Decoding Cardiac Reinnervation from Cardiac Autonomic Markers: A Mathematical Model Approach.

BACKGROUND: Although cardiac autonomic markers are commonly used to assess cardiac reinnervation in heart transplant patients (HTx), their relationship to the degree of sympathetic and vagal cardiac reinnervation is not well understood yet. To study this relationship, we applied a mathematical model of the cardiovascular system and its autonomic control.

METHODS: By simulating varying levels of sympathetic and vagal efferent sinoatrial reinnervation, we analyzed the induced changes in cardiac autonomic markers including resting heart rate (HR), bradycardic and tachycardic HR response to Valsalva Maneuver, root mean square of successive differences between normal heartbeats (RMSSD), low-frequency- (LF), high-frequency- (HF), and total spectral power.

RESULTS: The results suggest that for assessment of vagal cardiac reinnervation levels >20%, resting HR (ρ=0.99, p<0.05), RMSSD (ρ=0.97, p<0.05), and total spectral power (ρ=0.96, p<0.05) may be equally suitable as the commonly used measure of HF-power (ρ=0.97, p<0.05). To assess sympathetic reinnervation, our results suggest that the LF/HF-ratio (ρ=0.87, p<0.05) and tachycardic response to Valsalva maneuver (ρ=0.9, p<0.05) may be more suitable than the regularly used measure of LF-power (ρ=0.77, p<0.05).

CONCLUSIONS: Our model reports, for the first time, mechanistic relationships between the cardiac autonomic markers and the level of efferent autonomic sinoatrial reinnervation. The results indicate differences in the suitability of these markers to assess vagal and sympathetic reinnervation. Although our analysis is purely conceptual yet, the developed mathematical model can help to gain important insights into the genesis of cardiac autonomic markers and their relationship to efferent sinoatrial reinnervation and, thus, provide indications for clinical study evaluation.