{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T11:22:28Z","timestamp":1782300148054,"version":"3.54.5"},"reference-count":79,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T00:00:00Z","timestamp":1615766400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006087","name":"Direcci\u00f3n General de Asuntos del Personal Acad\u00e9mico, Universidad Nacional Aut\u00f3noma de M\u00e9xico","doi-asserted-by":"publisher","award":["PAPIIT IN113619"],"award-info":[{"award-number":["PAPIIT IN113619"]}],"id":[{"id":"10.13039\/501100006087","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006087","name":"Direcci\u00f3n General de Asuntos del Personal Acad\u00e9mico, Universidad Nacional Aut\u00f3noma de M\u00e9xico","doi-asserted-by":"publisher","award":["PAPIIT IA100120"],"award-info":[{"award-number":["PAPIIT IA100120"]}],"id":[{"id":"10.13039\/501100006087","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CONACYT","award":["Fordecyt-Pronaces\/610285\/2019"],"award-info":[{"award-number":["Fordecyt-Pronaces\/610285\/2019"]}]},{"name":"CONACYT","award":["263377\/2019"],"award-info":[{"award-number":["263377\/2019"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Achalasia is a disease characterized by the inability to relax the esophageal sphincter due to a degeneration of the parasympathetic ganglion cells located in the wall of the thoracic esophagus. Achalasia has been associated with extraesophageal dysmotility, suggesting alterations of the autonomic nervous system (ANS) that extend beyond the esophagus. The purpose of the present contribution is to investigate whether achalasia may be interpreted as the esophageal manifestation of a more generalized disturbance of the ANS which includes alterations of heart rate and\/or blood pressure. Therefore simultaneous non-invasive records of the heart inter-beat intervals (IBI) and beat-to-beat systolic blood pressure (SBP) of 14 patients (9 female, 5 male) with achalasia were compared with the records of 34 rigorously screened healthy control subjects (17 female, 17 male) in three different conditions: supine, standing up, and controlled breathing at 0.1 Hz, using a variety of measures in the time and spectral domains. Significant differences in heart rate variability (HRV) and blood pressure variability (BPV) were observed which seem to be due to cardiovagal damage to the heart, i.e., a failure of the ANS, as expected according to our hypothesis. This non-invasive methodology can be employed as an auxiliary clinical protocol to study etiology and evolution of achalasia, and other pathologies that damage ANS.<\/jats:p>","DOI":"10.1371\/journal.pone.0248106","type":"journal-article","created":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T17:28:28Z","timestamp":1615829308000},"page":"e0248106","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cardiovascular dysautonomia in Achalasia Patients: Blood pressure and heart rate variability alterations"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0296-7966","authenticated-orcid":true,"given":"Ana Leonor","family":"Rivera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Esta\u00f1ol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio 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Pandolfino","year":"2008","journal-title":"Gastroenterology"},{"issue":"8","key":"pone.0248106.ref008","doi-asserted-by":"crossref","first-page":"e0201676","DOI":"10.1371\/journal.pone.0201676","article-title":"An original Eurasian haplotype, HLA-DRB1*14:54-DQB1*05:03, influences the susceptibility to idiopathic achalasia","volume":"13","author":"J Furuzawa-Carballeda","year":"2018","journal-title":"PLoS One"},{"key":"pone.0248106.ref009","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1136\/gut.33.2.150","article-title":"Histological studies of Auerbach\u2019s plexuses of the oesophagus, stomach, jejunum, and colon in patients with achalasia of the oesophagus: presence of parietal cells and gastric emptying of solids","volume":"33","author":"A Csendes","year":"1992","journal-title":"Gut"},{"key":"pone.0248106.ref010","first-page":"55","volume-title":"Electron Microscopy (5th