MASQUERADES OF MYOCARDIAL INFARCTION WILLIAM B. BEAN, M.D. GALVESTON
FOREWORD
At least once every second, seventy times a minute, four thousand times or more an hour, one hundred thousand times a day, three or four million times a month, sleeping or waking, active or quiet, heedful or heedless, summer, winter, spring, and fall, our heart spins out its irrevocable time as it beats its muffled marches to the grave. Our living, throbbing pulse, a meter of life, tells out the seconds, minutes, and hours which will never return. Who has not marveled as his heart's regular beat measures out its small punctuation marks on the ineluctible abscissa of time? It is characteristic of the human mind to oversimplify. This leads us to self-deception. Another mental habit tends to reduce the expenditure of intellectual energy by developing patterns which protect their owner f'rom the trauma of' actual thinking. The thoughtful know that all disease entities are useful fictions, and physicians deal only with a unique person and unique processes of illness. But without the ability to generalize our experience into patterns, every feature of life would be but another manifestation of unmanageable chaos. This is not the place to discuss civilized man's everchanging conception of disease nor our highly specialized fractional and partial diagnostic patterns. Myocardial infarction, "heart attack," is an important contemporary disease and serves as a useful model. Myocardial infarction and other aspects of coronary artery disease have a reasonably clear and well-known history. Our understanding is relatively recent. Study of the history of diseases not produced by trauma, parasite or germ discloses that many result from the acceleration of ordinary aging which, by altering structure, interferes with function. Such lesions in a vital coronary artery are life-threatening and may be life-ending. Disease has existed throughout the evolutionary development of man. In the past genetically determined handicaps have steadily eliminated themselves from the gene pool. New ones keep occurring. No matter how Institute for the Medical Humanities and Department of Internal Medicine. The University of Texas Medical Branch, Galveston, Texas 77550. 128
MASQUERADES OF MYOCARDIAL INFARCTION
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simple life may be, accidents and injuries are inevitable. Some diseases are byproducts of' civilization. Others are inherent in our biological f'abric. Our list of new diseases grows apace. Fifty years ago what did we call disseminated intravascular coagulopathy or today's autoimmune disorganizations? One has the nightmarish thought that the discovery of an abnormality creates a demand for it which nature arranges to meet. A clinical disease may not have been recognized, though widespread for a long time. It emerges from its subterranean caverns when some perceptive person recognizes and describes its signs, symptoms, lesions and malf'unctions. It may become popular overnight. Though its incidence and frequency are steady, the increase in diagnosis may reach epidemic proportions. As the information gets around, caution in diagnosis lets the incidence of diagnosis approach the incidence of' the disease. An early phase may see the frequency of' diagnosis surpass the actual frequency of the disease. Heart attack, myocardial inf'arction, occurred in the older people in every society that became well enough organized to permit a man or woman to last beyond the stage of physical utility as a warrior, hunter, planter or harvester. Nonetheless, the major developments of' our understanding of coronary thrombosis, myocardial infarction and angina pectoris have occurred during the lifetime of some of' our older members. The reason for the long delay in recognizing the distinction between angina pectoris and myocardial infarction or coronary thrombosis lies in the hands of pathologists and authorities like Sir Clifford Allbutt, who thought that all "heart" pain came from the aorta. Everyone assumed that a clot in a coronary artery was fatal, promptly fatal. The anterior descending branch of the left coronary artery came to be called "the artery of sudden death." The malapropism "coroner's thrombosis" vividly expresses what, until the end of the first decade in this century, was thought to be the inevitable and rapid end of' the life of anybody whose coronary artery was blocked by a clot. Hammer diagnosed coronary thrombosis-actually coronary embolism-in a living person nearly 100 years ago."2 In 1896 George Dock recorded three examples of myocardial infarction he recognized during lif'e.8 In 1910 Obrastzow and Strascheso diagnosed three more cases of coronary thrombosis before death. It remained for James Herrick, in two classical papers,14' 15 to demonstrate that coronary thrombosis need not be instantly fatal or fatal at all. In doing so he delineated "the clinical f'eatures of' sudden obstruction of the coronary arteries," using those very words as the title of his 1912 paper. This paper was presented to the
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Association of American Physicians. It got small attention and no discussion. Repetition of much the same material in 1919 evoked discussion and excitement. There are many reasons for this. Soon after the end of World War I, great and growing interest in the electrocardiogram arose. Many American internists and cardiologists in the U.S. Army in France had spent time in London observing or working with Thomas Lewis, renowned electrocardiographer. Lewis thought the electrocardiogram was valuable mainly in arrhythmias. Electrocardiograms obtained by Fred M. Smith after occluding coronary arteries in dogs showed characteristic changes. Later on, Herrick described no less than eighty conditions he had encountered in consultation with false-positive diagnoses of myocardial infarction. 16 They ranged from herpes zoster to pneumothorax, from pulmonary embolus to fractured rib. My brief note is to emphasize the missed diagnosis rather than the readily recognized classic example or the interloper, a disease which mimics with varying degrees of faithfulness the ordinary clinical manifestations of myocardial infarction. Thus, I focus on the false-negative, the diagnosis missed. My interest in the problem began nearly 40 years ago when I found a shockingly high proportion of myocardial infarcts at autopsy which had not been recognized during life.1' 2, 3 It is towards elucidating these errors that my thoughts are directed. Unsuspected myocardial infarction is disclosed to the wary or the unwary by an unexpected electrocardiogram or by finding a myocardial infarct at autopsy. Routine autopsy examination is eminently desirable to give just such a corrective. Without it, we can make the same kind of' error repeatedly and be blissfully unaware. Masquerades of myocardial infarction occur when there is disproportionate prominence of a regular sign or symptom and when usual clinical clues are absent. The most commonly encountered masquerades of' myocardial infarction are given in rank order of frequency-the rarer ones, somewhat at random. 1. Congestive heart failure either beginning de novo or as a worsening of established failure is the commonest masquerade of' myocardial infarction. Differentiating a sense of tightening in the chest with trouble breathing, from pain, is puzzling. It is hardly surprising that a damaged heart should fail in its function. Yet, for many years, it was taught that angina and dyspnea were rare together, if not indeed incompatible. The same went for the myocardial infarction and severe congestive f'ailure. Angina is a pre-eminent example of a disease in which the history is our major, sometimes our only, diagnostic ally. Severe attacks of dyspnea on exertion or at rest, nocturnal orthopnea often with peripheral edema, in a person who has no complaint of pain in the chest may be the only
