Arrhythmic Manifestations and Outcomes of Definite and Probable Cardiac Sarcoidosis

Background The 2014 HRS consensus statement defines histological (definite) and clinical (probable) diagnostic categories of cardiac sarcoidosis (CS), but few studies have compared their arrhythmic phenotypes and outcomes. Objective Evaluate the electrophysiologic/arrhythmic phenotype and outcomes of patients with definite and probable CS. Methods We analyzed the arrhythmic/electrophysiologic phenotype in a single-center North American cohort of 388 patients (median age 56 years, 39% female) diagnosed with definite (n=58) or probable (n=330) CS (2000-2022). The primary composite outcome was survival to first ventricular tachycardia/fibrillation (VT/VF) or sudden cardiac death (SCD). Key secondary outcomes were also assessed. Results At index evaluation, in situ cardiac implantable electronic devices and antiarrhythmic drug use were more common in definite CS. At median follow-up 3.1 years, the primary outcome occurred in 22 (38%) definite and 127 (38%) probable CS patients (log-rank p=0.55). In multivariable analysis, only higher 18F-FDG SUVmax myocardium:SUVmax blood pool ratio (HR 1.09 [95% CI 1.03, 1.15], p=0.003, per 1 unit increase) was associated with the primary outcome. During follow-up, definite CS patients had higher burden of device-treated VT/VF events (mean 2.86 vs 1.56 per patient-year) and higher rate of progression to heart transplant/left ventricular assist device implantation, but no difference in all-cause mortality compared to probable CS patients. Conclusion Definite and probable CS patients had similarly high risks of first sustained VT/VF/SCD and all-cause death though definite CS patients had a higher overall arrhythmic burden. Both CS diagnostic groups as defined by the 2014 HRS criteria require an aggressive approach to prevent arrhythmic complications.