Unstable Angina

Identification of a characteristic morphology of a coronary stenosis likely to result in myocardial infarction would facilitate the prospective evaluation of infarct prevention strategies and identification of high-risk patients. We postulated that coronary lesions associated with recent myocardial infarction or unstable angina would have an angiographic morphology suggesting disruption of an atherosclerotic plaque and would appear morphologically different from lesions associated with chronic stable angina. To test this hypothesis, quantitative coronary angiography (Brown-Dodge method) was performed in 15 patients 4 to 30 days after myocardial infarction, in 10 patients with the abrupt onset of unstable angina and single-vessel coronary disease, and in 15 patients with chronic stable angina without prior myocardial infarction. Serial arterial diameters (20 to 40) within each lesion were determined and the degree of luminal irregularity was quantitated by calculation of an "ulceration" index. The majority of all lesions analyzed resulted in severe luminal stenosis (mean 78% area stenosis, all groups). Despite small differences in mean lesion severity among groups, overlap in the degree of luminal compromise prevented precise classification of lesions associated with myocardial infarction or unstable angina based on percent stenosis or minimum luminal cross-sectional area. The mean ulceration index of lesions in patients with unstable angina and in the infarct-related vessel in those with acute myocardial infarction was 0.62 ± 0.05 ( ± SEM) and 0.61 ± 0.03, respectively. These were significantly different from the mean ulceration indexes of lesions in patients with stable angina (0.96 ± 0.01, p<.05) or from indexes of lesions in the noninfarct-related vessel of patients with acute infarction (0.90 ± 0.02, p<.05)). None of 10 lesions associated with unstable angina and 14 of 15 infarct-related lesions had an ulceration index less than 0.78. All lesions associated with stable angina and each lesion in the noninfarct-related vessel in patients wth infarction had an ulceration index of greater than 0.83. The ulceration index did not vary significantly with the degree of luminal stenosis or prior treatment with thrombolytic agents. These data provide quantitative evidence that lesions associated with myocardial infarction or the abrupt onset of unstable angina are of a similar characteristic angiographic morphology that is suggestive of plaque disruption and not commonly seen in lesions associated with chronic stable angina. The ulceration index may provide a mechanism for the prospective identification of high-risk coronary lesions. Circulation 73, No. 2, 286-293, 1986. ACUTE MYOCARDIAL INFARCTION usually occurs as a discrete event caused by sudden occlusion of a single coronary artery. ' Although the occlusion often occurs at the site of a severe atherosclerotic lesion, many patients with acute myocardial infarction have From the Department of Internal Medicine and the Cardiovascular Center, University of Iowa, and Veterans Administration Hospital, Iowa City. Supported by grants from the National Heart, Lung, and Blood Institute (HL27633, 14388, and 29976), the Ischemic SCOR (HL3229501), and the Veterans Administration (MRIS 1 100.2). Address for correspondence: Robert F. Wilson, M.D., Cardiovascular Division, Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA 52240. Received July 2, 1985; revision accepted Sept. 26, 1985. 286 coronary stenoses of equal or greater severity in other coronary vessels that have not occluded.2 Methods for predicting the occurrence of myocardial infarction have focused primarily on the anatomic distribution of atherosclerotic coronary lesions and, to a lesser extent, on the degree of coronary luminal compromise produced by each lesion. In individual patients, however, the distribution and overall extent of coronary artery disease are only weak predictors of subsequent myocardial infarction and death.3'4 Hence, efforts to predict the likelihood that a single coronary lesion will eventuate in myocardial infarction have been generally unsuccessful.5 This inability to predict the occurrence CIRCULATION by gest on N ovem er 6, 2017 http://ciajournals.org/ D ow nladed from PATHOPHYSIOLOGY AND NATURAL HISTORY-UNSTABLE ANGINA of total occlusion of an individual coronary lesion has hampered our assessment of infarct prevention strategies. We hypothesized that coronary lesions associated with acute myocardial infarction would be morphologically different from lesions associated with stable angina pectoris. Pathologic studies of coronary stenoses associated with sudden death or myocardial infarction have demonstrated that atherosclerotic plaque disruption (fissuring or hemorrhage) is present in up to 100% of recently thrombosed lesions.6 Since the angiographic appearance of coronary lesions should reflect their anatomic structure, we postulated that a detailed quantitative evaluation of coronary stenoses associated with these syndromes might reflect underlying disruption of atherosclerotic plaque. The use of thrombolytic therapy for acute infarction has now provided a patient population in whom detailed angiographic evaluation