Morphologic comparison of frequency and types of acute lesions in the major epicardial coronary arteries in unstable angina pectoris, sudden coronary death and acute myocardial infarction.

The frequency and type of acute lesions in the four major (right, left main, left anterior descending, left circumflex) epicardial coronary arteries were examined at necropsy in 14 patients with unstable angina pectoris, 21 patients with sudden coronary death and 32 patients with a fatal first acute myocardial infarction. None of the 67 patients had a grossly visible left ventricular scar (healed myocardial infarct) and only the group with acute myocardial infarction had left ventricular myocardial necrosis. Although the frequency of intraluminal thrombus was similar in patients with unstable angina (29%) and sudden death (29%) and significantly lower than in those with acute infarction (69%) (p = 0.02), the thrombus in the patients with unstable angina and sudden death consisted almost entirely of platelets and was nonocclusive, whereas the thrombus in the group with acute infarction consisted almost entirely of fibrin and was occlusive. The frequency of plaque rupture was insignificantly different in the groups with unstable angina (36%) and sudden death (19%), and was significantly lower than in the group with acute infarction (75%) (p = 0.02). The frequency of plaque hemorrhage was insignificantly different in the groups with unstable angina (64%) and sudden death (38%) and was significantly lower than in the group with acute infarction (90%) (p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Anomalous origin of either the right or left main coronary artery from the aorta with subsequent coursing between aorta and pulmonary trunk: analysis of 32 necropsy cases.

Anomalous origin of either the left main coronary artery (LMCA) or right coronary artery (RCA) from the aorta with subsequent coursing between the aorta and pulmonary trunk is a rare and sometimes fatal coronary artery anomaly. Thirty-two cases of these anomalies were reviewed, with particular attention to the exact location and shape of the anomalistically positioned ostium and coronary dominance. The LMCA (7 cases) arose either from behind the right coronary sinus (6 cases) or as a single ostium with the RCA straddling the right-left commissure and right coronary sinus (1 case). In 5 of the 7 cases, the anomaly was fatal. In 6 cases of anomalous origin of the LMCA, the RCA was dominant and in 4 the anomaly was fatal. In only 1 case of anomalous origin of the LMCA was the left circumflex coronary artery dominant, and in this case the anomaly also was fatal. The RCA (25 cases) arose either from behind the left coronary sinus (8 cases), above the left coronary sinus (5 cases), from above the right-left commissure (10 cases) or as a single ostium with the LMCA above the right-left commissure and left coronary sinus (2 cases). In 8 of these 25 cases the anomaly was fatal. In 7 cases of anomalous origin of the RCA, the left circumflex coronary artery was dominant and in no case was the anomaly clinically significant. In 1 case, both the RCA and left circumflex coronary artery were hypoplastic and the anomaly was fatal. Coronary dominance, not ostial shape, was useful in separating the clinically significant from the clinically insignificant anomalies.

Anomalous origin of either the right or left main coronary artery from the aorta without coursing of the anomalistically arising artery between aorta and pulmonary trunk.

Clinical and necropsy findings are described in 12 adults (10 men) in whom either the left main coronary artery or the right coronary artery arose abnormally from the aorta and the anomalistically arising artery coursed thereafter either normally or abnormally, but if abnormally not between the pulmonary trunk and ascending aorta. None of the 12 patients had symptoms of myocardial ischemia that unequivocally could be attributed to the anomalously arising coronary artery. One patient, a 19-year-old man, however, died suddenly and no abnormality other than the anomalistically arising right coronary artery from the posterior aortic valve sinus was found.

Composition of atherosclerotic plaques in coronary arteries in women less than 40 years of age with fatal coronary artery disease and implications for plaque reversibility.

This study analyzes the composition of atherosclerotic plaques in the 4 major epicardial coronary arteries in 8 women less than 40 years of age (mean 34) with fatal coronary artery disease (CAD) and compares these data to previous studies of 37 adults greater than 45 years of age (mean 59) with fatal CAD. Histologic sections were taken at 5-mm intervals from the entire lengths of the right, left main, left anterior descending and left circumflex coronary arteries. With the use of a computerized morphometry system, analysis of the 4 major epicardial coronary arteries showed the major component of plaque to be a combination of cellular (mean percent total plaque area = 65%, standard error = 6%) and dense (19%, standard error = 6%) fibrous tissue. Arterial segments narrowed greater than 75% in cross-sectional area from these young women were compared with similarly narrowed arteries from 37 older patients (32 men [86%]) with fatal CAD previously reported by this laboratory, and showed significantly more cellular fibrous tissue and lipid-rich foam cells, and lesser amounts of dense fibrous and heavily calcified tissue. The large amount of lipid-containing foam cells and relative lack of acellular scar tissue in coronary plaques in these young women suggests a greater potential for reversibility of these plaques in this subset of patients with CAD.

