Transmural
Myocardial
LEWIS SASSE, MD, FACC RICHARD WAGNER, MD FRANK E. MURRAY, MD
Los Angeles and Harbor City California
Infarction During Pregnancy
Two young pregnant women with no known risk factors had a transmural myocardial infarction while they were lying in the supine position. Coronary arteriograms 3 l/2 and 4 months later, respectively, were normal. Coronary arterial spasm related to renin release from the transiently ischemic chorion is the proposed cause.
In the overwhelming majority of patients coronary arteriosclerosis is the underlying cause of acute myocardial infarction, and abnormal coronary arteriograms are the rule in these patients (99 percent in a recent series).l Factors other than organic obstruction may adversely influence coronary perfusion, creating an imbalance between requirements for oxygen and its availability. There have been sporadic reports of transmural myocardial infarction in patients who were subsequently found to have normal coronary arteriographic studies.2v3 We recently observed two young women who had an acute transmural myocardial infarction during the last trimester of pregnancy. Both patients subsequently had normal deliveries at term, and both had normal coronary arteriographic studies 3 l/2 and 4 months, respectively, after infarction. Case
From the Departments of internal Medicine, Southern California Permanente Medical Group and Kaiser Foundation Hospital, Los Angeles and Harbor City, Calif. Manuscript accepted April 18, 1974. Address for reprints: Lewis Sasse, MD, Department of Internal Medicine, Southern California Permanente Medical Group, 1505 No. Edgemont St., Los Angeles, Calif. 90027.
440
March 1975
Reports
Case 1: A 16 year old Mexican-American primipara with an expected date of confinement of February 4, 1972 was admitted to the Los Angeles County General Hospital on January 14,1972 with a history of sudden severe and oppressive pain in the left side of the chest and both arms, in association with nausea, vomiting and diaphoresis. The symptoms began 4 days before hospitalization while she was lying down after doing housework. She gave no other history of previous cardiorespiratory difficulty, rheumatic fever, hypertension, renal disease or cigarette smoking. There was no family history of diabetes mellitus, heart disease, hypertension or vascular disease, but her mother died of pregnancy complications in Mexico. Physical examination was normal; there were no third or fourth heart sounds. Values for hemoglobin, electrolytes, blood urea nitrogen, fasting blood sugar, Venereal Disease Research Laboratory test, bilirubin, lupus erythematosus preparation, serum cholesterol, phospholipids, triglycerides and total lipids were normal. The admission leukocyte count was 11,800 cells/ mm3. Serial creatinine phosphokinase and serum glutamic oxaloacetic transaminase studies were normal; lactic dehydrogenase levels were initially elevated but returned to normal in several days. Posteroanterior and lateral chest X-ray studies, arterial blood gases and a lung isotope scan on admission were normal. Serial electrocardiograms are shown in Figure 1; a vectorcardiogram was compatible with inferior wall infarction. The patient was transferred to the Kaiser Foundation Hospital on February 11, for continued care relative to her pregnancy and had an uneventful delivery of a 3 kg normal boy on February 13. Coronary arteriograms and a left ventriculogram obtained on April 28 were normal.
Case 2: A 26 year old Caucasian woman in the 30th week of her second pregnancy gave a history of acute onset of dyspnea while she was watching television 4 days before hospitalization. Simultaneously she experienced se-
The American Journal of CARDIOLOGY
Volume 35
MYOCARDIAL
11 Feb72
14 Feb
15 Feb
2 May 72
19 Dee
INFARCTION DURING PREGNANCY-SASSE
20 Dee
27 Dee
30 Dee
ET AL.
6 Jan 73
aVL
aVF
aVL
aVF ‘6 FIGURE 2. Case 2. Serial electrocardiograms revealing an acute anterior wall transmural myocardial infarction.
v6 FIGURE 1. Case 1. Serial electrocardiograms revealing an acute inferior wall transmural myocardial infarction.
vere oppressive pain in the anterior area of the chest and neck and sought help at a neighbor’s house where she had syncope and was taken by ambulance to the emergency room of another hospital. An electrocardiogram and chest X-ray film were obtained and the patient required endotracheal ‘intubation because of respiratory arrest. She became asymptomatic and was discharged. On the day of admission to Kaiser Foundation Hospital on December 19, 1971 she again experienced severe retrosternal pain with radiation into the neck and lower jaw and a feeling of heaviness and discomfort in both arms while lying down. The electrocardiogram in our emergency room revealed an acute anterior wall myocardial infarction. There was no prior history of chest pain or dyspnea. The first pregnancy, 2 years previously, was without complication, and she had no difficulty during the current pregnancy. The patient’s mother died at age 54 years after cardiac surgery for mitral valve disease and coarctation of the aorta. There was no other family history of heart disease, hypertension, diabetes mellitus, thyroid disease, hyperlipoproteinemia or syphilis. Physical examination was normal except for a transient third heart sound. Values for serum cholesterol, triglycerides and lipoprotein immediately and 3 months after myocardial infarction, hemoglobin, blood urea nitrogen, 3 hour glucose tolerance, creatinine, lupus erythematosus preparation and Venereal Disease Research Laboratory test were normal. The leukocyte count was 15,600 cells/mm3 while serial serum enzyme studies were indicative of an acute myocardial infarction. Results of chest X-ray examination, arterial blood gas determinations, lung isotope scan, and viral study sera during the acute and convalescent period
were also normal. Serial electrocardiograms are shown in Figure 2; serial vectorcardiograms were confirmatory of transmural anterior myocardial infarction. The patient was discharged after a 4 week uneventful course. She had a spontaneous, uneventful vaginal delivery on March 3. Coronary arteriograms April 12, 1972 were normal (Fig. 3), and a left ventriculogram (Fig. 4) revealed anterior wall dyskinesis. Since October 1972 she has been symptom-free without medication.
