J Neurogastroenterol Motil 2023; 29(3): 403-404  https://doi.org/10.5056/jnm23061
Autonomic Dysfunction and Somatization in Young Patients With Irritable Bowel Syndrome and Mitral Valve Prolapse Syndrome
Jannis Kountouras,1* Apostolis Papaefthymiou,1,2,3 Stergios A Polyzos,3 Elisabeth Vardaka,1,4 Foteini Kyrailidi,1 Maria C Mouratidou,1 Christos Zavos,1 Evangelos Kazakos,1,5 Dimitrios Chatzopoulos,1 Maria Tzitiridou-Chatzopoulou,1,5 Dimitrios Tzilves,6 Christos Liatsos,7 Maria Touloumtzi,1 and Michael Doulberis1,3,8,9
1Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece; 2Pancreaticobiliary Medicine Unit, University College London Hospitals (UCLH), London, UK; 3First Laboratory of Pharmacology, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece; 4Department of Nutritional Sciences and Dietetics, School of Health Sciences, International Hellenic University, Alexander Campus, Thessaloniki, Macedonia, Greece; 5School of Helthcare Sciences, Midwifery Department, University of West Macedonia, Koila, Kozani, Macedonia, Greece; 6Department of Gastroenterology, Theageneio Hospital, Thessaloniki, Macedonia, Greece; 7Department of Gastroenterology, General Military Hospital of Athens, Attiki, Greece; 8Gastroklinik, Private Gastroenterological Practice, Horgen, Switzerland; and 9Department of Gastroenterology and Hepatology, University of Zurich, Zurich, Switzerland
Received: April 23, 2023; Revised: June 11, 2023; Accepted: June 26, 2023; Published online: July 30, 2023
© The Korean Society of Neurogastroenterology and Motility. All rights reserved.

cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

TO THE EDITOR: Semen et al1 concluded that adolescents with diverse types of irritable bowel syndrome (IBS) were correlated with the signs of autonomic dysfunction and augmented levels of somatization, thereby signifying a potential connection between the altered psycho-emotional condition and autonomic regulation in IBS patients.

In this regard, there are only a few studies investigating the potential correlation among IBS, peptic ulcer disease (PUD) and mitral valve prolapse syndrome (MVP).2-5 Our prospective studies indicate that patients with IBS (including young adults) are connected with MVP2,3 also associated with signs of autonomic dysfunction and somatization;6,7 psycho-emotional manifestations including fatigue, anxiety and/or depression may be also associated with MVP-related moderate and/or severe mitral regurgitation (MR). Specifically, when compared with 32 control healthy members of the medical and laboratory staff, a high prevalence of MVP was observed in 67 consecutive patients with IBS (2% vs 47.8%, P < 0.01) linked with autonomic dysfunction (supine bradycardia), systolic murmurs and blood group A, thereby suggesting a possible genetic and clinical relationship between IBS and MVP syndrome.2,3 The supine bradycardia suggests the occurrence of an augmented vagal tone at resting position, thus supporting the hypothesis that an autonomic dysfunction could account for some of the clinical manifestations of MVP associated with IBS; excessive vagal tone might be responsible for bradycardia and sinus arrest; and these syndromes may be linked with baseline respiratory sinus arrhythmia, denoting cardiac vagal activity.

MVP symptoms including chest pain or palpitations, poor exercise tolerance or fatigue, dyspnea, orthostatic phenomena, and syncope cannot be explained only on the basis of mitral valve abnormality.7 The pathophysiology of these symptoms in patients with MVP seems to be further attributed to metabolic neuroendocrine dysfunction. As the pathophysiology of IBS is heterogeneous, MVP, responsible for a considerable disease burden, phenotypically is also widely heterogeneous; the natural history MVP is heterogeneous and widely determined by the severity of MR.8 Although most patients remain asymptomatic with a near-normal life expectancy, approximately 5-10% progress to severe MR; the course of MVP is mostly benign, but it can lead to the development of severe MR complicated by heart failure, supraventricular arrhythmia, ventricular arrhythmias, and occasionally sudden death. Related data indicate a correlation among ventricular arrhythmias and sudden cardiac death, independent of the severity of MR or ventricular dysfunction;9 MVP with left ventricular remodeling can induce heart failure, ventricular arrhythmias, and sudden cardiac death, the most devastating complication particularly in myxomatous bileaflet prolapse (Barlow’s disease). In this regard, a comprehensive prognostic instrument covering the entire MVP spectrum, encompassing the quantified consequent degenerative MR, and hindering clinical management and therapeutic trials is lacking.

It is important to note that, the only 2 additional letters, considered the possible association between IBS and MVP, were published in past years,3,5 obviously by using old IBS diagnostic criteria. Since, the Rome IV diagnostic criteria were released in May 2016, therefore, novel large-scale related prospective studies are warranted to validate IBS correlation based on large number of patients with MVP and IBS using updated validated questionnaires including Rome IV.