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indication that a myocardial infarction has occurred. An electrocardiogram or a surprising autopsy finding reveal the true nature of the underlying mischief. 2. 6, 11, 17, 27 2. The second hiding place for myocardial infarction is in patients who have classical angina pectoris without any particularly severe or prolonged attack. A large myocardial infarction may occur in a patient who is conscious of no variation upon the ordinary recurring clinical theme of his old friend, angina pectoris. Macroscopic infarction may represent the coalescence of multiple miliary infarcts in the territory supplied by a severely sclerotic coronary artery.6' 32, 33 3. Patients with acute myocardial infarction may have just about any arrythmia. Some persons with acute myocardial infarction have no other sign or symptom except irregularity of the heart. It may or may not be described as palpitation, fluttering of the heart, or a heart racing. Careful questioning fails to reveal any pain.6 3 4. Atypical locus of pain, or pain only in the area to which it is usually referred, is another masquerade. I well remember a patient I saw, as an undergraduate student, who was very 'sick but complained of nothing but "a misery" in her elbow. She got an electrocardiogram which was ordered for another patient. It disclosed classical signs of acute myocardial infarction. She could never be persuaded that she had any pain in her chest or anywhere but in her elbow. The dean of a medical school I used to be connectdb 'with liked to play golf. He had pains in his left shouldeir and upper Arm; Pis neurosurgeon partner gave him a learned outline of what he had done to his brachial plexus. Peripheral neuritis was what everyone had diagnosed. It was not until he developed a femoral embolus and, later, a remarkable infarct of the soft palate, that myocardial infarction was recognized.6 5. Central nervous system manifestations include an important though not large group of masquerades. A person may have stroke, classical in all its features, with hemiparesis, hemiplegia, convulsion or bizarre mental aberrations with varying degrees of confusion, mania or delirium. Such patients often have no embolus, thrombus or cerebral hemorrhage. Instead, severely sclerotic vessels supply certain areas of the brain. When myocardial infarction occurs, cardiac output is reduced. The patient may approach shock. Areas in the brain with narrow vessels are selectively damaged, since, under optimal circumstances, the region is getting just enough blood. Though we think of embolus from a mural thrombus, or thrombosis in situ when stroke follows days after myocardial infarction, complete clinical patterns of the cerebrovascular calamity may occur without any acute change in the blood vessels of the brain. Also, many strokes associated with or following soon after myocardial
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infarction come from local thrombosis or hemorrhage rather than from cerebral embolism.2' 3, 4, 5, 6 6. Apprehension and nervousness. An occasional patient who described no pain whatever with acute myocardial infarction may present clinically with nothing but an overwhelming sense of apprehension, nervousness and a weird all pervading anxiety. This may merge into a condition called angor animi, which is described by its victims as the feeling that they are actually dying. This is not the rational conviction such as a physician with myocardial infarction might have that he might die. Nor is it the desire for death in a victim of overwhelming pain. Again, it is not the fear of' death which may be rational or totally unrealistic. Precisely the same sensation of being in the process of dying has been described in patients with tumors of the medulla oblongata. The kind of patient I describe has more terror than anxiety, a consuming, haunting nervousness that is as hard to understand as it is to treat.2 6, 31 7. Sudden mania or psychosis, either de novo or as recurrence, may herald an acute myocardial infarction. Whether such events represent an overwhelming stimulus from pain or whether the person's control of himself' is lost by circulatory or reflex troubles, we do not know. But such events occur and differ from the so-called cardiac delirium associated with congestive failure sometimes caused by digitalis intoxication.6' I 8. Syncope is not so rare in angina. Parry, the earliest describer of thyrotoxicosis, wrote a book on it, called Syncope Anginosa.25 A faint, rather than a fit, may usher in acute myocardial infarction. Should the patient remain unconscious for a long time or move from the syncopal attack into shock, the history might be inadequate. Some patients who f'aint with myocardial infarction recover from the faint and have felt no pain at all. Stupor or unconsciousness from any cause makes the diagnosis diff'icult. This is seen particularly in institutions for the psychotic where something like prefrontal lobotomy robs pain of its usual significance. The patient reacts inappropriately if at all. I have not, myself, been able to use with any predictive value Libman's method of' detecting insensitivity to pain. He believed that dyspnea, for example, was a pain equivalent in those whose response to painful stimuli was blunted. 9. Overwhelming weakness without anxiety, fright or fear, sometimes attended by considerable sweating may occur with very little else suggesting shock. Presumably this sort of occurrence would be found in somebody whose sensitivity to pain was weak or undeveloped.6 10. Our medical forebears often called myocardial infarction acute indigestion. We are all aware of' the difficulty sometimes encountered in distinguishing between a symptomatic hiatal hernia and angina. Overabundant wining and dining, the crushing pain in the epigastrium,
MASQUERADES OF MYOCARDIAL INFARCTION
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vomiting, sweating, and collapse do, indeed, have features suggesting the alimentary canal rather than the heart as the source of trouble. Flatulence, pressure, belching, a sense of fullness, constriction, compressing or crushing pain in dyspnea may characterize the clinical pattern. 11. A peripheral embolism may be the signal of myocardial infarction, just as it rarely may lead to the diagnosis of cardiac myxoma. Another clue, particularly in post-operative patients, is the sudden appearance of coldness in the foot, a clammy, pulseless extremity. Remember that post-operative myocardial infarction is about fifty times as common in persons who have had an earlier infarct; and it is increasingly frequent with advancing age. 6,1013,19 12. Neurosis, or indeed, cardiac neurosis is in itself no protection against the development of myocardial infarct. A complaining patient has pulled out all the stops regularly. He has spent his capacity to get attention. Nothing new he can say could be as bad as the things he has said in the past. His cry of "wolf! wolf!" no longer alerts the shepherd. The infarct is missed. 13. The most frustrating examples of myocardial inf'arcts are totally silent ones in people who have paced out their uneventful existence in regular daily activities. They have had good medical attention but no signs or symptoms. They return for another annual medical review. The routine electrocardiogram reveals a large infarct. Whether this represents the coalescence of a multitude of miliary infarcts from twig thrombosis, no one of which passed through the threshold of perception or whether it happened in an instant but for unknown reasons evoked no sign or symptom, we cannot say. In the game of clinical charades nature plays us many tricks. There are reports of what was really myocardial infarction which seemed to be (14) congestive cardiomyopathy,27 (15) dissecting aneurysm in a patient with carotid disease and subclavian steal where myocardial infarction was responsible,34 and (16) a bi-geminal rhythm which recurred only in recumbency.29 A further search would, I am sure, reveal others. Many masquerades are those produced by other diseases or some problem requiring extensive operation and long anesthesia. Usually upper abdominal or thoracic operations are prominent causes. Obviously, where senility is advanced, where the sensorium is clouded, where the history is non-existent or vague, one has to remember that a mysterious turn for the worse may signify myocardial infarction. SUMMARY
I summarize these observations in Figure 1. It represents every person in a hypothetical population who has myocardial infarction. A large but unknown number, some believe almost half, never get help. Mobile
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WILLIAM B. BEAN
INCIDENCE AND DIAGNOSIS OF MYOCARDIAL INFARCTION
100
ACTUAL
INCIDENCE .4OF C
-
i
C)~ ~ 9V~
75
ER OF CLINICAL 50 IGNORANCE NO DIAGNOSIS a. W
-x
td
0-
-TIME-
VICTIMS DYING WITHOUT MEDICAL CARE
FIG. 1. Time and Tides in the Diagnosis of Myocardial Infarction.