Composition of atherosclerotic plaques in the four major epicardial coronary arteries in patients greater than or equal to 90 years of age.

The composition of atherosclerotic plaques in 733 five-mm segments of the 4 major (left main, left anterior descending, left circumflex and right) epicardial coronary arteries of 18 patients greater than or equal to 90 years of age was determined by computerized planimetric analysis. By analysis of all coronary segments of all patients greater than 90, the plaques consisted primarily of fibrous tissue (87 +/- 8%) with calcific deposits (7 +/- 6%), pultaceous debris (5 +/- 4%) and foam cells (1 +/- 1%) occupying a much smaller percentage of plaque area. Analysis of composition according to the 4 degrees of luminal cross-sectional area narrowing revealed marked step-wise increases in pultaceous debris (from 0 +/- 0% at 0 to 25% narrowing to 18 +/- 22% at 76 to 100% narrowing, p = 0.0001) and calcific deposits (from 0 +/- 0 to 10 +/- 15%, p = 0.002), and decreases in fibrous tissue (from 99 +/- 3 to 71 +/- 23%, p = 0.0001) and area occupied by the media (from 35 +/- 8 to 16 +/- 8%, p = 0.0001). When the analysis was restricted to sections narrowed greater than 75%, no significant differences were found in plaque components or medial area between patients with (11 patients) and without (7 patients) myocardial infarcts at necropsy.

The heart in fatal unstable angina pectoris.

Compared to patients with sudden coronary death and acute myocardial infarction, relatively little morphologic data has been reported in patients with unstable angina pectoris. This article reviews necropsy data collected from one laboratory on unstable angina pectoris. From these data, several observations are appropriate: (1) Patients with unstable angina as a group have more coronary narrowing by atherosclerotic plaque than do patients with sudden coronary death or acute or healed myocardial infarction. (2) Patients with unstable angina have a much higher frequency of severe narrowing of the left main coronary artery than do patients in other coronary subsets. (3) The coronary atherosclerotic plaques in unstable angina consist primarily of fibrous tissue, and they are more similar to those found in patients with sudden coronary death than in patients with acute myocardial infarction. (4) The frequency of acute coronary lesions (thrombi, plaque rupture, and plaque hemorrhage) is similar to that observed in patients with sudden coronary death and significantly less than that observed in acute myocardial infarction. (5) The frequency of multiluminal channels throughout the major coronary arteries is significantly higher in unstable angina compared to sudden coronary death or acute myocardial infarction. (6) The major epicardial arteries and the heart are smaller in patients with unstable angina than in patients with sudden coronary death or acute myocardial infarction. (7) The left ventricular cavity is usually of normal size in patients with unstable angina and therefore left ventricular function is usually normal.

Morphometric analysis of the composition of coronary arterial plaques in isolated unstable angina pectoris with pain at rest.

Coronary artery plaque morphology was studied in 354 five-mm segments of the 4 major (left main, left anterior descending, left circumflex and right) epicardial coronary arteries in 10 patients with isolated unstable angina pectoris with pain at rest. The 4 major coronary arteries were sectioned at 5-mm intervals and a drawing of each of the resulting 354 Movat-stained histologic sections was analyzed using a computerized morphometry system. The major component of plaque was a combination of dense acellular and cellular fibrous tissue with much smaller portions of plaque being composed of pultaceous debris, calcium, foam cells with and without inflammatory infiltrates and inflammatory infiltrates without foam cells. There were no differences in plaque composition among any of the 4 major epicardial coronary arteries. Plaque composition varied as a function of the degree of luminal narrowing. Linear increases were observed in the mean percent of dense fibrous tissue (from 5 to 50%), calcific deposits (from 1 to 10%), pultaceous debris (from 0 to 10%) and inflammatory infiltrates without significant numbers of foam cells (from 0 to 5%), and a linear decrease was observed in the mean percent of cellular fibrous tissue (from 94 to 22%) in sections narrowed up to 25% to more than 95% in cross-sectional area. Multiluminal channels were seen in all 10 patients (28 [19%] of the 146 sections narrowed greater than 75% in cross-sectional area and in 36 [10%] of all 354 segments); occlusive thrombi in no patient; nonocclusive thrombi in 2 patients (1 section each of 2 arteries); plaque rupture in 2 patients (4 segments from 2 arteries); and plaque hemorrhages in 6 patients (11 sections from 10 arteries).

