One Surprise after Another
http://www.100md.com
《新英格兰医药杂志》
To the Editor: In the report by Leeper et al. (April 7 issue),1 the endomyocardial-biopsy specimen in their Figures 2 and 3 shows chronic changes, including extensive fibrosis, as stated by the authors, but it does not support a diagnosis of myocarditis.
The most widely accepted histologic criteria for the diagnosis of active myocarditis2 require the presence of an inflammatory infiltrate and associated myocyte damage (Figure 1). Myocardial changes, including myocyte hypertrophy, degeneration, and varying degrees of myocardial fibrosis, are typical of a chronic process, such as idiopathic dilated cardiomyopathy.3 The occasional presence of lymphocytes may be associated with areas of fibrosis.4 Cocaine use may have contributed to the multifocal fibrosis.5 Patients with dilated cardiomyopathy may undergo acute clinical decompensation without a secondary or superimposed pathologic process.
Figure 1. Active Myocarditis Consisting of an Interstitial Lymphocytic Infiltrate with Associated Myocyte Damage.
It has become increasingly apparent that histologic descriptors alone may not be sufficient to characterize myocarditis fully. However, despite limited sensitivity and specificity, the endomyocardial biopsy is an important diagnostic tool, particularly when the findings are positive. Those of the biopsy discussed by Leeper and colleagues are not.
Gayle L. Winters, M.D.
Brigham and Women's Hospital
Boston, MA 02115
gwinters@partners.org
Bruce M. McManus, M.D., Ph.D.
University of British Columbia
Vancouver, BC V6Z 1Y6, Canada
References
Leeper NJ, Wener LS, Dhaliwal G, Saint S, Wachter RM. One surprise after another. N Engl J Med 2005;352:1474-1479.
Aretz HT, Billingham ME, Edwards WD, et al. Myocarditis: a histopathologic definition and classification. Am J Cardiovasc Pathol 1987;1:3-14.
Winters GL, McManus BM. Myocarditis. In: Silver MD, Gotlieb AI, Schoen FJ, eds. Cardiovascular pathology. 3rd ed. New York: Churchill Livingstone, 2001:256-84.
Tazelaar HD, Billingham ME. Leukocytic infiltrates in idiopathic dilated cardiomyopathy: a source of confusion with active myocarditis. Am J Surg Pathol 1986;10:405-412.
Tazelaar HD, Karch SB, Stephens BG, Billingham ME. Cocaine and the heart. Hum Pathol 1987;18:195-199.
To the Editor: Leeper et al. do not mention polymerase-chain-reaction (PCR) testing for viral genomes in the endomyocardial-biopsy material. Such testing could have provided valuable additional information in the differential diagnosis of dilated cardiomyopathy. Where resources permit, it is important for practitioners who are performing catheterization and endomyocardial biopsy in suspected myocarditis to consider special handling of tissue in order to complete the PCR viral study, since the Dallas criteria1 for the diagnosis of active or borderline myocarditis are insufficiently sensitive to confirm a diagnosis of lymphocytic myocarditis, inflammatory cardiomyopathy, or both in many cases.
James D. Fett, M.D., M.P.H.
H?pital Albert Schweitzer
Deschapelles, Haiti
jdftlsc@techline.com
References
Aretz HT, Billingham ME, Edwards WD, et al. Myocarditis: a histopathologic definition and classification. Am J Cardiovasc Pathol 1987;1:3-14.
The authors and a colleague reply: The Dallas criteria for the microscopical diagnosis of myocarditis, to which Winters and McManus refer, have been criticized for both low sensitivity and poor interobserver concordance.1 Part of the problem is the wide spectrum of inflammatory activity seen in myocarditis. Winters and McManus's Figure 1, which clearly shows florid inflammation, is on one end of the spectrum. On the other end, we consider our patient's sparse lymphocytic infiltrate and rare myocyte damage to be more typical.2 In light of this, we believe that the biopsy findings, when viewed in the context of the patient's profound acute deterioration (with dynamic electrocardiographic abnormalities and rapidly escalating levels of troponins) and clinical rebound, are consistent with the presence of active myocarditis, perhaps superimposed on a chronic process.
Given the shortcomings of histology-based strategies, we appreciate Fett's comments regarding PCR. Though initially plagued by technical problems and variable sensitivities, nested PCR is becoming an important and reliable tool in the identification of causative viral agents in acute myocarditis. Recent advances now allow detection of ongoing viral replication, which may help direct antiviral therapy, and the identification of enterovirus in myocardium, which has been associated with a poor prognosis.3,4 As test standardization and test characteristics improve and the significance of viral presence in myocardium is better defined, the use of PCR is likely to become a standard approach to the diagnosis of acute myocarditis.
Nicholas J. Leeper, M.D.
