The Diagnosis and Management of Immune Checkpoint Inhibitor Cardiovascular Toxicity: Myocarditis and Beyond

Abstract

Recent years have brought major advancements in the use of immune therapy and specifically immune checkpoint inhibitors (ICIs) in cancer patients, with expanding indications for various malignancies resulting in the treatment of a large and increasing number of patients. While this therapy significantly improves outcomes in a variety of hematologic and solid tumors, the use of ICIs is associated with a substantial risk of immune-related adverse events. Cardiovascular toxicity, while not the most common side effect of ICIs, is associated with significant morbidity and mortality. It is therefore crucial for oncologists and cardiologists, as well as internists and emergency room physicians, to have a good understanding of this increasingly common clinical problem. In the present review, we discuss the cardiac aspects of ICI therapy with special emphasis on the clinical manifestations of their cardiovascular toxicity, diagnostic approaches, treatment and suggested surveillance.

Keywords: cancer; cardiovascular toxicity; immune checkpoint inhibitors; immune therapy; myocarditis.

Figure 1

(A) Number of ICI treatment-related publications in recent years. (B) Number of ICI cardiovascular toxicities-related publications in recent years.

Figure 2

(A) Arrow 1—Dense infiltrate of inflammatory cells, mainly lymphocytes and neutrophils, with evidence of necrosis (on the left). Arrow 2—A region with edema but many more normal nuclei and without an infiltration of lymphocytes and neutrophils. (B) Enlarged image of Figure 1: Left: Significant infiltration of inflammatory cells with necrosis and loss of normal myocardial tissue. Right: Near normal tissue with mild edema. (C) CD163 staining for macrophages with a very intense and large area positive for macrophages. (D) CD3 staining of lymphocytes. (E) CD4 staining representing a subpopulation of lymphocytes. (F) Staining for CD8 representing another subpopulation of lymphocytes. (G) Cells with CD20 staining demonstrating the near complete absence of B cells.

Figure 2

(A) Arrow 1—Dense infiltrate of inflammatory cells, mainly lymphocytes and neutrophils, with evidence of necrosis (on the left). Arrow 2—A region with edema but many more normal nuclei and without an infiltration of lymphocytes and neutrophils. (B) Enlarged image of Figure 1: Left: Significant infiltration of inflammatory cells with necrosis and loss of normal myocardial tissue. Right: Near normal tissue with mild edema. (C) CD163 staining for macrophages with a very intense and large area positive for macrophages. (D) CD3 staining of lymphocytes. (E) CD4 staining representing a subpopulation of lymphocytes. (F) Staining for CD8 representing another subpopulation of lymphocytes. (G) Cells with CD20 staining demonstrating the near complete absence of B cells.