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• W3003306390 abstract "Best Practice Advice 1A diagnosis of functional heartburn should be considered when retrosternal burning pain or discomfort persists despite maximal (double-dose) proton pump inhibitor (PPI) therapy taken appropriately before meals during a 3-month period.Best Practice Advice 2A diagnosis of functional heartburn requires upper endoscopy with esophageal biopsies to rule out anatomic and mucosal abnormalities, esophageal high-resolution manometry to rule out major motor disorders, and pH monitoring off PPI therapy (or pH-impedance monitoring on therapy in patients with proven gastroesophageal reflux disease [GERD]), to document physiologic levels of esophageal acid exposure in the distal esophagus with absence of reflux–symptom association (ie, negative symptom index and symptom association probability).Best Practice Advice 3Overlap of functional heartburn with proven GERD is diagnosed according to Rome IV criteria when heartburn persists despite maximal PPI therapy in patients with history of proven GERD (ie, positive pH study, erosive esophagitis, Barrett’s esophagus, or esophageal ulcer), and pH impedance testing on PPI therapy demonstrates physiologic acid exposure without reflux–symptom association (ie, negative symptom index and symptom association probability).Best Practice Advice 4PPIs have no therapeutic value in functional heartburn, the exception being proven GERD that overlaps with functional heartburn.Best Practice Advice 5Neuromodulators, including tricyclic antidepressants, selective serotonin reuptake inhibitors, tegaserod, and histamine-2 receptor antagonists have benefit as either primary therapy in functional heartburn or as add-on therapy in functional heartburn that overlaps with proven GERD.Best Practice Advice 6Based on available evidence, acupuncture and hypnotherapy may have benefit as monotherapy in functional heartburn, or as adjunctive therapy combined with other therapeutic modalities.Best Practice Advice 7Based on available evidence, anti-reflux surgery and endoscopic GERD treatment modalities have no therapeutic benefit in functional heartburn and should not be recommended. A diagnosis of functional heartburn should be considered when retrosternal burning pain or discomfort persists despite maximal (double-dose) proton pump inhibitor (PPI) therapy taken appropriately before meals during a 3-month period. A diagnosis of functional heartburn requires upper endoscopy with esophageal biopsies to rule out anatomic and mucosal abnormalities, esophageal high-resolution manometry to rule out major motor disorders, and pH monitoring off PPI therapy (or pH-impedance monitoring on therapy in patients with proven gastroesophageal reflux disease [GERD]), to document physiologic levels of esophageal acid exposure in the distal esophagus with absence of reflux–symptom association (ie, negative symptom index and symptom association probability). Overlap of functional heartburn with proven GERD is diagnosed according to Rome IV criteria when heartburn persists despite maximal PPI therapy in patients with history of proven GERD (ie, positive pH study, erosive esophagitis, Barrett’s esophagus, or esophageal ulcer), and pH impedance testing on PPI therapy demonstrates physiologic acid exposure without reflux–symptom association (ie, negative symptom index and symptom association probability). PPIs have no therapeutic value in functional heartburn, the exception being proven GERD that overlaps with functional heartburn. Neuromodulators, including tricyclic antidepressants, selective serotonin reuptake inhibitors, tegaserod, and histamine-2 receptor antagonists have benefit as either primary therapy in functional heartburn or as add-on therapy in functional heartburn that overlaps with proven GERD. Based on available evidence, acupuncture and hypnotherapy may have benefit as monotherapy in functional heartburn, or as adjunctive therapy combined with other therapeutic modalities. Based on available evidence, anti-reflux surgery and endoscopic GERD treatment modalities have no therapeutic benefit in functional heartburn and should not be recommended. Functional heartburn consists of retrosternal burning similar to that experienced in gastroesophageal reflux disease (GERD), but without evidence of abnormal esophageal acid exposure on ambulatory reflux monitoring, major esophageal motor disorders on high-resolution manometry, or esophageal mucosal pathology (such as erosive esophagitis, Barrett’s esophagus, or eosinophilic esophagitis) on endoscopy with esophageal biopsies.1Aziz Q. Fass R. Gyawali C.P. et al.Functional esophageal disorders.Gastroenterology. 