Highlight
This randomized controlled crossover trial investigates the cardiopulmonary effects of acute high-altitude exposure (2500 m) in stable patients with pulmonary vascular disease (PVD). Key findings include significant increases in systolic pulmonary arterial pressure and total pulmonary resistance, along with deteriorated right ventricular (RV)–arterial coupling, while oxygen delivery remains maintained despite reduced oxygen content.
Study Background
Pulmonary vascular disease, encompassing pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), imposes considerable hemodynamic burden on the right ventricle and limits cardiopulmonary reserve. High altitude exposure is known to exacerbate hypoxemia and increase pulmonary arterial pressures due to hypoxic pulmonary vasoconstriction, potentially worsening RV function and clinical status in these patients. However, the acute cardiopulmonary effects during brief altitude exposure, including functional RV adaptation and systemic oxygen delivery, remain incompletely characterized. Robust evidence is lacking to guide safe altitude travel recommendations for this vulnerable population.
Study Design and Methods
This study employed a randomized controlled crossover design involving 27 clinically stable, low-risk PVD patients without resting hypoxemia residing at 470 m. Subjects were transported by cable car to 2500 m altitude, where they stayed for two days. Pulmonary hemodynamics and RV function were assessed by echocardiography, including systolic pulmonary arterial pressure (sPAP), total pulmonary resistance (TPR), pulmonary arterial elastance (EA), compliance (PAC), and RV–arterial coupling calculated by TAPSE/sPAP ratio (tricuspid annular plane systolic excursion over sPAP). Arterial blood gases measured oxygen content and delivery. The crossover aspect allowed within-patient comparison of parameters at baseline low altitude and high altitude exposure.
Key Findings
At 2500 m altitude, patients demonstrated a significant increase in sPAP by 18 mmHg (40% rise), from baseline values (95% CI 9 to 28 mmHg, p<0.001). Total pulmonary resistance rose by 2.8 Wood units (32%), reflecting increased RV afterload (95% CI 0.7 to 4.9 WU, p=0.007). Pulmonary arterial elastance (EA) increased by 0.2 mmHg/mL (33%), while pulmonary arterial compliance (PAC) decreased by 1.6 mL/mmHg (38%), indicating stiffer pulmonary vascular properties at altitude.
RV–arterial coupling, an index of efficiency between RV contractility and afterload, significantly deteriorated as reflected by a 31% reduction in the TAPSE/sPAP ratio from 0.55 to 0.38 mm/mmHg (p<0.001). These findings suggest an impaired coupling between the right ventricle and the pulmonary arterial system early after altitude exposure.
Despite these hemodynamic challenges, arterial oxygen content was lower at high altitude due to hypoxemia. However, oxygen delivery—a product of cardiac output and arterial oxygen content—remained similar at both altitudes, indicating the cardiovascular system’s ability to partly compensate for reduced oxygen saturation.
Expert Commentary
This study provides important mechanistic insight into acute cardiovascular adaptations to moderate high-altitude exposure in PVD patients. The observed rise in pulmonary arterial pressures and resistance aligns with expected hypoxic pulmonary vasoconstriction, which increases RV afterload and compromises RV–arterial coupling. The decline in TAPSE/sPAP ratio reflects reduced RV contractile efficiency relative to afterload, a predictor of adverse outcomes in pulmonary hypertension.
Notably, despite worsened RV-pulmonary artery coupling, oxygen delivery was preserved over the two-day exposure, implying that patients’ cardiac compensatory mechanisms remain intact in the short term. This compensatory capacity may be transient, underscoring a need for caution with longer or more strenuous altitude exposure.
Limitations include the relatively small sample size and inclusion of low-risk stable patients, potentially limiting generalizability to patients with advanced PVD or hypoxemia. Longer duration studies and exploration of clinical outcomes such as exercise capacity or symptom burden would be valuable. However, this trial provides a rigorous controlled assessment of altitude’s acute effects and may inform safety guidelines for this population.
Conclusion
In clinically stable, low-risk patients with pulmonary vascular disease, short-term exposure to 2500 m altitude significantly increases right ventricular afterload and impairs ventricular-arterial coupling. Despite these cardiovascular stresses and reduced arterial oxygen content, overall oxygen delivery is maintained, illustrating compensatory capacity. These findings highlight potential risks associated with altitude travel in PVD and underline the importance of individualized risk assessment and monitoring. Further research is warranted to define safe altitude limits and guide clinical recommendations.
Funding and Trial Registration
The study was registered with Clinicaltrials.gov (NCT05107700). No specific funding details were reported in the abstract.
References
1. Hoeper MM, et al. Pulmonary hypertension. Nat Rev Dis Primers. 2017;3:17086.
2. Peacock AJ, et al. Pulmonary hypertension and hypoxia: the cardiovascular response to altitude. Lancet Respir Med. 2016;4(5):394-406.
3. Dousset B, et al. Evaluation of pulmonary vascular response to hypoxia: clinical relevance. Eur Respir J. 2019;54(3):1900056.
4. Vonk Noordegraaf A, et al. Right heart failure in pulmonary hypertension: pathophysiology and treatment. J Am Coll Cardiol. 2013;62(25 Suppl):D22-D33.
5. Farina S, et al. Echocardiographic assessment of right ventricular-arterial coupling in pulmonary hypertension. Int J Cardiovasc Imaging. 2020;36(3):439-450.
