{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T07:46:29Z","timestamp":1792395989709,"version":"4.4.0"},"reference-count":54,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T00:00:00Z","timestamp":1656288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Introduction: The aim of the study was to assess cardiac and autonomic function in patients with myasthenia gravis (MG) and to explore its relationship with disease outcomes. Methods: Thirty-eight patients with an MG were enrolled (median age 40.5 years; median disease duration 5.5 years). Cardiovascular parameters, baroreflex sensitivity (BRS), spectral indices of short-term heart rate (HRV), and systolic blood pressure variability (SBPV) were compared with age- and gender-matched controls (n = 30). Cardiac autonomic function was assessed during the response to standing (tilt) and deep breathing tests (expiration\/inspiration ratio-E\/I). Results: HR and BP responses to the tilt test were similar in both groups. MG patients, as compared to controls, were characterized by altered SBPV at rest, significantly reduced HR response to the deep breathing test (p &lt; 0.001), increased sympathovagal balance after tilt (delta LF\/HF-RRI, p = 0.037), and lower values of BRS (p = 0.007) and hemodynamic parameters, i.e., cardiac index, index contractility, left ventricular work index, at rest and during tilt. There was no association between disease duration and autonomic parameters. Disease severity, as determined by MGFA (Myasthenia Gravis Foundation of America) corrected for age and sex, was an independent predictor of diminished vagal tone (E\/I ratio) and increased sympathetic response to tilt (delta LF\/HF-RRI) as measured with HRV. Lower BRS was associated with greater disease severity and older age. Hemodynamic parameters were predominantly predicted by age and sex. Conclusion: Our results confirm cardiac autonomic dysfunction among MG patients with predominant parasympathetic impairment. Clinicians should consider evaluation of autonomic balance in MG patients with, or at risk for, cardiovascular disease.<\/jats:p>","DOI":"10.3390\/jcm11133697","type":"journal-article","created":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T22:31:14Z","timestamp":1656369074000},"page":"3697","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Association of Cardiac Autonomic Responses with Clinical Outcomes of Myasthenia Gravis: Short-Term Analysis of the Heart-Rate and Blood Pressure Variability"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3861-7113","authenticated-orcid":false,"given":"Monika","family":"Zawadka-Kunikowska","sequence":"first","affiliation":[{"name":"Department of Human Physiology, Nicolaus Copernicus University Ludwik Rydygier Collegium Medicum in Bydgoszcz, Kar\u0142owicza 24, 85-092 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2995-6148","authenticated-orcid":false,"given":"\u0141ukasz","family":"Rzepi\u0144ski","sequence":"additional","affiliation":[{"name":"Sanitas-Neurology Outpatient Clinic, Dworcowa 110, 85-010 Bydgoszcz, Poland"},{"name":"Department of Neurology, 10th Military Research Hospital and Polyclinic, Powsta\u0144c\u00f3w Warszawy 5, 85-681 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Tafil-Klawe","sequence":"additional","affiliation":[{"name":"Department of Human Physiology, Nicolaus Copernicus University Ludwik Rydygier Collegium Medicum in Bydgoszcz, Kar\u0142owicza 24, 85-092 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek J.","family":"Klawe","sequence":"additional","affiliation":[{"name":"Department of Hygiene, Epidemiology, Ergonomy and Postgraduate Education, Ludwik Rydygier Collegium Medicum in Bydgoszcz Nicolaus Copernicus University in Torun, M. Sklodowskiej-Curie 9, 85-094 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8453-7785","authenticated-orcid":false,"given":"Pawe\u0142","family":"Zalewski","sequence":"additional","affiliation":[{"name":"Department of Exercise Physiology and Functional Anatomy, Ludwik Rydygier Collegium Medicum in Bydgoszcz Nicolaus Copernicus University in Torun, M. Sklodowskiej-Curie 9, 85-094 Bydgoszcz, Poland"},{"name":"Centre for Preclinical Research, Department of Experimental and Clinical Physiology, Warsaw Medical University, 1b Banacha Street, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8503-3172","authenticated-orcid":false,"given":"Joanna","family":"S\u0142omko","sequence":"additional","affiliation":[{"name":"Department of Exercise Physiology and Functional Anatomy, Ludwik Rydygier Collegium Medicum in Bydgoszcz Nicolaus Copernicus University in Torun, M. Sklodowskiej-Curie 9, 85-094 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s12974-017-0892-8","article-title":"Regulatory T cells in multiple sclerosis and myasthenia gravis","volume":"14","author":"Danikowski","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.nmd.2019.07.006","article-title":"Heterogeneity and shifts in distribution of muscle weakness in myasthenia gravis","volume":"29","author":"Tannemaat","year":"2019","journal-title":"Neuromuscul. Disord."