2016; 150: 1368-1379Abstract Full Text Full Text PDF Scopus (302) Google Scholar In contrast, despite identical clinical presentation, a diagnosis of nonerosive reflux disease (NERD) requires the presence of abnormal esophageal acid exposure on ambulatory reflux monitoring.1Aziz Q. Fass R. Gyawali C.P. et al.Functional esophageal disorders.Gastroenterology. 2016; 150: 1368-1379Abstract Full Text Full Text PDF Scopus (302) Google Scholar,2Gyawali C.P. Kahrilas P.J. Savarino E. et al.Modern diagnosis of GERD: the Lyon Consensus.Gut. 2018; 67: 1351-1362Crossref PubMed Scopus (584) Google Scholar The prevalence of functional heartburn in the community is difficult to determine, but as many as 21%–39% of patients with heartburn refractory to proton pump inhibitor (PPI) undergoing pH-impedance monitoring fulfill criteria for functional heartburn.3Savarino E. Marabotto E. Zentilin P. et al.The added value of impedance-pH monitoring to Rome III criteria in distinguishing functional heartburn from non-erosive reflux disease.Dig Liver Dis. 2011; 43: 542-547Abstract Full Text Full Text PDF PubMed Scopus (139) Google Scholar, 4Zerbib F. Belhocine K. Simon M. et al.Clinical, but not oesophageal pH-impedance, profiles predict response to proton pump inhibitors in gastro-oesophageal reflux disease.Gut. 2012; 61: 501-506Crossref PubMed Scopus (100) Google Scholar, 5Spechler S.J. Hunter J.G. Jones K.M. et al.Randomized trial of medical versus surgical treatment for refractory heartburn.N Engl J Med. 2019; 381: 1513-1523Crossref PubMed Scopus (108) Google Scholar, 6Yamasaki T. Fass R. Reflux hypersensitivity: a new functional esophageal disorder.J Neurogastroenterol Motil. 2017; 23: 495-503Crossref PubMed Scopus (45) Google Scholar Functional heartburn is important to recognize because without investigation, this condition might be considered equivalent with GERD, and treating physicians could continue acid suppressive therapy unnecessarily or escalate antireflux treatments, which might even lead to harm. Importantly, acid suppressive therapies are typically not effective, and antireflux surgery or other invasive antireflux modalities should be avoided. This is primarily because acid does not trigger functional heartburn symptoms, as evident from acid perfusion studies comparing functional heartburn to NERD patients.7Weijenborg P.W. Smout A.J. Bredenoord A.J. Esophageal acid sensitivity and mucosal integrity in patients with functional heartburn.Neurogastroenterol Motil. 2016; 28: 1649-1654Crossref PubMed Scopus (22) Google Scholar There have been advances in esophageal testing to differentiate functional heartburn from refractory reflux disease. Studies of afferent nerves in esophageal mucosa have demonstrated that functional heartburn patients have deep localization of nerves similar to that of healthy volunteers rather than superficial localization seen in NERD, supporting a nociceptive pathophysiologic mechanism in functional heartburn similar to other functional gastrointestinal disorders.8Nikaki K. Woodland P. Lee C. et al.Esophageal mucosal innervation in functional heartburn: closer to healthy asymptomatic subjects than to non-erosive reflux disease patients.Neurogastroenterol Motil. 2019; 31e13667Crossref PubMed Scopus (12) Google Scholar Furthermore, balloon distension studies have demonstrated a similar degree of visceral hypersensitivity in the esophagus and the rectum in patients with functional heartburn, supporting a generalized increase in perception of visceral stimuli.9Freede M. Leasure A.R. Proskin H.M. et al.Comparison of rectal and esophageal sensitivity in women with functional heartburn.Gastroenterol Nurs. 2016; 39: 348-358Crossref PubMed Scopus (3) Google Scholar There is also a high likelihood of anxiety and other affective disorders in patients with functional heartburn.10de Bortoli N. Frazzoni L. Savarino E.V. et al.Functional heartburn overlaps with irritable bowel syndrome more often than GERD.Am J Gastroenterol. 