coronary care units are reducing this group, but so far only a little. When the diagnosis is not understood the disease is not recognized. Then come discovery and popularization. Hereafter masquerades hide some cases and the diagnosis is missed. Somewhere fairly early the diagnostic fad leads to false positive diagnosis. As new techniques are discovered, perfected and mastered, false positive errors and masquerades leading to oversights diminish but still exist. All the skill and technical virtuosity in the world will not be applied if we do not think of the disease. When we think of it, even obscure cases may be resolved easily. CONCLUSIONS
The history of our understanding of myocardial infarction ranges over the epoch of ignorance, the discovery of clinical signs and symptoms, a period of overdiagnosis, and our present stage of diagnostic accuracy marred a bit by sins of omission and commission. Awareness of various masquerades should diminish the frequency of missed diagnosis. This will lead to better care of and for the patient. REFERENCES 1. BEAN, W. B.: Infarction of the Heart: A Morphological and Clinical Appraisal of Three Hundred Cases. Part I. Predisposing and Precipitating Conditions. Am. Heart J., 14: 684, 1937. 2. BEAN, W. B.: Infarction of the Heart: A Morphological and Clinical Appraisal of Three Hundred Cases. Part II. Symptomatology of Acute Attack. Ann. Intern. Med., 11: 2086, 1938.
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3. BEAN, W. B.: Infarction of the Heart: A Morphological and Clinical Appraisal of Three Hundred Cases. Part III. Clinical Course and Morphological Findings. Ann. Intern. Med., 12: 71, 1938. 4. BEAN, W. B. AND READ, C. T.: Central Nervous System Manifestations in Acute Myocardial Infarction. Am. Heart J., 23: 362, 1942. 5. BEAN, W. B., FLAMM, G. W., AND SAPADIN, A.: Hemiplegia Attending Acute Myocardial Infarction. Am. J. Med., 7: 765, 1949. 6. BEAN, W. B.: Clinical Masquerades of Acute Myocardial Infarction. J. Iowa Med. Soc., 52: 781, 1962. 7. DAVIS, N. S., III.: Coronary Thrombosis Without Pain: Its Incidence and Pathology. JAMA, p. 1806, 1932. 8. DOCK, G.: Notes on the Coronary Arteries. The Inland Press, Ann Arbor, Michigan. 1896. 9. FAGIN, D. I. AND CHAPNICK, H. A.: Clinical Patterns of Myocardial Infarction in Ambulant Patients. Ann. Intern. Med., 32: 243, 1950. 10. FRANK, N.: Cold Foot-Postoperative Sign of Silent Myocardial Infarction. JAMA, 170: 1147, 1959. 11. GOULD, W. E. AND CAWLEY, L. P.: Unsuspected Healed Myocardial Infarction in Patients Dying in a General Hospital. AMA Arch. Intern. Med., 101: 524, 1958. 12. HAMMER, A.: A Case of Thrombotic Occlusion of One of the Coronary Arteries of the Heart. Wien. med. Wchnschr., 28: 102, 1878. 13. HARRISON, C. E. JR., SPIrFELL, J. A., JR., AND MANKIN, H. T.: Sudden Arterial Occlusion: A Clue to Silent Myocardial Infarction. Proceedings of the Staff Meetings of The Mayo Clinic, 37: 293, 1962. 14. HERRICK, J. B.: Clinical Features of Sudden Obstruction of the Coronary Arteries. JAMA, 49: 2015, 1912. 15. HERRICK, J. B.: Thrombosis of' the Coronary Arteries. JAMA, 72: 387, 1919. 16. HERRICK, J. B.: On Mistaking Other Diseases for Acute Coronary Thrombosis. Ann. Intern. Med., 11: 2079, 1938. 17. HILL, H. N.: Masked Myocardial Infarction. Am. J. Med. Sci., 219: 394, 1950. 18. JARVINEN, A. J.: Physical Activity of Patients After the Onset of Acute Cardiac Infarction. Brit. Med. J.. 1: 922, 1960. 19. JOHNSON, W. J., ACHOR, R. W. P., BURCHELL, H. B., et al: Unrecognized Myocardial Infarction: A Clinicopathologic Study. AMA Arch. Intern. Med., 103: 253, 1959. 20. LADuE, J. S. AND Panel: Occult Myocardial Infarction: Dis. Chest, 43: 120, 1963. 21. MARCHAND, W. E.: Occurrence of Painless Myocardial Infarction in Psychotic Patients. New Eng. J. Med., 253: 51, 1955. 22. MARGOLIS, J. R., KANNEL, W. B., FEINLEIB, M., et al.: Clinical Features of Unrecognized Myocardial Infarction-Silent and Symptomatic: Eighteen Year Follow-Up: The Framingham Study. Am. J. Cardiol., 32: 1, 1973. 23. MASTER, A. M. AND GELLER, A. J.: Magnitude of Silent Coronary Disease. New York State J. Med., 64: 2865, 1964. 24. OBERMAN, A., OSTRANDER, L. D., JR., AND EPSTEIN, F. H.: Myocardial Infarction and Individual Characteristics. AMA Arch. Intern. Med., 120: 661, 1967. 25. PARRY, C. H.: An Inquiry into the Symptoms and Causes of the Syncope Anginosa commonly called Angina Pectoris; illustrated by Dissections, Bath and London, R. Crutwell, 1799. 26. PATON, B. C.: The Accuracy of Diagnosis of Myocardial Infarction, a Clinicopathologic Study. Am. J. Med., 23: 761, 1957. 27. RAFrERY, E. B., BANKS, D. C., AND ORAM, S.: Occlusive Disease of the Coronary Arteries Presenting as Primary Congestive Cardiomyopathy. Lancet, 2: 1147, 1962.
