0.84±0.14 ml/min/g, respectively (p<0.01). Systolic thickening in the septum was reduced from 1.36±0.20 to 0.98±0.04 (p<0.01) after the induction of LBBB, and the intramyocardial pressure in the septum in diastolic phase, in which the major flow of left anterior descending coronary artery (LAD) exists, increased from 26.6±10.5 to 57.8±22.2 mm Hg (p<0.02). Mean aortic pressure, IAD flow, and lactate extraction rate showed no significant change. ConclusionsLBBB itself may reduce myocardial perfusion and glucose uptake in the septum because of impaired systolic thickening and augmented intramyocardial pressure in the septum; however, this is not necessarily related to septal ischemia.

Detection and evaluation of tricuspid regurgitation using a real-time, two-dimensional, color-coded, Doppler flow imaging system: Comparison with contrast two-dimensional echocardiography and right ventriculography

To detect and evaluate regurgitant flow in tricuspid regurgitation (TR) with a newly developed, realtime, 2-dimensional (2-D), color-coded, Doppler flow imaging system (Doppler 2-D echo), 27 patients (18 with suspected TR and 9 normal subjects) were examined and the findings were compared with those obtained using contrast 2-D echocardiography (contrast 2-D echo) and right ventriculography. In 16 of 18 patients with suspected TR, Doppler 2-D echo easily visualized the color-coded regurgitant flow in the right atrium and estimated the severity of TR from the distance of the visible TR jet. On the basis of the QRS synchronized appearance of contrast in the inferior vena cava by the subxiphoid approach or of the negative contrast effect above the tricuspid valve just after the contrast entered the right ventricle with its subsequent back-and-forth movements across the tricuspid valve, Doppler 2-D echo was more sensitive and specific in detecting TR (100% and 100%) than contrast 2-D echo (75% and 82% in the subxiphoid view, 56% and 100% in the 4-chamber view) when the fast Fourier transformation frequency analysis was used as the standard of TR, and it was more sensitive in detecting TR (85%) than contrast 2-D echo (69% in the subxiphoid approach, 46% in the 4-chamber view) when right ventriculography was used as the standard of TR. Additionally, the severity of TR as shown by Doppler 2-D echo correlated fairly well with that shown by right ventriculography. Thus, Doppler 2-D echo is clinically useful for detecting and evaluating TR.

Stress thallium-201 transaxial emission computed tomography: Quantitative versus qualitative analysis for evaluation of coronary artery disease

Stress thallium-201 myocardial distribution was quantitatively evaluated by emission transaxial tomography in 104 patients who underwent coronary arteriography. The initial uptake and percent washout of thallium were assessed by the circumferential profile curves of the three short-axis sections and one middle right anterior oblique long-axis section. This quantitative tomographic analysis showed abnormal distribution in all but two patients (98%) with coronary artery disease, whereas qualitative analysis showed abnormality in 76 of the patients (93%). Quantitative analysis showed better sensitivity (91%) for detecting involved coronary vessels than qualitative analysis (80%, p less than 0.01), especially in three vessel disease (82 versus 67%, p less than 0.05). For localization of individual vessel involvement, quantitative analysis showed high sensitivity (right coronary artery: 96%, left anterior descending artery: 90% and left circumflex artery: 88%) as compared with qualitative analysis (88, 83 and 63%, respectively, p less than 0.05), while similar specificity was observed (92% for quantitative and 93% for qualitative analyses). Furthermore, in the study of patients without infarction, myocardial segments supplied by coronary vessels with moderate stenosis (51 to 75%) revealed abnormality more often with quantitative (81%) than with qualitative (56%) analysis. Thus, quantitative analysis of stress thallium emission tomography provides improved sensitivity for the detection of diseased coronary vessels in patients with three vessel disease and those with moderate stenosis. It is a valuable technique for the evaluation of coronary artery disease.

Relation of left ventricular perfusion and wall motion with metabolic activity in persistent defects on thallium-201 tomography in healed myocardial infarction

Myocardial viability in persistent thallium (TI)-201 defect is a controversial subject. To assess metabolic activity in segments with persistent defect, stress TI-201 tomography and positron emission tomography using nitrogen-13 ammonia and fluorine-18 2-fluoro-deoxyglucose (FDG) were performed in 28 patients with healed myocardial infarction. The segments with TI-201 perfusion defect in electrocardiogram-determined infarcted areas were selected for assessment. Stress perfusion defect was detected in 61 segments by TI-201 tomography. Twenty-two patients (36%) showed transient defects with redistribution (group 1) and 39 showed persistent defects (group 2). Increase in FDG uptake was observed in 95% in group 1. Among group 2 patients, 15 segments (38%) showed an increase in FDG uptake (group 2A) while the remaining 24 (62%) did not have an increased uptake (group 2B). The decrease in nitrogen-13 ammonia perfusion was more severe in group 2B (-23 +/- 7%) than in group 2A (-13 +/- 9%) (p less than 0.005) and group 1 (-10 +/- 4%) (p less than 0.001). In addition, wall motion scores tended to be lower in group 2B (0.21 +/- 0.71), compared with group 2A (0.67 +/- 0.70) (p = 0.05) and group 1 (0.77 +/- 0.60) (p less than 0.01). These data indicate that metabolic viability was observed in approximately 40% of the segments with persistent TI-201 defect. Preservation of regional perfusion and wall motion in these areas was similar to that in areas with transient TI-201 defect.

