Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology
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Cardiovasc. Pathol. · Jul 2020
Case ReportsImmunomodulatory treatment of immune checkpoint inhibitor-induced myocarditis: Pathway toward precision-based therapy.
Immune checkpoint inhibitor (ICI)-induced myocarditis carries a poor prognosis and is not fully understood. Similar to lymphocytic myocarditis and acute cellular rejection in heart transplant, ICI-induced myocarditis requires immune suppressive strategies. We aimed to describe ICI-induced myocarditis by presenting findings of comprehensive cardiovascular evaluations and outcomes of patients following a therapeutic approach similar to autoimmune disorders or allograft transplant rejection, and to discuss the molecular basis of the benefits of immune modulation and statins in ICI-myocarditis. ⋯ Cancer therapy was resumed in all patients. One patient expired 10 months after the myocarditis episode due to advanced malignancy; two patients were alive, free of heart failure symptoms and cancer progression, at 1-year follow-up, and 1 patient was rechallenged with ICI. We suggest that treatment with IVIG and statins may allow for a prompt resumption of anti-cancer therapy (including ICI) and improve outcomes.
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Cardiovasc. Pathol. · May 2020
Case ReportsAcute fatal myocarditis after a single dose of anti-PD-1 immunotherapy, autopsy findings: a case report.
Nivolumab (PD-1 inhibitor) and Ipilimumab (CTLA-34 inhibitor) are both commonly used immune checkpoint inhibitor therapies for various cancers. Various adverse events are associated with these therapies, including hepatitis, nephritis, dermatitis, and myocarditis. It is believed these adverse events occur in part because modified cellular receptors lead to enhanced CD4 and CD8 lymphoproliferation. ⋯ C4d staining was negative in the interstitial capillaries, suggesting that antibody-mediated injury of endothelial cells did not play a significant role in the pathogenesis of this myocarditis. Additional studies ruled out an infectious etiology. Immune checkpoint inhibitors are increasingly more common, and it is important clinicians are aware patients can present with myocarditis early in the course of treatment.
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Cardiovasc. Pathol. · May 2020
Relationships between visceral/subcutaneous adipose tissue FABP4 expression and coronary atherosclerosis in patients with metabolic syndrome.
Cytoplasmic fatty acid-binding proteins facilitate the transport of lipids to specific compartments in cells. Fatty acid-binding protein 4 (FABP4), also known as aP2 or A-FABP, plays a key role in the development of atherosclerosis, insulin resistance, obesity, and metabolic syndrome (MS). The FABP4 polymorphisms are associated with protein expression changes in vitro and metabolic and vascular alterations in vivo. The aim of this study was to investigate the association between FABP4 messenger ribonucleic acid (mRNA) expression levels in epicardial (EAT), pericardial (PAT), and subcutaneous adipose tissues (SAT), and the extent of coronary atherosclerosis in coronary artery disease (CAD) patients with MS. Furthermore, the relationship between the extent of coronary atherosclerosis and epicardial adipose tissue volume (EATV) and FABP4 gene variations was evaluated. ⋯ Our study results suggest that FABP4 expression in EAT is strongly associated with the extent of atherosclerosis and EATV in MS CAD patients.
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Cardiovasc. Pathol. · Jan 2020
Case ReportsIntramyocardial dissecting hematoma: fatal complication of reperfusion damage in myocardial infarction - an autopsy case report.
Intramyocardial dissection or intramyocardial dissecting hematoma is uncommon complication either of myocardial infarction or severe thoracic injury. Intramyocardial dissecting hematoma is caused by intersecting bleeding between the layers of myocardial fibers. In contrast to cardiac rupture, the myocardial wall maintains its integrity. ⋯ In the necropsy, the large intramyocardial dissecting hematoma in the very superficial layer of the left ventricular myocardium was found, accompanied with very small extent of necrotic myocardium in the neighborhood of the intramyocardial dissecting hematoma. The prevailing majority of the left ventricle thickness was vital. The lack of developed transmural infarction in our case leads us to hypothesis that the increased intravascular pressure during the reperfusion is the main contributor to the intramyocardial dissecting hematoma development, together with reduced biomechanical resistance of the capillaries affected by chronic ischemia.
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Cardiovasc. Pathol. · Nov 2019
Comparative StudyImmune checkpoint inhibition alters the inflammatory cell composition of human coronary artery atherosclerosis.
Immune checkpoint inhibition (ICI) has emerged as a promising new approach to treat malignancy. Such therapies can result in autoimmune-related complications such as myocarditis and hepatitis. The impact of ICI on sites of preexisting chronic inflammation has been less clear. Atherosclerosis is a chronic vascular disease with a significant inflammatory component. ⋯ In cancer patients, treatment with immune checkpoint inhibition is associated with an altered inflammatory cell composition in coronary artery atherosclerotic plaques with an increased ratio of CD3+ T cells to CD68+ macrophages. Thus, immune checkpoint inhibition may influence plaque progression and/or clinical coronary events.