2016; 111: 1711-1717Crossref PubMed Scopus (48) Google Scholar These etiological factors indicate that functional heartburn is a separate entity that warrants multimodal management distinct from GERD patients because patients with functional heartburn, either alone or overlapping with GERD, will likely not improve unless esophageal perception and underlying affective disorders are managed adequately. This expert review was commissioned and approved by the American Gastroenterological Association (AGA) Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology. This review highlights clinical presentation, modern diagnosis, and management of functional heartburn. Many patients with GERD-like symptoms who fail PPI therapy may, in fact, have a functional disorder, including functional heartburn,5Spechler S.J. Hunter J.G. Jones K.M. et al.Randomized trial of medical versus surgical treatment for refractory heartburn.N Engl J Med. 2019; 381: 1513-1523Crossref PubMed Scopus (108) Google Scholar,11Abdallah J. George N. Yamasaki T. et al.Most patients with gastroesophageal reflux disease who failed proton pump inhibitor therapy also have functional esophageal disorders.Clin Gastroenterol Hepatol. 2019; 17: 1073-1080 e1Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar,12Herregods T.V. Troelstra M. Weijenborg P.W. et al.Patients with refractory reflux symptoms often do not have GERD.Neurogastroenterol Motil. 2015; 27: 1267-1273Crossref PubMed Scopus (61) Google Scholar diagnosed in as many as one-quarter of patients with persistent heartburn on PPI therapy, either by itself or overlapping with established GERD.13Ribolsi M. Cicala M. Zentilin P. et al.Prevalence and clinical characteristics of refractoriness to optimal proton pump inhibitor therapy in non-erosive reflux disease.Aliment Pharmacol Ther. 2018; 48: 1074-1081Crossref PubMed Scopus (25) Google Scholar Heartburn is defined as a burning sensation with pain or discomfort that starts from the epigastrium and radiates retrosternally. While patients may use various terms to describe GERD-like symptoms, including reflux, heartburn, regurgitation, chest pain, chest discomfort, fullness, throat burning, mouth burning, epigastric burning, water brash, belching, and sour and bitter taste in the mouth, their association with gastroesophageal reflux needs to be determined by careful history.14Broderick R. Fuchs K.H. Breithaupt W. et al.Clinical presentation of gastroesophageal reflux disease: a prospective study on symptom diversity and modification of questionnaire application.Dig Dis. 2019; : 1-8Crossref PubMed Scopus (10) Google Scholar The clinical presentation of functional heartburn is similar to heartburn due to GERD, but the diagnosis of functional heartburn is commonly considered only in patients with persistent heartburn symptoms, typically without improvement (or even worsening) while on PPI therapy. Diagnostic criteria for NERD, reflux hypersensitivity (heartburn triggered by physiologic reflux episodes) and functional heartburn were redefined by Rome IV criteria,1Aziz Q. Fass R. Gyawali C.P. et al.Functional esophageal disorders.Gastroenterology. 2016; 150: 1368-1379Abstract Full Text Full Text PDF Scopus (302) Google Scholar leading to stricter diagnostic criteria and less confusion between true GERD/NERD and functional heartburn.15Zhang M. Chen M. Peng S. et al.The Rome IV versus Rome III criteria for heartburn diagnosis: a comparative study.United European Gastroenterol J. 2018; 6: 358-366Crossref PubMed Scopus (8) Google Scholar Clinical description of heartburn, whether obtained in the office by a primary care provider/gastroenterologist, or from validated symptom questionnaires, has only modest sensitivity and specificity compared to objective reflux evidence on testing, or to symptom relief with PPI therapy.16Jones R. Junghard O. Dent J. et al.Development of the GerdQ, a tool for the diagnosis and management of gastro-oesophageal reflux disease in primary care.Aliment Pharmacol Ther. 2009; 30: 1030-1038Crossref PubMed Scopus (396) Google Scholar, 17Dent J. Vakil N. Jones R. et al.Accuracy of the diagnosis of GORD by questionnaire, physicians and a trial of proton pump inhibitor treatment: the Diamond study.Gut. 2010; 59: 714-721Crossref PubMed Scopus (219) Google Scholar, 18Bolier E.A. Kessing B.F. Smout A.J. et al.Systematic review: questionnaires for assessment of gastroesophageal reflux disease.Dis Esophagus. 