Simon Raphael Schneider

Background: Patients with pulmonary arterial hypertension (PAH), who permanently live at high altitude (>2500 m) face particular challenges due to hypobaric hypoxia, which may exacerbate pulmonary hypertension and impair exercise capacity .We therefore investigated the effect of low-dose supplemental oxygen therapy (SOT) on 6-minute walk distance (6MWD) in high altitude residents diagnosed with PAH. Methods: Adults diagnosed with PAH, who permanently live >2500 m performed two 6MWD tests, once with SOT (1–2 l·min ⁻¹ via nasal cannula provided by a portable back-packed concentrator) and once while breathing ambient air (air) at 2850 m according to a randomized-controlled, cross-over trial. The primary outcome was the difference in 6MWD between SOT and air. Secondary outcomes were effects of SOT on heart rate, blood pressure and peripheral oxygen saturation (SpO ₂ ) and Borg scale. Results: 28 patients (86% women, mean± sd age 45±12 years, resting SpO ₂ 93±3%, mPAP 52±16 mmHg, 6MWD at 2850 m 462±100 m) were included. SOT compared to hypoxic air at 2850 m did not improve 6MWD (mean difference −5 m, CI 95%: −24 to 14 m, p=0.576), dyspnea, leg discomfort or end-exercise SpO ₂ , but did increase resting SpO ₂ . Conclusion: In high altitude residents diagnosed with PAH, low-dose SOT as commonly prescribed via protable concentrator did not improve 6MWD nor dyspnea perception, most likely due to insufficient flow provided by the concentrator during exercise, further lowered by exertional mouth breathing and the weight of the backpacked concentrator.

Background: Patients with pulmonary arterial hypertension (PAH) living at high altitudes experience exacerbated hypoxaemia. This study aimed to assess the effects of relocating PAH patients from high altitude (2850 m) to sea level on nocturnal hypoxaemia, sleep-disordered breathing, and autonomic cardiovascular function. Methods: In a repeated measures design, PAH patients underwent evaluations near their living altitude at 2850m and at sea level. The primary outcome was the change in mean nocturnal SpO2, while secondary outcomes included changes in time spent with SpO2 <90% (t<90), apnoea-hypopnoea index (AHI), heart rate variability (HRV), and blood pressure. Measurements were taken using cardio-respiratory polygraphy at 2850m and during the first two nights following relocation f to sea level. Results: 28 patients (86% women) with a mean mPAP of 52±17 mmHg and PVR of 16.6±8.8 Wood units were included. Relocation to sea level resulted in significant improvements in nocturnal hypoxaemia, with mean SpO2 increasing by 6.9% (95% CI 5.9 to 7.9) and t<90 decreasing by -53% (95% CI -67.1 to -39.0). AHI and supine AHI decreased, and sleep quality significantly improved. HRV analysis showed increased parasympathetic activity, with RMSSD, pRR50, LF, and HF rising, and the LF/HF ratio decreasing. Morning PaO2 increased by 3.0 kPa (95% CI 2.3 to 3.7), and blood pressure significantly decreased. Conclusions: Relocation of PAH-patients from high to low altitude led to significant improvements in nocturnal oxygenation and SDB, and enhanced parasympathetic activity, suggesting that short-term exposure to sea level may offer benefits for PAH-patients living at high altitude.

