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

ObjectiveTo 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.Methods24-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.ResultsΔFS 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<0.001) and bulbar symptoms (P<0.001). In addition, ALS patients in King's Stage 4 exhibited elevated HR-min (P=0.007) and decreased RR intervals (RRI) (P=0.032), SDNN (P=0.004), and standard deviation of the averages of NN intervals in all 5-min segments (SDANN) values (P=0.020) compared to controls. Patients in the ΔFS-fast group had a higher HR-min than those in the ΔFS-slow group (P=0.013) and controls (P=0.003) and lower SDNN (P=0.018) than controls. Both Kaplan-Meier estimator (P=0.03) and multivariable Cox regression analysis (P=0.019) showed that lower SDNN (cut-off value: 111 ms) was associated with poor survival in ALS patients.ConclusionUpon diagnosis, ALS patients in King's Stage 4 and with faster disease progression demonstrated significantly diminished cardiac autonomic control. Lower SDNN was associated with poor survival in ALS.