| |||||||||||||||||||||||||||||||
From 1984 to 1991, 164 patients at our institution underwent antimyosin myocardial scintigraphy and right ventricular endomyocardial biopsy for suspected myocarditis. A review of their clinical presentations revealed that eight patients had been admitted to the coronary care unit with an initial diagnosis of acute myocardial infarction based on prolonged chest pain and electrocardiographic abnormalities diagnostic of ischemia. The fact that these eight patients were found to have normal coronary arteries later in their hospital stay led us to suspect that they may have had myocarditis. This report describes the clinical presentations of these eight patients and the adjunctive use of myocardial scintigraphy with antimyosin antibody in making the diagnosis of myocarditis. The antimyosin scans in these patients were compared with images obtained from 45 patients with acute myocardial infarction and angiographic evidence of coronary artery occlusion.
Case Reports
Patients with Myocarditis Mimicking Myocardial Infarction
Clinical Presentation
The study group comprised four men and four women (age, 26 to 70 years; mean ±SE, 51 ±6) (Table 1). Five patients had two or three coronary risk factors, two had one risk factor, and the remaining patient had none. No patient was febrile at the time of admission or during hospitalization, although two had an antecedent viral illness of the upper respiratory tract. Because a diagnosis of myocarditis was not considered initially by the patients' physicians, viral antibody titers were not serially evaluated.
|
After admission, five patients continued to have intractable or recurrent episodes of chest pain despite therapy directed at reversing ischemia. In all eight patients, the electrocardiographic changes failed to evolve in a pattern typical of acute myocardial infarction. Serum enzyme levels in one patient indicated mild but persistent release of creatine kinase. All eight patients underwent coronary angiography because of recurrent chest pain or doubts about the initial diagnosis of myocardial infarction due to coronary artery disease.
Coronary Angiography and Left Ventriculography
All eight patients had normal coronary arteries on angiography. Coronary artery spasm was not observed in two patients who had spontaneous chest pain during angiography or in one other patient who underwent a challenge test with the vasoconstrictor ergonovine. Left ventriculography revealed normal wall motion in three patients, and three patients had global left ventricular hypokinesia. Two patients had strikingly abnormal regional wall motion inconsistent with ischemia in a single coronary artery territory: one had dyskinesia of the mid-anterolateral wall, with normal contraction of the remaining ventricular regions, and the other had impairment of most of the left ventricle ranging from akinesia to dyskinesia, except for normally contracting basal and apical segments. The left ventricular ejection fractions were normal in Patients 2, 3, 4, and 8 (55 to 72 percent) (Table 1) and low in the remaining four patients (34 to 46 percent).
All eight patients underwent a right ventricular endomyocardial biopsy (performed and interpreted as previously described10,11,12) and indium-111-labeled antimyosin-antibody imaging13,14 to evaluate the possibility that myocarditis was causing the cardiac problem.
Antimyosin Scintigraphy and Endomyocardial Biopsy
Monoclonal antimyosin antibody (500 µg, R11D10 Fab, Centocor, Malvern, Pa.) coupled to diethylenetriamine pentaacetic acid was radiolabeled with 111In (1.8 mCi) and administered through a peripheral vein after informed consent had been obtained. Planar images (anterior and left anterior oblique, 60 to 70 degrees) and tomographic images (reconstructed into transverse, sagittal, and coronal projections) were obtained with a gamma camera (medium-energy collimator) 48 hours after the administration of the radiotracer13,14. Antimyosin scans were interpreted as positive when there was evidence of the uptake of tracer in the planar image and at least two of the three tomographic reconstructions. Scans were considered negative when no uptake of tracer was demonstrated in either the planar or tomographic images. The scans were analyzed without knowledge of the patients' identities and clinical or histologic findings. The use of antimyosin scintigraphy for the detection of acute myocardial infarction and myocarditis has been approved by our institutional research and radiation-safety boards.
