{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:07:36Z","timestamp":1791490056667,"version":"4.3.4"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Pulmonary artery pressure (PAP) is increased and right ventricular (RV) function is well preserved in healthy subjects upon exposure to high altitude (HA). An increase in PAP may trigger notching of the right ventricular outflow tract Doppler flow velocity envelope (RVOT notch), which is associated with impaired RV function in patients with pulmonary hypertension. However, whether HA exposure can induce RVOT notch formation and the subsequent impact on cardiac function in healthy subjects remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 99 subjects (69 males and 30 females) with a median age of 25 years were enrolled in this study; they traveled from 500 to 4100 m by bus over a 2-day period. All subjects underwent a comprehensive physiological and echocardiographic examination 1 day before ascension at low altitude and 15 \u00b1 3 h after arrival at HA. The RVOT notch was determined by the presence of a notched shape in the RVOT Doppler flow velocity envelope. The systolic PAP (SPAP) was calculated as Bernoulli equation SPAP = 4 \u00d7 (maximum tricuspid regurgitation velocity)<jats:sup>2<\/jats:sup>+5 and mean PAP (mPAP) = 0.61 \u00d7 SPAP+2. Cardiac output was calculated as stroke volume \u00d7 heart rate. Pulmonary capillary wedge pressure (PCWP) was calculated as 1.9+1.24 \u00d7 mitral E\/e\u2019. Pulmonary vascular resistance (PVR) was calculated as (mPAP-PCWP)\/CO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After HA exposure, 20 (20.2%) subjects had an RVOT notch [notch (+)], and 79 (79.8%) subjects did not have an RVOT notch [notch (\u2212)]. In the multivariate logistic regression analysis, the SPAP, right ventricular global longitude strain (RV GLS), and tricuspid E\/A were independently associated with the RVOT notch. The SPAP, mPAP, PVR, standard deviations of the times to peak systolic strain in the four mid-basal RV segments (RVSD4), peak velocity of the isovolumic contraction period (ICV), and the peak systolic velocity (s\u2019) at the mitral\/tricuspid annulus were increased in all subjects. Conversely, the pulse oxygen saturation (SpO<jats:sub>2<\/jats:sub>), RV GLS, and tricuspid annulus plane systolic excursion (TAPSE)\/SPAP were decreased. However, the increases of SPAP, mPAP, PVR, and RVSD4 and the decreases of SpO<jats:sub>2<\/jats:sub>, RV GLS, and TAPSE\/SPAP were more pronounced in the notch (+) group than in the notch (\u2212) group. Additionally, increased tricuspid ICV and mitral\/tricuspid s\u2019 were found only in the notch (\u2212) group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>HA exposure-induced RVOT notch formation is associated with impaired RV function, including no increase in the tricuspid ICV or s\u2019, reduction of RV deformation, deterioration in RV-pulmonary artery coupling, and RV intraventricular synchrony.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphys.2021.639761","type":"journal-article","created":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T07:39:26Z","timestamp":1617262766000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["The Association Between Notching of the Right Ventricular Outflow Tract Flow Velocity Doppler Envelope and Impaired Right Ventricular Function After Acute High-Altitude Exposure"],"prefix":"10.3389","volume":"12","author":[{"given":"Fangzhengyuan","family":"Yuan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizhu","family":"Bian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohan","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingbin","family":"Ke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanqi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongsheng","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaojun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1016\/j.echo.2005.06.012","article-title":"Which Doppler parameters are load independent? a study in normal volunteers after blood donation.","volume":"18","author":"Abali","year":"2005","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"B2","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1164\/rccm.201004-0601oc","article-title":"Shape of the right ventricular doppler envelope predicts hemodynamics and right heart function in pulmonary hypertension.","volume":"183","author":"Arkles","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1016\/j.jcmg.2015.02.009","article-title":"Right intraventricular dyssynchrony in idiopathic, heritable, and anorexigen-induced pulmonary arterial hypertension: clinical impact and reversibility.","volume":"8","author":"Badagliacca","year":"2015","journal-title":"JACC Cardiovasc. Imaging"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.echo.2012.10.009","article-title":"Echocardiography in pulmonary arterial hypertension: from diagnosis to prognosis.","volume":"26","author":"Bossone","year":"2013","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1152\/japplphysiol.00697.2016","article-title":"The reservoir-wave approach to characterize pulmonary vascular-right ventricular interactions in humans.","volume":"121","author":"Ghimire","year":"2016","journal-title":"J. Appl. Physiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1136\/hrt.2009.171728","article-title":"Deformation imaging describes right ventricular function better than longitudinal displacement of the tricuspid ring.","volume":"96","author":"Giusca","year":"2010","journal-title":"Heart"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1001\/jamacardio.2019.3345","article-title":"Association of mild echocardiographic pulmonary hypertension with mortality and right ventricular function.","volume":"4","author":"Huston","year":"2019","journal-title":"JAMA Cardiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2251","DOI":"10.1111\/echo.14532","article-title":"The evaluation of right ventricular systolic function in patients with repaired tetralogy of fallot by conventional echocardiographic methods and speckle tracking echocardiography: compared with the gold standard cardiac mangenetic resonance.","volume":"36","author":"Kavurt","year":"2019","journal-title":"Echocardiography"},{"key":"B9","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.pcad.2016.06.001","article-title":"Methods for evaluating right ventricular function and ventricular-arterial coupling.","volume":"59","author":"Kubba","year":"2016","journal-title":"Prog. Cardiovasc. Dis."},{"key":"B10","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1089\/ham.2017.0019","article-title":"Echocardiographic assessment of right ventricle dimensions and function after exposure to extreme altitude: is an expedition to 8000 m hazardous for right ventricular function?","volume":"18","author":"Kurdziel","year":"2017","journal-title":"High Alt. Med. Biol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1002\/clc.22493","article-title":"Shape of the pulmonary artery doppler-flow profile predicts the hemodynamics of pulmonary hypertension caused by left-sided heart disease.","volume":"39","author":"Kushwaha","year":"2016","journal-title":"Clin. Cardiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1093\/ehjci\/jev014","article-title":"Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American society of echocardiography and the European association of cardiovascular imaging.","volume":"16","author":"Lang","year":"2015","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1007\/s10554-018-1423-0","article-title":"The value of speckle-tracking echocardiography in identifying right heart dysfunction in patients with chronic thromboembolic pulmonary hypertension.","volume":"34","author":"Li","year":"2018","journal-title":"Int. J. Cardiovasc. Imaging"},{"key":"B14","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1007\/s10554-012-0114-5","article-title":"Right ventricular regional and global systolic function is diminished in patients with pulmonary arterial hypertension: a two-dimensional ultrasound speckle tracking echocardiography study.","volume":"29","author":"Li","year":"2013","journal-title":"Int. J. Cardiovasc. Imaging"},{"key":"B15","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1093\/ejechocard\/jer235","article-title":"Shape of the right ventricular outflow doppler envelope and severity of pulmonary hypertension.","volume":"13","author":"Lopez-Candales","year":"2012","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"B16","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCIMAGING.118.007813","article-title":"Effect of cardiac resynchronization therapy on exercise-induced pulmonary hypertension and right ventricular-arterial coupling.","volume":"11","author":"Martens","year":"2018","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1093\/ehjci\/jew286","article-title":"Heart mechanics at high altitude: 6 days on the top of Europe.","volume":"18","author":"Maufrais","year":"2017","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"B18","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1113\/ep087350","article-title":"Medex 2015: the key role of cardiac mechanics to maintain biventricular function at high altitude.","volume":"104","author":"Maufrais","year":"2019","journal-title":"Exp. Physiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1089\/ham.2014.1035","article-title":"Cardiac biomarkers at high altitude.","volume":"15","author":"Mellor","year":"2014","journal-title":"High Alt. Med. Biol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.echo.2018.06.004","article-title":"Guidelines for performing a comprehensive transthoracic echocardiographic examination in adults: recommendations from the american society of echocardiography.","volume":"32","author":"Mitchell","year":"2019","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1161\/circulationaha.105.605527","article-title":"Role of endothelin-1 in exposure to high altitude: acute mountain sickness and endothelin-1 (ACME-1) study.","volume":"114","author":"Modesti","year":"2006","journal-title":"Circulation"},{"key":"B22","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.00985-2019","article-title":"Pulmonary hypertension at high altitude.","volume":"53","author":"Naeije","year":"2019","journal-title":"Eur. Respir. J."