Cardiac sarcoidosis: systematic review of the literature on corticosteroid and immunosuppressive therapies

Abstract

BackgroundCardiac sarcoidosis (CS) is a life-threatening condition in which clear recommendations are lacking. We aimed to review systematically the literature on cardiac sarcoidosis treated by corticosteroids and/or immunosuppressive agents in order to update the management of CS.MethodsUsing Pubmed, Embase and Cochrane Library databases, we found original articles on corticosteroid and/or standard immunosuppressive therapies for CS which provided at least fair SIGN overall assessment of quality and analyse the relapse rate, major cardiac adverse events (MACEs) and adverse events. We base our methods on Prisma statement and checklist.ResultsWe retrieved 21 studies. Mean quality provided by SIGN assessment was 6.8/14 (range 5–9). Corticosteroids appeared to have a positive impact on left ventricular function, atrioventricular block, and ventricular arrhythmias. For corticosteroids alone, nine (45%) studies (n=351) provided data on relapses, representing an incidence of 34% (n=119). Three studies (14%, n=73) provided data on MACEs (n=33), representing 45% of MACEs in patients treated by corticosteroid alone. Nine studies provided data on adjunctive immunosuppressive therapy in which four studies (n=78) provided data on CS relapse, representing an incidence of 33% (n=26). Limitations consisted in no randomised control trial retrieved and unclear data on MACEs in patients treated by combined immunosuppressive agents and corticosteroids.ConclusionsCorticosteroids should be started early after diagnosis but the exact scheme is still unclear. Studies concerning adjunctive conventional immunosuppressive therapies are lacking and benefits of adjunctive immunosuppressive therapies are unclear. Homogenous data on CS long-term outcomes under corticosteroids, immunosuppressive therapies and other adjunctive therapies are lacking.

What cardiologists should know about cardiac sarcoidosis in 2022?

“…Studies regarding IT for CS are usually retrospective, monocentric and nonrandomized [30 ▪ ]. In patients with pulmonary sarcoidosis spontaneous remission is highly variable (55–90%) and depends on the stage of the disease [31–33].…”

“…There are however many questions remaining regarding steroid treatment in CS such as weaning schedule and duration of therapy [1 ▪ ,30 ▪ ,35,36,39 ▪ ,40,41]. Many centers advocate progressive weaning with a minimum of 6–12 months duration therapy, targeting the minimal dosage for complete or 'significant’ reduction in FDG uptake on controlled imaging performed 3–6 months after the last diminution of steroids [1 ▪ ,40].…”

“…A recent review by Stievenart et al on corticosteroids and IT [excluding tumor necrosis factor (TNF) inhibitors] in CS including 950 patients from studies selected between 1980 and June 2019, demonstrated that more than 75% of patients were treated with steroids alone and less than 25% with steroids and another immunosuppressive drug. After a mean follow-up ranging from 12 to 119 months about one-third of the patients had relapse when treated with steroids alone [30 ▪ ].…”

“…Also, Nagai et al reported that maintenance of low dose prednisone (5–10 mg/day) was associated with a better 10-year survival compared to discontinuation of corticosteroids [55]. However, most reviews agreed that data quality is too limited to draw any firm conclusion regarding steroids and IT on mortality and also on ventricular arrhythmias [30 ▪ ,35,36,39 ▪ ,40,41].…”

“…In a systematic recent review, Stievenart et al found a similar rate of relapse in patients receiving corticosteroids alone (34%) and combined IT (33%). Due to the heterogeneity of study design, follow-up, treatment schemes, different end points and missing data, a meta-analysis on CS was deemed impossible [30 ▪ ]. The actively enrolling CHASM-CS study, comparing a low-dose prednisone and methotrexate combination with standard-dose prednisone (maximum 30 mg/d) for 6 months, is poised to add much needed data to the field [67].…”