of the morphology of coronary lesions associated with recent acute infarction is now possible. Since patients with the abrupt onset of very unstable angina are known to have a high incidence of rapid progression to myocardial infarction, we also postulated that coronary lesions associated with unstable angina might have a similar morphology to those associated with acute infarction. Recent studies by Falk,7 in which an 80% incidence of atherosclerotic plaque disruption in patients with unstable angina was found have pioneered this concept. Angiographic features of atherosclerotic plaque disruption have been qualitatively described. Autopsy specimens of coronary arteries with atherosclerotic plaque disruption have a "complicated" angiographic appearance characterized by irregular arterial borders and intraluminal filling defects.' Similar qualitative irregularities of the arterial lumen can be seen on coronary angiograms obtained from patients with unstable angina.9 Visual interpretation of coronary angiograms obtained in vivo, however, is frought with marked intraobserver and interobserver variability10 and prior qualitative studies have not provided an objective basis for the evaluation of the morphology of a stenosis. Moreover, prior angiographic analysis of the morphology of a stenosis in vivo have dealt primarily with lesions associated with unstable angina. In this study, we used Brown-Dodge quantitative coronary angiography to quantitatively define the "irregular" appearance of lesions leading to infarction or unstable angina. l In a preliminary study, we divided coronary stenoses into angiographically complicated and uncomplicated lesions according to the postmortem angiographic definitions of Levin and Fallon. 8 An uncomplicated lesion was defined as one with only one area of narrowing per lesion. A complicated lesion contained multiple areas of narrowing within the same lesion. After these preliminary studies, we found that most coronary lesions contained some degree of luminal irregularity and were, therefore, complicated to some extent. We reasoned that, if the angiographically complicated lesions were the site of a fissured atherosclerotic plaque as pathologists have suggested, then the depth of the fissure (or angiographic ulceration) could be quantitated by comparing the maximal arterial diameter at the site of plaque disruption to the diameter of the vessel just adjacent to the disruption. In addition, we related this aniographic index of ulceration to quantitative measurements of the degree of luminal narrowing. Methods Patient characterisics. Patients (n = 40) were selected in a retrospective manner by review of all consultations performed by one of the authors (R. F. W.) from 1982 to 1983. All patients meeting the clinical criteria for study defined below and who underwent coronary angiography within 2 weeks of consultation were included. Each patient had received nitroglycerin (intracoronary or sublingual) before angiography. Five patients were excluded from the study because their angiograms were of insufficient quality for quantitative angiographic analysis. Three angiograms were excluded because they appeared to contain intraluminal thrombus. Three patient subgroups were studied. The first subgroup comprised 15 patients who underwent coronary angiography within 1 month of acute myocardial infarction and were found to have a patent vessel supplying the infarcted area. Angiograms from 12 of these patients were obtained during routine followup coronary angiography performed 4 to 12 days after thrombolytic therapy for acute Q wave myocardial infarction. Three additional patients underwent coronary angiography 14 to 30 days after non-Q wave myocardial infarction, but had not received thrombolytic therapy. Infarction was documented by the triad of a classical clinical history, threefold elevation in total creatine kinase with an elevated creatine kinase-MB fraction, and evolutionary electrocardiographic changes consistent with acute myocardial infarction. The acutely occluded vessel was the left anterior descending in nine patients, the circumflex artery in one patient, and the right coronary artery in five patients. In six of the patients, another stenosis adequate for quantitative studies (i.e., stenosis with patent lumen demonstrated in orthogonal views) was present (two left anterior descending, two circumflex, two right coronary artery). The second subgroup comprised 10 patients with abrupt onset of unstable angina and with only one coronary lesion with more than 50% diameter stenosis (unstable angina associated with single-vessel coronary artery disease). Unstable angina was specifically defined as (1) the new onset of angina pectoris with angina occurring frequently at rest or (2) the abrupt worsening of previously stable angina pectoris by two New York Heart Association functional classes with angina at rest. The lesion was in the left anterior descending in five patients, in the circumflex artery in four patients, and in the right coronary artery in the remaining patient. The third subgroup comprised 15 patients with a history of Vol. 73, No. 2, February 1986 287 by gest on N ovem er 6, 2017 http://ciajournals.org/ D ow nladed from