Expression of T-cell populations and molecular markers of human myocardium with checkpoint-induced myocarditis.

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79 Background: Checkpoint Inhibitors have become first line therapy for a variety of solid and liquid malignancy. Immunotherapeutic agents predominantly target CTLA-4 and PD-L1. Efficacy has been demonstrated, and toxicities, especially cardiac manifested as myocarditis. The incidence of myocarditis is relatively low, fatality with monotherapy approaches 50% and with dual Immunotherapy is over 75%. No screening biomarkers or cardiac imaging predict a priori whom will develop myocarditis, nor which patients will be at risk. The frequency of these targets are unknown in the human heart. Methods: We present a case study of a patient with a diagnosis of urothelial carcinoma to lung and lymph nodes treated with systemic nivolumab plus NKTR after cycle 2 he presented with one week history of shortness of breath and hemodynamically unstable complete heart block requiring temporary transvenous pacemaker. Initial Troponin = 356, BNP = 2106. Given high suspicion for cardiovascular disease and or myocarditis, a left heart angiogram, right heart catheterization and endomyocardial biopsy of right ventricle were performed. RV biopsies were obtained percutaneously from right internal jugular approach with fluoroscopic guidance. Pulmonary capillary wedge pressure was 23mmHg. Persistent complete heart block was present during weaning attempts from temporary pacemaker and a percutaneous dual chamber pacemaker was implanted. Results: Coronary angiogram showed non obstructive disease, endomyocardial biopsy revealed lymphocytic infiltrate with necrosis based on Dallas Criteria. Immunohistochemistry showed, predominance of CD3,CD4,CD8,CD20,CD68 and PD-L1 staining was grossly positive compared to control samples. The patient was treated with methylprednisone 1mg/kg IV BID, plasmapheresis times 5 cycles, mycophenolate mofetil 500mg IV BID with resolution of symptoms and discharged to home. Conclusions: We present a patient with nivolumab induced myocarditis complicated with myocarditis and complete heart block. The pathological approach of T-Cell phenotyping is unique and identifies a novel approach to precision driven diagnosis, the incidence of PD-L1 expression in the human heart is unknown.