Heart Rate Variability as a Physiological Marker of Autonomic Dysfunction in ALS with Preserved Respiratory Function

Topic:

Clinical Trials

Poster Number: 105 S

Author(s):

Ushna Khan, MD, University of Florida, Wagner Souza Leite, MS, University of Florida, May Smith-Hublou, PhD, CCC-SLP, University of Florida, Sandra Kay Morgan, PhD, MSN, University of Florida, James Wymer, MD, University of Florida, Alicia Vose, PhD, CCC-SLP, University of Florida - JAX, Priscila Sales de Campos, PhD, State University of Santa Catarina, Michael T Pulley, MD, PhD, University of Florida- JAX, Nicholas Napoli, PhD, University of Florida, Gordon S Mitchell, PhD, University of Florida, Barbara K Smith, PhD, PT, University of Florida

Background:
Autonomic nervous system dysfunction is increasingly recognized in amyotrophic lateral sclerosis (ALS), yet it is unclear if this dysfunction is secondary to respiratory complications in ALS. Heart rate variability (HRV) provides a noninvasive index of parasympathetic and sympathetic cardiac modulation and may reveal autonomic impairment prior to clinically significant respiratory decline.
Objective:
To test whether HRV is reduced in individuals with ALS versus control subjects, and whether HRV metrics correlate with forced vital capacity (FVC % predicted).
Methods:
In this secondary analysis from two independent randomized trials, 23 adults with ALS and 19 age-matched controls completed 2, 5-min resting ECG sessions, 14 ± 5 days apart. Primary endpoints were SD1 and RMSSD; secondary metrics included HF power, SDNN, and LF/HF. Group differences were analyzed with t-tests or Wilcoxon tests, with effect sizes (Cohen’s d). Pearson correlations and multivariable linear models adjusting for age and sex assessed group effects.
Results:
ALS participants had lower FVC % than controls (ΔFVC =17.0 %, p = 0.0003) and FVC did not correlate with any HRV metric (|r| ≤ 0.26; all p > 0.20). ALS participants demonstrated reduced SD1 (d = 0.78, p = 0.038), with a non-significant trend towards reduced RMSSD (d = 0.75, p = 0.06). HF (d = 0.57, p = 0.174) and SDNN (d = 0.48, p = 0.13) showed subtle reductions, and LF/HF did not differ (p = 0.48). ALS group remained a significant predictor of reduced HRV after adjusting for age and sex (SD1: β = –5.35, p = 0.042; RMSSD: β = –7.12, p = 0.054).
Conclusion:
Individuals with ALS show modest reductions in HRV despite preserved lung function. Thus, autonomic dysfunction can occur independently of respiratory dysfunction, suggesting involvement of central autonomic pathways. HRV may serve as a sensitive physiological marker of autonomic alterations in ALS.