Kimio Satomura

Angioscopic Evaluation of Coronary-Artery Thrombi in Acute Coronary Syndromes

BACKGROUND Disruption of an atherosclerotic plaque in a coronary artery followed by the formation of a thrombus is believed to be the cause of both unstable angina and acute myocardial infarction. Although thrombolytic therapy is efficacious in patients with acute myocardial infarction, for unknown reasons it is far less effective in patients with unstable angina. We postulated that there might be differences in the composition of the coronary-artery thrombi in unstable angina and acute myocardial infarction. METHODS To investigate the appearance of coronary-artery thrombi, we performed percutaneous transluminal coronary angioscopy in 15 patients with unstable angina and 16 with acute myocardial infarction. Angioscopy was performed within 48 hours after an episode of pain at rest in the patients with unstable angina and within 8 hours of onset in those with acute myocardial infarction. RESULTS Angioscopy revealed coronary thrombi in all but two patients (one in each group). Of the 29 patients with thrombi, those with unstable angina were frequently observed to have grayish-white thrombi (10 of 14, 71 percent), but none were seen in the 15 patients with acute myocardial infarction (P less than 0.01). By contrast, reddish thrombi were observed in all 15 patients with acute myocardial infarction who had thrombi, but in only 4 of the 14 patients with unstable angina and thrombi (P less than 0.01). As assessed by coronary angiography, occlusive thrombi occurred frequently in patients with acute myocardial infarction (13 of 16 patients) but were not seen in any of the 15 patients with unstable angina (P less than 0.01). CONCLUSIONS Coronary-artery thrombi play an important part in the pathogenesis of unstable angina and acute myocardial infarction. However, the appearance of the thrombi is different in the two conditions, possibly reflecting differences in the composition of age of the thrombi or the presence or absence of blood flow in the artery. This difference may account for the contrasting results of thrombolytic therapy.

Endothelium-dependent flow-mediated vasodilation in coronary and brachial arteries in suspected coronary artery disease.

Previous studies showed a weak correlation between endothelial function of the coronary arteries as assessed by acetylcholine and brachial artery vasomotion during reactive hyperemia. When the same stimulus was used, we obtained a strong correlation between flow-mediated dilation in the coronary and brachial arteries (r=0.78, p <0.001), so that noninvasive assessment of flow-mediated dilation in the brachial artery could be used as a surrogate measure for coronary artery endothelial function.

Angioscopic coronary macromorphology in patients with acute coronary disorders.

To investigate the pathogenesis of acute coronary disorders and to clarify what type of plaque precedes these disorders, percutaneous transluminal coronary angioscopy, by means of a new angioscope, was carried out during catheterisation in 100 consecutive patients anatomically suitable for such investigations. The quality of the angioscopic image was good enough for analysis in 84 patients (14 with acute myocardial infarction [within 8 h of onset], 16 with recent myocardial infarction [3 days-2 months since onset], 24 with old myocardial infarctions, 10 with unstable angina, and 20 with stable angina). Thrombi were observed in most patients with acute coronary disorders (all 14 with acute myocardial infarction, 9 of 10 with unstable angina). Occlusive thrombi were more common in patients with acute myocardial infarction than in those with unstable angina (11 [79%] vs 1 [10%]; p less than 0.001), whereas mural (non-occlusive) thrombi were more common in the unstable angina than in the acute myocardial infarction group (8 [80%] vs 3 [21%]; p less than 0.001). Xanthomatous ulcerated plaques or ragged irregular surfaces were seen in patients with acute coronary disorders and in those with recent myocardial infarction. Xanthomatous plaques were more common in patients with acute coronary disorders (50%) than in those with stable angina (15%) or old myocardial infarction (8%). By contrast white and smooth plaques were seen in cases of stable angina and old myocardial infarction. Angioscopy could display the intracoronary lumen more precisely than could coronary arteriography. This angioscopic study suggested that, although a thrombus overlying a rupture in the lining of the plaque was common in both unstable angina and acute myocardial infarction, the character of the thrombus may differ between these disorders, and lipid-rich xanthomatous plaque may precede rupture.