Background/Objective: Continuous blood pressure (BP) monitoring is essential in clinical settings, where rapid hemodynamic changes influence patient management. While intra-arterial measurement remains the reference standard, non-invasive volume-clamp systems offer a potential alternative. We assessed the accuracy of finger-cuff-based continuous BP monitoring compared to invasive measurement in patients with pulmonary hypertension (PH). Methods: This post hoc analysis from a crossover RCT included PH patients who underwent repetitive hemodynamic assessments at rest and during exercise. The participants had simultaneous invasive BP monitoring via the radial artery and a non-invasive finger-cuff device (Finapres^® NOVA Basic). The mean blood pressure (mBP) was compared at rest, 50% of the maximal workload, and at the end of exercise using Bland–Altman and Taffé analysis. Results: In the study, 24 patients (seven female; 59 ± 14 years) contributed 385 paired mBP measurements. The invasive and non-invasive methods showed similar values at rest (96.1 ± 16.7 vs. 96.4 ± 17.2 mmHg) and during maximal exercise (106.8 ± 18.6 vs. 111.8 ± 21.6 mmHg). The overall Bland–Altman bias was 2.8 mmHg with wide limits of agreement (−39.6 to 45.3 mmHg), which remained broad across all exercise intensities. The Taffé analysis revealed a non-uniform, directionally dependent bias: the non-invasive system overestimated the mBP at low pressures and underestimated it at higher pressures. The measurement variability was substantially greater for the non-invasive method than for the invasive reference. Conclusions: In PH patients, finger-cuff-based continuous BP monitoring demonstrated acceptable group-level agreement but insufficient individual-level accuracy for clinical decision-making.

Background and aims: Exercise capacity is limited in patients with pulmonary vascular disease (PVD) exposed to high altitude. The PVD-drug sildenafil, a phospodiesterase-5 inhibitor, has improved exercise capacity and hemodynamics in healthy exposed to hypoxia. This study examined effects of additive sildenafil on pulmonary hemodynamics during rest and exercise in PVD exposed to normobaric hypoxia. Method: PVD-patients diagnosed as pulmonary arterial or chronic thromboembolic pulmonary hypertension underwent right heart catheterization assessed at rest and during mild exercise while breathing hypoxic air (FiO2 15%) in a sequence-randomized crossover design. Main outcomes were mean pulmonary artery pressure (mPAP), cardiac output (CO) and mPAP/CO-slope before and ∼60 min after additive sildenafil (50 mg oral). Results: 22 patients were included, 64% had PAH and 36% CTEPH; 41% were female with mean± sd age 54±14 y, and a BMI of 26.3±4.0 kg·m ⁻² . 73% received PH targeted therapy and 56% were on double or triple combination therapy. MPAP remained unchanged at rest, while it was significantly lower at end-exercise compared to the values without sildenafil. The mPAP/CO slope during exercise in hypoxia was reduced with additive sildenafil from 9.9±5.1 to 8.2±4.1 mmHg (mean difference (95% CI) of −1.9 (−3.8 to −0.1) mmHg, p=0.043). Conclusions: In PVD patients exposed to normobaric hypoxia, additional 50 mg of oral sildenafil improves exercise pulmonary hemodynamics. Whether the improved hemodynamics would translate into better tolerance or an enhancement in exercise capacity during hypoxia exposure needs to be studied further.

Aim: We investigated the effect of an overnight-stay at high altitude (HA, 2500 m) on constant work-rate exercise test (CWRET) time and cardiorespiratory function in patients with pulmonary vascular disease (PVD) and the impact of supplemental oxygen therapy (SOT) in case of severe altitude-induced hypoxemia. Methods: In a randomized crossover trial, stable patients diagnosed with pulmonary arterial or distal chronic thromboembolic pulmonary hypertension (PVD, PAH/CTEPH) performed a symptom-limited cycling CWRET at 470 m and after an overnight stay at 2500 m. For safety, patients with a SpO ₂ 30 min received SOT during the subsequent HA-stay. The primary outcome was CWRET-time, secondary outcomes were changes in ergospirometric parameters. Clinicaltrials.gov: NCT05107700 &NCT05112172. Results: Of 27 PVD-patients (44% female; mean age 62±14 y, 20 PAH, 7 distal CTEPH), 10 (37%) required SOT. Overall at HA versus 470 m, CWRET-time decreased to 292±181 s versus 454±411 s (mean difference −162 s, 95%CI −290 to −34 s; p=0.026), driven by patients without need for SOT (261±187 s versus 519±497 s; p=0.017), who revealed lower resting PaO ₂ (7.4±0.7 kPa versus 10.6±1.4 kPa, p2 -desaturation was not significantly different (−0.9%, 95%CI −3.9 to 2). In 10/27 patients needing SOT, SOT restored CWRET time to 470 m-values (344±170 s versus 345±167 s; p=0.990), corrected altitude-induced hypoxemia and attenuated hyperventilation. Conclusion: The majority of PVD-patients tolerated an overnight stay at 2500 m well. In those without need for SOT at HA, CWRET-time was reduced with increased hypoxemia and hyperventilation. In PVD-patients who received SOT due to severe nocturnal hypoxemia, SOT restored CWRET-time to 470 m levels and dampened the exercise-induced hypoxemia.