2015; 28: 105-120Crossref PubMed Scopus (50) Google Scholar Furthermore, the Montreal Consensus heartburn-related definitions encompass not just true GERD, but also functional esophageal disorders, both reflux hypersensitivity and functional heartburn, as well as various degrees of overlap between GERD and functional esophageal disorders.19Hungin A.P.S. Molloy-Bland M. Scarpignato C. Revisiting Montreal: new insights into symptoms and their causes, and implications for the future of GERD.Am J Gastroenterol. 2019; 114: 414-421Crossref PubMed Scopus (22) Google Scholar,20Katzka D.A. Pandolfino J.E. Kahrilas P.J. Phenotypes of gastroesophageal reflux disease: where Rome, Lyon, and Montreal meet.Clin Gastroenterol Hepatol. 2020; 18: 767-776Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar This overlap with functional disorders, as well as other non-GERD mechanisms for heartburn, may be partly responsible for the 40% dissatisfaction rate with PPI therapy in patients with heartburn.21Hillman L. Yadlapati R. Thuluvath A.J. et al.A review of medical therapy for proton pump inhibitor nonresponsive gastroesophageal reflux disease.Dis Esophagus. 2017; 30: 1-15Google Scholar In a prospective study of 366 patients with refractory heartburn who were enrolled in a Veterans Affairs study, 99 (27%) had functional heartburn on the basis of negative esophageal testing, including pH-impedance monitoring off acid suppression, while 23 (6%) had non-GERD esophageal disorders, and 7 (2%) had esophageal motility disorders. The lack of, or partial, symptom relief despite optimal therapy is an important starting point for consideration of the diagnosis of functional heartburn.1Aziz Q. Fass R. Gyawali C.P. et al.Functional esophageal disorders.Gastroenterology. 2016; 150: 1368-1379Abstract Full Text Full Text PDF Scopus (302) Google Scholar The impact of heartburn symptoms on quality of life needs to be factored into clinical decision-making and the degree of invasive investigation needed for evaluation and management.22Josefsson A. Palsson O. Simren M. et al.Oesophageal symptoms are common and associated with other functional gastrointestinal disorders (FGIDs) in an English-speaking Western population.United European Gastroenterol J. 2018; 6: 1461-1469Crossref PubMed Scopus (6) Google Scholar,23Myers J.P. vom Saal F.S. Akingbemi B.T. et al.2009. Why public health agencies cannot depend on Good Laboratory Practices as a criterion for selecting data: the case of bisphenol A.Environmental Health Perspectives. 2009; 117: 309-315Crossref PubMed Scopus (232) Google Scholar The purpose of invasive investigation is to make a conclusive diagnosis in order to provide precision, personalized management of esophageal symptoms targeted toward the mechanisms of symptom generation.2Gyawali C.P. Kahrilas P.J. Savarino E. et al.Modern diagnosis of GERD: the Lyon Consensus.Gut. 2018; 67: 1351-1362Crossref PubMed Scopus (584) Google Scholar,20Katzka D.A. Pandolfino J.E. Kahrilas P.J. Phenotypes of gastroesophageal reflux disease: where Rome, Lyon, and Montreal meet.Clin Gastroenterol Hepatol. 2020; 18: 767-776Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar In functional heartburn, this involves not just initiation of neuromodulators, but potentially, discontinuation of ineffective approaches, such as acid suppressive therapy. Thus, functional heartburn should be considered only in patients who report troublesome heartburn symptoms at least 2 times per week for the previous 3 months despite double-dose PPI taken appropriately before meals.1Aziz Q. Fass R. Gyawali C.P. et al.Functional esophageal disorders.Gastroenterology. 2016; 150: 1368-1379Abstract Full Text Full Text PDF Scopus (302) Google Scholar The presence of concurrent functional gastrointestinal disorders and somatization disorder should also be considered.24Choung R.S. Richard Locke 3rd, G. Schleck C.D. et al.Multiple functional gastrointestinal disorders linked to gastroesophageal reflux and somatization: a population-based study.Neurogastroenterol Motil. 