Standardisation of Respiratory Sinus Arrhythmia testing in the context of autonomic function testing

Background: Respiratory Sinus Arrhythmia (RSA) is used as an index of parasympathetic activity of the autonomic nervous system. It is most often measured at a fixed, slow breathing rate (0.1 Hz). The excursion in heart rate within each breath cycle is RSA. RSA testing has limited clinical uptake, in part likely due to low specificity and sensitivity, likely due to unconstrained physiological confounders. This thesis investigates the clinical utility of the existing form of RSA testing and investigates whether controlling the known correlate, tidal volume, improves the relationship of RSA testing with known changes in parasympathetic activity. Methods: RSA was quantified in Ehlers-Danlos Syndrome (EDS) patients (a condition with known autonomic dysfunction, n=19) and healthy controls (n=16) to discover if RSA was able to differentiate between groups. In a separate study, RSA was quantified in healthy subjects (n=20) under conditions of free and controlled tidal volume while performing physiological challenges to alter parasympathetic activity (isometric hand-grip exercise and meditation). Results: RSA testing was unable to differentiate between healthy and EDS patients (p=0.34). Controlling tidal volume reduced the tidal volume and RSA (p<0.001) compared to free tidal volume. RSA was not correlated with parasympathetic activity (as defined by the physiological directional change with exercise and meditation) with free tidal volume. Controlling tidal volume did not improve the correlation with parasympathetic activity. Conclusions: RSA testing in its existing form is not sensitive enough to detect a difference in people with autonomic dysfunction. Tidal volume is correlated with RSA and testing can be performed with a controlled tidal volume. However, this does not improve RSA as a correlate of parasympathetic activity. The results presented in this thesis question the reliability and sensitivity of RSA as a surrogate of parasympathetic activity and raise the need of new method to non-invasively estimate parasympathetic activity.