Antimyosin myocardial scintigraphy revealed diffuse, heterogeneous, and global left ventricular uptake in seven patients (Patients 1 through 7) (Table 1 and Figure 1A). Diffuse uptake was occasionally associated with marked regional variability (i.e., more intense uptake in particular regions) that did not correspond to a single coronary artery territory. Of the seven patients with positive scans, three (Patients 1, 2, and 3) had biopsy specimens positive for myocarditis (Figure 1B). Although the fourth patient's initial endomyocardial biopsy was nondiagnostic, he returned five months later with shortness of breath; a second biopsy revealed myocarditis, and an antimyosin scan was also positive. The biopsy specimen of Patient 5 showed nonspecific interstitial fibrosis and myocytic hypertrophy (despite a mild, persistent increase in serum creatine kinase and a positive scan). The clinical condition of this patient deteriorated over the next three months, and congestive heart failure developed. A follow-up antimyosin scan revealed more intense diffuse left ventricular uptake than did the initial scan. A follow-up biopsy showed focal lymphocytic myocarditis. Thus, the initial antimyosin scan detected myocytic necrosis before there was clinical evidence of heart failure and despite the fact that the biopsy evidence was inconclusive. The sixth and seventh patients with positive scans had borderline myocarditis, according to defined histologic criteria11,12.
|
Treatment and Follow-up
At the time of the most recent assessment, the study group had been followed for 5 to 77 months (mean ±SE, 34 ±12). The six patients with biopsy evidence of myocarditis received prednisone and azathioprine. Of the four patients with normal left ventricular ejection fractions on initial examination, two (Patients 2 and 8) continued to have normal systolic function and remained asymptomatic (Table 1). No follow-up data on the ejection fraction were available for the other two patients (Patients 3 and 4). Of the four patients who initially had impaired systolic left ventricular function, one died of congestive heart failure after nine months (Patient 5). The remaining three (two of whom were admitted in cardiogenic shock) were asymptomatic, and their ejection fractions had returned to normal at the most recent assessment (Patients 1, 6, and 7).
Electrocardiographic abnormalities persisted for more than one year in four patients (Patients 1, 2, 7, and 8) and until death in Patient 5 and virtually disappeared within six months in Patient 4. Follow-up electrocardiograms were not available for Patients 3 and 6.
Patients with Myocardial Infarction
Antimyosin myocardial scans were also obtained in 45 patients with acute myocardial infarction and angiographic evidence of coronary occlusion. All 45 patients arrived at the emergency room with chest pain and electrocardiographic changes typical of myocardial infarction. In all patients, the electrocardiographic changes and enzyme elevations evolved typically. Coronary angiography performed at the time of admission showed occlusion of the left anterior descending artery in 23 patients, the left circumflex artery in 6 patients, and the right coronary artery in 16 patients. All 45 patients received thrombolytic therapy; perfusion was reestablished in 37.
The uptake of antimyosin antibody in these patients was intense, discrete, and localized and was evident within 24 hours after injection (Figure 2). Scintigraphically defined regions of myocytic necrosis conformed to territories of occluded coronary arteries and correlated with electrocardiographic abnormalities. There was no uptake in the normal coronary artery territories, and no diffuse or global uptake.
|
All eight patients in our study presented with prolonged chest pain, which occurred suddenly, leading to an erroneous initial diagnosis of acute myocardial infarction. Although their hospital courses were usually associated with recurrent or intractable chest pain, there was no further evolution of the electrocardiographic changes indicative of ischemia. Coronary arteriography was performed to determine the extent and location of the coronary artery disease. The atypical evolution of illness in these eight patients, along with findings of normal coronary arteries and inexplicable abnormalities of left ventricular wall motion, led to the consideration of a primary myopathic process. Antimyosin myocardial scintigraphy or right ventricular endomyocardial biopsy subsequently demonstrated the presence of myocarditis in all eight patients.
