Quantification of Coronary Arterial Narrowing at Necropsy in Acute Transmural Myocardial Infarction

Transcription

1 Quantification of Coronary Arterial Narrowing at Necropsy in Acute Transmural Myocardial Infarction Analysis and Comparison of Findings in 27 Patients and 22 Controls WILLIAM C. ROBERTS, M.D., AND ANCIL A. JONES, M.D. SUMMARY We quantitatively analyzed the degree and extent of coronary arterial narrowing by atherosclerotic plaques in the entire length of each of the four major coronary arteries in 27 necropsy patients with transmural acute myocardial infarction (AMI) and compared the findings with those in 22 control subjects. Of the mm segments examined in the 27 AMI patients, 484 (34%; controls 3%) were 76-1% narrowed in cross-sectional area by atherosclerotic plaques, 528 (38%; controls 25%) were 51-75% narrowed, 319 (23%; controls 44%) were 26-5% narrowed, and only 72 segments (5%; controls 28%) were 25% narrowed. The amount of severe (> 75%) narrowing of the right, left anterior descending and left circumflex coronary arteries by atherosclerotic plaques was similar, as was the amount of severe narrowing in the distal and proximal halves of these three arteries. The number of severely narrowed 5-mm segments did not correlate significantly with the patient's age at death, the presence or absence of a history of angina pectoris or healed myocardial infarction, or with heart weight. The men, however, had a significantly greater number of severely narrowed 5-mm segments of coronary artery than the women (p <.5), and the patients with associated transmural left ventricular scars had significantly more severely narrowed segments than did patients without transmural scars. POSTMORTEM angiographic studies by Blumgart and associates' nearly 4 years ago disclosed severe luminal narrowing in usually two of the three major (right, left anterior descending and left circumflex) coronary arteries in patients with fatal acute myocardial infarction (AMI). By histologic study of cross sections of 5-mm segments of the three major coronary arteries in patients with fatal AMI, Roberts and Buja2 also found that usually at least two of the three major coronary arteries were > 75% narrowed in crosssectional area by atherosclerotic plaques. The latter study was qualitative, in that it sought to determine only the number of major coronary arteries narrowed > 75% in cross-sectional area by atherosclerotic plaque per patient. The present study is quantitative, in that we sought to determine not only if a coronary artery was > 75% narrowed in cross-sectional area at some point along its course, but also what percentage of its entire length was narrowed to lesser degrees (51-75%, 26-5% and -25%). This study is the first attempt to our knowledge to quantitate the degree and extent of narrowing in the major coronary arteries in patients with fatal AMI. Patients and Methods We studied 27 necropsy patients with transmural3 AMI. Clinical and cardiac morphologic observations in these AMI patients are summarized in table 1. In From the Pathology Branch, NHLBI, NIH, Bethesda, Maryland 225. Address for correspondence: William C. Roberts, M.D., Building IOA, Room 3E3, National Institutes of Health, Bethesda, Maryland 225. Received December 4, 1978; revision accepted September 24, Circulation 61, No. 4, of the 27 patients the ECG was either diagnostic or strongly suggestive of AMI. In all 27 patients, however, AMI was diagnosed clinically. Death appeared to result from cardiogenic shock unassociated with cardiac rupture in 13 patients, from uncontrollable arrhythmias or conduction disturbances in five, from rupture of the left ventricular free wall in two and of the ventricular septum in three, from acute pulmonary edema not associated with shock in two, from intracerebral hemorrhage while on heparin therapy in one and from uncertain cause in one. The interval from onset of symptoms compatible with AMI to death ranged from 12 hours to 38 days (average 8 days), and was less than 24 hours in three patients and over 2 days in two. Except for two of the three patients who died during the first 24 hours after the onset of AMI, the infarcts were easily visible on gross inspection. The acute infarcts were transmural in all patients, defined as involvement of some portion of the inner half and all or portions of the outer half of the left ventricular wall.' In 19 of the 25 patients who had easily discernible