2017; 29Crossref PubMed Scopus (19) Google Scholar Indeed, both functional dyspepsia and irritable bowel syndrome are frequently associated with functional heartburn10de Bortoli N. Frazzoni L. Savarino E.V. et al.Functional heartburn overlaps with irritable bowel syndrome more often than GERD.Am J Gastroenterol. 2016; 111: 1711-1717Crossref PubMed Scopus (48) Google Scholar,25Frazzoni M. Savarino E. Manno M. et al.Reflux patterns in patients with short-segment Barrett's oesophagus: a study using impedance-pH monitoring off and on proton pump inhibitor therapy.Aliment Pharmacol Ther. 2009; 30: 508-515Crossref PubMed Scopus (52) Google Scholar and negatively impact symptom response to therapies.26Domingues G.R. Moraes-Filho J.P. Domingues A.G. Impact of prolonged 48-h wireless capsule esophageal pH monitoring on diagnosis of gastroesophageal reflux disease and evaluation of the relationship between symptoms and reflux episodes.Arq Gastroenterol. 2011; 48: 24-29Crossref PubMed Scopus (11) Google Scholar, 27Nojkov B. Rubenstein J.H. Adlis S.A. et al.The influence of co-morbid IBS and psychological distress on outcomes and quality of life following PPI therapy in patients with gastro-oesophageal reflux disease.Aliment Pharmacol Ther. 2008; 27: 473-482Crossref PubMed Scopus (87) Google Scholar, 28Roman S. Zerbib F. Queneherve L. et al.The Chicago classification for achalasia in a French multicentric cohort.Dig Liver Dis. 2012; 44: 976-980Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar Endoscopy is indicated in patients with heartburn who fail an adequate trial of empirical PPI therapy in order to rule out other esophageal or gastric diseases, including structural abnormalities, such as strictures or webs, eosinophilic esophagitis, pill-induced esophagitis, Barrett’s esophagus, and neoplasia (Figure 1). The prevalence of erosive esophagitis is <10% in patients refractory to PPI therapy29Poh C.H. Gasiorowska A. Navarro-Rodriguez T. et al.Upper GI tract findings in patients with heartburn in whom proton pump inhibitor treatment failed versus those not receiving antireflux treatment.Gastrointest Endosc. 2010; 71: 28-34Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar,30Ang D. Teo E.K. Ang T.L. et al.To Bravo or not? A comparison of wireless esophageal pH monitoring and conventional pH catheter to evaluate non-erosive gastroesophageal reflux disease in a multiracial Asian cohort.J Dig Dis. 2010; 11: 19-27Crossref PubMed Scopus (17) Google Scholar; when identified, this indicates poorly controlled persistent acid reflux or true refractory GERD according to Rome IV criteria.1Aziz Q. Fass R. Gyawali C.P. et al.Functional esophageal disorders.Gastroenterology. 2016; 150: 1368-1379Abstract Full Text Full Text PDF Scopus (302) Google Scholar Although the prevalence of eosinophilic esophagitis does not exceed 8% in patients presenting with refractory heartburn,30Ang D. Teo E.K. Ang T.L. et al.To Bravo or not? A comparison of wireless esophageal pH monitoring and conventional pH catheter to evaluate non-erosive gastroesophageal reflux disease in a multiracial Asian cohort.J Dig Dis. 2010; 11: 19-27Crossref PubMed Scopus (17) Google Scholar, 31Garcia-Compean D. Gonzalez Gonzalez J.A. Marrufo Garcia C.A. et al.Prevalence of eosinophilic esophagitis in patients with refractory gastroesophageal reflux disease symptoms: a prospective study.Dig Liver Dis. 2011; 43: 204-208Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar, 32Abe N. Takeuchi H. Ohki A. et al.Long-term outcomes of combination of endoscopic submucosal dissection and laparoscopic lymph node dissection without gastrectomy for early gastric cancer patients who have a potential risk of lymph node metastasis.Gastrointestinal Endoscopy. 2011; 74: 792-797Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar eosinophilic esophagitis should be ruled out by adequate biopsy sampling to comply with the current definition of functional heartburn. Because most patients with refractory heartburn unresponsive to PPIs have normal endoscopy and esophageal biopsies, ambulatory reflux monitoring is performed to evaluate for evidence for gastroesophageal reflux (Figure 1). By definition, there should be no link between reflux and symptoms in functional heartburn. According to recent consensus statements,1Aziz Q. Fass R. Gyawali C.P. et al.Functional esophageal disorders.Gastroenterology. 