Heart Rate Variability Provides Prognostic value in Multiple System Atrophy

Abstract Purpose Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by autonomic dysfunction, parkinsonism, and cerebellar impairment. Predicting disease severity and survival remains challenging due to the heterogeneity of disease progression. Heart rate variability (HRV), a non-invasive measure of autonomic nervous system function, has been used as a biomarker of autonomic failure. However, the role of non/linear HRV in MSA remains underexplored, and its prognostic value is yet to be fully established. Methods This study aimed to evaluate the predictive value of HRV features in MSA, identifying HRV features most predictive of mortality and survival, and assessing whether HRV provides unique, complementary insights beyond traditional clinical severity measures (n = 214). Regression models were employed to assess the association between HRV features and disease severity, as assessed by the Unified MSA Rating Scale (UMSARS), or time-to-death. Survival analyses were used to investigate HRV’s prognostic value. Mediation analysis explored the relationship between HRV, UMSARS, and survival. Results HRV features demonstrated negative correlations with disease severity, mirroring clinical deterioration. While no single HRV feature showed strong correlations with the UMSARS, their combination was a significant predictor. HRV alone predicted time-to-death almost as well as the UMSARS and combining HRV with UMSARS significantly improved survival prediction accuracy. HRV maintained a direct effect on survival, independent of the UMSARS, highlighting its distinct physiological relevance. Conclusions HRV provides valuable, complementary information beyond UMSARS in predicting disease severity and survival in MSA. While HRV alone has only moderate predictive power, it captures distinct physiological processes not reflected by traditional clinical scales.