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28. ROSENMAN, R. H., FRIEDMAN, M., JENKINS, C. D., et al.: Recurring and Fatal Myocardial Infarction in the Western Collaborative Group Study-Clinically Unrecognized Myocardial Infarction in the Western Collaborative Group Study. Am. J. Cardiol., 19: 771, 1967. 29. RUBLER, H. B. AND DIEFENBACH, W. C. L.: An Unusual Complication of Myocardial Infarction: Persistent Bigeminy Only in the Recumbent Position. Am. J. Cardiol., 6: 989, 1960. 30. RYLE, J.: The Study of Symptoms, In The Natural History of Disease, 2nd Ed., Published by the Oxford University Press, p. 69, 1949. 31. RYLE, J.: Angina Pectoris and Allied Seizures, In The Natural History of Disease, 2nd Ed., Published by the Oxford University Press, p. 323, 1949. 32. STEIN, I.: Myocardial Infarction Simulating Angina Pectoris. Am. Heart J., 40: 325, 1950. 33. STEIN, I. AND WEINSTEIN, J.: Unusual Causes of Angina Pectoris. American Practitioner and Digest of Treatment, 6: 64, 1955. 34. STEINKE, W. E. AND CURRY, J. H.: "Subclavian Steal" Syndrome in Acute Myocardial Infarction Masquerading as Dissection Aneurysm of the Aorta. Am. J. Cardiol., 22: 436, 1968. 35. STOKES, J.. III AND DAWBER, T. R.: The "Silent Coronary": The Frequency and Clinical Characteristics of Unrecognized Myocardial Infarction in the Framingham Study. Ann. Intern. Med., 50: 1359, 1959. 36. TARHAN, S., MOFFIrr, E. A., TAYLOR, W. F., et al.: Myocardial Infarction After General Anesthesia. JAMA, 220: 1451, 1972. 37. WAGNER, M. L. AND ARBEIT, S. R.: Myocardial Infarction Unmasked by an Unusual Arrhythmia. Am. J. Cardiol., 13: 81, 1964. 38. WARNER, H. R.: "Painless" Myocardial Infarction. Minnesota Medicine, p. 49, 1951.
DISCUSSION DR. RICHARD S. Ross (Baltimore): The methods for establishing the diagnosis of myocardial infarction, and indeed the definition of the disease, changes with improved techniques. First only the electrocardiogram was available and then enzyme studies added a degree of sensitivity. Most recently isotope studies have improved the precision still further by making it possible to detect areas of infarcted and even ischemic tissue. Isotopes like Thallium go into normal myocardium and give a negative image of the infarct. Other isotopes are concentrated in the injured tissue and give a positive image on a gamma camera study. It is possible to detect infarction in the absence of either electrocardiographic or enzyme changes. As diagnostic techniques improve the number of "masqueraders" will be decreased. DR. FRANCIS C. WOOD (Philadelphia): There is one omission from almost all histories of early reports of the diagnosis of Coronary Occlussion: In 1884, E. Leyden, the director of the first Medical Clinic in Berlin, published an article in the Zeitschrift fur Klinische Medecine, Vol. 7, pages 459-486, and 539-580 entitled "Ueber die selerose der Coronararterin und die davon abhangigen Krankheitszustande." On page 553 he describes "Case 9:"-The patient had a severe attack of pain in the chest, then got partly well, and some time later, died of heart failure. Leyden says "Dieser erste anfall Entsprickt der Thrombose der Kranzarterien." This was 26 years before Herrick's first paper. Leyden's article seems to have escaped the attention of Coronary historians. I found this reference years ago when reading in Nothnagel's System of Medicine. DR. BEAN: Fran, thank you very much. Interestingly enough, Nothnagel, whom you mentioned, described what he called angina vasomotoria, an atypical form of angina which
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he thought was related to some kind of autonomic vasomotor storm. It is true that von Leyden, whom you cite for having diagnosed the disease clinically, was a pathologist. At least many of his papers were published in pathology journals, which probably did not impress clinicians and thus did not get within the ken of those interested in clinical matters. In the patient you approved for prostatic surgery who had had an infarct, it is important to remember that post-operative myocardial infarction is about fifty times commoner in those with a previous infarct than those without. DR. JEREMIAH A. BARONDESS (New York): This is, I understand, a little bit off the main point of your paper, but I am a little disturbed about that nipple.* I wonder whether that was just a bizarre type of graft or is there something about the milk line in lower animals that was either lacking in my education or that I forgot. Is there any lower species which the milk line extends cephalad to this degree? DR. BEAN: The milk line in mammals, as you know, runs along the two sides of the abdomen, up the chest, and occasionally up the shoulder. The example of ectopic or displaced nipple we found seems to be unique. It may indeed represent an embryological transfer. And it was a nipple as indicated by the fact that it underwent changes during the menstrual cycle and became increasingly vascular during pregnancy. We suggested its removal but she would not hear of it. I conclude these weighty matters by telling you that William Osler, once on making rounds, observed a woman who had several extra mammary glands, not just nipples, six all told. She was nursing twins and when he inquired of her, she said that she had three other children. He said, "Oh what a pity, with the table set for six." * Dr. Bean had shown two slides, the first of which appeared to be a normal breast; the second picture demonstrating that it was an ectopic nipple on the chin. He had studied this woman with intense interest in 1940 when she was admitted to the Cincinnati General Hospital with pneumonia. She was astonished that the doctors rarely listened to her chest but were always looking at her chin.