infarct margins, the infarcts were large, involving more than 5% of a longitudinal dimension (i.e., from base to apex of left ventricle or involvement of more than one-third of the circumference of at least two of the six or seven ventricular slices cut at 1-cm intervals from apex to base parallel to the posterior atrioventricular sulcus). In the other six patients, the infarcts were of moderate size, involving 2-35% of the circumference of at least two ventricular slices or less than half of the longitudinal dimension of the left ventricle. No patient had a small infarct. At least two histologic sections extending from epicardium to endocardium and at least 2 cm wide from each patient were examined and the presence of coagulative type myocardial necrosis was confirmed in each by histologic examination. Patients

2 CORONARY QUANTITATION IN AMI/Roberts and Jones 787 TABLE 1. Clinical Observations and Cardiac Morphologic Findings Autopsy data Age Historical data Ieart Increased Gross LV scars No. range Sex Past Chronic weight heart Wall thickness of (yrs) M F AP AMI CHF DM SH range (g) weight* < 32 > X Group pts (mean) n n n n n n n (mean) n n n AMI /26 6/26 5/26 8/24 13/ t (59) (78%) (22%) (42%) (23%o) (19%) (33%5) (57%) (463)$ (74%) (22%) (19%) Control (55) (68%) (32%) (37)t *Heart weight > 4 g in men and > 35 g in women. tposterior in four patients and anterior in one. tp <.5. Abbreviations: AP = angina pectoris; AMI = acute myocardial infarction; CHF = congestive heart failure; DM = diabetes mellitus; SH = systemic hypertension; LV = left ventricular. who had another cardiac disease in addition to coronary heart disease, for example, valvular heart disease or myocardial disease of noncoronary origin, were excluded, as were patients who had had a cardiac operation and those with unequivocal evidence of coronary embolism. Control subjects were similar in age and sex to the AMI patients and had the following characteristics: 1) death from a noncardiac condition, 2) absence of symptoms of myocardial ischemia or cardiac dysfunction during life, 3) absence of systemic hypertension (> 14/9 mm Hg), 4) absence of therapeutic mediastinal irradiation, 5) absence of cardiomegaly (> 4 g for men and > 35 g for women) at necropsy, and 6) absence of left ventricular necrosis and fibrosis. Twenty-two subjects fulfilled these criteria and were selected as controls: 12 died of carcinoma (breast in five, pancreas in three, prostate gland in one, colon in one, ovary in one and tongue in one), four of acute leukemia, three of lymphoma, and one each of heat stroke, gunshot wound and acute infection. The coronary arteries in all AMI patients and in the control subjects were studied in uniform fashion. The hearts were fixed for at least 1 day in formalin. The four major epicardial coronary arteries then were excised intact, x-rayed and fixed for at least 1 day more. After decalcification (if necessary), each artery was cut transversely to the longitudinal axis into approximately 5-mm segments and each segment was labeled sequentially from either its aortic ostium or from its origin from the left main. The number of segments examined in the AMI patients and control subjects is summarized in table 2. The segments were labeled, dehydrated with alcohol and xylene and embedded in paraffin, and two histologic sections from each paraffin block were cut and stained. The Movat stain was used on one histologic section, which was used for all determinations of luminal narrowing. The degrees of narrowing were based on histologic examination of each cross section magnified 25-5 times. The judgment regarding the degree of luminal narrowing of each 5-mm segment was based on the degree of luminal obliteration within the luminal circle bordered by the internal elastic membrane. The circle TAB3LE 2. Controls Maximl Narrowing of One or More Coronary Arteries by Atherosclerotic Plaques in Patients and Percent cross-sectional luminal narrowing Artery Total AMI C AMI C AMI C AMI C AMII C 1. R LAD a 3. R, LAD R, LC LAD, LC R, LAD, LC , LM*, LAD, LC Total (%) () () () (14) () (5) (1) (36) (1) (1) Values nlot in parentheses refer to number of patients. *Sections of LM not examined in one AMI patient and in two control subjects. Abbreviations: lr = right coronary artery; LM = left main coronary artery; LAD = left anterior descending coronary artery; LC = left circumflex coronary artery; AMI = acute myocardial infarction; C = control.