Discussion Myocardial infarction with normal coronary arteriograms: Among the causes suggested for normal coronary arteriograms in patients who have had a myocardial infarction are polycythemia, thrombocytosis, connective tissue disease, pulmonary emboli, hypotension, coronary arteriovenous shunting, anemia, aortic valve disease, dissection or aneurysm (or both) of coronary arteries, obstructive cardiomyopathy, syphilis and trauma.4 These causes were ruled out in our two patients by history and physical and laboratory examinations. Metabolic abnormalities, small coronary vessel disease and impaired hemoglobin-oxygen diffusion have also been proposed.5,6 Since the coronary circulation is least proficient at the endocardial and subendocardial levels,7 these abnormalities tend to produce subendocardial ischemia rather than transmural myocardial infarction.4 Another suggested cause, thromboembolism, is ruled out because with or without estrogen therapy,* abnormal coronary arteriograms are demonstrable in patients with this lesion, even when recanalization has occurred.s*g Spontaneous complete lysis of coronary arterial thromboemboli without a residual anatomic lesion has not been documented.‘O The use of oral contraceptive agents is associated with an increased incidence of venous thrombosis, pulmonary
March 1975
The American Journal of CARDIOLOGY
Volume 35
449
MYOCARDIAL
INFARCTION DURING PREGNANCY-SASSE
ET AL.
FIGURE 3. Case 2. Coronary anteriograms. A, left coronary artery in right anterior oblique position. B, right coronary artery in right anterior
FIGURE 4. Case 2. Left ventriculogram in right anterior oblique position. A, during end-systole,
demonstrating
anterior
wall dyskinesis.
B, during
end-diastole.
emboli and cerebral arterial thromboembolism, but not with increased incidence of myocardial infarcti0n.l’ However, administration of large doses of estrogen in patients with prostatic carcinoma is associated with an increased incidence of cardiac and cerebrovascular deaths.i2 Normal coronary arteriographic studies have been found in patients with angina pectoris13n14 or subendocardial infarction.sJ4Js-is Neurocirculatory asthenia has also been implicated as a cause of chest pain in women with normal coronary arteriograms.lg Coronary arterial spasm: Spasm of coronary arteries, especially of the right coronary artery, can occur during coronary arteriography and usually can be resolved by sublingual administration of nitroglycerin or isosorbide dinitrate, or both.1 Sphincter-like muscle has been demonstrated at the origin of the human right coronary artery.20 Transmural myocar-
450
March 1975
The American Journal of CARDIOLOGY
dial infarction has occurred after apparent catheterinduced spasm of the left circumflex artery despite use of sublingually administered nitroglycerin and isosorbide dinitrate 21* the patient had normal coronary arteriograms 3 months later. Nine of 200 patients with long-term industrial exposure to nitroglycerin had ischemic heart disease with chest pain and S-T changes on withdrawal from this exposure.22 In one of these patients diffuse irregularity of the left anterior descending artery and two segmental narrowings of the right coronary artery were reversed by sublingual administration of nitroglycerin. Digital plethysmography also indicated digital arterial spasm. There are other cases of fatal cardiac ischemia related to withdrawal from industrial exposure to nitroglycerin in which postmortem study revealed normal coronary arteries.2s,24 Single cases and small groups of patients demonstrating transmural myo-
Volume 35
MYOCARDIAL
cardial infarction with normal or mildly abnormal coronary arteriograms performed 4 weeks to 9 years myocardial after infarction have been described.2*3,gJ0J7*1g~s5-sl Arteriograms in some of these reports show segmental smooth narrowings of coronary arteries suggestive of spasm.1g,25 The studies do not mention use of sublingually administered nitroglycerin or isosorbide dinitrate during the coronary arteriographic studies. Prinzmetal’s variant angina was originally thought to represent spasm in a main coronary arterys2 with partial atheromatous segmental occlusion. In one recent study of Prinzmetal’s variant four of five patients had normal coronary arteriograms with one patient demonstrating reversible spasm of the right coronary artery and one having normal coronary arteries at postmortem examination.33 In another report of Prinzmetal’s angina, spasm in various areas of the right coronary artery during coronary arteriography caused transient inferior wall ischemia and heart block.34 Upon relief of the attacks the coronary arteriograms were normal. Variant angina has also been precipitated by immersing the hand in cold water.35 Myocardial infarction in pregnancy: In two series, each reviewing about 40,000 deliveries, myocardial infarction during pregnancy was rare and seemed to occur more frequently in older multigravidae.36,37 In one of these reports two of the three patients had a postpartum myocardial infarction.37 As in the study of Glancy et al.,3 our patients had no history of angina prior to myocardial infarction. The coronary arteriograms were normal and showed all branches in both cases. In Case 1, the enzymes were first studied 4 days after chest pain, and it is not surprising that the creatinine phosphokinase and serum glutamic oxaloacetic transaminase levels were normal. Serum lactic dehydrogenase may be increased in 18 percent of normal pregnant women,36,38
INFARCTION DURING PREGNANCY-SASSE
ET AL.
