S.David Gertz

Hemodynamic shear force in rupture of coronary arterial atherosclerotic plaques

A ngiographic and necropsy studies have suggested a direct pathogenetic relation among rupture of a coronary arterial atherosclerotic plaque, coronary thrombus formation, and acute myocardial infarction (AMI).‘-” However, the local pathophysiologic factor or factors responsible for the initiation of plaque rupture have not been identified, Suggestions have included hemorrhage into a plaque after injury to vasa vasora; mechanical compression associated with coronary spasm; increased intraluminal arterial pressure; and circumferential tensile stress on the “fibrous cap” of the plaque. In this article we summarize the evidence for and against each of these theories and present the case for hemodynamic (rheologic) shear forces as a factor in the pathogenesis of plaque rupture. Rupture of vasa vasora: Damage to small vascular channels within atherosclerotic plaques has been suggested by a number of investigators to be a source of plaque hemorrhage,12-15 but none has shown how this might result in plaque rupture. Extravasation of erythrocytes from injury to intraplaque vascular channels is known to occur in large plaques, but this has been distinguished from hemorrhage associated with plaque rupture by the absence in the former of associated fibrin and platelets. I6 Moreover, Constantinides,17 in an analysis of serial sections of 17 cases of fatal coronary thrombosis, showed that the associated plaque hemorrhage could always be traced to an entry of blood from the lumen through the same crack in the plaque. Thus, although intraplaque vascular channels are seen often, it is our experience that they are not seen within lipid-rich pultaceous debris, and there is no evidence that such channels are associated with plaque hemorrhage which accompanies rupture of a coronary atherosclerotic plaque. Plaque compression by coronary vasospasm: Vasoconstriction or spasm has been proposed as a cause of rupture of an atherosclerotic plaque,18-20 but can vasospasm occur in severely narrowed coronary arteries? The dominant histopathologic component of coronary atherosclerotic plaques is fibrous tissue, and, when the luminal narrowing is severe, the underlying media is often severely attenuated. 21,22 Nevertheless, angiographic

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)

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

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).

Composition of atherosclerotic plaques in the four major epicardial coronary arteries in patients ≥ 90 years of age

Abstract The composition of atherosclerotic plaques in 733 five-mm segments of the 4 major (left main, legt anterior descending, left circumflex and right) epicardial coronary arteries of 18 patients ≥90 years of age was determined by computerized planimetric analysis. By analysis of all coronary segments of all patients >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 >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.

Coronary arteries in unstable angina pectoris, acute myocardial infarction, and sudden coronary death

The amount of coronary arterial narrowing observed at autopsy in patients with UAP, AMI, and SCD is generally enormous.l As shown in Table I, from a study of 80 patients at autopsy with these three coronary events (SCD in 31, AM1 in 27, and UAP in 22), an average of 2.9 of the four major (right, left main, left anterior descending, and left circumflex) coronary arteries were severely (>75 % decrease in cross-sectional area) narrowed at some points, and no significant differences were observed among the three coronary subsets1 Patients with UAP had a much higher frequency of severe narrowing of the left main coronary artery (10 of 22 patients [45 % 1) compared with those with AM1 (3 of 27 patients [ll % ]) and SCD (3 of 31 patients [lo%]). A more sophisticated approach to determining degrees of luminal narrowing is to examine the entire lengths of the four major epicardial coronary arteries. One technique involves incising each of the four major coronary arteries transversely at 5 mm intervals and then preparing a histologic section from each 5

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)

Reoperation for persistant outflow obstruction in hypertrophic cardiomyopathy

This study compares results of a second left ventricular myotomy and myectomy (M + M) with those of mitral valve replacement (MVR) as reoperative procedures for persistent left ventricular outflow obstruction after M + M in hypertrophic cardiomyopathy. Comparison of the second M + M group (n = 12) with the MVR group (n = 11) disclosed significant difference (p less than 0.05) in mean age at the initial operation (29 +/- 11 years versus 40 +/- 8 years), interval between operations (46 +/- 57 months versus 18 +/- 13 months), and age at reoperation (33 +/- 10 years versus 42 +/- 8 years); and insignificant differences in mean preoperative functional class, cardiac index, left ventricular outflow gradients at rest or with provocation, and hospital mortality at reoperation (2/12 versus 1/11). At 6 months after reoperation, comparison of results of a second M + M with MVR showed that mean functional class, cardiac index, and left ventricular outflow gradient at rest were similarly improved, but the outflow gradient with provocation was significantly higher in the second M + M group (57 +/- 44 mm Hg versus 14 +/- 9 mm Hg, p less than 0.05). Total follow-up was 108 patient-years (100% complete) with an average of 5.9 years per patient in the second M + M group and 3.4 years per patient in the MVR group. Actuarial survival, including hospital mortality, at 3 and 5 years was 83% and 76%, respectively, after the second M + M, which was similar to 92% and 77% after MVR.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Appearance of or persistence of severe mitral regurgitation without left ventricular outflow obstruction after partial ventricular septal myotomy-myectomy in hypertrophic cardiomyopathy

Abstract At the National Heart, Lung, and Blood Institute from 1959 through October 1989, 626 patients underwent operative treatment of obstructive hypertrophic cardiomyopathy: ventricular septal myotomy-partial myectomy alone in 539 patients; mitral valve replacement alone in 68 patients; and both procedures, not necessarily simultaneously, in 27 patients. The septal myotomy-myectomy procedure in most patients provided clinical improvement, but in some patients the results of this procedure have been unsatisfactory and reoperation has been performed. 1 In the 27 patients who underwent reoperation after septal myotomy-myectomy, the indication was persistent left ventricular outflow obstruction in 24 patients 2 and pure mitral regurgitation, without outflow obstruction, in 3 patients. This report describes certain clinical and morphologic features in the latter 3 patients.

Lessons from Animal Models of Arterial Aneurysm.

We review the results from the most common animal models of arterial aneurysm, including recent findings from our novel, laparoscopy-based pig model of abdominal aortic aneurysm, that contribute important insights into early pathogenesis. We emphasize the relevance of these findings for evaluation of treatment protocols and novel device prototypes for mechanism-based prevention of progression and rupture.