New percutaneous transluminal coronary angioscope

Abstract A new percutaneous transluminal coronary angioscopic catheter has been developed for visualization of the coronary artery. A specially made balloon, fixed at the catheter tip, and an angulation mechanism made a precise coaxial alignment possible in the coronary lumen. This angioscopic catheter, 1.22 mm in outer diameter, has four channels, one for irrigation in which a 0.36 mm (0.014 in.) angioplasty guide wire can be used. With the use of this angioscope, coronary lumens in 8 dogs, thrombi that were produced with copper coils in the left anterior descending coronary artery in 11 dogs, atherosclerotic coronary arteries in 20 patients during cardiac catheterization and the sequence of transluminal coronary angioplasty in 1 patient were observed. The angioscopic catheter was introduced into the coronary artery by an 8F guide catheter. The steerable guide wire enabled the angioscopic catheter to be accurately and safely inserted into the target lesion in all cases. The inflated balloon and angulation mechanism allowed a curved coronary lumen and atheroma to be seen with a limited volume of irrigation fluid. Visualization was good (complete visualization of the inner lumen) in 46% (10 of 22 lesions), moderate (visualization of >50% of the inner lumen) in 36% (8 of 22 lesions) and poor (visualization of These preliminary experiences in closed chest cardiac catheterization in dogs and in humans indicate the feasibility of this angioscope. The information yielded by angioscopy may be clinically useful in the study of the pathophysiologic changes in coronary disease that are not detected by coronary arteriography.

Angioscopic identification of coronary thrombus in patients with postinfarction angina

OBJECTIVES The purpose of this study was to determine the prevalence of intracoronary thrombus and associated anatomic abnormalities in patients with postinfarction angina using coronary angioscopy and angiography. BACKGROUND Postinfarction angina, previously studied by angiographic methods only, identifies patients at high risk for sudden death, recurrent angina and refractory angina. The recent development of coronary angioscopy, which permits direct observation of a thrombus or atheroma and is especially used for the detection of intraluminal changes, encourages a reexamination of the pathogenesis of postinfarction angina. METHODS Fifty-one consecutive patients with a diagnosis of acute myocardial infarction underwent cardiac catheterization. Coronary angiography followed immediately by coronary angioscopy was performed in 17 patients with and 34 without postinfarction angina during the same period of time (10.2 +/- 3.7 or 15.7 +/- 5.5 days [mean +/- SD]) after the onset of acute myocardial infarction. RESULTS The frequency of thrombus, as observed by angioscopy, was significantly higher in patients with than without postinfarction angina (17 of 17 vs. 5 of 34, respectively, p < 0.01). There were no significant differences between groups with respect to degree of stenosis in the infarct-related artery, number of vessels with significant stenosis, presence of collateral flow, type of therapy and risk factors. CONCLUSIONS Infarct-related artery thrombus is universally present in postinfarction angina and may be the primary pathogenic factor. Angioscopy is much more sensitive than coronary angiography for the detection of coronary thrombus.

Angioscopy in variant angina : coronary artery spasm and intimal injury

Studies in pigs and dogs show that intimal injury is related to coronary artery spasm; it is not known whether intimal injury is related to coronary artery spasm in human beings. We examined intima at the site of coronary artery spasm by percutaneous transluminal coronary angioscopy in 10 of 13 consecutive patients with variant angina. Coronary artery spasms occurred spontaneously or were induced by intracoronary acetylcholine (10-100 micrograms). Angioscopy showed intimal injuries (haemorrhage, flap, thrombus, or ulcer) in 4 of the 10. We suggest that intimal injury is related to coronary artery spasm in human beings.

Differences in plasma β-endorphin and bradykinin levels between patients with painless or with painful myocardial ischemia

To verify whether plasma beta-endorphin and bradykinin affects the pathophysiology of myocardial ischemia and the perception of cardiac pain, 35 patients with coronary artery disease were subjected to treadmill testing and 48-hour Holter ECG monitoring to measure their pain thresholds. Patients were divided into two groups during exercise testing: group 1 (N = 19) who had ST segment depression, and group 2 (N = 16), who had chest pain. Both groups were then compared with 12 age-matched control subjects. Pain thresholds were measured after Holter ECG monitoring, and blood samples were drawn before and immediately after exercise. No statistical differences were noted between groups 1 and 2 with regard to the severity of myocardial ischemia as assessed by ST segment depression or exercise tolerance time. The frequency of the episodes of silent myocardial ischemia in group 1 was found to be significantly (p less than 0.05) higher than that in group 2. The duration of the episodes of silent myocardial ischemia in group 1 was 41.9 minutes (range 3 to 343 minutes), which was significantly (p less than 0.05) longer than that in group 2 (11.5 minutes; range 0 to 74). The pain threshold in group 1 was a statistically (p less than 0.05) higher value than that in group 2. Although the resting plasma beta-endorphin level in group 1 was not statistically significantly different from values in either group 2 or the control group, during exercise the plasma beta-endorphin levels in both group 1 and the control group were significantly (p less than 0.05) elevated in comparison with their resting levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Significance of plasma nitric oxide/endothelial-1 ratio for prediction of coronary artery disease.