FOREWORD
At least once every second, seventy times a minute, four thousand times or more an hour, one hundred thousand times a day, three or four million times a month, sleeping or waking, active or quiet, heedful or heedless, summer, winter, spring, and fall, our heart spins out its irrevocable time as it beats its muffled marches to the grave. Our living, throbbing pulse, a meter of life, tells out the seconds, minutes, and hours which will never return. Who has not marveled as his heart's regular beat measures out its small punctuation marks on the ineluctible abscissa of time? It is characteristic of the human mind to oversimplify. This leads us to self-deception. Another mental habit tends to reduce the expenditure of intellectual energy by developing patterns which protect their owner f'rom the trauma of' actual thinking. The thoughtful know that all disease entities are useful fictions, and physicians deal only with a unique person and unique processes of illness. But without the ability to generalize our experience into patterns, every feature of life would be but another manifestation of unmanageable chaos. This is not the place to discuss civilized man's everchanging conception of disease nor our highly specialized fractional and partial diagnostic patterns. Myocardial infarction, "heart attack," is an important contemporary disease and serves as a useful model. Myocardial infarction and other aspects of coronary artery disease have a reasonably clear and well-known history. Our understanding is relatively recent. Study of the history of diseases not produced by trauma, parasite or germ discloses that many result from the acceleration of ordinary aging which, by altering structure, interferes with function. Such lesions in a vital coronary artery are life-threatening and may be life-ending. Disease has existed throughout the evolutionary development of man. In the past genetically determined handicaps have steadily eliminated themselves from the gene pool. New ones keep occurring. No matter how Institute for the Medical Humanities and Department of Internal Medicine. The University of Texas Medical Branch, Galveston, Texas 77550. 128
MASQUERADES OF MYOCARDIAL INFARCTION
129
simple life may be, accidents and injuries are inevitable. Some diseases are byproducts of' civilization. Others are inherent in our biological f'abric. Our list of new diseases grows apace. Fifty years ago what did we call disseminated intravascular coagulopathy or today's autoimmune disorganizations? One has the nightmarish thought that the discovery of an abnormality creates a demand for it which nature arranges to meet. A clinical disease may not have been recognized, though widespread for a long time. It emerges from its subterranean caverns when some perceptive person recognizes and describes its signs, symptoms, lesions and malf'unctions. It may become popular overnight. Though its incidence and frequency are steady, the increase in diagnosis may reach epidemic proportions. As the information gets around, caution in diagnosis lets the incidence of diagnosis approach the incidence of' the disease. An early phase may see the frequency of' diagnosis surpass the actual frequency of the disease. Heart attack, myocardial inf'arction, occurred in the older people in every society that became well enough organized to permit a man or woman to last beyond the stage of physical utility as a warrior, hunter, planter or harvester. Nonetheless, the major developments of' our understanding of coronary thrombosis, myocardial infarction and angina pectoris have occurred during the lifetime of some of' our older members. The reason for the long delay in recognizing the distinction between angina pectoris and myocardial infarction or coronary thrombosis lies in the hands of pathologists and authorities like Sir Clifford Allbutt, who thought that all "heart" pain came from the aorta. Everyone assumed that a clot in a coronary artery was fatal, promptly fatal. The anterior descending branch of the left coronary artery came to be called "the artery of sudden death." The malapropism "coroner's thrombosis" vividly expresses what, until the end of the first decade in this century, was thought to be the inevitable and rapid end of' the life of anybody whose coronary artery was blocked by a clot. Hammer diagnosed coronary thrombosis-actually coronary embolism-in a living person nearly 100 years ago."2 In 1896 George Dock recorded three examples of myocardial infarction he recognized during lif'e.8 In 1910 Obrastzow and Strascheso diagnosed three more cases of coronary thrombosis before death. It remained for James Herrick, in two classical papers,14' 15 to demonstrate that coronary thrombosis need not be instantly fatal or fatal at all. In doing so he delineated "the clinical f'eatures of' sudden obstruction of the coronary arteries," using those very words as the title of his 1912 paper. This paper was presented to the
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Association of American Physicians. It got small attention and no discussion. Repetition of much the same material in 1919 evoked discussion and excitement. There are many reasons for this. Soon after the end of World War I, great and growing interest in the electrocardiogram arose. Many American internists and cardiologists in the U.S. Army in France had spent time in London observing or working with Thomas Lewis, renowned electrocardiographer. Lewis thought the electrocardiogram was valuable mainly in arrhythmias. Electrocardiograms obtained by Fred M. Smith after occluding coronary arteries in dogs showed characteristic changes. Later on, Herrick described no less than eighty conditions he had encountered in consultation with false-positive diagnoses of myocardial infarction. 16 They ranged from herpes zoster to pneumothorax, from pulmonary embolus to fractured rib. My brief note is to emphasize the missed diagnosis rather than the readily recognized classic example or the interloper, a disease which mimics with varying degrees of faithfulness the ordinary clinical manifestations of myocardial infarction. Thus, I focus on the false-negative, the diagnosis missed. My interest in the problem began nearly 40 years ago when I found a shockingly high proportion of myocardial infarcts at autopsy which had not been recognized during life.1' 2, 3 It is towards elucidating these errors that my thoughts are directed. Unsuspected myocardial infarction is disclosed to the wary or the unwary by an unexpected electrocardiogram or by finding a myocardial infarct at autopsy. Routine autopsy examination is eminently desirable to give just such a corrective. Without it, we can make the same kind of' error repeatedly and be blissfully unaware. Masquerades of myocardial infarction occur when there is disproportionate prominence of a regular sign or symptom and when usual clinical clues are absent. The most commonly encountered masquerades of' myocardial infarction are given in rank order of frequency-the rarer ones, somewhat at random. 1. Congestive heart failure either beginning de novo or as a worsening of established failure is the commonest masquerade of' myocardial infarction. Differentiating a sense of tightening in the chest with trouble breathing, from pain, is puzzling. It is hardly surprising that a damaged heart should fail in its function. Yet, for many years, it was taught that angina and dyspnea were rare together, if not indeed incompatible. The same went for the myocardial infarction and severe congestive f'ailure. Angina is a pre-eminent example of a disease in which the history is our major, sometimes our only, diagnostic ally. Severe attacks of dyspnea on exertion or at rest, nocturnal orthopnea often with peripheral edema, in a person who has no complaint of pain in the chest may be the only
