Final Diagnosis -- Acute Myocardial Infarction




Early atherosclerosis is characterized by atheromatous plaques, which are 0.3-1.5 cm raised white-yellow fibro-fatty lesions composed of central soft yellow lipid-rich "atheroma" covered by a firm white fibrous cap.1 On microscopic examination, atheromas are primarily composed of amorphous eosinophilic debris, cholesterol clefts, fibrin and foam cells (lipid-laden macrophages and smooth muscle cells). Their fibrous caps are primarily composed of collagen, proliferating smooth muscle cells, macrophages, lymphocytes and foam cells. The thickening of the tunica intima causes neovascularization, ingrowth of capillaries through the tunica adventitia and tunica media into the tunica intima, creating abnormal vessels prone to rupture.

In the later stages of disease, atherosclerosis is complicated by calcification, ulceration, fissure, rupture, intraplaque hemorrhage or superimposed thrombosis.1 Calcification causes hardening and loss of adaptability of the arteries. Ulceration or rupture of an atherosclerotic plaque can release atheroemboli, which can cause sudden ischemia or infarction. Intraplaque hemorrhage due to rupture of one of the small abnormal neovascular channels can acutely expand a plaque, causing ischemia or infarction. An acute change in a plaque, which exposes subendothelial collagen and atheroma to platelets, causes adhesion, aggregation and activation of platelets. These platelets then release adenosine diphosphate (ADP), aggregating more platelets. The platelets also release thromboxane A2, serotonin and platelet factors 3 and 4, all of which predispose to coagulation and vasospasm. Release of tissue thromboplastin from an atheroma can activate the extrinsic pathway of coagulation.2 Thrombosis superimposed on atherosclerosis of a coronary artery is associated with transmural myocardial infarction, but it is a dynamic process, with only 60% of coronary thromboses showing total occlusion after 12-24 hours.

Myocardial infarction is irreversible necrosis of heart muscle from prolonged ischemia (>20 minutes). There are approximately 1.5 million myocardial infarctions/year in the US. Acute myocardial infarction is classically associated with substernal chest pain, frequently described by the patient as a "tightness", "squeezing" or "pressure". This chest pain radiates to the left arm, shoulder or neck in 80% of cases. The patients commonly also have sweating, nausea, vomiting, dyspnea, low-grade fever, an S4 gallop, an S3 gallop (if the heart is failing), a friction rub (if there is pericarditis), mitral regurgitation (if the left ventricle is severely dilated) and low-grade leukocytosis. Transmural infarction involves the full thickness of the heart wall and is associated with plaque rupture in approximately 75% of cases and is associated with occlusive thrombosis superimposed on complicated plaque with an acute change in approximately 90% of cases. Subendocardial infarction involves the inner portion of the heart, and is associated with the risk of subsequent extension. Subendocardial infarction is sometimes patchy or in the distribution of multiple coronary arteries (e.g. if due to shock).

The clinical diagnosis of acute myocardial infarction is based on the history, physical examination, EKG findings and laboratory blood test results. The classic EKG findings of ST segment elevation, followed by T wave inversion and Q waves, are associated with transmural infarction, while ST segment depression and T wave inversion alone are associated with subendocardial infarction. The laboratory diagnosis of myocardial infarction since the 1970s has been based on elevation of creatine phosphokinase (CPK), with an MB fraction >5% of the total CPK or a relative index >3 (if the MB fraction is measured in mass units instead of activity units). The elevation of CPK begins around 8 hours after the onset of infarction, peaks around 18 hours and ends around 48 hours. The late diagnosis of myocardial infarction can be based on elevation of lactate dehydrogenase (LDH), with an LDH-1 fraction >40% of the total LDH or LDH-1/LDH-2 ratio >1, because this peaks around 5 days.