Vascular tone is regulated by vasodilators and vasoconstrictors. Endothelin-1 (ET-1) is the predominant vasoconstrictor peptide that constricts vascular smooth muscle, whereas nitric oxide (NO) is the primary vasodilator peptide that relaxes vascular smooth muscle. In this study, the authors examined whether NO/ET-1 ratio is a useful marker for detecting coronary artery disease (CAD), by comparison with evaluation based on vascular endothelial (VE) function. They measured plasma NOX and ET-1 by using ENO-200 and radioimmunoassay, in 38 subjects with normal (NL) coronary arteries (NL group; mean age, 60 ±12 years) and 25 subjects with CAD (CAD group; mean age, 69 ±6 years). VE function (randomized endothelium-dependent [D] and endothelium-independent [I] VE function) was assessed by measuring brachial artery (BA) diameter by using high-resolution ultrasound (7.5 MHz). Soon after these procedures, symptom-limited exercise testing was performed. There were no statistically significant differences in serum lipid concentrations or VED function between the groups. However, the CAD group had a significantly lower NO/ET-1 ratio (1.2 ±1.1 vs 2.7 ±2.2, p<0.01) and BA diameter after sublingual nitroglycerin (VEID function: 6 ±7% vs 10 ±4%, p<0.05). As expected, the ST segment and treadmill exercise duration were significantly lower in the CAD group. Sensitivity and specificity for detecting CAD by plasma NO/ET-1 ratio (≥2.0) were 90% and 85%, respectively; sensitivity and specificity for detecting CAD by ST depression (≥1 mm) were 80% and 78%, respectively. The present results suggest that plasma NO/ET-1 ratio is a useful biological marker for predicting CAD.

Angioscopy, coronary thrombi and acute coronary syndromes

Coronary angioscopy is a new diagnostic imaging technique in which optic fibres are used to directly observe the intracoronary lumen. Angioscopy provides a full colour, high resolution, three-dimensional image of the intracoronary artery surface morphology. Studies using angioscopy revealed that the frequency of coronary thrombi in patients with acute coronary syndromes was higher than previous studies, based on arteriography, had reported. Arteriographic recognition of thrombus in unstable angina was from 1.3% to 52%. On the other hand, thrombi were observed in 88% by angioscopy in patients with rest angina in our study. Whereas ordinary arteriography provides only two-dimensional black and white images, angioscopy can distinguish between a thrombus and a plaque, even if the clot is very small. In a study of 17 unstable angina and 22 myocardial infarction patients, the frequencies of coronary thrombi in the two groups were essentially the same. Grayish-white thrombi were observed in most of the unstable angina patients but in none of the infarction patients. On the other hand, red or mixed red and white thrombi were observed in all infarction patients but in only a few unstable angina patients. This difference may account for the contrasting results of thrombolytic therapy.

Effect of Nipradilol on Silent Myocardial Ischemia and Heart Rate Variability in Chronic Stable Angina

AbstractPurpose: Silent myocardial ischemic episodes as well as decreased heart rate variability (HRV) indices are associated with an unfavorable outcome in patients with coronary artery disease. Nipradilol, which is a non-selective beta-adrenergic and nitrate-like vasodilator anti-anginal agent developed in Japan, may ameliorate silent myocardial ischemia, while it also improves exercise tolerance and HRV indices in patients with chronic stable angina. Methods: To investigate the effect of nipradilol (6 mg daily) on silent myocardial ischemic episodes and HRV indices, and to study its effect on the relationship between them, 24 patients with chronic stable angina underwent exercise treadmill testing and a 24-hour ambulatory electrocardiogram (ECG). The study protocol utilized a single blind, 4-week placebo-controlled design. The HRV indices from ambulatory ECG included mean RR (ms), SDNN (ms), SDANN (ms), SD (ms), rMSSD (ms), pNN50 (%); frequency analysis of HRV consisted of total (ms, 0.01–1.00 Hz), low (ms, 0.04–0.15 Hz) and high (ms, 0.15–0.40 Hz) components. Results: Nipradilol significantly decreased the mean heart rate at submaximal and maximal exercise and the mean pressure rate product at submaximal and maximal exercise. It significantly improved exercise-induced maximal ST segment depression from −1.7 ± 0.6 mm to −1.1 ± 0.7 mm (p > 0.05). Silent myocardial ischemic episodes recorded during the 24-hour ambulatory ECG significantly decreased after nipradilol administration. Nipradilol also significantly influenced several HRV indices as well as the relationship between silent myocardial ischemic episodes and the HRV indices. Nipradilol significantly increased SD, rMSSD, pNN50, total spectra, low frequency spectra and high frequency spectra. In addition, nipradilol significantly decreased the LF/HF ratio from 1.7 (1.5–2.0) to 1.5 (1.3–1.8). These effects of nipradilol on HRV indices concomitantly occurred with the reduction in silent myocardial ischemic episodes. Conclusion: Nipradilol was found to effectively improve the episodes of silent myocardial ischemia as well as exercise-induced ischemia probably due to its beta-blocking properties and not nitrate-like actions. In addition, nipradilol also had a favorable effect on the HRV indices.