Epidemiology of long-term mortality and cardiovascular events in cardiac sarcoidosis

Background Sarcoidosis is a systemic granulomatous disease of unknown etiology. Cardiac sarcoidosis (CS) can lead to arrhythmias and heart failure (HF), which are often recurrent and associated with fatal outcomes. However, large-scale epidemiological data on the incidence of cardiovascular events and mortality in patients with CS, particularly those accounting for recurrent events during long-term follow-up, remain limited. Purpose To describe the incidence of cardiovascular events and mortality, as well as cause of death, in patients with CS and to examine their characteristics using a nationwide CS registry. Methods We analyzed data from a Japanese multicenter retrospective registry including patients with systemic and isolated CS. Consecutive patients with CS who visited participating institutions between April 2012 and March 2021 were included in this registry. Results A total of 2,747 patients were analyzed in this study. The mean age was 61.8 ± 11.3 years, and 64.4% were female. A total of 803 patients (29.2%) had isolated CS. The median follow-up duration was 6.0 years (interquartile range, 3.7–9.3 years). During the follow-up period, 356 deaths (13.0%) occurred, corresponding to a mortality rate of 1.82 (95% confidence interval [CI], 1.64–2.02) per 100 patient-years. Among the deaths, 49.0% were due to cardiovascular causes, with pump failure death as the leading cause (23.6%) followed by sudden cardiac death (11.8%), death due to arrhythmia (6.5%), and stroke (2.2%), while 49.3% were due to non-cardiovascular causes with infection as the leading cause (13.8%). Hospitalizations for HF were observed in 462 patients (16.8%), and 47.0% of these patients experienced recurrent rehospitalizations after the first hospitalization for HF. The incidence rate of hospitalization for HF was 2.55 per 100 patient-years (95% CI, 2.33–2.80). Fatal arrhythmic events occurred in 245 patients (8.9%). These events included implantable cardioverter-defibrillator shock (0.91 per 100 patient-years [95% CI, 0.79–1.06]), ventricular tachycardia storm (0.41 per 100 patient-years [95% CI, 0.33–0.51]), and resuscitated ventricular tachycardia or fibrillation (0.44 per 100 patient-years [95% CI, 0.36–0.55]), respectively. In the analysis by sarcoidosis subtype, mortality rates were 1.58 (95% CI, 1.39–1.80) in systemic sarcoidosis, and 2.46 (95% CI, 2.10–2.92) in isolated CS. The incidence rate of hospitalization for HF was 2.12 per 100 patient-years (95% CI, 1.89–2.39) in systemic sarcoidosis, and 3.75 (95% CI, 3.23–4.35) in isolated CS. Conclusion This large nationwide multicenter registry provides comprehensive epidemiological data on long-term cardiovascular events and mortality in patients with CS. These findings underscore the substantial burden of cardiovascular complications in this population and support the importance of long-term follow-up.