Orthostatic hypotension in precapillary pulmonary hypertension: prevalence, clinical profile and hemodynamic mechanisms

Precapillary Pulmonary Hypertension (PreCapPH) is a rare condition that progresses with impaired right ventricular (RV) function due to elevated RV afterload. Current PreCapPH pharmacological treatments often produce undesirable systemic vasodilatory effects. Furthermore, patients with PreCapPH exhibit reduced arterial baroreflex sensitivity and effectiveness. Collectively, these factors may compromise the regulation of systemic arterial pressure in PreCapPH, particularlyin response to sudden postural changes such as transitioning from lying to standing. However, orthostatic hypotension (OH) has only been indirectly interpreted via the Valsalva maneuver in a small cohort of patients with PreCapPH. Furthermore, evidence from other patient groups shows that OH occurrence is often poorly correlated with resting systemic arterial pressure and may be asymptomatic in up to 50% of cases. These findings suggest that OH could be an underrecognized yet clinically relevant issue in PreCapPH. The present study, therefore, sought to: 1) investigate the prevalence of OH and its subtypes (initial, delayed, and sustained OH) in patients with PreCapPH; 2) characterize the clinical profile of patients with PreCapPH who experience OH and its subtypes; and 3) explore hemodynamic mechanisms underlying the different OH subtypes in this patient population. Sixty outpatients with PreCapPH participated in the study. OH was verified by an active standing maneuver. Beat-by-beat heart rate and arterial pressure were measured by electrocardiography and volume clamp finger photoplethysmography, respectively. Stroke volume (SV) was estimated from the arterial pressure waveform, and cardiac output (CO) and total peripheral resistance (TPR) were calculated considering heart rate (HR), SV, and mean arterial pressure data. Initial OH was defined as a decrease in systolic arterial pressure (SAP) or diastolic arterial pressure (DAP) exceeding 40 or 20 mmHg within the first 15 seconds of standing. Delayed OH was defined as SAP or DAP decreases greater than 20 or 10 mmHg within 30 to 40 seconds, and sustained OH was identified as SAP or DAP decreases exceeding 20 or 10 mmHg between 60 and 600 seconds. Thirty-one patients had some type of OH (i.e., prevalence = 51.6%), with 19 presenting more than one OH subtype. Among these 31 patients with OH, 23 presented initial, 18 delayed, and 13 sustained OH. No significant differences were found between patients with and without OH regarding sex, age, resting pulmonary hemodynamics, resting arterial pressure, medications, functional class, and aerobic exercise capacity (P > 0.05). HR, SV, CO, and TPR responses (% change from supine baseline) were not different between groups with initial OH and without OH from the beginning to the end of standing (P > 0.05). However, SV decay was greater in the group with delayed OH than without OH (-31 ± 21 vs. -19 ± 14%; P = 0.033). Additionally, TPR compensatory increase was attenuated in the group with sustained OH than without OH (-6 ± 21 vs. 7 ± 15%; P = 0.023). In sum, patients with PreCapPH frequently experience OH when transitioning from a supine to a standing position, with initial OH being the most common subtype. Notably, no specific clinical characteristic was associated with OH occurrence. Initial OH did not appear to result from a single, identifiable hemodynamic mechanism. In contrast, delayed OH was linked to an exaggerated SV decay, while sustained OH was associated with insufficient TPR increase. CAPES; FAPESP, Numbers: 17/17027-0, 22/12176-5; CNPq, Numbers: 307610/2022-5, 313284/2021-0; NSERC Canada; Foundation Institut Universitaire Cardiologie Pneumologie This abstract was presented at the American Physiology Summit 2025 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.