Immune Checkpoint Inhibitor Associated Myocarditis and Cardiomyopathy: A Translational Review

SIMPLE SUMMARY: Immune checkpoint inhibitors (ICIs) are novel cancer therapeutics that address the immune system to attack malignancies. While this therapy has significantly improved the outcome of a variety of tumor patients, it has been associated with a new class of side effects, so-called immune-related adverse effects (irAEs). IrAEs can appear in various forms and involve any organ. Cardiovascular irAEs are highly feared due to their very high mortality and morbidity, and their underlying pathomechanisms are far from being understood. Researchers in immunology, molecular biology, and translational medicine need to work hand in hand to close these gaps in knowledge. At the same time, it is crucial for healthcare professionals, particularly cardiologists and oncologists, to have a good understanding of this increasingly common clinical problem. In this review, we discuss the various forms of cardiotoxicity of ICI therapy with emphasis on the currently known pathophysiology, clinical presentation, and diagnostics, as well as available treatment strategies. ABSTRACT: Immune checkpoint inhibitors (ICIs) have revolutionized oncology and transformed the treatment of various malignancies. By unleashing the natural immunological brake of the immune system, ICIs were initially considered an effective, gentle therapy with few side effects. However, accumulated clinical knowledge reveals that ICIs are associated with inflammation and tissue damage in multiple organs, leading to immune-related adverse effects (irAEs). Most irAEs involve the skin and gastrointestinal tract; however, cardiovascular involvement is associated with very high mortality rates, and its underlying pathomechanisms are poorly understood. Ranging from acute myocarditis to chronic cardiomyopathies, ICI-induced cardiotoxicity can present in various forms and entities. Revealing the inciting factors, understanding the pathogenesis, and identifying effective treatment strategies are needed to improve the care of tumor patients and our understanding of the immune and cardiovascular systems.