Background/Objectives: It is widely acknowledged that healthy highlanders (HL) present with significantly higher pulmonary arterial pressure (PAP) compared to healthy lowlanders (LL). However, whether this elevated PAP solely signifies a response to hypoxia at altitude or is also linked to right ventricular (RV) dysfunction is still unknown. Therefore, we assessed RV function in HL and LL using speckle-tracking-derived strain analysis. Methods: This case-control study evaluates echocardiographic RV free wall strain (RVFWS) in LL and HL in Kyrgyzstan. A RVFWS over −20% for men and a RVFWS of −21% for women were considered indicators of RV dysfunction. Subgroup analysis included individuals with and without risk for pulmonary hypertension (PH), defined as a TRV > 2.8 m/s. Results: A total of 59 participants (21 LL, 38 HL), with a mean ± SD age of 43 ± 8 versus 48 ± 10 years, were included and assessed at their living altitude. RVFWS in HL and LL was −27.3% ± 4.7 versus −27.0% ± 6.0 (mean difference 0.13%, 95%CI −2.65 to 2.92, p = 0.852). The conventional RV indices RV FAC (42% ± 6 vs. 38% ± 8), TAPSE (2.2 cm ± 0.2 vs. 2.0 cm ± 0.3), and TDI S’ (14.2 cm/s ± 1.9 vs. 12.1 cm/s ± 1.8), however, did differ significantly between LL and HL. HL with and without risk for PH did not differ in RVFWS and in the conventional RV indices. Conclusions: Despite significant differences in conventional RV markers, healthy highlanders generally did not differ in RVFWS compared with lowlanders, indicating maintained RV systolic function at high altitude. Our findings suggest that elevated PAP in HL reflects adaptation rather than RV dysfunction, underscoring the need for refined diagnostic criteria for clinically relevant high-altitude pulmonary hypertension.

Background/Objectives: Measuring cardiac output (CO) is essential for diagnosis and therapeutic monitoring in pulmonary hypertension (PH). CO assessment based on thermodilution (TD) or Direct Fick (DF) during standard right heart catheterization (RHC) is impractical for regular follow-up. We evaluated the accuracy and agreement of non-invasive Modelflow (MF)-based CO assessment compared with TD and DF during rest and exercise RHC in PH. Methods: This post hoc analysis from a crossover RCT included 24 PH patients (7 females, 59 ± 14 years; mean pulmonary artery pressure 37 ± 11 mmHg) who underwent RHC with repetitive CO assessments at rest and during exercise. CO was measured by TD, DF, and non-invasive MF by fingertip pulse contour analysis at rest and during stepwise cycling to maximal exertion. Results: At rest, mean CO was comparable between methods: TD = 6.05 ± 1.80 L/min, DF = 5.68 ± 1.88 L/min, MF = 6.09 ± 1.84 L/min. At end-exercise, CO increased to TD = 11.18 ± 4.38 L/min, DF = 11.84 ± 4.74 L/min, MF = 8.38 ± 2.93 L/min. Bland–Altman showed minimal bias at rest (MF vs. TD: 0.04 L/min; MF vs. DF: −0.07 L/min) but substantial variability during exercise, with underestimation of CO by MF with increasing workloads (MF vs. TD bias = −2.80 L/min; MF vs. DF bias = −4.38 L/min). Limits of agreement were wide across all workloads. Linear regression confirmed an increasing CO with workload, but MF slope was shallower than TD/DF, suggesting proportional bias. Taffé analysis identified a significant differential (5.847) and proportional bias (0.195) indicative of CO overestimation by MF at low CO and underestimation at high CO. Conclusions: MF group-level agreement is acceptable, but individual-level accuracy is limited, indicating that MF may be suitable for trend monitoring but its applicability for clinical decision-making is restricted, especially during exercise.

