Defining the contributors to sudden cardiac death in sarcoidosis: a nationwide study

Background Sarcoidosis can cause granulomatous inflammation and fibrosis in the heart, resulting in an increased risk of sudden cardiac death(SCD). Whether inflammation or fibrosis confers greatest risk is unknown. Objectives To identify risk factors for SCD in sarcoidosis. Methods A retrospective cohort study was performed using Australian data from the National Coronial Information System, a database of deaths referred to coroners from 2000 onwards. Individuals with sarcoidosis undergoing autopsy including cardiac examination and histology were identified by keyword/ICD-10 code search. Odds ratios(OR) were calculated with 95% confidence intervals(CI). Results Among 287 decedents with sarcoidosis(median age 54 years(IQR 44-65), 63% male), 67% experienced SCD. SCD cases had a greater overall burden of sarcoidosis(median 3(IQR 2-4) vs. 2(IQR 1-3) organs involved, p=0.002), and more frequent cardiac involvement(76% vs. 26%, p<0.001). SCD cases were less likely to have sarcoid diagnosed antemortem(20% vs. 40%, p=0.001). Associations of SCD were the presence of myocardial granulomas alone(OR 11.5, 95%CI2.2-59.7, p=0.004) or in combination with fibrosis(OR 5.4, 95%CI2.3-12.5, p<0.001). Isolated myocardial fibrosis was not associated with SCD(p=0.300). Coronary artery disease (OR 2.6, 95%CI1.3-5.2, p=0.009), cardiomegaly(OR3.6, 95%CI1.8-7.0, p<0.001) and conduction system fibrosis/inflammation(OR4.2, 95%CI 1.3-13.2, p=0.015) were associated with SCD. Conclusions SCD in sarcoidosis was associated with more extensive organ involvement, the presence of cardiac involvement and comorbid atherosclerotic coronary disease. Key pathological associations of SCD were myocardial granulomatous inflammation with or without fibrosis, and conduction system lesions. These findings highlight the need for more sensitive antemortem methods to identify inflammation in sarcoidosis, which is potentially modifiable with treatment.