but the falling levels in Case 1 are in agreement with the electrocardiographic and vectorcardiographic changes of recent acute transmural inferior wall infarction. Our second patient had enzyme as well and vectorcardiographic as electrocardiographic changes confirmatory of acute transmural anterior wall infarction. Major coronary arterial atherosclerotic or thrombotic occlusion would be unlikely to clear completely in 4 months. Mechanism: Although myocardial infarction has been documented during pregnancy,36,37 pregnant women rarely undergo coronary arteriography. The chest pain in both of our patients occurred while they were lying in the supine position during the 3rd trimester of pregnancy, past the time of maximal hemodynamic stress of pregnancy. The supine position in the 3rd trimester of pregnancy decreases uterine blood fl~w,~~ as well as inferior vena caval venous return to the heart. The uterus is the site of renin production in the anephric woman,40 and the human chorion contains 160 times the renin concentration of maternal plasma .*l The hypertension of preeclampsia is of humoral rather than neurogenic origin,42 and the abnormally increased pressor response to angiotensin, norepinephrine and epinephrine precedes by up to 3 months the development of hypertension in pregnant women.3g,43 Thus, all but one of the previously proposed causes for transmural myocardial infarction with normal coronary arteriograms have been ruled out. The transient physiologic setting in which prolonged supine recumbency leads to uterine renin release and angiotensin production causing coronary arterial spasm was present. Although our hypothesis is speculative, we suggest that prolonged but reversible coronary arterial spasm is the most likely of the previously proposed mechanisms for the myocardial infarction in our two patients.
References 1. Proudfit WL, Shirey EK, Sones FM Jr: Selective tine coronary arteriography. Circulation 33:901-910, 1966 2. Sldd JJ, Kemp HG, Gorlln R: Acute myocardial infarction in a nineteen-year-old student in the absence of coronary obstructive disease. N Engl J Med 282:1306-1307, 1970 3. Glancy DL, Marcus ML, Epstein SE: Myocardial infarction in young women with normal coronary arteriograms. Circulation 44495-502, 1971 4. Llkoff W: Myocardial infarction in subjects with normal coronary arteriograms. Am J Cardiol28:742-743, 1971 5. Eliot RS, Bratt G: The paradox of myocardial ischemia and necrosis in young women with normal coronary arteriogramsrelation to abnormal hemoglobin-oxygen dissociation. Am J Cardiol 23:633-638, 1969 James TN: Pathology of small coronary arteries. Am J Cardiol 20:679-691, 1967 McAlpfn R: Coronary spasm as a cause of angina. N Engl J Med 288:788, 1973 Spring DA, Thomsen JH: Recanalization in a coronary artery thrombosis. JAMA 224:i 152-1156, 1973 Bruschke AVG, Bruyneel KJJ, Bloch A, et al: Acute myocardial infarction without obstructive coronary artery disease demonstrated by selective cinearteriography. Br Heart J 33:585-594,
1971 10. Klmblrls D, Segal BL, Munlr M, et al: Myocardial infarction in patients with normal patent coronary arteries as visualized by cinearteriography. Am J Cardiol 29:724-728. 1972 11. Vessey MP, Doll R: Investigation of relation between use of oral contraceptives and thromboembolic disease: a further report. Br Med J 2:651-857, 1969 Administration Cooperative Urological Research 12. Veterans Group: Treatment and survival of patients with cancer of the prostate. Surg Gynecol Obstet 124:1011-1017, 1967 13. Kemp HG. Elliot WC, Gorlln R: The angina1 syndrome with normal coronary arteriography. Trans Assoc Am Physicians 80: 59-70, 1967 14. Dwyer EM Jr, Wiener L, Cox JW: Angina pectoris in patients with normal and abnormal coronary arteriograms. Am J Cardiol 23:639-646, 1969 15. Llkoff W, Segal BL, Kasparian H: Paradox of normal selective coronary arteriograms in patients considered to have unmistakable coronary heart disease. N Engl J Med 278:1063-1066. 1967 16. Allison RB, Rodriguez FL, Higgins EA Jr, et al: Clinico-pathological correlations in coronary atherosclerosis: four hundred thirty patients studied with post-mortem coronary angiography.