},{"key":"B23","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1086\/677354","article-title":"Biomechanics of the right ventricle in health and disease (2013 grover conference series).","volume":"4","author":"Naeije","year":"2014","journal-title":"Pulm. Circ."},{"key":"B24","article-title":"Comparing right ventricular function and pulmonary artery pressure before and shortly after hemodialysis in patients with end-stage renal disease.","volume":"4","author":"Najafian","year":"2015","journal-title":"Adv. Biomed. Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1016\/j.echo.2017.08.005","article-title":"Effect of gravitational gradients on cardiac filling and performance.","volume":"30","author":"Negishi","year":"2017","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"B26","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1111\/apha.12740","article-title":"Right ventricle dimensions and function in response to acute hypoxia in healthy human subjects.","volume":"219","author":"Netzer","year":"2017","journal-title":"Acta Physiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1093\/ehjci\/jev166","article-title":"Effects of hypobaric hypoxia exposure at high altitude on left ventricular twist in healthy subjects: data from HIGHCARE study on mount everest.","volume":"17","author":"Osculati","year":"2016","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"B28","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.1093\/eurheartj\/ehx720","article-title":"Clinical recommendations for high altitude exposure of individuals with pre-existing cardiovascular conditions: a joint statement by the european society of cardiology, the council on hypertension of the european society of cardiology, the european society of hypertension, the international society of mountain medicine, the italian society of hypertension and the italian society of mountain medicine.","volume":"39","author":"Parati","year":"2018","journal-title":"Eur. Heart J."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1161\/circulationaha.106.624544","article-title":"The heart and pulmonary circulation at high altitudes: healthy highlanders and chronic mountain sickness.","volume":"115","author":"Penaloza","year":"2007","journal-title":"Circulation"},{"key":"B30","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1097\/01.ccm.0000250357.35250.a2","article-title":"Thoracic epidural anesthesia impairs the hemodynamic response to acute pulmonary hypertension by deteriorating right ventricular\u2013pulmonary arterial coupling.","volume":"35","author":"Rex","year":"2007","journal-title":"Crit. Care Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/s00134-007-0831-8","article-title":"Epoprostenol treatment of acute pulmonary hypertension is associated with a paradoxical decrease in right ventricular contractility.","volume":"34","author":"Rex","year":"2008","journal-title":"Intensive Care Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1164\/rccm.201906-1195le","article-title":"Evaluation and prognostic relevance of right ventricular-arterial coupling in pulmonary hypertension.","volume":"201","author":"Richter","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/j.echo.2010.05.010","article-title":"Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American society of echocardiography endorsed by the european association of echocardiography, a registered branch of the european society of cardiology, and the canadian society of echocardiography.","volume":"23","author":"Rudski","year":"2010","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1007\/s10554-020-01803-x","article-title":"Preserved right ventricular function but increased right atrial contractile demand in altitude-induced pulmonary hypertension.","volume":"36","author":"Sareban","year":"2020","journal-title":"Int. J. Cardiovasc. Imaging"},{"key":"B35","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1161\/01.res.80.5.699","article-title":"Myocyte adaptation to chronic hypoxia and development of tolerance to subsequent acute severe hypoxia.","volume":"80","author":"Silverman","year":"1997","journal-title":"Circ. Res."},{"key":"B36","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1183\/09031936.00013908","article-title":"Regulation of hypoxic pulmonary vasoconstriction: basic mechanisms.","volume":"32","author":"Sommer","year":"2008","journal-title":"Eur. Respir. J."