Stress scintigraphy using single-photon emission computed tomography in the evaluation of coronary artery disease

Twenty-seven patients with angina pectoris, 24 with postmyocardial infarction angina and 7 with normal coronary arteries were examined by exercise thallium-201 emission computed tomography (SPECT) and planar scintigraphy. Exercise SPECT was compared with the reperfusion imaging obtained approximately 2 to 3 hours after exercise. The sensitivity and specificity of demonstrating involved coronary arteries by identifying the locations of myocardial perfusion defects were 96 and 87% for right coronary artery, 88 and 89% for left anterior descending artery (LAD) and 78 and 100% for left circumflex artery (LC). These figures are higher than those for planar scintigraphy (85 and 87% for right coronary artery, 73 and 89% for LAD and 39 and 100% for LC arteries). In patients with 3-vessel disease, sensitivity of SPECT (100, 88 and 75% for right coronary artery, LAD and LC, respectively) was higher than planar imaging (88, 63 and 31%, respectively), with a significant difference for LC (p less than 0.05). In 1, 2 and 0-vessel disease the sensitivity and specificity of the 2 techniques were comparable. Multivessel disease was more easily identified as multiple coronary involvement than planar imaging with a significant difference in 3-vessel disease (p less than 0.05). In conclusion, stress SPECT provides useful information for the identification of LC lesions in coronary heart disease, including 3-vessel involvement.

Collateral function in early acute myocardial infarction

The role of the collateral circulation less than 6 hours after the onset of acute myocardial infarction (MI) was evaluated in 34 consecutive patients without previous MI. There were 19 patients with and 15 without collaterals. The group was subdivided into those with nonjeopardized collaterals (group A, 14 patients) and those with jeopardized collaterals (group B, 5 patients), and the group without collaterals into those with partially obstructed coronary arteries (group C, 5 patients) and those with totally obstructed coronary arteries (group D, 10 patients). These groups had similar sites of coronary stenoses and MI. Eleven of 14 collaterals in group A were poor, but MI mass measured by peak creatine kinase (CK) was smaller in group A than in group B (p less than 0.01) or group D (p less than 0.01), and cardiac function was significantly better in group A than in group D (cardiac index, p less than 0.05; stroke index, p less than 0.01; ejection fraction, p less than 0.01; regional wall motion, p less than 0.01). Group C was not statistically different from group A in myocardial function and CK. Group B was similar to group D in MI mass and cardiac function (cardiac index, stroke index, ejection fraction and regional wall motion). Thus, patients with nonjeopardized collaterals and those with partially obstructed coronary arteries had less myocardial damage and better cardiac function than did those with jeopardized collaterals and those with totally obstructed coronary arteries. A nonjeopardized collateral circulation may play a role in limiting MI mass and preserving myocardial function in the early stages of acute MI.

Detection of coronary artery disease with 13N-ammonia and high-resolution positron-emission computed tomography

In order to evaluate the detectability of coronary artery disease (CAD) with positron-emission computed tomography (PET), we performed 13N-ammonia myocardial PET scanning at rest and with exercise loading in 20 normal subjects and 40 patients with CAD, by means of a high-resolution, multi-slice, whole-body PET scanner. Myocardial PET scanning was performed 3 minutes after injection of 13N-ammonia at rest and during exercise. The circumferential profile analysis of resting PET images revealed regional hypoperfusion in 96% of CAD patients with previous myocardial infarction and in 29% of those without infarction. Exercise PET studies showed high sensitivity (93%) in detecting CAD without myocardial infarction, whereas no abnormal hypoperfusion was detected in normal subjects. Segmental analysis of regional myocardial perfusion with exercise stress identified 67 of 75 stenosed vessels (89%). We conclude that 13N-ammonia myocardial PET with exercise loading provides high-quality tomographic images of regional myocardial perfusion and is a valuable technique for detecting CAD.

Myocardial positron computed tomography with 13N-ammonia at rest and during exercise

To assess the value of myocardial-perfusion positron computed tomography (PCT) for the evaluation of coronary artery disease (CAD), 13N-ammonia PCT using a whole-body multislice PCT device was performed at rest and during exercise in 6 normal subjects and 19 patients with angiographically documented CAD. The 13N-ammonia distribution in the myocardium was assessed both qualitatively and quantitatively. At rest and during exercise, the tracer distribution was homogeneous in the 6 normal cases. In the 19 patients with CAD, regional hypoperfusion was observed in 14 cases (74%) at rest and in 18 cases (95%) during exercise. Additional perfusion abnormalities were detecting during exercise in 12 cases. Segmental analysis of the myocardial perfusion identified 30 out of 34 stenosed vessels (88%) during exercise, with only one false-positive finding of diseased vessels (specificity, 98%). For the quantitative analysis of myocardial perfusion by PCT, the percentage of change in the tracer concentration in the same region between the rest and stress images was calculated. The concentration was slightly increased in normal myocardial segments (14.4%±5.8%; P<0.001), whereas in CAD, it was significantly decreased in segments with stenosed vesels (-18.0%±18.3%; P<0.02). We conclude that 13N-ammonia PCT at rest and during exercise provides highquality images, and is a sensitive and effective technique for detecting CAD and identifying individual stenosed vessels. Furthermore, this technique makes possible quantitative assessment of the coronary reserve function.