March 1975
The American Journal of CARDIOLOGY
Volume 35
451
MYOCARDIAL
INFARCTION DURING PREGNANCY-SASSE
ET AL
Circulation 27:170-184, 1963 17. De Pesquale NP, Bruno MS: Normal arteriography in a patient with clinical evidence of myocardial infarction. Chest 63:618619, 1973 18. Barcala RP: Acute myocardial infarction in the presence of patent coronary arteries. J Thorac Cardiovasc Surg 65786-791, 1973 19. Waxier EB, Klmbiris D, Drelfus LS: The fate of women with normal coronary arteriograms and chest pain resembling angina pectoris. Am J Cardiol 28:25-32, 1971 20. Boucek RJ, Takeshlta R, Brady AH: lntimal hypertrophy in coronary arteries and consideration of the papillary muscle arteries (man). Anat Ret 153:243-253. 1965 21. Cheng TO, Bashour T, Singh BK, et al: Myocardial infarction in the absence of coronary atherosclerosis: caused by coronary spasm? Am J Cardiol30:680-682, 1972 22. Lange RL, Reid MS, Tresch DD, et al: Nonathermatous ischemit heart disease following withdrawal from chronic industrial nitroglycerin exposure. Circulation 46:666-678, 1972 23. Symanski VH: Schwere gesundheitsschldigungen durch beruflithe nitroglykoleinwirkung. Arch Hyg Bakteriol 136:139-158, 1952 24. Lund RP, HBggendel J, Johnsson 0: Withdrawal symptoms in workers exposed to nitroglycerin. Br J Ind Med 25136-138, 1968 25. Henderson RR, Hanslng CE, Razavl M, et al: Resolution of an obstructive coronary lesion as demonstrated by selective angiography in a patient with transmural myocardial infarction. Am J Cardiol 31:785-788, 1973 26. Welch CC, Proudflt WS, Sones FM Jr, et al: Cine-coronary arteriography in young men. Circulation 42:647-652, 1970 27. Campeau L, Lesperance J, Bourassa MG, et al: Myocardial infarction without obstructive disease at coronary arteriography. Can Med Assoc J 99:837-843, 1968 26. Potts KH, Sieln PD, Houk PC: Transmural myocardial infarction with arteriographically normal appearing coronary arteries. Chest 62:549-552, 1972 29. Nlzel PM, Robertson L: Normal coronary arteriogram following myocardial infarction in a 17 year old boy. Am J Cardiol 28:
452
March 1975
The American Journal of CARDIOLOGY
715-717,197l 30. Dear HD, Russell RO, Jones WB, et al: Myocardial infarction in the absence of coronary occlusion. Am J Cardiol 28:718-721, 1971 31. Stout C: Coronary thrombosis without coronary atherosclerosis. Am J Cardiol 24:564-569, 1969 32. Prlnzmetal M, Kennamer R, Merllss R, et al: Angina pectoris: I. A variant form of angina pectoris. Am J Med 27:375-388, 1959 33. Cheng TO, Bashour T, Kelser GA, et al: Variant angina of Prinzmetal with normal coronary arteriogram. Circulation 47: 476-485, 1973 34. Ollva PB, Potts DE, Pluss RG: Coronary arterial spasm in Prinzmetal angina. N Engl J Med 288:745-750. 1973 35. Hllal H, Maseuml R: Variant angina pectoris. Am J Cardiol 19: 607-608, 1967 36. Fletcher E, Knox EW, Morton P: Acute myocardial infarction in pregnancy. Br Med J 3:586-588, 1967 37. Glnz B: Myocardial infarction in pregnancy. J Obstet and Gynaecol Br Commonw 77:610-614, 1970 38. Stone ML, Lending M, Slobody LD, et al: Glutamic oxalacetic transaminase and lactic dehydrogenase in pregnancy. Am J Obstet Gynecol 80: 104- 107, 1960 39. Page EW: On the pathogenesis of pre-eclampsia and eclampsia. J Obstet Gynaecol Br Commonw 79:883-894, 1972 40. Capelll JP, Wesson LG Jr, Aponte GE, et al: Characterization and source of a renin-like enzyme in anephric humans. J Clin Endocrinol Metab 28:221-230, 1968 41. Skinner SL, Lumbers ER, Symonds EM: Renin concentration in human fetal and maternal tissues. Am J Obstet Gynecol 101: 529-533, 1968 42. Aseall NS, Vergon JM, Tada Y, et al: Studies on autonomic blockade. VI. The mechanisms regulating the hemodynamic changes in pregnant women and their relation to the hypertensive toxemia of pregnancy. Am J Obstet Gynecol 63:978-988, 1952 43. Raab W, Schroeder G, Wagner R, el al: Vascular reactivity and electrolytes in normal and toxemic pregnancy. J Clin Endocrinol Metab 16:1196-1216. 1956
Volume 35
Myocardial
LEWIS SASSE, MD, FACC RICHARD WAGNER, MD FRANK E. MURRAY, MD
Los Angeles and Harbor City California
Infarction During Pregnancy
Two young pregnant women with no known risk factors had a transmural myocardial infarction while they were lying in the supine position. Coronary arteriograms 3 l/2 and 4 months later, respectively, were normal. Coronary arterial spasm related to renin release from the transiently ischemic chorion is the proposed cause.