Comparison of coronary and myocardial morphologic findings in patients with and without thrombolytic therapy during fatal first acute myocardial infarction. The TIMI Investigators.

The hearts of 61 patients (39 men aged 64 +/- 11 years) who died from 5 hours to 42 days (median 3 days) after a fatal first acute myocardial infarction without having undergone percutaneous transluminal coronary angioplasty or coronary bypass surgery were studied to compare clinical and cardiac morphologic features of patients receiving thrombolytic therapy with tissue-plasminogen activator (t-PA) to those not receiving thrombolytic therapy. Comparison of findings in the 23 patients who received t-PA intravenously 3 +/- 1 hours after onset of symptoms, with the 38 patients who did not, showed similar baseline characteristics with respect to: age, gender, history of hypertension; location of the infarct; heart weight; severity and numbers of coronary arteries narrowed; and frequencies of plaque rupture, plaque hemorrhage and coronary thrombi. Among the patients receiving t-PA, however, there was a greater frequency of platelet-rich (fibrin-poor) thrombi in the infarct-related coronary arteries (6 of 11 vs 4 of 25 thrombi; p = 0.02), more nonocclusive than occlusive thrombi (6 of 11 vs 4 of 25 thrombi; p = 0.02), and a lower frequency of myocardial rupture (left ventricular free wall or ventricular septum) (5 of 23 [22%] vs 18 of 38 [46%]; p = 0.045).

Cardiac morphologic findings in patients with acute myocardial infarction treated with recombinant tissue plasminogen activator.

The hearts of 52 patients (aged 61 +/- 11 years, 34 men) who participated in the Thrombolysis in Myocardial Infarction (TIMI) Study and died from 5 hours to 260 days (median 2.7 days) after onset of chest pain were studied. One heart became available at cardiac transplantation. Of the 52 patients, 38 received recombinant tissue plasminogen activator (rt-PA) not followed by percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG). Eight had PTCA, and 6 had CABG. The infarcts were hemorrhagic by gross inspection (with histologic confirmation) in 23 patients, nonhemorrhagic in 20, not visible grossly in 2 and, in 7, there was no myocardial necrosis by either gross or histologic examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathologic findings associated with interleukin-2-based immunotherapy for cancer: a postmortem study of 19 patients.

The use of interleukin-2 (IL-2), either alone or in combination with lymphokine-activated killer cells, tumor infiltrating lymphocytes, or other immunotherapeutic agents has added a new list of alternatives to conventional antineoplastic regimens. Little information is available about the pathologic changes occurring in patients treated with these agents. In this study, we reviewed the necropsy materials from 19 patients, 12 men and 7 women, with a variety of malignancies including melanoma, renal cell carcinoma, gastrointestinal and pulmonary adenocarcinoma, and metastatic gastrinoma, who died after receiving IL-2-based immunotherapy. Death occurred at intervals ranging from less than 1 hour to 143 days following the last dose of therapy. All patients dying at or less than 43 days following cessation of therapy had lymphoid infiltrates of varying intensity in residual tumor. At necropsy, the major cause of death unrelated to the presence of metastatic tumor was bacterial sepsis. In addition, we found evidence of significant cardiac and pulmonary toxicity: two patients with acute myocardial infarction, one with and one without significant coronary artery disease, two cases of unexplained lymphocytic myocarditis, and one case of fatal pulmonary capillary plugging following an infusion of lymphokine-activated killer cells. Thus, not unlike other forms of therapy for cancer, IL-2-based immunotherapy does not appear to be without significant toxicity.

Right atrial compression related to defibrillator patches.

Acceptable function of an internal defibrillator can be achieved with different patch orientations. For patients requiring defibrillator patches concomitant with a cardiac procedure requiring extracorporeal circulation, application of one of the patches within the pericardium adjacent to the right atrium has provided excellent defibrillation thresholds. We describe 4 such patients in whom a compressing thrombus subsequently developed between the patch and the atrium. The thrombus was small and asymptomatic in 1 patient, but caused localized tamponade requiring reexploration in 2 patients and a fatal superior vena caval obstruction in 1. The precise etiology of this serious complication remains unclear, but its occurrence argues against the application of intrapericardial defibrillator patches in this orientation.