International Congress of Electron Microscopy, Philadelphia, Pennsylvania)","author":"C Franzini","year":"1962"},{"key":"pone.0248106.ref011","first-page":"160474","article-title":"Achalasia of the esophagus: pathologic and etiologic considerations","author":"RR Cassella","year":"1964","journal-title":"Ann Surg"},{"key":"pone.0248106.ref012","first-page":"279","article-title":"Fine-structure changes in achalasia of the esophagus","volume":"46","author":"RR Cassella","year":"1965","journal-title":"Am I. Pathol"},{"key":"pone.0248106.ref013","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1136\/gut.11.5.388","article-title":"The neurological lesion in achalasia of the cardia","volume":"11","author":"B Smith","year":"1970","journal-title":"Gut"},{"key":"pone.0248106.ref014","first-page":"659","article-title":"Alteraciones ultraestructurales del nervio vago en la acalasia del esofago","volume":"51","author":"A De la Fuente","year":"1977","journal-title":"Rev ESP Enf Ap Digest"},{"key":"pone.0248106.ref015","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/0016-5085(84)90079-9","article-title":"Esophageal Lewy bodies associated with ganglion cell loss in achalasia. 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Hopkins","year":"1974","journal-title":"The Lancet"},{"key":"pone.0248106.ref027","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1016\/S0140-6736(78)91268-0","article-title":"Familial glucocorticoid deficiency with achalasia of the cardia and deficient tear production","volume":"17","author":"J Allgrove","year":"1978","journal-title":"Lancet"},{"issue":"1","key":"pone.0248106.ref028","doi-asserted-by":"crossref","first-page":"62","DOI":"10.7326\/0003-4819-106-1-62","article-title":"Glucocorticoid insufficiency, achalasia, alacrima with autonomic and motor neuropathy","volume":"106","author":"BG Stuckey","year":"1987","journal-title":"Ann Intern Med"},{"issue":"6","key":"pone.0248106.ref029","first-page":"729","article-title":"Megaesophagus and recurrent apnea in an adult patient with familial dysautonomia","volume":"85","author":"C Maayan","year":"1990","journal-title":"Am J Gastroenterol"},{"issue":"9","key":"pone.0248106.ref030","first-page":"1585","article-title":"Guillain-Barr\u00e9 syndrome and achalasia: Two manifestations of a viral disease or coincidental association?","volume":"89","author":"M Firouzi","year":"1994","journal-title":"Am J Gastroenterol"},{"key":"pone.0248106.ref031","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1136\/thx.31.3.278","article-title":"Oesophageal motor changes in diabetes mellitus","volume":"31","author":"IM Stewart","year":"1976","journal-title":"Thorax"},{"key":"pone.0248106.ref032","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1016\/S0016-5085(19)31865-7","article-title":"Esophageal function in diabetes mellitus and its relation to peripheral neuropathy","volume":"73","author":"JB Hollis","year":"1977","journal-title":"Gastroenterology"},{"key":"pone.0248106.ref033","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/BF01324943","article-title":"Relationship among esophageal dysfunction diabetic gastroenteropathy and peripherical neuropathy","volume":"28","author":"C Russell","year":"1983","journal-title":"Dig Dis Sci"},{"key":"pone.0248106.ref034","first-page":"237","article-title":"Neuropat\u00eda auton\u00f3mica y peristaltismo esof\u00e1gico en la diabetes mellitus: an\u00e1lisis de 30 pacientes","volume":"41","author":"F Espi","year":"1987","journal-title":"Cir Esp"},{"key":"pone.0248106.ref035","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1111\/j.1572-0241.1999.987_j.x","article-title":"Gastroesophagealrefluxin diabetes mellitus","volume":"94","author":"I Lluch","year":"1999","journal-title":"Am J Gastroenterol"},{"key":"pone.0248106.ref036","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1111\/j.1365-2982.2006.00799.x","article-title":"Oesophageal motility disorders in type I diabetes mellitus and their relation to cardiovascular autonomic neuropathy","volume":"18","author":"JF Ascaso","year":"2006","journal-title":"Neurogastroenterol