In the overwhelming majority of patients coronary arteriosclerosis is the underlying cause of acute myocardial infarction, and abnormal coronary arteriograms are the rule in these patients (99 percent in a recent series).l Factors other than organic obstruction may adversely influence coronary perfusion, creating an imbalance between requirements for oxygen and its availability. There have been sporadic reports of transmural myocardial infarction in patients who were subsequently found to have normal coronary arteriographic studies.2v3 We recently observed two young women who had an acute transmural myocardial infarction during the last trimester of pregnancy. Both patients subsequently had normal deliveries at term, and both had normal coronary arteriographic studies 3 l/2 and 4 months, respectively, after infarction. Case
From the Departments of internal Medicine, Southern California Permanente Medical Group and Kaiser Foundation Hospital, Los Angeles and Harbor City, Calif. Manuscript accepted April 18, 1974. Address for reprints: Lewis Sasse, MD, Department of Internal Medicine, Southern California Permanente Medical Group, 1505 No. Edgemont St., Los Angeles, Calif. 90027.
440
March 1975
Reports
Case 1: A 16 year old Mexican-American primipara with an expected date of confinement of February 4, 1972 was admitted to the Los Angeles County General Hospital on January 14,1972 with a history of sudden severe and oppressive pain in the left side of the chest and both arms, in association with nausea, vomiting and diaphoresis. The symptoms began 4 days before hospitalization while she was lying down after doing housework. She gave no other history of previous cardiorespiratory difficulty, rheumatic fever, hypertension, renal disease or cigarette smoking. There was no family history of diabetes mellitus, heart disease, hypertension or vascular disease, but her mother died of pregnancy complications in Mexico. Physical examination was normal; there were no third or fourth heart sounds. Values for hemoglobin, electrolytes, blood urea nitrogen, fasting blood sugar, Venereal Disease Research Laboratory test, bilirubin, lupus erythematosus preparation, serum cholesterol, phospholipids, triglycerides and total lipids were normal. The admission leukocyte count was 11,800 cells/ mm3. Serial creatinine phosphokinase and serum glutamic oxaloacetic transaminase studies were normal; lactic dehydrogenase levels were initially elevated but returned to normal in several days. Posteroanterior and lateral chest X-ray studies, arterial blood gases and a lung isotope scan on admission were normal. Serial electrocardiograms are shown in Figure 1; a vectorcardiogram was compatible with inferior wall infarction. The patient was transferred to the Kaiser Foundation Hospital on February 11, for continued care relative to her pregnancy and had an uneventful delivery of a 3 kg normal boy on February 13. Coronary arteriograms and a left ventriculogram obtained on April 28 were normal.
Case 2: A 26 year old Caucasian woman in the 30th week of her second pregnancy gave a history of acute onset of dyspnea while she was watching television 4 days before hospitalization. Simultaneously she experienced se-
The American Journal of CARDIOLOGY
Volume 35
MYOCARDIAL
11 Feb72
14 Feb
15 Feb
2 May 72
19 Dee
INFARCTION DURING PREGNANCY-SASSE
20 Dee
27 Dee
30 Dee
ET AL.
6 Jan 73
aVL
aVF
aVL
aVF ‘6 FIGURE 2. Case 2. Serial electrocardiograms revealing an acute anterior wall transmural myocardial infarction.
v6 FIGURE 1. Case 1. Serial electrocardiograms revealing an acute inferior wall transmural myocardial infarction.
vere oppressive pain in the anterior area of the chest and neck and sought help at a neighbor’s house where she had syncope and was taken by ambulance to the emergency room of another hospital. An electrocardiogram and chest X-ray film were obtained and the patient required endotracheal ‘intubation because of respiratory arrest. She became asymptomatic and was discharged. On the day of admission to Kaiser Foundation Hospital on December 19, 1971 she again experienced severe retrosternal pain with radiation into the neck and lower jaw and a feeling of heaviness and discomfort in both arms while lying down. The electrocardiogram in our emergency room revealed an acute anterior wall myocardial infarction. There was no prior history of chest pain or dyspnea. The first pregnancy, 2 years previously, was without complication, and she had no difficulty during the current pregnancy. The patient’s mother died at age 54 years after cardiac surgery for mitral valve disease and coarctation of the aorta. There was no other family history of heart disease, hypertension, diabetes mellitus, thyroid disease, hyperlipoproteinemia or syphilis. Physical examination was normal except for a transient third heart sound. Values for serum cholesterol, triglycerides and lipoprotein immediately and 3 months after myocardial infarction, hemoglobin, blood urea nitrogen, 3 hour glucose tolerance, creatinine, lupus erythematosus preparation and Venereal Disease Research Laboratory test were normal. The leukocyte count was 15,600 cells/mm3 while serial serum enzyme studies were indicative of an acute myocardial infarction. Results of chest X-ray examination, arterial blood gas determinations, lung isotope scan, and viral study sera during the acute and convalescent period
were also normal. Serial electrocardiograms are shown in Figure 2; serial vectorcardiograms were confirmatory of transmural anterior myocardial infarction. The patient was discharged after a 4 week uneventful course. She had a spontaneous, uneventful vaginal delivery on March 3. Coronary arteriograms April 12, 1972 were normal (Fig. 3), and a left ventriculogram (Fig. 4) revealed anterior wall dyskinesis. Since October 1972 she has been symptom-free without medication.