Antimyosin antibody binds specifically to myocardial cells whose sarcolemma has lost its integrity15. Scintigraphic examination with this antibody has been used for the noninvasive detection of myocytic necrosis associated with acute myocardial infarction, with a sensitivity and specificity of over 90 percent16,17,18,19,20. Since myocytic necrosis is an essential component of myocarditis,11 almost all patients with biopsy-proved myocarditis have an abnormal antimyosin scan (sensitivity, 83 to 100 percent)13,14. Although the specificity of antimyosin scintigraphy for myocarditis is 53 to 58 percent, almost all normal antimyosin scans are associated with a biopsy negative for myocarditis (negative predictive value, 92 to 100 percent). The high sensitivity and high negative predictive value of a normal antimyosin scan make it a useful screening tool for patients with suspected myocarditis13,14.
Myocytic necrosis in myocarditis is associated with a pattern of antimyosin-antibody uptake distinctly different from that of myocardial infarction. Myocarditis is usually characterized by diffuse, faint, and heterogeneous uptake of antimyosin antibody (Figure 1A), because myocytic necrosis in this illness is typically multifocal. Acute myocardial infarction, on the other hand, is almost always characterized by intense, localized uptake of antibody in the region of an occluded coronary vessel (Figure 2). Intense, localized uptake of antimyosin antibody also occasionally occurs in myocarditis, but it is invariably associated with diffuse and global uptake of antibody.
Although an endomyocardial biopsy is the standard procedure for diagnosing myocarditis, our results demonstrate that antimyosin scintigraphy can be of substantial diagnostic usefulness in patients with presumed myocardial infarction but normal coronary arteries. In this context, diffuse myocytic necrosis beyond a coronary territory detected by antimyosin scintigraphy would indicate a strong likelihood of myocarditis. On the other hand, a pattern of antimyosin-antibody uptake conforming to an individual coronary vascular distribution despite the presence of normal coronary arteries would indicate other causes of nonatherosclerotic coronary artery disease, such as spasm or coronary embolism. A normal antimyosin scan would exclude both acute myocardial infarction and myocarditis.
This small series seems to confirm that myocarditis can masquerade as acute myocardial infarction. After the presence of normal coronary arteries has been confirmed in a patient presumed to have myocardial infarction, this alternative diagnosis should be considered if there is evidence of myocardial damage that does not conform to a particular coronary vascular distribution. The presence of diffuse myocardial involvement can be indicated by widespread electrocardiographic or wall-motion abnormalities. A diffusely positive antimyosin scan provides additional corroboration of a myopathic rather than an ischemic process.
Drs. Khaw and Haber own common stock in Centocor, the company that manufactures the monoclonal antibody used in this investigation.
We are indebted to Mr. Thomas J. McVarish for assistance in the preparation of the manuscript.
Source Information
From the Cardiac Unit (J.N., B.A.K., G.W.D., I.F.P., T.Y.), Division of Nuclear Medicine (J.N., B.A.K., H.W.S., T.Y.), and Department of Pathology (J.F.S., J.T.F.), Massachusetts General Hospital; Harvard Medical School (J.N., B.A.K., G.W.D., I.F.P., J.F.S., J.T.F., H.W.S., E.H., T.Y.); Northeastern University (J.N., B.A.K.); and Harvard School of Public Health (E.H.) -- all in Boston.
Address reprint requests to Dr. Yasuda at the Cardiac Unit and Division of Nuclear Medicine, Tilton 2, Massachusetts General Hospital, 32 Fruit St., Boston, MA 02114.
References
| |||||||||||||||||||||||||||||||
Related Letters:
Acute Myocarditis Masquerading as Acute Myocardial Infarction
Mascarenhas D.A.N., Spodick D. H., Dec G. W., Narula J., Yasuda T.
Extract |
Full Text
N Engl J Med 1993;
328:1714-1715, Jun 10, 1993.
Correspondence
This article has been cited by other articles:
HOME | SUBSCRIBE | SEARCH | CURRENT ISSUE | PAST ISSUES | COLLECTIONS | PRIVACY | TERMS OF USE | HELP | beta.nejm.org Comments and questions? Please contact us. The New England Journal of Medicine is owned, published, and copyrighted © 2009 Massachusetts Medical Society. All rights reserved. |
Previous