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indication that a myocardial infarction has occurred. An electrocardiogram or a surprising autopsy finding reveal the true nature of the underlying mischief. 2. 6, 11, 17, 27 2. The second hiding place for myocardial infarction is in patients who have classical angina pectoris without any particularly severe or prolonged attack. A large myocardial infarction may occur in a patient who is conscious of no variation upon the ordinary recurring clinical theme of his old friend, angina pectoris. Macroscopic infarction may represent the coalescence of multiple miliary infarcts in the territory supplied by a severely sclerotic coronary artery.6' 32, 33 3. Patients with acute myocardial infarction may have just about any arrythmia. Some persons with acute myocardial infarction have no other sign or symptom except irregularity of the heart. It may or may not be described as palpitation, fluttering of the heart, or a heart racing. Careful questioning fails to reveal any pain.6 3 4. Atypical locus of pain, or pain only in the area to which it is usually referred, is another masquerade. I well remember a patient I saw, as an undergraduate student, who was very 'sick but complained of nothing but "a misery" in her elbow. She got an electrocardiogram which was ordered for another patient. It disclosed classical signs of acute myocardial infarction. She could never be persuaded that she had any pain in her chest or anywhere but in her elbow. The dean of a medical school I used to be connectdb 'with liked to play golf. He had pains in his left shouldeir and upper Arm; Pis neurosurgeon partner gave him a learned outline of what he had done to his brachial plexus. Peripheral neuritis was what everyone had diagnosed. It was not until he developed a femoral embolus and, later, a remarkable infarct of the soft palate, that myocardial infarction was recognized.6 5. Central nervous system manifestations include an important though not large group of masquerades. A person may have stroke, classical in all its features, with hemiparesis, hemiplegia, convulsion or bizarre mental aberrations with varying degrees of confusion, mania or delirium. Such patients often have no embolus, thrombus or cerebral hemorrhage. Instead, severely sclerotic vessels supply certain areas of the brain. When myocardial infarction occurs, cardiac output is reduced. The patient may approach shock. Areas in the brain with narrow vessels are selectively damaged, since, under optimal circumstances, the region is getting just enough blood. Though we think of embolus from a mural thrombus, or thrombosis in situ when stroke follows days after myocardial infarction, complete clinical patterns of the cerebrovascular calamity may occur without any acute change in the blood vessels of the brain. Also, many strokes associated with or following soon after myocardial
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infarction come from local thrombosis or hemorrhage rather than from cerebral embolism.2' 3, 4, 5, 6 6. Apprehension and nervousness. An occasional patient who described no pain whatever with acute myocardial infarction may present clinically with nothing but an overwhelming sense of apprehension, nervousness and a weird all pervading anxiety. This may merge into a condition called angor animi, which is described by its victims as the feeling that they are actually dying. This is not the rational conviction such as a physician with myocardial infarction might have that he might die. Nor is it the desire for death in a victim of overwhelming pain. Again, it is not the fear of' death which may be rational or totally unrealistic. Precisely the same sensation of being in the process of dying has been described in patients with tumors of the medulla oblongata. The kind of patient I describe has more terror than anxiety, a consuming, haunting nervousness that is as hard to understand as it is to treat.2 6, 31 7. Sudden mania or psychosis, either de novo or as recurrence, may herald an acute myocardial infarction. Whether such events represent an overwhelming stimulus from pain or whether the person's control of himself' is lost by circulatory or reflex troubles, we do not know. But such events occur and differ from the so-called cardiac delirium associated with congestive failure sometimes caused by digitalis intoxication.6' I 8. Syncope is not so rare in angina. Parry, the earliest describer of thyrotoxicosis, wrote a book on it, called Syncope Anginosa.25 A faint, rather than a fit, may usher in acute myocardial infarction. Should the patient remain unconscious for a long time or move from the syncopal attack into shock, the history might be inadequate. Some patients who f'aint with myocardial infarction recover from the faint and have felt no pain at all. Stupor or unconsciousness from any cause makes the diagnosis diff'icult. This is seen particularly in institutions for the psychotic where something like prefrontal lobotomy robs pain of its usual significance. The patient reacts inappropriately if at all. I have not, myself, been able to use with any predictive value Libman's method of' detecting insensitivity to pain. He believed that dyspnea, for example, was a pain equivalent in those whose response to painful stimuli was blunted. 9. Overwhelming weakness without anxiety, fright or fear, sometimes attended by considerable sweating may occur with very little else suggesting shock. Presumably this sort of occurrence would be found in somebody whose sensitivity to pain was weak or undeveloped.6 10. Our medical forebears often called myocardial infarction acute indigestion. We are all aware of' the difficulty sometimes encountered in distinguishing between a symptomatic hiatal hernia and angina. Overabundant wining and dining, the crushing pain in the epigastrium,
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vomiting, sweating, and collapse do, indeed, have features suggesting the alimentary canal rather than the heart as the source of trouble. Flatulence, pressure, belching, a sense of fullness, constriction, compressing or crushing pain in dyspnea may characterize the clinical pattern. 11. A peripheral embolism may be the signal of myocardial infarction, just as it rarely may lead to the diagnosis of cardiac myxoma. Another clue, particularly in post-operative patients, is the sudden appearance of coldness in the foot, a clammy, pulseless extremity. Remember that post-operative myocardial infarction is about fifty times as common in persons who have had an earlier infarct; and it is increasingly frequent with advancing age. 6,1013,19 12. Neurosis, or indeed, cardiac neurosis is in itself no protection against the development of myocardial infarct. A complaining patient has pulled out all the stops regularly. He has spent his capacity to get attention. Nothing new he can say could be as bad as the things he has said in the past. His cry of "wolf! wolf!" no longer alerts the shepherd. The infarct is missed. 13. The most frustrating examples of myocardial inf'arcts are totally silent ones in people who have paced out their uneventful existence in regular daily activities. They have had good medical attention but no signs or symptoms. They return for another annual medical review. The routine electrocardiogram reveals a large infarct. Whether this represents the coalescence of a multitude of miliary infarcts from twig thrombosis, no one of which passed through the threshold of perception or whether it happened in an instant but for unknown reasons evoked no sign or symptom, we cannot say. In the game of clinical charades nature plays us many tricks. There are reports of what was really myocardial infarction which seemed to be (14) congestive cardiomyopathy,27 (15) dissecting aneurysm in a patient with carotid disease and subclavian steal where myocardial infarction was responsible,34 and (16) a bi-geminal rhythm which recurred only in recumbency.29 A further search would, I am sure, reveal others. Many masquerades are those produced by other diseases or some problem requiring extensive operation and long anesthesia. Usually upper abdominal or thoracic operations are prominent causes. Obviously, where senility is advanced, where the sensorium is clouded, where the history is non-existent or vague, one has to remember that a mysterious turn for the worse may signify myocardial infarction. SUMMARY
I summarize these observations in Figure 1. It represents every person in a hypothetical population who has myocardial infarction. A large but unknown number, some believe almost half, never get help. Mobile
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INCIDENCE AND DIAGNOSIS OF MYOCARDIAL INFARCTION
100
ACTUAL
INCIDENCE .4OF C
-
i
C)~ ~ 9V~
75
ER OF CLINICAL 50 IGNORANCE NO DIAGNOSIS a. W
-x
td
0-
-TIME-
VICTIMS DYING WITHOUT MEDICAL CARE
FIG. 1. Time and Tides in the Diagnosis of Myocardial Infarction.