Discussion Myocardial infarction with normal coronary arteriograms: Among the causes suggested for normal coronary arteriograms in patients who have had a myocardial infarction are polycythemia, thrombocytosis, connective tissue disease, pulmonary emboli, hypotension, coronary arteriovenous shunting, anemia, aortic valve disease, dissection or aneurysm (or both) of coronary arteries, obstructive cardiomyopathy, syphilis and trauma.4 These causes were ruled out in our two patients by history and physical and laboratory examinations. Metabolic abnormalities, small coronary vessel disease and impaired hemoglobin-oxygen diffusion have also been proposed.5,6 Since the coronary circulation is least proficient at the endocardial and subendocardial levels,7 these abnormalities tend to produce subendocardial ischemia rather than transmural myocardial infarction.4 Another suggested cause, thromboembolism, is ruled out because with or without estrogen therapy,* abnormal coronary arteriograms are demonstrable in patients with this lesion, even when recanalization has occurred.s*g Spontaneous complete lysis of coronary arterial thromboemboli without a residual anatomic lesion has not been documented.‘O The use of oral contraceptive agents is associated with an increased incidence of venous thrombosis, pulmonary
March 1975
The American Journal of CARDIOLOGY
Volume 35
449
MYOCARDIAL
INFARCTION DURING PREGNANCY-SASSE
ET AL.
FIGURE 3. Case 2. Coronary anteriograms. A, left coronary artery in right anterior oblique position. B, right coronary artery in right anterior
FIGURE 4. Case 2. Left ventriculogram in right anterior oblique position. A, during end-systole,
demonstrating
anterior
wall dyskinesis.
B, during
end-diastole.
emboli and cerebral arterial thromboembolism, but not with increased incidence of myocardial infarcti0n.l’ However, administration of large doses of estrogen in patients with prostatic carcinoma is associated with an increased incidence of cardiac and cerebrovascular deaths.i2 Normal coronary arteriographic studies have been found in patients with angina pectoris13n14 or subendocardial infarction.sJ4Js-is Neurocirculatory asthenia has also been implicated as a cause of chest pain in women with normal coronary arteriograms.lg Coronary arterial spasm: Spasm of coronary arteries, especially of the right coronary artery, can occur during coronary arteriography and usually can be resolved by sublingual administration of nitroglycerin or isosorbide dinitrate, or both.1 Sphincter-like muscle has been demonstrated at the origin of the human right coronary artery.20 Transmural myocar-
450
March 1975
The American Journal of CARDIOLOGY
dial infarction has occurred after apparent catheterinduced spasm of the left circumflex artery despite use of sublingually administered nitroglycerin and isosorbide dinitrate 21* the patient had normal coronary arteriograms 3 months later. Nine of 200 patients with long-term industrial exposure to nitroglycerin had ischemic heart disease with chest pain and S-T changes on withdrawal from this exposure.22 In one of these patients diffuse irregularity of the left anterior descending artery and two segmental narrowings of the right coronary artery were reversed by sublingual administration of nitroglycerin. Digital plethysmography also indicated digital arterial spasm. There are other cases of fatal cardiac ischemia related to withdrawal from industrial exposure to nitroglycerin in which postmortem study revealed normal coronary arteries.2s,24 Single cases and small groups of patients demonstrating transmural myo-
Volume 35
MYOCARDIAL
cardial infarction with normal or mildly abnormal coronary arteriograms performed 4 weeks to 9 years myocardial after infarction have been described.2*3,gJ0J7*1g~s5-sl Arteriograms in some of these reports show segmental smooth narrowings of coronary arteries suggestive of spasm.1g,25 The studies do not mention use of sublingually administered nitroglycerin or isosorbide dinitrate during the coronary arteriographic studies. Prinzmetal’s variant angina was originally thought to represent spasm in a main coronary arterys2 with partial atheromatous segmental occlusion. In one recent study of Prinzmetal’s variant four of five patients had normal coronary arteriograms with one patient demonstrating reversible spasm of the right coronary artery and one having normal coronary arteries at postmortem examination.33 In another report of Prinzmetal’s angina, spasm in various areas of the right coronary artery during coronary arteriography caused transient inferior wall ischemia and heart block.34 Upon relief of the attacks the coronary arteriograms were normal. Variant angina has also been precipitated by immersing the hand in cold water.35 Myocardial infarction in pregnancy: In two series, each reviewing about 40,000 deliveries, myocardial infarction during pregnancy was rare and seemed to occur more frequently in older multigravidae.36,37 In one of these reports two of the three patients had a postpartum myocardial infarction.37 As in the study of Glancy et al.,3 our patients had no history of angina prior to myocardial infarction. The coronary arteriograms were normal and showed all branches in both cases. In Case 1, the enzymes were first studied 4 days after chest pain, and it is not surprising that the creatinine phosphokinase and serum glutamic oxaloacetic transaminase levels were normal. Serum lactic dehydrogenase may be increased in 18 percent of normal pregnant women,36,38
INFARCTION DURING PREGNANCY-SASSE
ET AL.
