# Heart Rate Variability and Intrinsic Autonomic Coupling in Ehlers–Danlos Syndrome

## TL;DR

People with Ehlers-Danlos syndrome show signs of autonomic dysfunction, including higher heart rates and reduced heart rate variability compared to healthy individuals.

## Contribution

This study provides empirical evidence of autonomic dysregulation in EDS using HRV and standard autonomic testing.

## Key findings

- EDS patients had higher resting heart rates and lower parasympathetic activity compared to controls.
- Resting heart rate in EDS patients correlated inversely with HRV indices, indicating impaired autonomic integration.
- Orthostatic intolerance was more common in EDS patients than in controls.

## Abstract

Background

Ehlers-Danlos syndrome (EDS) encompasses a group of connective tissue disorders often extending beyond musculoskeletal involvement. Emerging evidence indicates a high prevalence of cardiovascular autonomic dysfunction in this population, yet systematic physiologic evaluations remain limited.

Objective

To characterize cardiovascular autonomic function in EDS using standardized autonomic testing and heart rate variability (HRV) indices, and to explore intrinsic autonomic coupling by correlating resting heart rate with HRV parameters.

Methods

This cross-sectional study included 30 clinically diagnosed patients with EDS and 30 age- and sex-matched healthy controls. Short-term HRV analysis (five-minute supine ECG) and standard autonomic testing, including head-up tilt, were performed under controlled laboratory conditions. HRV indices were derived using Fast Fourier Transform (FFT) algorithms. Group differences were evaluated with independent t-tests, and correlations between resting heart rate and HRV measures were analyzed using Pearson’s correlation.

Results

Compared with controls, patients with EDS exhibited higher resting heart rate (87.3±11.6 vs 75.2±9.8 bpm), lower parasympathetic time-domain indices (standard deviation of normal-to-normal intervals or SDNN 35.4±9.7 vs 49.1±11.4 ms; root mean square of successive differences (RMSSD; 20.7±6.9 vs 31.6±8.8 ms), and altered frequency-domain markers (low frequency (LF) power 671±205 vs 542±176 ms²; high frequency (HF) power 174±81 vs 272±106 ms²; LF/HF ratio 3.7±1.3 vs 1.8±0.7). Orthostatic intolerance was observed in 16 (53.3%) of the patients with EDS versus three (10%) of the controls. Correlation analysis revealed that in EDS, resting HR correlated negatively with SDNN (r=-0.45, p=0.01), RMSSD (r=-0.52, p<0.01), and HF power (r=-0.39, p=0.03), while showing a positive correlation with LF/HF ratio (r=0.58, p<0.001).

Conclusion

Patients with EDS had autonomic dysregulation, with sympathetic predominance and diminished vagal modulation. The intrinsic coupling between resting heart rate and HRV indices suggests impaired cardiovascular autonomic integration. HRV profiling is a valuable noninvasive biomarker for early identification and longitudinal monitoring of autonomic dysfunction in EDS, potentially enhancing disease characterization and guiding individualized therapeutic strategies.