Motil"},{"issue":"1","key":"pone.0248106.ref037","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1365-2982.1995.tb00209.x","article-title":"Autonomic dysfunction in patients with achalasia","volume":"7","author":"VF Eckardt","year":"1995","journal-title":"Neurogastroenterol Motil"},{"issue":"5","key":"pone.0248106.ref038","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1046\/j.1365-2982.1998.00120.x","article-title":"Autonomic dysfunction in patients with achalasia of the oesophagus","volume":"10","author":"A von Herbay","year":"1998","journal-title":"Neurogastroenterol Motil"},{"issue":"10","key":"pone.0248106.ref039","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1023\/A:1026638822259","article-title":"Extraesophageal autonomic dysfunction in patients with achalasia","volume":"44","author":"W Olk","year":"1999","journal-title":"Dig Dis Sci"},{"issue":"6","key":"pone.0248106.ref040","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1080\/00365520410004460","article-title":"Achalasia: a vagal disease","volume":"39","author":"B Ohlsson","year":"2004","journal-title":"Scand J Gastroenterol"},{"issue":"240","key":"pone.0248106.ref041","first-page":"297","article-title":"Vagal function in achalasia of the cardia","volume":"63","author":"M Atkinson","year":"1987","journal-title":"Q J Med"},{"issue":"12","key":"pone.0248106.ref042","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1097\/00042737-199912000-00002","article-title":"Studies of autonomic function in patients with achalasia and nutcracker oesophagus","volume":"11","author":"NJ Trudgill","year":"1999","journal-title":"Eur J Gastroenterol Hepatol"},{"issue":"4","key":"pone.0248106.ref043","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1023\/A:1005472400263","article-title":"Cardiovascular autonomic function in patients with primary achalasia","volume":"45","author":"R Rinaldi","year":"2000","journal-title":"Dig Dis Sci"},{"issue":"8","key":"pone.0248106.ref044","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1111\/j.1365-2982.2007.00920.x","article-title":"Absence of cardiovascular autonomic dysfunction and vagal pancreatic impairment in idiopathic achalasia of the oesophagus","volume":"19","author":"B Herreros","year":"2007","journal-title":"Neurogastroenterol Motil"},{"issue":"8","key":"pone.0248106.ref045","doi-asserted-by":"crossref","first-page":"084007","DOI":"10.1088\/1361-6579\/aad8db","article-title":"A physicist\u2019s view of homeostasis: How time series of continuous monitoring reflect the function of physiological variables in regulatory mechanisms","volume":"39","author":"R Fossion","year":"2018","journal-title":"Physiol Meas"},{"key":"pone.0248106.ref046","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1016\/S0140-6736(06)68735-7","article-title":"Deceleration capacity of heart 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Esta\u00f1ol","year":"2016","journal-title":"Physiol Rep"},{"issue":"4504","key":"pone.0248106.ref050","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1126\/science.6166045","article-title":"Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat to beat cardiovascular control","volume":"213","author":"S Akselrod","year":"1981","journal-title":"Science"},{"key":"pone.0248106.ref051","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1161\/01.CIR.84.2.482","article-title":"Cardiovascular neural regulation explored in the frequency domain","volume":"84","author":"A Malliani","year":"1991","journal-title":"Circulation"},{"key":"pone.0248106.ref052","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1093\/oxfordjournals.eurheartj.a014868","article-title":"Heart rate variability. Standards of measurement, physiological interpretation, and clinical use","volume":"17","author":"Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology","year":"1996","journal-title":"Eur Heart J"},{"key":"pone.0248106.ref053","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1111\/j.1469-8986.1997.tb02140.x","article-title":"Heart rate variability: origins, methods, and interpretive caveats","volume":"34","author":"GG Berntson","year":"1997","journal-title":"Psychophysiology"},{"issue":"2","key":"pone.0248106.ref054","doi-asserted-by":"crossref","first-page":"e0148378","DOI":"10.1371\/journal.pone.0148378","article-title":"Heart