Background: In patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension (summarized as pulmonary vascular disease; PVD), it is unclear whether the brain is protected against acute hypoxia and whether acute pulmonary vascular dilatation by sildenafil would influence cerebral and muscle tissue oxygenation whilst breathing normoxia or hypoxia. Methods: Adult patients with PVD underwent right heart catheterization, while cerebral and muscular tissue oxygenation and tissue hemoglobin index were measured using near-infrared spectroscopy along with arterial and mixed-venous blood gases. Participants underwent a four-stage protocol in which they were blinded to breathing either normoxia (FiO₂ 0.21) or normobaric hypoxia (FiO₂ 0.15), both before and after a single oral dose of sildenafil (50 mg) according to a randomized, cross-over design. Results: In 22 PVD patients (9 women, age 54 ± 14 y) under hypoxia, mean cerebral tissue oxygenation decreased by −2% (95% CI −4 to 0%, p = 0.046), muscular tissue oxygenation by −1% (95% CI −3 to 0%, p = 0.011) and mean arterial partial pressure of oxygen by −2.3 kPa (95% CI −2.7 to −1.8 kPa, p < 0.0001). Sildenafil improved the cerebral tissue hemoglobin index under hypoxia compared to hypoxia without sildenafil by 0.12 (95% CI 0.00 to 0.23, p = 0.049), but not the muscular tissue hemoglobin index. Conclusions: In PVD patients, acute exposure to normobaric hypoxia leads to a reduction in arterial oxygenation as well as cerebral and muscular tissue oxygenation. Sildenafil improves cerebral blood flow but has no effect on arterial, cerebral or muscular oxygenation.

Background: Little is known about the effects of portable supplemental oxygen therapy (SOT) to improve exercise performance in highlanders at risk for high altitude pulmonary hypertension (HAPH). We aimed to investigate whether SOT improves six-minute walk distance (6MWD) and reduces perceived dyspnea in highlanders at risk for HAPH. Methods: In a pragmatic randomized open-label crossover trial, adult highlanders, living >2500 m, with a peak tricuspid regurgitation velocity >2.8 m·s⁻¹ corresponding to a tricuspid regurgitation pressure gradient ≥31 mmHg by echocardiography were included. Highlanders were randomized to perform two 6MWD tests at 3250 m with and without SOT (50 mLpulse volume, via nasal cannula, provided by portable device). The primary outcome was the effect of SOT on the 6MWD compared to ambient air (air). Secondary outcomes were vital parameters and dyspnea assessed by BORG CR10 scale with SOT versus air. Results: 47 highlanders (44% male, mean±sd age of 52±12 years, TRPG 41±10 mmHg and oxygen saturation (SpO₂) of 88±3% were included. SOT did not improve 6MWD compared to air (457±90 m versus 475±84 m; mean difference with SOT of −18 m (95%CI, −30 to 8, p=0.241)). End-exercise dyspnea was significantly lower with SOT compared to air, along with reduced heart rate and higher SpO₂. Conclusion: In hypoxemic highlanders at risk for HAPH, portable low-dose SOT did not improve 6MWD, despite lower dyspnea perception, lower heart rates, and higher SpO₂ at end-exercise. This indicates that low-dose SOT oxygen as commonly applied in various clinical settings, does not increase 6MWD. Whether it reduces cardiovascular stress during exercise needs to be further studied.