coronary care units are reducing this group, but so far only a little. When the diagnosis is not understood the disease is not recognized. Then come discovery and popularization. Hereafter masquerades hide some cases and the diagnosis is missed. Somewhere fairly early the diagnostic fad leads to false positive diagnosis. As new techniques are discovered, perfected and mastered, false positive errors and masquerades leading to oversights diminish but still exist. All the skill and technical virtuosity in the world will not be applied if we do not think of the disease. When we think of it, even obscure cases may be resolved easily. CONCLUSIONS
The history of our understanding of myocardial infarction ranges over the epoch of ignorance, the discovery of clinical signs and symptoms, a period of overdiagnosis, and our present stage of diagnostic accuracy marred a bit by sins of omission and commission. Awareness of various masquerades should diminish the frequency of missed diagnosis. This will lead to better care of and for the patient. REFERENCES 1. BEAN, W. B.: Infarction of the Heart: A Morphological and Clinical Appraisal of Three Hundred Cases. Part I. Predisposing and Precipitating Conditions. Am. Heart J., 14: 684, 1937. 2. BEAN, W. B.: Infarction of the Heart: A Morphological and Clinical Appraisal of Three Hundred Cases. Part II. Symptomatology of Acute Attack. Ann. Intern. Med., 11: 2086, 1938.
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3. BEAN, W. B.: Infarction of the Heart: A Morphological and Clinical Appraisal of Three Hundred Cases. Part III. Clinical Course and Morphological Findings. Ann. Intern. Med., 12: 71, 1938. 4. BEAN, W. B. AND READ, C. T.: Central Nervous System Manifestations in Acute Myocardial Infarction. Am. Heart J., 23: 362, 1942. 5. BEAN, W. B., FLAMM, G. W., AND SAPADIN, A.: Hemiplegia Attending Acute Myocardial Infarction. Am. J. Med., 7: 765, 1949. 6. BEAN, W. B.: Clinical Masquerades of Acute Myocardial Infarction. J. Iowa Med. Soc., 52: 781, 1962. 7. DAVIS, N. S., III.: Coronary Thrombosis Without Pain: Its Incidence and Pathology. JAMA, p. 1806, 1932. 8. DOCK, G.: Notes on the Coronary Arteries. The Inland Press, Ann Arbor, Michigan. 1896. 9. FAGIN, D. I. AND CHAPNICK, H. A.: Clinical Patterns of Myocardial Infarction in Ambulant Patients. Ann. Intern. Med., 32: 243, 1950. 10. FRANK, N.: Cold Foot-Postoperative Sign of Silent Myocardial Infarction. JAMA, 170: 1147, 1959. 11. GOULD, W. E. AND CAWLEY, L. P.: Unsuspected Healed Myocardial Infarction in Patients Dying in a General Hospital. AMA Arch. Intern. Med., 101: 524, 1958. 12. HAMMER, A.: A Case of Thrombotic Occlusion of One of the Coronary Arteries of the Heart. Wien. med. Wchnschr., 28: 102, 1878. 13. HARRISON, C. E. JR., SPIrFELL, J. A., JR., AND MANKIN, H. T.: Sudden Arterial Occlusion: A Clue to Silent Myocardial Infarction. Proceedings of the Staff Meetings of The Mayo Clinic, 37: 293, 1962. 14. HERRICK, J. B.: Clinical Features of Sudden Obstruction of the Coronary Arteries. JAMA, 49: 2015, 1912. 15. HERRICK, J. B.: Thrombosis of' the Coronary Arteries. JAMA, 72: 387, 1919. 16. HERRICK, J. B.: On Mistaking Other Diseases for Acute Coronary Thrombosis. Ann. Intern. Med., 11: 2079, 1938. 17. HILL, H. N.: Masked Myocardial Infarction. Am. J. Med. Sci., 219: 394, 1950. 18. JARVINEN, A. J.: Physical Activity of Patients After the Onset of Acute Cardiac Infarction. Brit. Med. J.. 1: 922, 1960. 19. JOHNSON, W. J., ACHOR, R. W. P., BURCHELL, H. B., et al: Unrecognized Myocardial Infarction: A Clinicopathologic Study. AMA Arch. Intern. Med., 103: 253, 1959. 20. LADuE, J. S. AND Panel: Occult Myocardial Infarction: Dis. Chest, 43: 120, 1963. 21. MARCHAND, W. E.: Occurrence of Painless Myocardial Infarction in Psychotic Patients. New Eng. J. Med., 253: 51, 1955. 22. MARGOLIS, J. R., KANNEL, W. B., FEINLEIB, M., et al.: Clinical Features of Unrecognized Myocardial Infarction-Silent and Symptomatic: Eighteen Year Follow-Up: The Framingham Study. Am. J. Cardiol., 32: 1, 1973. 23. MASTER, A. M. AND GELLER, A. J.: Magnitude of Silent Coronary Disease. New York State J. Med., 64: 2865, 1964. 24. OBERMAN, A., OSTRANDER, L. D., JR., AND EPSTEIN, F. H.: Myocardial Infarction and Individual Characteristics. AMA Arch. Intern. Med., 120: 661, 1967. 25. PARRY, C. H.: An Inquiry into the Symptoms and Causes of the Syncope Anginosa commonly called Angina Pectoris; illustrated by Dissections, Bath and London, R. Crutwell, 1799. 26. PATON, B. C.: The Accuracy of Diagnosis of Myocardial Infarction, a Clinicopathologic Study. Am. J. Med., 23: 761, 1957. 27. RAFrERY, E. B., BANKS, D. C., AND ORAM, S.: Occlusive Disease of the Coronary Arteries Presenting as Primary Congestive Cardiomyopathy. Lancet, 2: 1147, 1962.