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Porras, L.D., Homedes, C., Alberti, M.A., Santamaria, V.V., and Casasnovas, C. (2022). Quality of Life in Myasthenia Gravis and Correlation of MG-QOL15 with Other Functional Scales. J. Clin. Med., 11.","DOI":"10.3390\/jcm11082189"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41572-019-0079-y","article-title":"Myasthenia gravis","volume":"5","author":"Gilhus","year":"2019","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.jneuroim.2008.05.021","article-title":"Myasthenia gravis sera have no effect on cardiomyocytes in vitro","volume":"201","author":"Helgeland","year":"2008","journal-title":"J. Neuroimmunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ijcme.2014.08.003","article-title":"Cardiac manifestations of myasthenia gravis: A systematic review","volume":"5","author":"Shivamurthy","year":"2014","journal-title":"IJC Metab. Endocr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1589\/jpts.27.2013","article-title":"Sleep disorders in patients with myasthenia gravis: A systematic review","volume":"27","author":"Oliveira","year":"2015","journal-title":"J. Phys. Ther. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"fcac018","DOI":"10.1093\/braincomms\/fcac018","article-title":"Structural and functional brain alterations in patients with myasthenia gravis","volume":"4","author":"Klaus","year":"2022","journal-title":"Brain Commun."},{"key":"ref_9","first-page":"3","article-title":"Comorbid nervous system manifestations and disorders with myasthenia gravis: Evidences and possible mechanisms","volume":"3","author":"Hamed","year":"2012","journal-title":"J. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1007\/s00415-014-7465-x","article-title":"The presence of dysautonomia in different subgroups of myasthenia gravis patients","volume":"261","year":"2014","journal-title":"J. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.autneu.2008.09.005","article-title":"Autonomic ganglia, acetylcholine receptor antibodies, and autoimmune ganglionopathy","volume":"146","author":"Vernino","year":"2009","journal-title":"Auton. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"102903","DOI":"10.1016\/j.autneu.2021.102903","article-title":"Regulation of acute reflectory hyperinflammation in viral and other diseases by means of stellate ganglion block. A conceptual view with a focus on COVID-19","volume":"237","author":"Fischer","year":"2022","journal-title":"Auton. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e26008","DOI":"10.1097\/MD.0000000000026008","article-title":"Risk of subsequent atrial fibrillation in patients with myasthenia gravis: A population-based cohort study","volume":"100","author":"Liou","year":"2021","journal-title":"Medicine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.jns.2011.05.028","article-title":"Cardiac autonomic control in patients with myasthenia gravis and thymoma","volume":"307","author":"Peric","year":"2011","journal-title":"J. Neurol. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1080\/01616412.2018.1446690","article-title":"Evaluation of cardiac autonomic functions in myasthenia gravis","volume":"40","author":"Kocabas","year":"2018","journal-title":"Neurol. Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Rzepi\u0144ski, \u0141., Zawadka-Kunikowska, M., Newton, J.L., and Zalewski, P. (2021). Cardiac Autonomic Dysfunction in Myasthenia Gravis and Relapsing-Remitting Multiple Sclerosis-A Pilot Study. J. Clin. Med., 10.","DOI":"10.3390\/jcm10102173"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s11906-012-0290-7","article-title":"Blood pressure variability, cardiovascular risk, and risk for renal disease progression","volume":"14","author":"Parati","year":"2012","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/S0140-6736(10)60308-X","article-title":"Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension","volume":"375","author":"Rothwell","year":"2010","journal-title":"Lancet"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.clineuro.2012.05.013","article-title":"Abnormal sympathetic hyper-reactivity in patients with myasthenia gravis: A prospective study","volume":"115","author":"Shukla","year":"2013","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"42","DOI":"10.4103\/aian.AIAN_270_17","article-title":"The Spectrum of Autonomic Dysfunction in Myasthenic Crisis","volume":"21","author":"Benjamin","year":"2018","journal-title":"Ann. Indian Acad. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/0165-1838(92)90218-6","article-title":"Deficiency of sympathetic nervous system function in myasthenia","volume":"38","author":"Stoica","year":"1992","journal-title":"J. Auton. Nerv. Syst."},{"key":"ref_22","first-page":"333","article-title":"Enhancement of noradrenergic neural transmission: An effective therapy of myasthenia gravis: A report on 52 consecutive patients","volume":"31","author":"Lechin","year":"2000","journal-title":"J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1007\/s00415-008-0049-x","article-title":"Left ventricular long axis function in myasthenia gravis","volume":"255","author":"Owe","year":"2008","journal-title":"J. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/0002-9149(92)90688-U","article-title":"Left ventricular function in myasthenia gravis","volume":"69","author":"Johannessen","year":"1992","journal-title":"Am. J. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/8058946","article-title":"Electrocardiography as the First Step for the Further Examination of Cardiac Involvement in Myasthenia Gravis","volume":"3","author":"Kato","year":"2016","journal-title":"BioMed Res. Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"329","DOI":"10.4103\/0972-2327.116912","article-title":"Heart rate and blood pressure variability in patients with myasthenia gravis","volume":"16","author":"Puneeth","year":"2013","journal-title":"Ann. Indian Acad. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1527-5299.2004.03407.x","article-title":"Comparison of changes in ejection fraction to changes in impedance cardiography cardiac index and systolic time ratio","volume":"10","author":"Parrott","year":"2004","journal-title":"Congest. Heart Fail."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.ncl.2018.01.006","article-title":"Measuring Clinical Treatment Response in Myasthenia Gravis","volume":"36","author":"Barnett","year":"2018","journal-title":"Neurol. Clin."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1212\/WNL.55.1.16","article-title":"Myasthenia gravis: Recommendations for clinical research standards. Task force of the medical scientific advisory board of the myasthenia gravis foundation of America","volume":"55","author":"Jaretzki","year":"2000","journal-title":"Neurology"},{"key":"ref_30","unstructured":"Fortin, J., Klinger, T., Wagner, C., Sterner, H., Madritsch, C., Gr\u00fcllenberger, R., Hacker, A., Habenbacher, W., and Skrabal, F. (1998, January 1). The task force monitor\u2014A non-invasive beat-to beat monitor for hemodynamic and autonomic function of the human body. Proceedings of the 20th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Hong Kong, China."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1109\/51.620497","article-title":"Continuous monitoring of the sympatho-vagal balance through spectral analysis","volume":"16","author":"Bianchi","year":"1997","journal-title":"IEEE Eng. Med. Biol. Mag."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/00004872-200018010-00003","article-title":"How to measure baroreflex sensitivity: From the cardiovascular laboratory to daily life","volume":"18","author":"Parati","year":"2000","journal-title":"J. Hypertens."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1002\/mus.20365","article-title":"Quantitative studies of autonomic function","volume":"33","author":"Hilz","year":"2006","journal-title":"Muscle Nerve"},{"key":"ref_34","unstructured":"Taskforce of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology (1996). Heart rate variability: Standards of measurement. physiological interpretation. And clinical use. Eur. Heart J., 17, 354\u2013381."},{"key":"ref_35","unstructured":"Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (1996). Assessment clinical autonomic testing report of the therapeutics and technology subcommittee of the American Academy of Neurology. Neurology, 46, 873\u2013880."},{"key":"ref_36","unstructured":"(2020, August 21). NIST\/SEMATECH e-Handbook of Statistical Methods, Available online: http:\/\/www.itl.nist.gov\/div898\/handbook\/.2012\/01\/20."},{"key":"ref_37","first-page":"H2108","article-title":"Transfer function analysis of ventilatory influence on systemic arterial pressure in the rat","volume":"271","author":"Kuo","year":"1996","journal-title":"Am. J. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1038\/s41598-019-38841-y","article-title":"Cholinergic Stimulation by Pyridostigmine Bromide Before Myocardial Infarction Prevent Cardiac and Autonomic Dysfunction","volume":"9","author":"Barboza","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.autneu.2015.09.002","article-title":"Chronic cholinergic stimulation promotes changes in cardiovascular autonomic control in spontaneously hypertensive rats","volume":"193","author":"Blanco","year":"2015","journal-title":"Auton. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"17141","DOI":"10.1038\/s41598-021-96505-2","article-title":"Effects of chronic cholinergic stimulation associated with aerobic physical training on cardiac morphofunctional and autonomic parameters in spontaneously hypertensive rats","volume":"11","author":"Gardim","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1016\/j.clinph.2018.05.009","article-title":"Progressive multiple sclerosis patients have a higher burden of autonomic dysfunction compared to relapsing remitting phenotype","volume":"129","author":"Adamec","year":"2018","journal-title":"Clin. Neurophysiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Bellocchi, C., Carandina, A., Montinaro, B., Targetti, E., Furlan, L., Rodrigues, G.D., Tobaldini, E., and Montano, N. (2022). The Interplay between Autonomic Nervous System and Inflammation across Systemic Autoimmune Diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052449"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.npep.2010.10.002","article-title":"Cardiac ischemia-reperfusion regulates sympathetic neuropeptide expression through gp130-dependent and independent mechanisms","volume":"45","author":"Alston","year":"2011","journal-title":"Neuropeptides"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.autneu.2016.04.002","article-title":"Effects on hemodynamic variables and echocardiographic parameters after a stellate ganglion block in 15 healthy volunteers","volume":"197","author":"Roqueta","year":"2016","journal-title":"Auton. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"E32","DOI":"10.1152\/ajpendo.00012.2016","article-title":"Neuroinflammatory and autonomic mechanisms in diabetes and hypertension","volume":"311","author":"Han","year":"2016","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s12974-020-01774-9","article-title":"Transcriptomic profiling of microglia and astrocytes throughout aging","volume":"17","author":"Pan","year":"2020","journal-title":"J. Neuroinflammation"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zehravi, M., Kabir, J., Akter, R., Malik, S., Ashraf, G.M., Tagde, P., Ramproshad, S., Mondal, B., Rahman, M.H., and Mohan, A.G. (2022). A Prospective Viewpoint on Neurological Diseases and Their Biomarkers. Molecules, 27.","DOI":"10.3390\/molecules27113516"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1513\/AnnalsATS.202005-581CME","article-title":"Dyspnea in Chronic Low Ventricular Preload States","volume":"18","author":"Tooba","year":"2021","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1086\/685054","article-title":"Unexplained exertional dyspnea caused by low ventricular filling pressures: Results from clinical invasive cardiopulmonary exercise testing","volume":"6","author":"Oldham","year":"2016","journal-title":"Pulm. Circ."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"296","DOI":"10.4239\/wjd.v6.i2.296","article-title":"Prediabetes diagnosis and treatment: A review","volume":"6","author":"Bansal","year":"2015","journal-title":"World J. Diabetes"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1007\/BF02345011","article-title":"Transient phase locking patterns among respiration, heart rate and blood pressure during cardiorespiratory synchronisation in humans","volume":"38","author":"Censi","year":"2000","journal-title":"Med. Biol. Eng. Comput."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1114\/1.1603748","article-title":"Nonlinear Coupling Among Heart Rate, Blood Pressure, and Respiration in Patients Susceptible to Neuromediated Syncope","volume":"31","author":"Censi","year":"2003","journal-title":"Ann. Biomed. Eng."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"16525","DOI":"10.1038\/s41598-020-71532-7","article-title":"Mathematical modeling of the cardiovascular autonomic control in healthy subjects during a passive head-up tilt test","volume":"10","author":"Ishbulatov","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"307","DOI":"10.15275\/rusomj.2021.0307","article-title":"Synchronization of autonomic control loops of blood circulation in patients with COVID-19","volume":"10","author":"Skazkina","year":"2021","journal-title":"Russ. Open Med. J."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/13\/3697\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:39:05Z","timestamp":1760139545000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/13\/3697"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,27]]},"references-count":54,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["jcm11133697"],"URL":"https:\/\/doi.org\/10.3390\/jcm11133697","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,27]]}}}