Impaired cardiac autonomic regulation and respiratory-driven blood pressure oscillations underly classic and delayed orthostatic hypotension in precapillary pulmonary hypertension

Introduction: We recently showed that patients with PreCapPH who develop classic or delayed orthostatic hypotension (OH) fail to mount an adequate HR response to standing. This finding raises the unexplored possibility that impaired autonomic regulation of HR contributes to these forms of OH in PreCapPH. Additionally, increased systolic arterial pressure (SAP) variability during standing is a marker of unstable hemodynamic regulation and often precedes syncope in various conditions. Such variability may arise from exaggerated sympathetic vasoconstrictor activity [low-frequency (LF) oscillations] or respiratory influences [high-frequency (HF) oscillations]. Yet, SAP variability and its components have not been characterized in PreCapPH during orthostasis. Therefore, we aimed to investigate the regulation of HR and SAP during an orthostatic challenge in patients with PreCapPH, comparing those with and without OH. Methods: Sixty patients with PreCapPH completed a supine to standing transition, remaining upright for 10 minutes. Then, we selected two groups of patients: 1) 13 with classic or delayed OH, the most severe forms of OH; and 2) 26 who did not show any OH. Heart rate and beat-by-beat arterial pressure were continuously recorded by electrocardiography and volume clamp finger photoplethysmography, respectively. We used data from 5 minutes of rest and the last 5 minutes of standing for all analyses. The HR autonomic regulation was assessed by symbolic analysis, with 0V% and 2UV% representing sympathetic and parasympathetic control, respectively. The cardiac baroreflex sensitivity (cBRS) and efficiency (cBEI) were explored by the sequence method. Furthermore, the SAP regulation was examined by the Fast Fourier spectral analysis, setting the LF band at 0.04 to 0.14 Hz and the HF band at 0.15 to 0.40 Hz. Results: Although the group with OH showed a greater SAP reduction from supine to standing (P < 0.001), its heart rate increase, 0V% increase, and 2UV% decrease did not differ from the group without OH (P > 0.050). cBRS and BEI at rest, and their responses to standing did not differ between groups (P > 0.05). The standard deviation of systolic arterial pressure did not differ between groups at rest (P = 0.216). Still its response to standing was 3 times greater in the group with OH than without OH (median ± interquartile range: 2.0 ± 6.1 vs 0.6 ± 2.5 mmHg, P = 0.024). Resting LF power of SAP (P = 0.592) and its response to standing did not differ between groups (P = 0.964). Similarly, HF power of SAP at rest (P = 0.023) and its response to standing (P = 0.582) did not differ between groups. However, this variable was 2 times greater during standing in the group with than without OH (5.5 ± 6.3 vs 2.8 ± 2.8 ms2, P = 0.021). Conclusion: The results suggest that classic and delayed OH in patients with PreCapPH partially stem from an insufficient cardiac autonomic response to the arterial pressure drop induced by standing. Moreover, these forms of OH are associated with increased systolic arterial pressure variability due to high-frequency oscillations, indicating that respiratory instability likely contributes to impaired hemodynamic regulation during orthostasis. Sources of funding: MCRGT and ILB received scholarships from the Coordination for the Improvement of Higher Education Personnel (CAPES). BMS and RKFO received research productivity awards from the National Council for Scientific and Technological Development (CNPq; numbers: 307610/2022–5 and 313284/2021‐0). BMS received grants from The São Paulo Research Foundation (FAPESP; number: 23/08850-5) and the National Council for Scientific and Technological Development (CNPq, grant 408692/2025-1) to cover the study’s cost. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.