2016; 150: 1368-1379Abstract Full Text Full Text PDF Scopus (302) Google Scholar,33Bennett M.C. Patel A. Sainani N. et al.Chronic cough is associated with long breaks in esophageal peristaltic integrity on high-resolution manometry.J Neurogastroenterol Motil. 2018; 24: 387-394Crossref PubMed Scopus (15) Google Scholar patients without previous evidence of pathologic gastroesophageal reflux (ie, significant peptic esophagitis, Barrett’s esophagus, or positive pH study) should be investigated using pH or pH-impedance monitoring off anti-secretory medications to document the level of baseline reflux. High-resolution manometry is typically performed for localizing the proximal border of the lower esophageal sphincter for placement of pH and pH-impedance catheters, which should be evaluated for the presence of major esophageal motor disorders, which can be associated with esophageal perceptive symptoms, including heartburn and chest pain (Figure 1).34Kahrilas P.J. Bredenoord A.J. Fox M. et al.The Chicago Classification of esophageal motility disorders, v3.0.Neurogastroenterol Motil. 2015; 27: 160-174Crossref PubMed Scopus (1324) Google Scholar The prevalence of heartburn has been reported to be as high as 35% in achalasia35Ponce J. Ortiz V. Maroto N. et al.High prevalence of heartburn and low acid sensitivity in patients with idiopathic achalasia.Dig Dis Sci. 2011; 56: 773-776Crossref PubMed Scopus (31) Google Scholar,36Hirano I. Richter J.E. Practice Parameters Committee of the American College of Gastroenterology. ACG practice guidelines: esophageal reflux testing.Am J Gastroenterol. 2007; 102: 668-685Crossref PubMed Scopus (291) Google Scholar; while this diagnosis can be suspected on upper endoscopy, diagnosis requires esophageal high-resolution manometry. The presence of a minor motor disorder, such as ineffective esophageal motility, does not preclude the diagnosis of functional heartburn, provided reflux disease has been excluded. The most relevant and reliable parameter on ambulatory reflux monitoring is the percent time pH is <4 in the distal esophagus, termed the acid exposure time (AET). AET is considered to be reliably normal below 4% and abnormal above 6%.33Bennett M.C. Patel A. Sainani N. et al.Chronic cough is associated with long breaks in esophageal peristaltic integrity on high-resolution manometry.J Neurogastroenterol Motil. 2018; 24: 387-394Crossref PubMed Scopus (15) Google Scholar Abnormal AET has been reported in 26.3%–72% of patients in refractory heartburn.25Frazzoni M. Savarino E. Manno M. et al.Reflux patterns in patients with short-segment Barrett's oesophagus: a study using impedance-pH monitoring off and on proton pump inhibitor therapy.Aliment Pharmacol Ther. 2009; 30: 508-515Crossref PubMed Scopus (52) Google Scholar,28Roman S. Zerbib F. Queneherve L. et al.The Chicago classification for achalasia in a French multicentric cohort.Dig Liver Dis. 2012; 44: 976-980Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar,37Pritchett J.M. Aslam M. Slaughter J.C. et al.Efficacy of esophageal impedance/pH monitoring in patients with refractory gastroesophageal reflux disease, on and off therapy.Clin Gastroenterol Hepatol. 2009; 7: 743-748Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar, 38Hemmink G.J. Bredenoord A.J. Weusten B.L. et al.Esophageal pH-impedance monitoring in patients with therapy-resistant reflux symptoms: 'on' or 'off' proton pump inhibitor?.Am J Gastroenterol. 2008; 103: 2446-2453Crossref PubMed Scopus (180) Google Scholar, 39Elvevi A. Mauro A. Pugliese D. et al.Usefulness of low- and high-volume multiple rapid swallowing during high-resolution manometry.Dig Liver Dis. 2015; 47: 103-107Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar Extending recording time to 48 or 96 hours with the wireless pH monitoring system increases the likelihood of detecting reflux disease; several studies have shown a highest diagnostic yield when the worst day is considered for the diagnosis of GERD, thus reducing the proportion of patients with functional heartburn.39Elvevi A. Mauro A. Pugliese D. et al.Usefulness of low- and high-volume multiple rapid swallowing during high-resolution manometry.Dig Liver Dis. 2015; 47: 103-107Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 40Daum C. Sweis R. Kaufman E. et al.Failure to respond to physiologic challenge characterizes esophageal motility in erosive gastro-esophageal reflux disease.Neurogastroenterol Motil. 