Effects of tissue plasminogen activator therapy on the frequency of acute right ventricular myocardial infarction associated with acute left ventricular infarction.

To assess the effects of reperfusion therapy on acute right ventricular myocardial infarction, we studied at necropsy the hearts from 51 patients who died after receiving intravenous recombinant tissue plasminogen activator for acute left ventricular myocardial infarction as part of the Thrombolysis in Myocardial Infarction (TIMI) study. Right ventricular infarction occurred in none of 29 patients with infarction of the anterior wall of the left ventricle and in 8 of 22 patients (36%) with infarction of the posterior (inferior) wall of the left ventricle. Of the 22 patients with posterior wall infarction, the 8 patients with right ventricular infarction were compared to the 14 patients without right ventricular infarction. The patients with right ventricular infarction had a longer mean interval from tissue plasminogen activator infusion to peak creatine phosphokinase level (19 vs. 11 h, P < 0.03), a lower frequency of hemorrhagic necrosis (2 of 8 vs. 10 of 14, P < 0.04) and higher frequency of luminal thrombus in the infarct-related coronary artery (6 of 8 vs. 3 of 14, P = 0.054). Each of these findings is associated with the absence of coronary reperfusion. Thus, successful reperfusion following acute left ventricular myocardial infarction appears to be associated with a decreased frequency of concomitant right ventricular myocardial infarction.

Coronary arterial morphology 10 years after "endarterectomy".

Little information is available regarding coronary artery morphology after endarterectomy. In this report, we describe coronary artery morphology seen at necropsy 10 years after coronary artery endarterectomy and compare it with the morphology of the original endarterectomy specimen. Surprisingly, in some areas, all of the internal elastic membrane and most of the media were observed in the "endarterectomy" specimen.

Sudden death in hypertrophic cardiomyopathy with normal left ventricular mass.

An active, healthy, and symptom free 16 year old boy with a family history of hypertrophic cardiomyopathy died suddenly while walking home from school. Necropsy showed absence of left ventricular hypertrophy (that is, normal heart weight), though the characteristic histological abnormalities of hypertrophic cardiomyopathy, such as cardiac muscle cell disorganisation and abnormal intramural coronary arteries, were present. It is likely that this patient had hypertrophic cardiomyopathy and died before left ventricular hypertrophy developed.

Morphometric analysis of the composition of atherosclerotic plaques in the four major epicardial coronary arteries in acute myocardial infarction and in sudden coronary death.

We studied at necropsy atherosclerotic plaque composition in the four major (right, left main, left anterior descending, and left circumflex) epicardial coronary arteries in 15 patients who died of consequences of an acute myocardial infarction (AMI) and in 12 patients with sudden coronary death (SCD) without AMI. The coronary epicardial arteries were sectioned at 5-mm intervals, and a Movat-stained section of each segment of artery was prepared and analyzed using a computerized morphometry system. Within the AMI group and within the SCD group, there were no differences in plaque composition among any of the four major epicardial coronary arteries. Within both groups, plaque morphology varied as a function of cross-sectional-area narrowing of the segments. In both groups, the amount of dense relatively acellular fibrous tissue, calcified tissue, and pultaceous debris (amorphous debris containing cholesterol clefts, presumably rich in extracellular lipid) increased in a linear fashion with increasing degrees of cross-sectional-area narrowing of the segments, and the amount of cellular fibrous tissue decreased linearly. In the AMI group, the percentage of plaque consisting of pultaceous debris and of cellular fibrous tissue separated significantly narrowed (greater than 75% cross-sectional area) segments from less narrowed (less than 75%) segments. A comparison of the AMI group to the SCD group showed significant differences. The percentage of plaque consisting of pultaceous debris (16% in the AMI group and 7% in the SCD group), of cellular fibrous tissue (11% vs. 18%), and of heavily calcified tissue (8% vs. 16%) were significantly different in the severely narrowed segments in the AMI and SCD groups. When all arteries containing thrombi were deleted from the analysis, there were no significant changes in the results. Occlusive coronary thrombi were present in 13 of the 15 AMI patients and in one of the 12 SCD patients. Thus, the frequency of coronary thrombi and plaque composition differ in patients with AMI and in those with SCD without AMI.