Heart rate variability provides prognostic value in multiple system atrophy

PURPOSE: Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by autonomic dysfunction, parkinsonism, and cerebellar impairment. Understanding the physiological correlates of disease severity and survival remains challenging due to heterogeneity in disease progression. Heart rate variability (HRV) is a noninvasive measure of autonomic nervous system function. However, the role of nonlinear HRV in MSA remains incompletely understood. METHODS: This study investigated the association between HRV features, clinical severity, and survival in MSA (n = 214). Regression models were used to examine relationships between HRV and disease severity assessed by the Unified MSA Rating Scale (UMSARS), as well as time to death. Survival analyses evaluated the contribution of HRV features to risk stratification, and mediation analysis explored the relationships among HRV, UMSARS, and survival. RESULTS: HRV features were negatively associated with disease severity, consistent with progressive autonomic dysfunction. While individual HRV features showed limited associations with UMSARS, their combination demonstrated a stronger relationship. Models incorporating HRV features showed associations with time to death comparable to those based on UMSARS, and the combined inclusion of HRV and UMSARS was associated with improved accuracy. Mediation analyses suggested that HRV captures physiological information related to survival that is not fully reflected by clinical severity scores. CONCLUSIONS: HRV features are associated with disease severity and survival in MSA and provide complementary physiological information beyond established clinical scales. These findings support the relevance of HRV as an exploratory modeling tool for autonomic dysfunction in MSA and highlight candidate features for future longitudinal and validation studies, rather than establishing a validated prognostic model.