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28. ROSENMAN, R. H., FRIEDMAN, M., JENKINS, C. D., et al.: Recurring and Fatal Myocardial Infarction in the Western Collaborative Group Study-Clinically Unrecognized Myocardial Infarction in the Western Collaborative Group Study. Am. J. Cardiol., 19: 771, 1967. 29. RUBLER, H. B. AND DIEFENBACH, W. C. L.: An Unusual Complication of Myocardial Infarction: Persistent Bigeminy Only in the Recumbent Position. Am. J. Cardiol., 6: 989, 1960. 30. RYLE, J.: The Study of Symptoms, In The Natural History of Disease, 2nd Ed., Published by the Oxford University Press, p. 69, 1949. 31. RYLE, J.: Angina Pectoris and Allied Seizures, In The Natural History of Disease, 2nd Ed., Published by the Oxford University Press, p. 323, 1949. 32. STEIN, I.: Myocardial Infarction Simulating Angina Pectoris. Am. Heart J., 40: 325, 1950. 33. STEIN, I. AND WEINSTEIN, J.: Unusual Causes of Angina Pectoris. American Practitioner and Digest of Treatment, 6: 64, 1955. 34. STEINKE, W. E. AND CURRY, J. H.: "Subclavian Steal" Syndrome in Acute Myocardial Infarction Masquerading as Dissection Aneurysm of the Aorta. Am. J. Cardiol., 22: 436, 1968. 35. STOKES, J.. III AND DAWBER, T. R.: The "Silent Coronary": The Frequency and Clinical Characteristics of Unrecognized Myocardial Infarction in the Framingham Study. Ann. Intern. Med., 50: 1359, 1959. 36. TARHAN, S., MOFFIrr, E. A., TAYLOR, W. F., et al.: Myocardial Infarction After General Anesthesia. JAMA, 220: 1451, 1972. 37. WAGNER, M. L. AND ARBEIT, S. R.: Myocardial Infarction Unmasked by an Unusual Arrhythmia. Am. J. Cardiol., 13: 81, 1964. 38. WARNER, H. R.: "Painless" Myocardial Infarction. Minnesota Medicine, p. 49, 1951.
DISCUSSION DR. RICHARD S. Ross (Baltimore): The methods for establishing the diagnosis of myocardial infarction, and indeed the definition of the disease, changes with improved techniques. First only the electrocardiogram was available and then enzyme studies added a degree of sensitivity. Most recently isotope studies have improved the precision still further by making it possible to detect areas of infarcted and even ischemic tissue. Isotopes like Thallium go into normal myocardium and give a negative image of the infarct. Other isotopes are concentrated in the injured tissue and give a positive image on a gamma camera study. It is possible to detect infarction in the absence of either electrocardiographic or enzyme changes. As diagnostic techniques improve the number of "masqueraders" will be decreased. DR. FRANCIS C. WOOD (Philadelphia): There is one omission from almost all histories of early reports of the diagnosis of Coronary Occlussion: In 1884, E. Leyden, the director of the first Medical Clinic in Berlin, published an article in the Zeitschrift fur Klinische Medecine, Vol. 7, pages 459-486, and 539-580 entitled "Ueber die selerose der Coronararterin und die davon abhangigen Krankheitszustande." On page 553 he describes "Case 9:"-The patient had a severe attack of pain in the chest, then got partly well, and some time later, died of heart failure. Leyden says "Dieser erste anfall Entsprickt der Thrombose der Kranzarterien." This was 26 years before Herrick's first paper. Leyden's article seems to have escaped the attention of Coronary historians. I found this reference years ago when reading in Nothnagel's System of Medicine. DR. BEAN: Fran, thank you very much. Interestingly enough, Nothnagel, whom you mentioned, described what he called angina vasomotoria, an atypical form of angina which
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he thought was related to some kind of autonomic vasomotor storm. It is true that von Leyden, whom you cite for having diagnosed the disease clinically, was a pathologist. At least many of his papers were published in pathology journals, which probably did not impress clinicians and thus did not get within the ken of those interested in clinical matters. In the patient you approved for prostatic surgery who had had an infarct, it is important to remember that post-operative myocardial infarction is about fifty times commoner in those with a previous infarct than those without. DR. JEREMIAH A. BARONDESS (New York): This is, I understand, a little bit off the main point of your paper, but I am a little disturbed about that nipple.* I wonder whether that was just a bizarre type of graft or is there something about the milk line in lower animals that was either lacking in my education or that I forgot. Is there any lower species which the milk line extends cephalad to this degree? DR. BEAN: The milk line in mammals, as you know, runs along the two sides of the abdomen, up the chest, and occasionally up the shoulder. The example of ectopic or displaced nipple we found seems to be unique. It may indeed represent an embryological transfer. And it was a nipple as indicated by the fact that it underwent changes during the menstrual cycle and became increasingly vascular during pregnancy. We suggested its removal but she would not hear of it. I conclude these weighty matters by telling you that William Osler, once on making rounds, observed a woman who had several extra mammary glands, not just nipples, six all told. She was nursing twins and when he inquired of her, she said that she had three other children. He said, "Oh what a pity, with the table set for six." * Dr. Bean had shown two slides, the first of which appeared to be a normal breast; the second picture demonstrating that it was an ectopic nipple on the chin. He had studied this woman with intense interest in 1940 when she was admitted to the Cincinnati General Hospital with pneumonia. She was astonished that the doctors rarely listened to her chest but were always looking at her chin.
