Prognostic value of CMR versus FDG-PET in cardiac sarcoidosis: insights from the MYSTICS registry

Background Cardiac sarcoidosis (CS) is associated with heart failure and malignant ventricular arrhythmias. While FDG-PET assesses active inflammation and CMR characterizes myocardial function and fibrosis, their comparative value for long-term prognostication remains incompletely defined. Objectives To compare the prognostic performance of CMR-derived indices (LVEF and late gadolinium enhancement [LGE] extent) with FDG-PET inflammatory indices, and to explore practical risk stratification using their combination in a large, multicenter CS cohort. Methods This multicenter retrospective observational study analyzed 701 patients with CS from the MYSTICS registry (2012–2021) who underwent both CMR (including LGE assessment) and FDG-PET. The primary endpoint was a composite of all-cause death, heart failure hospitalization, and lethal ventricular arrhythmias. CMR variables included LVEF and LGE extent quantified by the number of involved segments on the 17-segment model. FDG-PET variables included presence/pattern of myocardial uptake and the number of segments with abnormal uptake. Cox proportional hazards modeling identified independent predictors, and Kaplan–Meier analyses assessed event-free survival across risk strata. Results Over a median follow-up of 4.0 years (IQR 2.5–6.2), 181 patients (26%) experienced the primary endpoint. In multivariable analysis, reduced LVEF, older age, male sex, chronic kidney disease, isolated CS, and greater LGE extent were independently associated with the primary endpoint. Receiver-operating characteristic analyses yielded optimal cutoffs of LVEF 46% and LGE extent of 3 segments. When stratified into four groups by these thresholds, the group with LVEF <46% and LGE ≥3 segments had the worst prognosis. In contrast, FDG-PET myocardial uptake extent was not an independent predictor of the primary endpoint, although it showed modest discrimination for relapse (optimal cutoff 6 segments; AUC 0.60). Conclusions In this large multicenter CS cohort, CMR-derived LVEF and LGE extent provided stronger long-term prognostic information than FDG-PET inflammatory indices for major adverse outcomes. A simple combination of LVEF and LGE extent enabled clinically practical risk stratification and may help guide intensity of follow-up and therapeutic decision-making.