Comparable data were also obtained in our patients with PUD which is also potentially associated with IBS.3,4,10 Specifically, when compared with 31 healthy controls, a high prevalence of MVP was observed in 79 patients with duodenal ulcers (3% vs 46%, P < 0.01) associated with dual autonomic dysfunction (supine bradycardia and standing tachycardia suggesting an augmented sympathetic tone), systolic murmurs and blood group O, thereby signifying a potential genetic and clinical relationship among PUD and MVP syndrome;4 autonomic dysfunction is involved in PUD pathophysiology;11 and both dual autonomic dysfunction responsible for some “dangerous” arrhythmias and genetic variants are also involved in MVP pathophysiology.4,12 Of note, to our knowledge, there is an absence of other related published studies investigating the correlation among PUD and MVP, and thus further studies are needed.

Viewing the aforementioned data, further large-scale prospective studies are warranted to elucidate in depth the pathophysiology of IBS- and PUD-related MVP, thereby offering important applications for the management of this critical topic.

Financial support


Conflicts of interest


Author contributions

Jannis Kountouras conceived the idea, wrote the draft, and authored the manuscript; and Apostolis Papaefthymiou, Stergios A Polyzos, Elisabeth Vardaka, Foteini Kyrailidi, Maria C Mouratidou, Christos Zavos, Evangelos Kazakos, Dimitrios Chatzopoulos, Maria Tzitiridou-Chatzopoulou, Dimitrios Tzilves, Christos Liatsos, Maria Touloumtzi, and Michael Doulberis read critically the manuscript and revised appropriately.

  1. Semen M, Lychkovska O, Kaminskyy D, Yavorskyi O, Semen KO, Yelisyeyeva O. Heart rate variability and somatization in adolescents with irritable bowel syndrome. J Neurogastroenterol Motil 2023;29:208-217.
    Pubmed KoreaMed CrossRef
  2. Kountouras J, Tsapas G, Magoula I, Boura P, Paletas K, Georgiadis I. Mitral valve prolapse in patients with irritable bowel syndrome. Sci Ann Fac Med 1992;192:107-116.
  3. Kountouras J, Zavos C, Papadopoulos A, Deretzi G, Polyzos S. Irritable bowel syndrome associated with mitral valve prolapse and autonomic and haemostatic abnormalities in children, adolescents and adults with migraine. Acta Neurol Scand 2011;123:366-367.
    Pubmed CrossRef
  4. Kountouras J, Magoula I, Tsapas G, Chatseras D, Sarrigiannides A. Mitral valve prolapse syndrome in patients with duodenal ulcer disease. Hellen Arm Forces Med Review 1987;21(suppl 1):101-105.
  5. Sataline L. Irritable bowel syndrome and mitral valve prolapse syndrome. JAMA 1985;253:41.
    Pubmed CrossRef
  6. Bona Olexova L, Visnovcova Z, Ferencova N, Jurko A Jr, Tonhajzerova I. Complex sympathetic regulation in adolescent mitral valve prolapse. Physiol Res 2021;70:S317-S325.
    Pubmed KoreaMed CrossRef
  7. Gottlieb SH. Mitral valve prolapse: from syndrome to disease. Am J Cardiol 1987;60:53J-58J.
    Pubmed CrossRef
  8. Battaglia V, Santangelo G, Bursi F, Simeoli P, Guazzi M. Arrhythmogenic mitral valve prolapse and sudden cardiac death: an update and current perspectives. Curr Probl Cardiol 2023;48:101724.
    Pubmed CrossRef
  9. Vermes E, Altes A, Iacuzio L, et al. The evolving role of cardiovascular magnetic resonance in the assessment of mitral valve prolapse. Front Cardiovasc Med 2023;10:1093060.
    Pubmed KoreaMed CrossRef
  10. Wu Y, Murray GK, Byrne EM, Sidorenko J, Visscher PM, Wray NR. GWAS of peptic ulcer disease implicates Helicobacter pylori infection, other gastrointestinal disorders and depression. Nat Commun 2021;12:1146.
    Pubmed KoreaMed CrossRef
  11. Katoh K, Nomura M, Nakaya Y, et al. Autonomic nervous activity before and after eradication of Helicobacter pylori in patients with chronic duodenal ulcer. Aliment Pharmacol Ther 2002;16(suppl 2):180-186.
    Pubmed CrossRef
  12. Delwarde C, Capoulade R, Mérot J, et al. Genetics and pathophysiology of mitral valve prolapse. Front Cardiovasc Med 2023;10:1077788.
    Pubmed KoreaMed CrossRef

This Article

Cited By Articles
  • CrossRef (0)

Author ORCID Information


Social Network Service



Aims and Scope