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      Altitude Travel in Patients With Pulmonary Hypertension: Randomized Pilot-Trial Evaluating Nocturnal Oxygen Therapy

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          Abstract

          Introduction: Stable patients with pulmonary arterial or chronic thromboembolic pulmonary hypertension (PH) wish to undergo altitude sojourns or air travel but fear disease worsening. This pilot study investigates health effects of altitude sojourns and potential benefits of nocturnal oxygen therapy (NOT) in PH patients.

          Methods: Nine stable PH patients, age 65 (47; 71) years, 5 women, in NYHA class II, on optimized medication, were investigated at 490 m and during two sojourns of 2 days/nights at 2,048 m, once using NOT, once placebo (ambient air), 3 L/min per nasal cannula, according to a randomized crossover design with 2 weeks washout at <800 m. Assessments included safety, nocturnal pulse oximetry (SpO 2), 6-min walk distance (6 MWD), and echocardiography.

          Results: At 2,048 m, two of nine patients required medical intervention, one for exercise-induced syncope, one for excessive nocturnal hypoxemia (SpO 2 < 75% for >30 min). Both recovered immediately with oxygen therapy. Two patients suffered from acute mountain sickness. In 6 patients with complete data, nocturnal mean SpO 2 and cyclic SpO 2 dips reflecting sleep apnea significantly differed from 490 to 2,048 m with placebo, and 2,048 m with NOT (medians, quartiles): SpO 2 93 (91; 95)%, 89 (85; 90)%, 97 (95; 97)%; SpO 2 dips 10.4/h (3.1; 26.9), 34.0/h (5.3; 81.3), 0.3/h (0.1; 2.3). 6 MWD at 490, 2,048 m without and with NOT was 620 m (563; 720), 583 m (467; 696), and 561 m (501; 688). Echocardiographic indices of heart function and PH were unchanged at 2,048 m with/without NOT vs. 490 m.

          Conclusions: 7/9 PH patients stayed safely at 2,048 m but revealed hypoxemia, sleep apnea, and reduced 6 MWD. Hemodynamic changes were trivial. NOT improved oxygenation and sleep apnea. The current pilot trial is important for designing further studies on altitude tolerance of PH patients.

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          Most cited references35

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          EEG arousals: scoring rules and examples: a preliminary report from the Sleep Disorders Atlas Task Force of the American Sleep Disorders Association.

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            Physiological adaptation of the cardiovascular system to high altitude.

            Altitude exposure is associated with major changes in cardiovascular function. The initial cardiovascular response to altitude is characterized by an increase in cardiac output with tachycardia, no change in stroke volume, whereas blood pressure may temporarily be slightly increased. After a few days of acclimatization, cardiac output returns to normal, but heart rate remains increased, so that stroke volume is decreased. Pulmonary artery pressure increases without change in pulmonary artery wedge pressure. This pattern is essentially unchanged with prolonged or lifelong altitude sojourns. Ventricular function is maintained, with initially increased, then preserved or slightly depressed indices of systolic function, and an altered diastolic filling pattern. Filling pressures of the heart remain unchanged. Exercise in acute as well as in chronic high-altitude exposure is associated with a brisk increase in pulmonary artery pressure. The relationships between workload, cardiac output, and oxygen uptake are preserved in all circumstances, but there is a decrease in maximal oxygen consumption, which is accompanied by a decrease in maximal cardiac output. The decrease in maximal cardiac output is minimal in acute hypoxia but becomes more pronounced with acclimatization. This is not explained by hypovolemia, acid-bases status, increased viscosity on polycythemia, autonomic nervous system changes, or depressed systolic function. Maximal oxygen uptake at high altitudes has been modeled to be determined by the matching of convective and diffusional oxygen transport systems at a lower maximal cardiac output. However, there has been recent suggestion that 10% to 25% of the loss in aerobic exercise capacity at high altitudes can be restored by specific pulmonary vasodilating interventions. Whether this is explained by an improved maximum flow output by an unloaded right ventricle remains to be confirmed. Altitude exposure carries no identified risk of myocardial ischemia in healthy subjects but has to be considered as a potential stress in patients with previous cardiovascular conditions.
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              European Association of Echocardiography recommendations for standardization of performance, digital storage and reporting of echocardiographic studies.

              In view of the European Association of Echocardiography (EAE) mission statement "To promote excellence in clinical diagnosis, research, technical development, and education in cardiovascular ultrasound in Europe" and the increasing demand for standardization and quality control, the EAE have established recommendations and guidelines for standardization of echocardiography performance, data acquisition (images, measurements and morphologic descriptors), digital storage and reporting of echocardiographic studies. The aim of these recommendations is to provide a European consensus document on the minimum acceptable requirements for the clinical practice of echocardiography today and thus improve the quality and consistency of echocardiographic practice in Europe.
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                Author and article information

                Contributors
                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                02 September 2020
                2020
                : 7
                : 502
                Affiliations
                Department of Pulmonology, University Hospital Zurich , Zurich, Switzerland
                Author notes

                Edited by: Anne Hilgendorff, Ludwig Maximilian University of Munich, Germany

                Reviewed by: Gunnar N. Hillerdal, Karolinska University Hospital, Sweden; Naresh Kumar, University of Miami, United States

                *Correspondence: Silvia Ulrich silvia.ulrich@ 123456usz.ch

                This article was submitted to Pulmonary Medicine, a section of the journal Frontiers in Medicine

                Article
                10.3389/fmed.2020.00502
                7492536
                32984379
                231b7ca8-8523-4cb6-8aa5-2b4b30b2482f
                Copyright © 2020 Lichtblau, Saxer, Latshang, Aeschbacher, Huber, Scheiwiller, Herzig, Schneider, Hasler, Furian, Bloch and Ulrich.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 April 2020
                : 21 July 2020
                Page count
                Figures: 3, Tables: 3, Equations: 0, References: 38, Pages: 9, Words: 5781
                Funding
                Funded by: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung 10.13039/501100001711
                Funded by: Lunge Zürich 10.13039/501100013363
                Categories
                Medicine
                Clinical Trial

                pulmonary hypertension,altitude,oxygen,exercise performance,sleep,echocardiography

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