Cardiac autonomic dysfunction is associated with advanced stage, fast progression and poor survival in amyotrophic lateral sclerosis

Objective To investigate the association of cardiac autonomic dysfunction with clinical staging and disease progression rate upon diagnosis of amyotrophic lateral sclerosis (ALS), and its impact on survival. Methods 24-hour Holter was performed in 95 ALS patients at diagnosis and 39 controls. Patients were grouped by King’s Clinical Staging and progression rate (ΔFS, median cut-off 0.67). Heart rate variability parameters were compared across groups. A survival-based cut-point optimization approach was used to determine the cut-off value of standard deviation of all normal-to-normal intervals (SDNN). Kaplan-Meier estimator and multivariable Cox regression analysis were used to evaluate of the effect of SDNN on survival during a median follow-up of 21.5 months. Results ΔFS in ALS patients in King’s Stage 4 upon diagnosis was faster ( P =0.007) compared to that of those diagnosed in earlier stages, featuring a higher incidence of respiratory ( P