Philip Ursell, M.D.
Robert M. Wachter, M.D.
University of California, San Francisco
San Francisco, CA 94143-0120
bobw@medicine.ucsf.edu
The most widely accepted histologic criteria for the diagnosis of active myocarditis2 require the presence of an inflammatory infiltrate and associated myocyte damage (Figure 1). Myocardial changes, including myocyte hypertrophy, degeneration, and varying degrees of myocardial fibrosis, are typical of a chronic process, such as idiopathic dilated cardiomyopathy.3 The occasional presence of lymphocytes may be associated with areas of fibrosis.4 Cocaine use may have contributed to the multifocal fibrosis.5 Patients with dilated cardiomyopathy may undergo acute clinical decompensation without a secondary or superimposed pathologic process.
Figure 1. Active Myocarditis Consisting of an Interstitial Lymphocytic Infiltrate with Associated Myocyte Damage.
It has become increasingly apparent that histologic descriptors alone may not be sufficient to characterize myocarditis fully. However, despite limited sensitivity and specificity, the endomyocardial biopsy is an important diagnostic tool, particularly when the findings are positive. Those of the biopsy discussed by Leeper and colleagues are not.
Gayle L. Winters, M.D.
Brigham and Women's Hospital
Boston, MA 02115
gwinters@partners.org
Bruce M. McManus, M.D., Ph.D.
University of British Columbia
Vancouver, BC V6Z 1Y6, Canada
References
Leeper NJ, Wener LS, Dhaliwal G, Saint S, Wachter RM. One surprise after another. N Engl J Med 2005;352:1474-1479.
Aretz HT, Billingham ME, Edwards WD, et al. Myocarditis: a histopathologic definition and classification. Am J Cardiovasc Pathol 1987;1:3-14.
Winters GL, McManus BM. Myocarditis. In: Silver MD, Gotlieb AI, Schoen FJ, eds. Cardiovascular pathology. 3rd ed. New York: Churchill Livingstone, 2001:256-84.
Tazelaar HD, Billingham ME. Leukocytic infiltrates in idiopathic dilated cardiomyopathy: a source of confusion with active myocarditis. Am J Surg Pathol 1986;10:405-412.
Tazelaar HD, Karch SB, Stephens BG, Billingham ME. Cocaine and the heart. Hum Pathol 1987;18:195-199.
To the Editor: Leeper et al. do not mention polymerase-chain-reaction (PCR) testing for viral genomes in the endomyocardial-biopsy material. Such testing could have provided valuable additional information in the differential diagnosis of dilated cardiomyopathy. Where resources permit, it is important for practitioners who are performing catheterization and endomyocardial biopsy in suspected myocarditis to consider special handling of tissue in order to complete the PCR viral study, since the Dallas criteria1 for the diagnosis of active or borderline myocarditis are insufficiently sensitive to confirm a diagnosis of lymphocytic myocarditis, inflammatory cardiomyopathy, or both in many cases.
James D. Fett, M.D., M.P.H.
H?pital Albert Schweitzer
Deschapelles, Haiti
jdftlsc@techline.com
References
Aretz HT, Billingham ME, Edwards WD, et al. Myocarditis: a histopathologic definition and classification. Am J Cardiovasc Pathol 1987;1:3-14.
The authors and a colleague reply: The Dallas criteria for the microscopical diagnosis of myocarditis, to which Winters and McManus refer, have been criticized for both low sensitivity and poor interobserver concordance.1 Part of the problem is the wide spectrum of inflammatory activity seen in myocarditis. Winters and McManus's Figure 1, which clearly shows florid inflammation, is on one end of the spectrum. On the other end, we consider our patient's sparse lymphocytic infiltrate and rare myocyte damage to be more typical.2 In light of this, we believe that the biopsy findings, when viewed in the context of the patient's profound acute deterioration (with dynamic electrocardiographic abnormalities and rapidly escalating levels of troponins) and clinical rebound, are consistent with the presence of active myocarditis, perhaps superimposed on a chronic process.
Given the shortcomings of histology-based strategies, we appreciate Fett's comments regarding PCR. Though initially plagued by technical problems and variable sensitivities, nested PCR is becoming an important and reliable tool in the identification of causative viral agents in acute myocarditis. Recent advances now allow detection of ongoing viral replication, which may help direct antiviral therapy, and the identification of enterovirus in myocardium, which has been associated with a poor prognosis.3,4 As test standardization and test characteristics improve and the significance of viral presence in myocardium is better defined, the use of PCR is likely to become a standard approach to the diagnosis of acute myocarditis.
Nicholas J. Leeper, M.D.
Philip Ursell, M.D.
Robert M. Wachter, M.D.
University of California, San Francisco
San Francisco, CA 94143-0120
bobw@medicine.ucsf.edu