3 788 CIRCULATION VOL 61, No 4, APRIL 198 was visually subdivided into four equal quadrants, and the percentage of cross-sectional area luminal narrowing in each 5-mm segment was categorized as -25%, 26-5%, 51-75% or 76-1%. All histologic sections from all patients were examined by one author and the degrees of narrowing in the sections were "spotchecked" by the other. The intra- and interobserver errors were approximately 5% each. The degrees of narrowing in four of the 27 patients were checked by planimetry and a 95% agreement was found between the visual estimation of the percentage of crosssectional area narrowing by microscopy (magnified 25-5 times) and that found by planimetry. Results Among the 27 AMI patients, 17 major coronary arteries were examined (the left main was not examined in one patient); among the 22 controls, 86 major coronary arteries were examined (the left main was not examined in two subjects). All 27 AMI patients had at least two of the four major coronary arteries narrowed > 75% in cross-sectional area by atherosclerotic plaque, whereas only four of the 22 controls (18%) had two or more arteries narrowed to this degree (table 2). Of the 27 AMI patients, three (11%) had > 75% narrowing by atherosclerotic plaque of all four major coronary arteries; 14 (52%) had three arteries narrowed > 75% and 1 (37%) had two arteries narrowed > 75%. Thus, of the possible 18 major coronary arteries in the 27 AMI patients (actually only 17 arteries were examined), 74 (69%) were > 75% narrowed by atherosclerotic plaque (average 2.7 of four arteries per AMI patient). If the left main coronary artery was excluded, 71 (88%) of the other 81 major (right, left anterior descending and left circumflex) coronary arteries were > 75% narrowed by atherosclerotic plaque (average 2,6 of 3 coronary arteries per study patient). Of the eight control subjects with > 75% narrowing of one or more major coronary arteries, all four arteries were > 75% narrowed in one subject, two arteries were > 75% narrowed in three subjects, and only one artery was > 75% narrowed in four subjects. Thus, of the possible 88 major coronary arteries in the 22 control subjects (only 86 arteries were examined), 14 (16%) were narrowed > 75% in cross-sectional area by atherosclerotic plaque (average.6 of four coronary arteries per control). Excluding the left main coronary artery, 13 (2%) of the 66 other major (right, left anterior descending and left circumflex) coronary arteries were narrowed > 75% (average.6 of three coronary arteries per control). Fifteen (56%) of the 27 AMI patients had thrombus superimposed on atherosclerotic plaque in one major coronary artery, but only the amount of luminal narrowing resulting from atherosclerotic plaque was considered. No control subject had a coronary thrombus. The results of the quantitative analysis of the 5-mm coronary segments in both AMI patients and control subjects are summarized in table 3. Of the 143 segments examined in the 27 AMI patients, 484 (34%; controls 3%) were 1% narrowed in cross-sectional area by atherosclerotic plaque, 528 (38%; controls 25%) were 51-75% narrowed, 319 (23%; controls 44%) were 26-5% narrowed, and 72 (5%; controls 28%) were -25% narrowed. The mean percentage of 5-mm coronary segments narrowed was significantly different (p <.5) between the AMI patients and the control subjects at each of the four levels of narrowing, as were the mean percentages of 5-mm segments of left anterior descending, left circumflex and right coronary arteries (p <.5) (fig. 1). There were no significant differences between AMI patients and controls in the mean percentage of left main coronary artery segments at each of the four levels of narrowing. The mean percentage of 5-mm segments of right, left anterior descending and left circumflex coronary arteries at each of the four levels of narrowing was similar in the AMI patients, as well as in the control subjects (fig. 1). In contrast, the degree of left main coronary artery narrowing was less in both AMI patients and control subjects. TABLE 3. Quantitative Analysis of 5-mm Coronary Artery Segments Percent cross-sectional area luminal narrowing Total AMI C AMI C AMI C AMI C AMI C Artery n (%) n(%) n(%) n(%) n(%) n(%) n(%) n(%) n(%) n(%) LM* 11 6 IS (24) (19) (4) (62) (27) (13) (9) (6) (1) (1) LAD (3) (26) (24) (43) (37) (25) (36) (6) (1) (1) LC (1) (36) (26) (43) (33) (2) (31) (1) (1) (1) R (3) (27) (18) (45) (41) (27) (38) (1) (1) (1) Total (5) (28) (23) (44) (38) (25) (34) (3) (1) (1) *LM not examined in one AMI patient and in two control subjects. Abbreviations: LM = left main coronary artery; LAD = left anterior descending coronary artery; LC = left circumflex coronary artery; R = right coronary artery; AMI = acute myocardial infarction; C = control.