},{"key":"B37","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1080\/17461391.2015.1071876","article-title":"Mechanisms underlying reductions in stroke volume at rest and during exercise at high altitude.","volume":"16","author":"Stembridge","year":"2016","journal-title":"Eur. J. Sport Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1016\/j.jcmg.2016.12.021","article-title":"Unraveling the RV ejection doppler envelope: insight into pulmonary artery hemodynamics and disease severity.","volume":"10","author":"Takahama","year":"2017","journal-title":"JACC Cardiovasc. Imaging"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3390\/medicina54050087","article-title":"Changes of left and right ventricle mechanics and function in patients with end-stage renal disease undergoing haemodialysis.","volume":"54","author":"Tamulenaite","year":"2018","journal-title":"Medicina"},{"key":"B40","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.ijcard.2018.01.053","article-title":"Relevance of the TAPSE\/PASP ratio in pulmonary arterial hypertension.","volume":"266","author":"Tello","year":"2018","journal-title":"Int. J. Cardiol."},{"key":"B41","article-title":"Validation of the tricuspid annular plane systolic excursion\/systolic pulmonary artery pressure ratio for the assessment of right ventricular-arterial coupling in severe pulmonary hypertension.","volume":"12","author":"Tello","year":"2019","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"B42","doi-asserted-by":"crossref","first-page":"324 e329","DOI":"10.1016\/j.crad.2017.10.019","article-title":"Validation of cardiac magnetic resonance tissue tracking in the rapid assessment of RV function: a comparative study to echocardiography.","volume":"73","author":"Tong","year":"2018","journal-title":"Clin. Radiol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1183\/09031936.99.13361699","article-title":"Proximal pulmonary emboli modify right ventricular ejection pattern.","volume":"13","author":"Torbicki","year":"1999","journal-title":"Eur. Respir. J."},{"key":"B44","first-page":"206","article-title":"Higher ultrafiltration rate is associated with right ventricular mechanical dispersion.","volume":"21","author":"Unlu","year":"2019","journal-title":"Anatol. J. Cardiol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"2511","DOI":"10.1016\/j.jacc.2011.06.068","article-title":"Progressive right ventricular dysfunction in patients with pulmonary arterial hypertension responding to therapy.","volume":"58","author":"van de Veerdonk","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.jacc.2016.10.047","article-title":"The relationship between the right ventricle and its load in pulmonary hypertension.","volume":"69","author":"Vonk Noordegraaf","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"B47","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCIMAGING.118.008455","article-title":"Left ventricular twist is augmented in hypoxia by beta1-adrenergic-dependent and beta1-adrenergic-independent factors, without evidence of endocardial dysfunction.","volume":"12","author":"Williams","year":"2019","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"B48","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2020.00703","article-title":"Preliminary study of right ventricular dyssynchrony under high-altitude exposure: determinants and impacts.","volume":"11","author":"Yang","year":"2020","journal-title":"Front. Physiol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1161\/01.cir.70.4.657","article-title":"Noninvasive estimation of right ventricular systolic pressure by doppler ultrasound in patients with tricuspid regurgitation.","volume":"70","author":"Yock","year":"1984","journal-title":"Circulation"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1111\/echo.14439","article-title":"Tricuspid annular plane systolic excursion is dependent on right ventricular volume in addition to function.","volume":"36","author":"Zhao","year":"2019","journal-title":"Echocardiography"},{"key":"B51","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1111\/echo.12389","article-title":"Evaluation of subclinical left ventricular dysfunction in diabetic patients: longitudinal strain velocities and left ventricular dyssynchrony by two-dimensional speckle tracking echocardiography study.","volume":"31","author":"Zoroufian","year":"2014","journal-title":"Echocardiography"}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.639761\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T07:39:39Z","timestamp":1617262779000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.639761\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,1]]},"references-count":51,"alternative-id":["10.3389\/fphys.2021.639761"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2021.639761","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,1]]},"article-number":"639761"}}