2011; 23 (517–e200)Crossref PubMed Scopus (83) Google Scholar, 41Ayazi S. Hagen J.A. Chan L.S. et al.Obesity and gastroesophageal reflux: quantifying the association between body mass index, esophageal acid exposure, and lower esophageal sphincter status in a large series of patients with reflux symptoms.J Gastrointest Surg. 2009; 13: 1440-1447Crossref PubMed Scopus (123) Google Scholar Adding impedance to pH monitoring is helpful for the characterization of reflux episodes, as it allows detection of weakly acidic reflux episodes, thereby increasing the likelihood of a temporal correlation between symptoms and reflux episodes.42Dulery C. Lechot A. Roman S. et al.A study with pharyngeal and esophageal 24-hour pH-impedance monitoring in patients with laryngopharyngeal symptoms refractory to proton pump inhibitors.Neurogastroenterol Motil. 2017; 29Crossref PubMed Scopus (25) Google Scholar Overall, studies performed with 24-hour pH-impedance monitoring report that between 21% and 40% of patients with refractory reflux symptoms have functional heartburn.25Frazzoni M. Savarino E. Manno M. et al.Reflux patterns in patients with short-segment Barrett's oesophagus: a study using impedance-pH monitoring off and on proton pump inhibitor therapy.Aliment Pharmacol Ther. 2009; 30: 508-515Crossref PubMed Scopus (52) Google Scholar,28Roman S. Zerbib F. Queneherve L. et al.The Chicago classification for achalasia in a French multicentric cohort.Dig Liver Dis. 2012; 44: 976-980Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar,38Hemmink G.J. Bredenoord A.J. Weusten B.L. et al.Esophageal pH-impedance monitoring in patients with therapy-resistant reflux symptoms: 'on' or 'off' proton pump inhibitor?.Am J Gastroenterol. 2008; 103: 2446-2453Crossref PubMed Scopus (180) Google Scholar,43de Bortoli N. Nacci A. Savarino E. et al.How many cases of laryngopharyngeal reflux suspected by laryngoscopy are gastroesophageal reflux disease-related?.World J Gastroenterol. 2012; 18: 4363-4370Crossref PubMed Scopus (102) Google Scholar However, in patients studied off therapy, the added value of pH impedance compared to pH alone monitoring is relatively limited.43de Bortoli N. Nacci A. Savarino E. et al.How many cases of laryngopharyngeal reflux suspected by laryngoscopy are gastroesophageal reflux disease-related?.World J Gastroenterol. 2012; 18: 4363-4370Crossref PubMed Scopus (102) Google Scholar,44Roman S. Bruley des Varannes S. Pouderoux P. et al.Ambulatory 24-h oesophageal impedance-pH recordings: reliability of automatic analysis for gastro-oesophageal reflux assessment.Neurogastroenterol Motil. 2006; 18: 978-986Crossref PubMed Scopus (73) Google Scholar Both pH alone and pH-impedance monitoring provide analysis of the temporal relationship between reflux events and symptoms. In patients with normal AET, symptom index (SI), and symptom association probability (SAP) are used to distinguish between functional heartburn and reflux hypersensitivity. These indices reflect the occurrence of symptoms (ie, activation of the event marker by the patient) and reflux events during the same 2-minute time window. SI is a simple parameter that determines the proportion of symptoms that are reflux-related (positive if >50%). SAP uses a statistical formula, Fisher exact test, which determines the probability that the observed temporal relationship between symptoms and reflux has not occurred by chance (positive if ≥95%). The 2 indices are complementary, but neither SI nor SAP are 100% reliable, and their relevance has been challenged b" @default.
• W3003306390 created "2020-02-07" @default.
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• W3003306390 date "2020-06-01" @default.
• W3003306390 modified "2023-09-30" @default.
• W3003306390 title "AGA Clinical Practice Update on Functional Heartburn: Expert Review" @default.
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