Utility of Mechanistic Target of Rapamycin Inhibitors in Cardiac Sarcoidosis

Abstract

Background: Cardiac sarcoidosis is an uncommon but potentially devastating manifestation of sarcoidosis, which is a multisystem inflammatory granulomatous disease. Although corticosteroids are the mainstay of treatment, given the number of complications associated with their long-term use, there is increasing interest in the use of steroid-sparing agents. Recent basic and translational studies have suggested a role for the mechanistic target of rapamycin (mTOR) pathway in cardiac sarcoidosis.

Methods: We identified 4 patients treated at the Cedars-Sinai Cardiac Sarcoidosis Clinic who had active cardiac sarcoidosis and contraindications to corticosteroid intensification. We sought to evaluate the role of mechanistic target of mTOR inhibitors on the change in cardiac inflammation via cardiac ¹⁸ F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging.

Results: Of the 4 patients, 2 showed substantial improvement in cardiac inflammation on follow-up FDG-PET imaging after 6 months of treatment with an mTOR inhibitor but without corticosteroid intensification. There was a greater than 80% reduction in the cardiometabolic activity. The other 2 patients treated with an mTOR inhibitor had persistent evidence of cardiac inflammation on follow-up FDG-PET, necessitating an augmented treatment regimen.

Discussion: This case series represents the first clinical use of mTOR inhibitors for cardiac sarcoidosis, and it suggests that these agents may have a role in the management of cardiac sarcoidosis.

Keywords: Cardiac sarcoidosis; cardiomyopathy; heart failure; mTOR inhibitors.