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

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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 <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. Conclusion Upon 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.

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