Effects of beta-adrenergic blockade on cardiorespiratory coupling markers in a clinically referred cardiopulmonary exercise test cohort with preserved left ventricular ejection fraction

OBJECTIVE: Cardiorespiratory coupling (CRC) subsumes diverse mechanisms of reciprocal influence between cardiac and respiratory rhythms. Its most studied manifestation, the respiratory sinus arrhythmia (RSA), is thought to be under full vagal control. However, some studies on healthy subjects observed an enhancement of RSA following beta-adrenergic blockade. In the present study, we investigated the effects of habitual beta-blocker therapy on CRC using non-directional and directional measures. APPROACH: A retrospective analysis was performed on heart period (HP) variability and respiration (R) in a cohort of subjects with preserved left ventricular ejection fraction scheduled for cardiopulmonary exercise test subdivided into those under beta-blocker therapy (BB: 67±9 yrs, 34 males, 21 females) and treatment-naïve participants (noBB: 63±10 yrs, 22 males, 35 females). CRC was assessed through the respiratory sinus arrhythmia, estimated as the high frequency (HF) power of HP variability, a non-directional linear measure such as HP-R squared coherence (K²), and a directional model-free nonlinear cross-predictability (CP) approach opening the HP-R closed loop. MAIN RESULTS: Spectral analysis showed a significant increase of the HF power of HP variability in the BB group. K² did not show significant between-group differences, while the CP was higher in the BB cohort regardless of the time direction of the HP-R interactions. SIGNIFICANCE: These findings support the hypothesis that CRC is not a pure vagal phenomenon but is also modulated by sympathetic activity. Furthermore, they highlight the importance of directional analysis to clarify the physiological pathways underlying CRC and their modulation by beta-adrenergic blockade.