Giant Cell Myocarditis: Diagnosis and Treatment

Abstract

Giant cell myocarditis is a rare but devastating disease that usually affects young otherwise healthy individuals. Associations with thymoma, inflammatory bowel disease, and a variety of autoimmune disorders have been reported. The rate of death or heart transplantation is approximately 70% at 1 year. Data from a Lewis rat model and from observational human studies suggest that giant cell myocarditis is mediated by T lymphocytes and may respond to treatment aimed at attenuating T cell function. Recent findings from the Giant Cell Myocarditis Registry, a clinical and pathologic database from 63 cases of giant cell myocarditis gathered from 36 medical centers, include the following: The sensitivity of endomyocardial biopsy for giant cell myocarditis for patients who undergo transplantation or autopsy is 82 to 85%. Registry subjects who received cyclosporine in combination with steroid, azathioprine, or muromonab-CD3 have prolonged transplant-free survival (12.6 months vs. 3.0 months for no immunosuppression). Post-transplantation survival is approximately 71% at 5 years despite a 25% rate of giant cell infiltration in the donor heart. To confirm and extend these findings, a randomized trial of immunosuppression including muromonab-CD3, cyclosporine, and steroids is underway.

Giant Cell Myocarditis: A Brief Review

“…[17][18][19] However, electron microscopic studies to date have not identified viral particles in GCM, and no microbiologic agent has been directly identified in cardiac tissue by microscopy, tissue culture, or inoculation in experimental animals. 4,20 GROSS AND HISTOLOGIC FINDINGS Giant cell myocarditis is most commonly diagnosed via endomyocardial biopsy (52%), evaluation of the heart at autopsy (23%) or explantation (21%), or via examination of apical wedge sections removed at the time of ventricular assist device placement (4%). 5 On gross examination, cardiomegaly is frequently noted: in one series, the average heart weight in GCM was 476 g with a range of 405 to 580 g. 21 Serial sections typically reveal left or biventricular hypertrophy with accompanying dilatation.…”

“…In the United States in the 1990s, a group of major heart failure referral centers reportedly diagnosed GCM (via autopsy, endomyocardial biopsy, apical wedge resection, or cardiac explantation) an average of once every 21 months. 4 Historically, GCM and cardiac sarcoidosis were often conflated, as both presented in similarly aged patients and could result in a myocarditis characterized by giant cells and granulomas. However, it has since been established that the two are distinct clinicopathologic entities with significant differences in presentation, histologic features, and prognosis.…”

“…However, it has since been established that the two are distinct clinicopathologic entities with significant differences in presentation, histologic features, and prognosis. 4,5 CLINICAL FEATURES Giant cell myocarditis generally affects otherwise healthy young and middle-aged adults. In a large multicenter registry of GCM cases (n ¼ 63), patients ranged in age from 16 to 69 years at the time of symptom onset, with an average patient age of 42.6 years.…”

“…6 While GCM appears to have no sex predilection, approximately 20% of cases occur in patients with an autoimmune disorder such as inflammatory bowel disease, celiac disease, thyroiditis, or rheumatoid arthritis-among others. 4,10,11 Some cases of GCM are associated with tumors, most often thymoma and lymphoma. 4 …”

Nothing new in heart failure? A current misconception!

“…In issue 6 of HERZ this year, we reexamined some of the most recent developments in experimental genetic models of heart failure, from zebrafish and mice by Kloos, Katus, and Meder [2] and patients with dilated cardiomyopathy by Ruppert and Maisch [3] and Wicks and Elliot [4], to the diagnosis and treatment of giant cell myocarditis by Cooper and ElAmm [5], viral myocarditis by Kühl et al [6], and autoreactive myocarditis by Maisch and Pankuweit [7], of right ventricular cardiomyopathy by Thiene et al [8], restrictive cardiomyopathy by Zwas et al [9], as well as the remodeling and adverse remodeling process after myocardial infarction by Brenner and Ertl [10]. Biomarkers of inflammation, particularly interleukin 10, were examined by Izumi and Nishii [11].…”