rate and systolic blood pressure variability in the time domain in patients with recent and long-standing Diabetes Mellitus","volume":"11","author":"AL Rivera","year":"2016","journal-title":"PLoS One"},{"issue":"11","key":"pone.0248106.ref055","doi-asserted-by":"crossref","first-page":"e0165904","DOI":"10.1371\/journal.pone.0165904","article-title":"Loss of breathing modulation of heart rate variability in patients with recent and long standing Diabetes Mellitus type II","volume":"11","author":"AL Rivera","year":"2016","journal-title":"PLoS One"},{"key":"pone.0248106.ref056","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/978-3-319-73975-5_6","volume-title":"Quantitative Models for Microscopic to Macroscopic Biological Macromolecules and Tissues","author":"AL Rivera","year":"2018"},{"key":"pone.0248106.ref057","first-page":"111","volume-title":"Quantitative Models for Microscopic to Macroscopic Biological Macromolecules and Tissues","author":"R Fossion","year":"2018b"},{"issue":"20","key":"pone.0248106.ref058","doi-asserted-by":"crossref","first-page":"55","DOI":"10.22201\/ceiich.24485705e.2020.20.71195","article-title":"On the stability and adaptability of human physiology: Gaussians meet heavy\u2013tailed distributions","volume":"8","author":"R Fossion","year":"2020","journal-title":"Interdisciplina"},{"key":"pone.0248106.ref059","first-page":"012024","article-title":"Symmetry, and signs of self-organized criticality in living organisms","volume":"1612","author":"A. L. Rivera","journal-title":"J. Phys.: Conf. Ser"},{"key":"pone.0248106.ref060","first-page":"155","article-title":"Heart rate variability in the assessment of autonomic diabetic neuropathy","volume":"4","author":"RI Kitney","year":"1982","journal-title":"Automedica"},{"key":"pone.0248106.ref061","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1016\/0735-1097(89)90408-7","article-title":"Beat to beat variability in cardiovascular variables: Noise or music?","volume":"14","author":"ML Appel","year":"1989","journal-title":"J Am Coll Cardiol"},{"issue":"2","key":"pone.0248106.ref062","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1001\/archneur.1991.00530140079020","article-title":"Spectral analysis of heart rate in diabetic autonomic neuropathy: a comparison with standard tests of autonomic function","volume":"48","author":"R Freeman","year":"1991","journal-title":"Arch Neurol"},{"issue":"Supp 1","key":"pone.0248106.ref063","first-page":"59","article-title":"Consensus statement: Standardized measure in diabetes neuropathy","volume":"18","author":"American Diabetes Association and the American Academy of Neurology","year":"1995","journal-title":"Diabetes Care"},{"key":"pone.0248106.ref064","doi-asserted-by":"crossref","first-page":"556","DOI":"10.2337\/dc07-1615","article-title":"Prediction of mortality using measures of cardiac autonomic dysfunction in the diabetic and nondiabetic population: the MONICA\/KORA Augsburg Cohort Study","volume":"31","author":"D Ziegler","year":"2008","journal-title":"Diabetes Care"},{"issue":"10","key":"pone.0248106.ref065","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.2337\/dc10-1303","article-title":"Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments","volume":"33","author":"S Tesfaye","year":"2010","journal-title":"Diabetes Care"},{"issue":"3","key":"pone.0248106.ref066","first-page":"276","article-title":"Variabilidade da frequ\u00eancia card\u00edaca e da press\u00e3o arterial sist\u00f3lica em Diab\u00e9ticos com diagn\u00f3stico recente","volume":"105","author":"A Michel-Ch\u00e1vez","year":"2015","journal-title":"Arq Bras Cardiol"},{"key":"pone.0248106.ref067","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1161\/01.RES.53.1.96","article-title":"Blood pressure and heart rate variabilities in normotensive and hypertensive human beings","volume":"53","author":"G Mancia","year":"1983","journal-title":"Circ Res"},{"key":"pone.0248106.ref068","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.cjca.2013.02.012","article-title":"Blood pressure variability: A novel and important risk factor","volume":"29","author":"JS Floras","year":"2013","journal-title":"Canad J Cardiol"},{"key":"pone.0248106.ref069","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/nrcardio.2013.1","article-title":"Assessment and management of blood-pressure variability","volume":"10","author":"G Parati","year":"2013","journal-title":"Nat Rev Cardiol"},{"key":"pone.0248106.ref070","doi-asserted-by":"crossref","first-page":"S312","DOI":"10.2337\/dcS13-2043","article-title":"Prognostic value of blood pressure variability and average blood pressure levels in patients with hypertension and diabetes","volume":"36","author":"G Parati","year":"2013","journal-title":"Diabetes Care"},{"issue":"3","key":"pone.0248106.ref071","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1097\/00126097-200206000-00006","article-title":"Comparison of Portapres non-invasive blood pressure measurement in the finger with intra-aortic pressure measurement during incremental bicycle exercise","volume":"7","author":"S Eckert","year":"2002","journal-title":"Blood Press Monit"},{"key":"pone.0248106.ref072","unstructured":"Lav\u00edn-P\u00e9rez R, Diferencias de g\u00e9nero y edad en la variabilidad a corto plazo de la frecuencia card\u00edaca. Master Degree Thesis. (Universidad Nacional Aut\u00f3noma de M\u00e9xico, M\u00e9xico, 2018). http:\/\/132.248.9.195\/ptd2018\/mayo\/0774746\/Index.html."},{"key":"pone.0248106.ref073","doi-asserted-by":"crossref","first-page":"377","DOI":"10.4236\/health.2012.47060","article-title":"Normal values of heart rate variability at rest in a young, healthy and active Mexican population","volume":"4","author":"M Corrales","year":"2012","journal-title":"Health"},{"key":"pone.0248106.ref074","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1098\/rspa.1998.0193","article-title":"The empirical mode decomposition and the Hilbert spectrum for nonlinear and non-stationary time series analysis","volume":"454","author":"NE Huang","year":"1998","journal-title":"Proc R Soc Lon Ser-A"},{"key":"pone.0248106.ref075","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1542\/peds.107.1.97","article-title":"Toward the early diagnosis of neonatal sepsis and sepsis-like illness using novel heart rate analysis","volume":"107","author":"MP Griffin","year":"2001","journal-title":"Pediatrics"},{"key":"pone.0248106.ref076","doi-asserted-by":"crossref","first-page":"258","DOI":"10.3389\/fpubh.2017.00258","article-title":"An overview of heart rate variability metrics and norms","volume":"5","author":"F Shaffer","year":"2017","journal-title":"Frontiers in Public Health"},{"issue":"1","key":"pone.0248106.ref077","doi-asserted-by":"crossref","first-page":"H215","DOI":"10.1152\/ajpheart.1999.276.1.H215","article-title":"Low-frequency component of the heart rate variability spectrum: a poor marker of sympathetic activity","volume":"276","author":"MS Houle","year":"1999","journal-title":"American Journal of Physiology-Heart and Circulatory Physiology"},{"issue":"5","key":"pone.0248106.ref078","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/psyp.12027","article-title":"The utility of low frequency heart rate variability as an index of sympathetic cardiac tone: a review with emphasis on a reanalysis of previous studies","volume":"50","author":"GA Reyes del Paso","year":"2013","journal-title":"Psychophysiology"},{"issue":"4","key":"pone.0248106.ref079","doi-asserted-by":"crossref","first-page":"041913","DOI":"10.1103\/PhysRevE.68.041913","article-title":"Synchronization between main rhythmic processes in the human cardiovascular system","volume":"68","author":"MD Prokhorov","year":"2003","journal-title":"Phys Rev E"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0248106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T17:29:29Z","timestamp":1615829369000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0248106"}},"subtitle":[],"editor":[{"given":"Jacobus P.","family":"van Wouwe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,3,15]]},"references-count":79,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0248106","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,15]]}}}