Inflammasome Formation in Granulomas in Cardiac Sarcoidosis.

September 2019 1 Cardiac sarcoidosis (CS) can occur in ≤25% of patients with sarcoidosis in other organ systems leading to life-threatening ventricular arrhythmias, heart block, heart failure, and death. An essential part of the innate immune system, the inflammasome is a macromolecular structure in the cell that responds to a danger signal by releasing IL (interleukin)-1β and amplifying the inflammatory response.1 IL-1β is indeed the prototypical proinflammatory cytokine processed within the inflammasome.1 A role for IL-1β in the pathogenesis of sarcoidosis has been proposed. IL-1β participates in the pathogenesis of granuloma formation in the mouse.2 The ratio of IL-1 receptor antagonist/IL-1β was a marker in predicting the persistence of pulmonary granulomatous lesions in patients.3 Importantly, the main mechanism of action of IL-1β is to activate the nuclear transcription factor NF-kB (nuclear factor-kappa B), also a target of glucocorticoids. We hypothesized that CS would lead to the formation of the inflammasome. We studied cardiac pathology specimens from 3 patients with a diagnosis of CS based on Heart Rhythm Society 2014 Consensus Statement Criteria4 obtained from the left ventricle during total artificial heart implantation in 1 patient and left ventricular assist device implantation and subsequent orthotopic heart transplant in 2 patients. The regions of the heart to be sampled were chosen based on abnormalities upon macroscopic inspection. The study was approved by the Institutional Review Board of the Virginia Commonwealth University, Richmond, VA. Patient No. 1 is a 59-year-old man with pulmonary sarcoidosis who presented with complete heart block, ventricular tachycardia, and left ventricular systolic dysfunction. The patient was treated with prednisone, mycophenolate mofetil, and hydroxychloroquine. Cardiac 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) 1 month before total artificial heart showed severe-intensity FDG uptake in the apical septum and inferior walls (Figure [A and B]). Because of progressive heart failure symptoms, he underwent total artificial heart followed 7 months later by orthotopic heart transplant. Patient No. 2 is a 60-year-old woman with biopsy-proven pulmonary sarcoidosis who presented with complete atrioventricular block and left ventricular systolic dysfunction. FDG-PET performed 2 months before left ventricular assist device showed moderate-intensity diffuse FDG uptake extending into the left ventricular apex (Figure [E and F]). She then underwent Heartmate II implantation followed 3 months later by orthotopic heart transplant. Patient No. 3 is a 64-year-old male with sinus node dysfunction and nonischemic cardiomyopathy. Cardiac PET showed FDG uptake concerning for CS and hilar and mediastinal lymphadenopathy. Carinal lymph node biopsy showed noncaseating granulomas. He was treated with prednisone and methotrexate. FDG-PET performed showed mild-intensity patchy hypermetabolic activity in the left ventricle with mild activity in the distal lateral wall extending into the distal anterolateral wall RESEARCH LETTER