Relationship of mild to moderate impairment of left ventricular ejection fraction with fatal ventricular arrhythmic events in cardiac sarcoidosis

Background Current guidelines recommend placing an implantable cardiac defibrillator for patients with cardiac sarcoidosis (CS) and severely impaired left ventricular ejection fraction (LVEF) of ≤35%. In this study, we aimed to explore the association between mild or moderate LVEF impairment and fatal ventricular arrhythmic event (FVAE). Methods Here, 401 patients with CS without sustained ventricular arrhythmia at diagnosis were retrospectively analyzed. The primary endpoint was an FVAE, which was defined as the combined endpoint of documented ventricular tachycardia or ventricular fibrillation and sudden cardiac death. Two cut-off points for LVEF were used; sex-specific lower threshold of normal range of LVEF, 52% for men and 54% for women, and LVEF of 35% which is used in the current guidelines. Results During a median follow-up of 3.2 years, 58 FVAEs were observed, and the 5- and 10-year estimated incidences of FVAE were 16.8% and 23.0%, respectively. All patients were classified into three groups according to LVEF: impaired LVEF group, mild to moderate impairment of LVEF group, and maintained LVEF group. Multivariable competing risk analysis showed that both the impaired LVEF group (HR: 3.02, 95% CI: 1.25–7.32) and the mild to moderate impairment of LVEF group (HR: 2.12, 95% CI: 1.02–4.40) were associated with a higher incidence of FVAE than the maintained LVEF group after adjustment for covariates. Conclusions Patients with CS are at a high risk of FVAEs, regardless of documented ventricular arrhythmia at the time of diagnosis. In patients with CS, even mild to moderate impairment of LVEF is associated with FVAEs. Clinical Perspective What is Known Patients with cardiac sarcoidosis (CS) are at a higher risk of fatal ventricular arrhythmic event (FVAE). Current guidelines adopt left ventricular ejection fraction (LVEF) ≤35% as a cut-off value for Class I indication for implantable cardioverter defibrillators (ICD) implantation. What the Study Adds Cumulative incidence curves showed that the 5-year FVAE risk in patients with CS with preserved LVEF was 7%, which was as high as that of non-ischemic cardiomyopathy with reduced LVEF. For risk stratification of future fatal ventricular arrhythmic events, even milder left ventricular ejection fraction impairment, compared to that currently suggested by guidelines, needs to be considered as a risk factor in patients with cardiac sarcoidosis. Preventive strategies for fatal ventricular arrhythmic events and sudden cardiac death using an implantable cardiac defibrillator according to individualized risk stratification need to be developed and evaluated in clinical studies of patients with cardiac sarcoidosis.