Heart rate variability provides prognostic value in multiple system atrophy

Bastos P(1)(2)(3), Kermorgant M(4)(5)(6), Fabbri M(7)(8)(4)(5)(6), Roche F(9),
Pichot V(9), Ory-Magne F(7)(4)(10), Leung C(7)(4)(10), Rascol O(7)(8)(4)(5), G
Meissner W(11)(12)(13), Foubert-Samier A(11)(12), Bendetowicz D(11)(12), Proust
Lima C(14), Pavy-le-Traon A(4)(5)(6).

Author information:
(1)Department of Clinical Pharmacology and Neurosciences, University of Toulouse
3, Hôpital Pierre Paul Riquet, Toulouse University Hospital, Place du Dr Baylac,
31059, Toulouse, France. .
(2)French Clinical Research Network (F-CRIN) for Parkinson’s Disease and
Movement Disorders (NS-Park-F-CRIN), Toulouse, France.
.
(3)Clinical Investigation Center CIC 1436, CHU de Toulouse, Toulouse, France.
.
(4)Clinical Investigation Center CIC 1436, CHU de Toulouse, Toulouse, France.
(5)French MSA Reference Center, Neurology Department, Toulouse University
Hospital, Toulouse, France.
(6)ToNIC – Toulouse Neuro Imaging Center – INSERM – UMR 1214, Toulouse, France.
(7)Department of Clinical Pharmacology and Neurosciences, University of Toulouse
3, Hôpital Pierre Paul Riquet, Toulouse University Hospital, Place du Dr Baylac,
31059, Toulouse, France.
(8)French Clinical Research Network (F-CRIN) for Parkinson’s Disease and
Movement Disorders (NS-Park-F-CRIN), Toulouse, France.
(9)Department of Clinical and Exercise Physiology Saint-Etienne University
Hospital, Jean Monnet University, Saint-Etienne, France.
(10)Centre de Référence Constitutif des Syndromes Paranéoplasiques et
Encéphalites Auto-Immunes, CHU Toulouse, Toulouse, France.
(11)Service de Neurologie des Maladies Neurodégénératives, IMNc, CRMR AMS, CHU
Bordeaux, Bordeaux, France.
(12)University of Bordeaux, CNRS, IMN, UMR 5293, Bordeaux, France.
(13)Department of Medicine, University of Otago, Christchurch, and New Zealand
Brain Research Institute, Christchurch, New Zealand.
(14)INSERM, UMR1219, Bordeaux Population Health Research Center, University of
Bordeaux, ISPED, Bordeaux, France.

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.

© 2026. Springer-Verlag GmbH Germany.

DOI: 10.1007/s10286-026-01190-8
PMID: 41731258

Conflict of interest statement: Declarations. Conflict of interest: Margherita
Fabbri has received honoraria to speak from AbbVie, ORKYN, and BIAL,
consultancies from BIAL and LVL Medical; grants from France Parkinson, Horizon
2022 French Ministry of Health and MSA Coalition. Professor Olivier Rascol has
received honoraria for scientific advice from Lundbeck, ONO Pharma and TEVA and
scientific grants from ARAMISE, MSA Coalition, Lundbeck, ONO Pharma and Takeda.
Ethical approval and consent to participate: This study was conducted in
accordance with the Declaration of Helsinki and approved by the Toulouse
University Hospital Ethics Committee as part of a broader prospective
longitudinal study on natural MSA progression (CNIL 1338780, CCTIRS 10.065).
Consent for publication: All patients have consented to be part of this study
and have their data published.

Auteurs Bordeaux Neurocampus