but the falling levels in Case 1 are in agreement with the electrocardiographic and vectorcardiographic changes of recent acute transmural inferior wall infarction. Our second patient had enzyme as well and vectorcardiographic as electrocardiographic changes confirmatory of acute transmural anterior wall infarction. Major coronary arterial atherosclerotic or thrombotic occlusion would be unlikely to clear completely in 4 months. Mechanism: Although myocardial infarction has been documented during pregnancy,36,37 pregnant women rarely undergo coronary arteriography. The chest pain in both of our patients occurred while they were lying in the supine position during the 3rd trimester of pregnancy, past the time of maximal hemodynamic stress of pregnancy. The supine position in the 3rd trimester of pregnancy decreases uterine blood fl~w,~~ as well as inferior vena caval venous return to the heart. The uterus is the site of renin production in the anephric woman,40 and the human chorion contains 160 times the renin concentration of maternal plasma .*l The hypertension of preeclampsia is of humoral rather than neurogenic origin,42 and the abnormally increased pressor response to angiotensin, norepinephrine and epinephrine precedes by up to 3 months the development of hypertension in pregnant women.3g,43 Thus, all but one of the previously proposed causes for transmural myocardial infarction with normal coronary arteriograms have been ruled out. The transient physiologic setting in which prolonged supine recumbency leads to uterine renin release and angiotensin production causing coronary arterial spasm was present. Although our hypothesis is speculative, we suggest that prolonged but reversible coronary arterial spasm is the most likely of the previously proposed mechanisms for the myocardial infarction in our two patients.
References 1. Proudfit WL, Shirey EK, Sones FM Jr: Selective tine coronary arteriography. Circulation 33:901-910, 1966 2. Sldd JJ, Kemp HG, Gorlln R: Acute myocardial infarction in a nineteen-year-old student in the absence of coronary obstructive disease. N Engl J Med 282:1306-1307, 1970 3. Glancy DL, Marcus ML, Epstein SE: Myocardial infarction in young women with normal coronary arteriograms. Circulation 44495-502, 1971 4. Llkoff W: Myocardial infarction in subjects with normal coronary arteriograms. Am J Cardiol28:742-743, 1971 5. Eliot RS, Bratt G: The paradox of myocardial ischemia and necrosis in young women with normal coronary arteriogramsrelation to abnormal hemoglobin-oxygen dissociation. Am J Cardiol 23:633-638, 1969 James TN: Pathology of small coronary arteries. Am J Cardiol 20:679-691, 1967 McAlpfn R: Coronary spasm as a cause of angina. N Engl J Med 288:788, 1973 Spring DA, Thomsen JH: Recanalization in a coronary artery thrombosis. JAMA 224:i 152-1156, 1973 Bruschke AVG, Bruyneel KJJ, Bloch A, et al: Acute myocardial infarction without obstructive coronary artery disease demonstrated by selective cinearteriography. Br Heart J 33:585-594,
1971 10. Klmblrls D, Segal BL, Munlr M, et al: Myocardial infarction in patients with normal patent coronary arteries as visualized by cinearteriography. Am J Cardiol 29:724-728. 1972 11. Vessey MP, Doll R: Investigation of relation between use of oral contraceptives and thromboembolic disease: a further report. Br Med J 2:651-857, 1969 Administration Cooperative Urological Research 12. Veterans Group: Treatment and survival of patients with cancer of the prostate. Surg Gynecol Obstet 124:1011-1017, 1967 13. Kemp HG. Elliot WC, Gorlln R: The angina1 syndrome with normal coronary arteriography. Trans Assoc Am Physicians 80: 59-70, 1967 14. Dwyer EM Jr, Wiener L, Cox JW: Angina pectoris in patients with normal and abnormal coronary arteriograms. Am J Cardiol 23:639-646, 1969 15. Llkoff W, Segal BL, Kasparian H: Paradox of normal selective coronary arteriograms in patients considered to have unmistakable coronary heart disease. N Engl J Med 278:1063-1066. 1967 16. Allison RB, Rodriguez FL, Higgins EA Jr, et al: Clinico-pathological correlations in coronary atherosclerosis: four hundred thirty patients studied with post-mortem coronary angiography.