Recently, the early and late diagnosis of acute myocardial infarction has been increasingly based on elevated serum levels of cardiac troponin. This elevation begins around 4 hours after the onset of infarction and lasts longer than LDH; this test has a sensitivity similar to CPK-MB fraction and better than LDH.3 For the diagnosis of acute myocardial infarction even earlier than detectable by troponin levels, myoglobin can be tested. Elevated levels of myoglobin can be detected around 2 hours after the onset of infarction, but this has only about 60% specificity for the heart. A new type of test being evaluated for the diagnosis of acute myocardial infarction is CPK MB isoform assay, which has a 96% sensitivity and 93% specificity for infarction within 6 hours of onset of chest pain.4 The combination of CPK MB and troponin testing can have even higher sensitivity and is increasingly employed for the purpose of "ruling out" myocardial infarction.5

One-third of patients with acute myocardial infarction die of it and the anatomic pathologic diagnosis of acute myocardial infarction at autopsy is based on gross and microscopic features. Acute myocardial infarction up to 12 hours old is associated with minimal gross pathologic findings, but over the period of 12-24 hours following infarction the myocardium manifests progressive pallor. During the period of 2-4 days following infarction, the dead muscle becomes yellow and softened, and 4-10 days following infarction it develops a hyperemic border and a softened yellow shrunken depressed center.

Thin wavy myocytes are the earliest light microscopic finding of acute myocardial infarction, visible as early as one hour following the onset of infarction.6 Coagulation necrosis, characterized by hypereosinophilia and nuclear pyknosis, followed by karyorrhexis, karyolysis, total loss of nuclei and loss of cytoplasmic cross-striations, is generally first visible in the period from 4-12 hours following infarction.2 Necrotic myocytes may retain their striations for a long time.7 Neutrophilic infiltration (acute inflammation), edema and hemorrhage are also first visible at 4-12 hours but generally closer to 12 hours. Acute inflammation is generally present in a narrow band of the periphery at 24 hours, in a broad band of the periphery at 48 hours and tends to be maximal around 72 hours, with extensive basophilic debris from degenerating neutrophils.7 Infiltration by macrophages, lymphocytes, eosinophils, fibroblasts and capillaries begins around the periphery at 3-10 days. Contraction band necrosis, characterized by hypereosinophilic transverse bands of precipitated myofibrils in dead myocytes is usually seen at the edge of an infarct or with reperfusion (e.g. with thrombolytic therapy).8 Reperfusion of an infarct is also associated with more hemorrhage, less acute inflammation, less limitation of the acute inflammation to the periphery in the first few days, reactive stromal cells, more macrophage infiltration earlier and a more patchy distribution of necrosis, especially around the periphery.8

Dating myocardial infarctions is an inexact science. The largest and most definitive study of the dating of myocardial infarctions by histopathologic criteria was based on the analysis of 192 cases in which the age of the infarct could be determined accurately.7 In this study, however, all of the 50 cases with death within the first day were lumped together and contrasted with the 23 cases with death within the second day and so on, so it provides data to support only dating an infarct within a particular day. Furthermore, there is data for only 4 cases with death within the sixth day, 3 cases for the seventh day and 1 case for the eighth day, so this study provides data to support only dating an infarct within a particular week, after the first week. The limitations of the scientific data and the biological variability of human disease leave ample room for the subjective experience and interpretation of the anatomic pathologist in the diagnosis and dating of acute myocardial infarction.


  1. Schoen FJ. Blood vessels. Chapter 11 in Robbins Pathologic Basis of Disease, fifth edition, 1994, Cotran RS, Kumar V, Schoen FJ, eds., Philadelphia, W.B.Saunders, pp.467-516.
  2. Schoen FJ. The heart. Chapter 12 in Robbins Pathologic Basis of Disease, fifth edition, 1994, Cotran RS, Kumar V, Schoen FJ, eds., Philadelphia, W.B.Saunders, pp.517-582.
  3. Brown CS, Bertolet D. Cardiac troponin: See ya later, CK. Chest 1997;111:2-4.
  4. Roberts R. Early diagnosis of myocardial infarction with MB CK isoforms. Clinica Chimica Acta 1998;272:33-45.
  5. Chung-Che C, Ip MPC, Hsu RM, Vrobel T. Evaluation of a proposed panel of cardiac markers for the diagnosis of acute myocardial infarction in patients with atraumatic chest pain. Arch Pathol Lab Med 1998;122:320-324.
  6. Bouchardy B, Majno G. Histopathology of early myocardial infarcts. Am J Pathol 1974;74:301-330.
  7. Fishbein MC, Maclean D, Maroko PR. The histopathologic evolution of myocardial infarction. Chest 1978;73:843-849.
  8. Reichenbach D, Cowan MJ. Healing of myocardial infarction with and without reperfusion. Chapter 5, in Cardiovascular Pathology, 1991, Virmani R, Atkinson JB, Fenoglio JJ, eds., Philadelphia, W.B.Saunders, pp. 86-98.

Contributed by Larry Nichols, MD


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