Interplay of Pulmonary Circulation, Cardiac Filling Pressures, and Sympathovagal Balance in Exercise Induced Hyperventilation among Cardiopulmonary Disorders

<b>Background:</b> Although chemosensitivity plays a role in exercise-induced hyperventilation in cardiopulmonary disorders, the integration of the underlying reflexes with cardiac hemodynamics is not fully understood. We aimed to explore the interplay between right- and left-heart pressure overload, right ventricular-pulmonary arterial (RV-PA) coupling, cardiovascular autonomic modulation, and ventilatory response in patients with cardiopulmonary disorders. <b>Methods:</b> Forty patients underwent echocardiography, cardiopulmonary exercise testing, and right heart catheterization. Spectral analysis of heart rate variability (HRV) was used to assess cardiovascular autonomic modulation of low- (LF) and high-frequency (HF) components, with LF/HF ratio as an index of sympatho-vagal interaction. Heart rate recovery (HRR) quantified vagal reactivation. RV-PA coupling was calculated through the TAPSE/PAPs ratio, and VE/VCO₂ slope defined ventilatory inefficiency. <b>Results:</b> Patients were classified as NoPH (no pulmonary hypertension, n=13), PCPH (pre-capillary pulmonary hypertension, n=15), and LVDD (left ventricular diastolic dysfunction, n=12). VE/VCO₂ slope was higher in PCPH than LVDD and NoPH (53.9 vs 43.7 vs 42.2, p<0.01). The LF/HF ratio was similar in PCPH and LVDD, but higher in NoPH (p<0.01), while HRR was significantly blunted in PCPH compared to LVDD and NoPH (p<0.01). TAPSE/PAPs was significantly reduced in PCPH and LVDD vs NoPH and was significantly correlated with all HRV parameters. <b>Conclusion:</b> Our findings support a tight interconnection between left- and right-heart hemodynamics, pulmonary circulation, sympatho-vagal control, and ventilatory response during exercise. Although additional mechanisms are involved, cardiopulmonary efficiency, captured by RV-PA coupling, emerges as a key determinant linking cardiopulmonary hemodynamic to autonomic modulation and ventilatory inefficiency.