4 CORONARY QUANTITATION IN AMI/Roberts and Jones E 2. Distal 1/2 Et E.9 3 uaa cco o * A.,, Q 2 _ a., a E 1 k 1 E Right Left Anterior Left Circumflet Totals A E Percent Luminal Narrowing in Cross-sectional Area by Atherosclerotic Plaque Decending FIGURE 2. Mean percentage of 5-mm segments of the right, left anterior descending and left circumflex coronary arteries narrowed > 75% in cross-sectional area in proximal and the distal halves of each of the three arteries. The mean percent of 5-mm segments severely narrowed was similar in both proximal and distal halves of these three arteries. *, o ' C C3 Eu a. ( Discussion Thousands of autopsies during this century have demonstrated severe narrowing in one or more major epicardial coronary arteries of patients with coronary heart disease, but there has never been an attempt to quantitate the degree and extent of coronary luminal B Percent Luminal Narrowing in Cross-sectional Area by Atherosclerotic Plaque FIGURE 1. Mean percentage of5-mm segments of each of the four major coronary arteries narrowed to various degrees in the 27 patients with acute myocardial infarction (A) and in the 22 control subjects (B). The amount of luminal narrowing of the left anterior descending (LAD), left circumflex (LC) and right (R) coronary arteries is similar. The degree of severe narrowing of the left main (LM) coronary artery is considerably less than that of the other three arteries in the study patients. The mean percentage of 5-mm segments narrowed > 75% was similar in proximal and distal halves of the right, left anterior descending and left circumflex coronary arteries (fig. 2). The percentage of segments narrowed > 75% in cross-sectional area by atherosclerotic plaque in the first 2 cm of the left anterior descending and right coronary arteries also tended to be higher, but not significantly so, than the percentage narrowed > 75% in the remainder of these arteries (44 ± 6% vs 41 ± 5% and 4 ± 7% vs 38 ± 7%, respectively). The mean percentage of 5-mm segments narrowed > 75% in the first 2 cm of the left circumflex artery was virtually identical to that of more distal segments narrowed > 75% (3 ± 5% vs 3 ± 7%). The relationship of five clinical or morphologic parameters to the mean percentage of 5-mm coronary segments narrowed > 75% in the AMI patients is summarized in table 4. The men had more severe coronary narrowing than the women, and patients with healed infarcts had more severe narrowing than those without. TABLLE 4. Subgroups Comparison of Certain Clinical and Morphologic Mean (- SEM) of 3-mm coronary segments narrowed > 75% in cross-sectional area Parameter n (%) p Age (years) < >.5 > Sex Male <.5 Female Prior clinical CHD AP and/or AMI-+healed >.5 None Heart weight Increased* > O.Oa Normal Healed left ventricular transmural infarct Present <.5 Absent *Heart weight > 4 g in men and > 35 g in women. Abbreviations: AP = angina pectoris; AMI = acute myocardial infarction; Cl-ID = coronary heart disease.

5 79 CIRCULATION narrowing in these patients. The present study attempts to fill this void. In 34% of the entire lengths of the four major epicardial coronary arteries in AMI patients (controls 3%), the lumens were > 75% narrowed in cross-sectional area by atherosclerotic plaque and 38% had 5-75% narrowing. Thus, 72% of the lengths of the four major epicardial coronary arteries were > 5% narrowed in cross-sectional area by atherosclerotic plaque in the 27 AMI patients (controls 28%). (A 75% cross-sectional area narrowing is equivalent to a 5% diameter reduction on angiogram.4) Severe narrowing was widespread in the AMI patients, and some degree of narrowing was present in virtually every 5-mm segment of coronary artery. In AMI patients, 95% of the lengths of all four major coronary arteries were > 25% narrowed in crosssectional area, leaving only 5% of the coronary tree narrowed < 25% in cross-sectional area (vs 28% in controls), and not a single 5-mm segment was entirely normal. The degree of severe narrowing in the distal halves of the right, left anterior descending and left circumflex coronary arteries in the 27 AMI patients and in the controls, surprisingly, was just as great as in VOL 61, No 4, APRIL 198 the proximal halves of these arteries. Similar degrees of narrowing were observed in the left anterior descending, left circumflex and right coronary arteries, but the left main coronary artery was considerably less narrowed. Thus, coronary atherosclerosis among patients with fatal transmural AMI is a diffuse process, involving, for practical purposes, all segments of-all four major epicardial coronary arteries. References 1. Blumgart H, Schlesinger MJ, Davis D: Studies on the relation of the clinical manifestations of angina pectoris, coronary thrombosis, and myocardial infarction to the pathologic findings with particular reference to the significance of the collateral circulation. Am Heart J 19: 1, Roberts WC, Buja LM: The frequency and significance of coronary arterial thrombi and other observations in fatal acute myocardial infarction. A study of 17 necropsy patients. Am J Med 52: 425, Roberts WC, Gardin JM: Location of myocardial infarcts. A confusion of terms and definitions. Am J Cardiol 42: 868, Arnett EN, Isner JM, Redwood DR, Kent KM, Baker WP, Ackerstein H, Roberts WC: Coronary artery narrowing in coronary heart disease: comparison of cineangiographic and necropsy findings. Ann Intern Med 91: 35, 1979