March 1975
The American Journal of CARDIOLOGY
Volume 35
451
MYOCARDIAL
INFARCTION DURING PREGNANCY-SASSE
ET AL
Circulation 27:170-184, 1963 17. De Pesquale NP, Bruno MS: Normal arteriography in a patient with clinical evidence of myocardial infarction. Chest 63:618619, 1973 18. Barcala RP: Acute myocardial infarction in the presence of patent coronary arteries. J Thorac Cardiovasc Surg 65786-791, 1973 19. Waxier EB, Klmbiris D, Drelfus LS: The fate of women with normal coronary arteriograms and chest pain resembling angina pectoris. Am J Cardiol 28:25-32, 1971 20. Boucek RJ, Takeshlta R, Brady AH: lntimal hypertrophy in coronary arteries and consideration of the papillary muscle arteries (man). Anat Ret 153:243-253. 1965 21. Cheng TO, Bashour T, Singh BK, et al: Myocardial infarction in the absence of coronary atherosclerosis: caused by coronary spasm? Am J Cardiol30:680-682, 1972 22. Lange RL, Reid MS, Tresch DD, et al: Nonathermatous ischemit heart disease following withdrawal from chronic industrial nitroglycerin exposure. Circulation 46:666-678, 1972 23. Symanski VH: Schwere gesundheitsschldigungen durch beruflithe nitroglykoleinwirkung. Arch Hyg Bakteriol 136:139-158, 1952 24. Lund RP, HBggendel J, Johnsson 0: Withdrawal symptoms in workers exposed to nitroglycerin. Br J Ind Med 25136-138, 1968 25. Henderson RR, Hanslng CE, Razavl M, et al: Resolution of an obstructive coronary lesion as demonstrated by selective angiography in a patient with transmural myocardial infarction. Am J Cardiol 31:785-788, 1973 26. Welch CC, Proudflt WS, Sones FM Jr, et al: Cine-coronary arteriography in young men. Circulation 42:647-652, 1970 27. Campeau L, Lesperance J, Bourassa MG, et al: Myocardial infarction without obstructive disease at coronary arteriography. Can Med Assoc J 99:837-843, 1968 26. Potts KH, Sieln PD, Houk PC: Transmural myocardial infarction with arteriographically normal appearing coronary arteries. Chest 62:549-552, 1972 29. Nlzel PM, Robertson L: Normal coronary arteriogram following myocardial infarction in a 17 year old boy. Am J Cardiol 28:
452
March 1975
The American Journal of CARDIOLOGY
715-717,197l 30. Dear HD, Russell RO, Jones WB, et al: Myocardial infarction in the absence of coronary occlusion. Am J Cardiol 28:718-721, 1971 31. Stout C: Coronary thrombosis without coronary atherosclerosis. Am J Cardiol 24:564-569, 1969 32. Prlnzmetal M, Kennamer R, Merllss R, et al: Angina pectoris: I. A variant form of angina pectoris. Am J Med 27:375-388, 1959 33. Cheng TO, Bashour T, Kelser GA, et al: Variant angina of Prinzmetal with normal coronary arteriogram. Circulation 47: 476-485, 1973 34. Ollva PB, Potts DE, Pluss RG: Coronary arterial spasm in Prinzmetal angina. N Engl J Med 288:745-750. 1973 35. Hllal H, Maseuml R: Variant angina pectoris. Am J Cardiol 19: 607-608, 1967 36. Fletcher E, Knox EW, Morton P: Acute myocardial infarction in pregnancy. Br Med J 3:586-588, 1967 37. Glnz B: Myocardial infarction in pregnancy. J Obstet and Gynaecol Br Commonw 77:610-614, 1970 38. Stone ML, Lending M, Slobody LD, et al: Glutamic oxalacetic transaminase and lactic dehydrogenase in pregnancy. Am J Obstet Gynecol 80: 104- 107, 1960 39. Page EW: On the pathogenesis of pre-eclampsia and eclampsia. J Obstet Gynaecol Br Commonw 79:883-894, 1972 40. Capelll JP, Wesson LG Jr, Aponte GE, et al: Characterization and source of a renin-like enzyme in anephric humans. J Clin Endocrinol Metab 28:221-230, 1968 41. Skinner SL, Lumbers ER, Symonds EM: Renin concentration in human fetal and maternal tissues. Am J Obstet Gynecol 101: 529-533, 1968 42. Aseall NS, Vergon JM, Tada Y, et al: Studies on autonomic blockade. VI. The mechanisms regulating the hemodynamic changes in pregnant women and their relation to the hypertensive toxemia of pregnancy. Am J Obstet Gynecol 63:978-988, 1952 43. Raab W, Schroeder G, Wagner R, el al: Vascular reactivity and electrolytes in normal and toxemic pregnancy. J Clin Endocrinol Metab 16:1196-1216. 1956
Volume 35
