The spectrum of macrophage-predominant inflammatory myocardial disease presenting as fulminant heart failure
Introduction
Inflammatory myocardial disease has been defined by the World Health Organization (WHO) as myocarditis with cardiac dysfunction [1]. Etiologies of myocarditis are infectious, autoimmune, and idiopathic, and myocarditis may be primary, i.e. limited to the heart, or secondary, i.e., occurring as part of a multisystemic process. Myocarditis is an important consideration in the differential diagnosis of unexplained heart failure, and endomyocardial biopsy (EMB) results are integral both in directing treatment and in determining prognosis [[2], [3], [4]–5]. The diagnosis of myocarditis by endomyocardial biopsy is principally based on identifying and characterizing myocardial inflammatory infiltrates by light microscopic morphology and immunohistochemical characterization of the inflammatory infiltrate, sometimes in conjunction with molecular identification of infectious agents, including viruses [2] Current morphological classification of myocarditis based on endomyocardial biopsy findings includes lymphocytic, eosinophilic, giant cell, and granulomatous subtypes [6].
Since 2019 we have seen 6 cases of fulminant heart failure in which endomyocardial biopsy showed inflammation with an infiltrate composed predominantly of macrophages (histiocytes), identified by immunohistochemistry for CD68. Three cases showed coagulative myocyte necrosis, and in three cases, biopsy findings resembled those described in antibody mediated rejection of cardiac allografts, 2 of these in patients with systemic lupus erythematosus (SLE). The details of histopathology and immunohistochemistry varied among the 6 biopsies, and the responses to clinical management also were variable, ranging from spontaneous remission to progressive heart failure. The purpose of this report is to describe and discuss the heterogeneous clinical and pathological details of these cases in order to better characterize the clinicopathological significance of endomyocardial biopsies showing predominantly histiocytic infiltrates.
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Patients
All 6 cases involve patients who presented to the Heart Failure and Transplant Unit of at University of Rochester Medical Center, Rochester New York. In the time interval in which these cases were received, a total of 48 endomyocardial biopsies for unexplained heart failure were performed at our institution. All patients presented in cardiogenic shock; patients 2, 3, 4, and 6 were referred from hospitals outside the URMC system. Cases were equally distributed among sexes. Cases 1 and 2 had no
Biopsy findings
Biopsy results are summarized in Table 2.
Discussion
Endomyocardial biopsies in all 6 of our cases showed myocardium with inflammation composed predominantly of CD68 positive macrophages and/or monocytes, and for this reason, we have classified them as representing histiocytic inflammatory myocardial disease or “histiocytic myocarditis.” This diagnostic designation conveys the essential pathoanatomical features of these biopsies and also reflects the acute clinical presentation of our 6 patients. However, histiocytic myocarditis per se is not
Conclusions
Macrophage predominant inflammation may be seen in endomyocardial biopsies of patients with acute heart failure, and we propose that HMID be recognized as one morphological subtype of acute myocarditis that may present in a variety of clinical contexts. The features of our cases that suggest antibody and/or complement mediated injury in patients with HMID could reflect a potential for therapeutic approaches analogous to those used for antibody-mediated allograft rejection, e.g. intravenous
Acknowledgments
The authors thank Sierra Kovar and Karen Vanderbilt for expert technical assistance.
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Funding: This project was funded by the Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Disclosures: Nothing to disclose.