Prevalence of gastroesophageal reflux disorder in arrhythmic patients and adjunctive effects of proton pump inhibitors on comorbid atrial fibrillation

Keita Odashiro, Taku Yokoyama, Shunsuke Yoda, Hirotaka Noda, Mitsuhiro Fukata, Takeshi Arita, Toru Maruyama, Koichi Akashi


Background: Although the coexistence of atrial fibrillation (AF) and gastroesophageal reflux disorder (GERD) has been reported, the prevalence of GERD in arrhythmic patients remains unknown. This study aimed to investigate the relationship between GERD and several kinds of arrhythmia, and the therapeutic effects of proton pump inhibitors (PPI) on AF.

Methods: In Study 1, patients with various kinds of arrhythmia (n=147) including AF (n=98) were administered a GERD-specific questionnaire (F-scale). In Study 2, patients with AF and GERD (n=27) responded to an AF-specific questionnaire (AFQLQ) before and after the additive PPI therapy to explore the effects of PPI on comorbid AF. In Study 3, device memory was assessed as it is related to PPI administration in pacemaker patients with GERD and AF (n=5) to study the effects of PPI on device-documented AF.

Results: Left atrial (LA) size and F-scale scores in AF patients were the largest among the arrhythmic patients in Study 1. Logistic regression analysis showed no independent determinants of GERD. F-scale scores and AFQLQ scores showed temporal and partial correlations and significant improvement after starting PPI in Study 2. However, device interrogation confirmed limited AF improvement by starting PPI in Study 3.

Conclusions: GERD is prevalent in AF patients. LA size is not an independent determinant of GERD. Symptoms of AF were improved, whereas device-documented paroxysms of AF were not ameliorated by PPI administration. A large-scale prospective study is required to conclude the efficacy of PPI on the comorbid AF.


Atrial fibrillation, Device interrogation, Gastroesophageal reflux disorder, Proton pump inhibitors, Questionnaire study

Full Text:



Friedenberg FK, Xanthopoulos M, Foster GD, Richter JE. The association between gastroesophageal reflux disease and obesity. Am J Gastroenterol. 2008;103(8):2111-22.

Shepherd KL, James AL, Musk AW, Hunter ML, Hillman DR, Eastwood PR. Gastro-oesophageal reflux symptoms are related to the presence and severity of obstructive sleep apnoea. J Sleep Res. 2011;20:241-9.

Moki F, Kusano M, Mizuide M, Shimoyama Y, Kawamura O, Takagi H, et al. Association between reflux oesophagitis and features of the metabolic syndrome in Japan. Aliment Pharmacol Ther. 2007;26(7):1069-75.

Fujiwara Y, Arakawa T. Epidemiology and clinical characteristics of GERD in the Japanese population. J Gastroenterol. 2009;44(6):518-34.

Ayazi S, Tamhankar A, DeMeester SR, Zehetner J, Wu C, Lipham JC, et al. The impact of gastric distension on the lower esophageal sphincter and its exposure to acid gastric juice. Ann Surg. 2010;252(1):57-62.

Gregersen H, Pedersen J, Drewes AM. Deterioration of muscle function in the human esophagus with age. Dig Dis Sci. 2008;53(12):3065-70.

Huang CC, Chan WL, Luo JC, Chen YC, Chen TJ, Chung CM, et al. Gastroesophageal reflux disease and atrial fibrillation: a nationwide population-based study. PLoS One. 2012;7(10):e47575.

Velagapudi P, Turagam MK, Leal MA, Kocheril AG. Atrial fibrillation and acid reflux disease. Clin Cardiol. 2012;35(3):180-6.

Roman C, Bruley des Varannes S, Muresan L, Picos A, Dumitrascu DL. Atrial fibrillation in patients with gastroesophageal reflux disease: a comprehensive review. World J Gastroenterol. 2014;20(28):9592-9.

Kunz JS, Hemann B, Edwin Atwood J, Jackson J, Wu T, Hamm C. Is there a link between gastroesophageal reflux disease and atrial fibrillation? Clin Cardiol. 2009;32(10):584-7.

Kannel WB, Wolf PA, Benjamin EJ, Levy D. Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol. 1998;82(8A):2N-9.

Kanagala R, Murali NS, Friedman PA, Ammash NM, Gersh BJ, Ballman KV, et al. Obstructive sleep apnea and the recurrence of atrial fibrillation. Circulation. 2003;107(20):2589-94.

Watanabe H, Tanabe N, Watanabe T, Darbar D, Roden DM, Sasaki S, et al. Metabolic syndrome and risk of development of atrial fibrillation: the Niigata preventive medicine study. Circulation. 2008;117(10):1255-60.

Shimazu H, Nakaji G, Fukata M, Odashiro K, Maruyama T, Akashi K, Fukuoka F-Scale Trial Group. Relationship between atrial fibrillation and gastroesophageal reflux disease: a multicenter questionnaire survey. Cardiology. 2011;119(4):217-23.

Kubota S, Nakaji G, Shimazu H, Odashiro K, Maruyama T, Akashi K. Further assessment of atrial fibrillation as a risk factor for gastroesophageal reflux disease: a multicenter questionnaire survey. Intern Med. 2013;52(21):2401-7.

European Heart Rhythm Association; European Association for Cardio-Thoracic Surgery, Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Europace. 2010;12(10):1360-420.

Kusano M, Shimoyama Y, Sugimoto S, Kawamura O, Maeda M, Minashi K, et al. Development and evaluation of FSSG: frequency scale for the symptoms of GERD. J Gastroenterol. 2004;39(9):888-91.

Tsuneda T, Yamashita T, Fukunami M, Kumagai K, Niwano S, Okumura K, et al. Rate control and quality of life in patients with permanent atrial fibrillation: the quality of life and Atrial Fibrillation (QOLAF) study. Circ J. 2006;70(8):965-70.

Yamamoto M, Watanabe E, Suzuki T, Yamazaki T, Ohtsu H, Ozaki Y, et al. Association between the quality of life and asymptomatic episodes of paroxysmal atrial fibrillation in the J-RHYTHM II study. J Cardiol. 2014;64(1):64-9.

Zhang JX, Ji MY, Song J, Lei HB, Qiu S, Wang J, et al. Proton pump inhibitor for non-erosive reflux disease: a meta-analysis. World J Gastroenterol. 2013;19(45):8408-19.

Boeckxstaens G, El-Serag HB, Smout AJ, Kahrilas PJ. Symptomatic reflux disease: the present, the past and the future. Gut. 2014;63(7):1185-93.

Bunch TJ, Packer DL, Jahangir A, Locke GR, Talley NJ, Gersh BJ, et al. Long-term risk of atrial fibrillation with symptomatic gastroesophageal reflux disease and esophagitis. Am J Cardiol. 2008;102(9):1207-11.

Lin K, Chen X, Zhang L, Wang Y, Shan Z. Proton pump inhibitors as also inhibitors of atrial fibrillation. Eur J Pharmacol. 2013;718(1-3):435-40.

Nakamura H, Nakaji G, Shimazu H, Yasuda S, Odashiro K, Maruyama T, et al. Case of paroxysmal atrial fibrillation improved after the administration of proton pump inhibitor for associated reflux esophagitis. Fukuoka Igaku Zasshi. 2007;98(6):270-6.

Weigl M, Gschwantler M, Gatterer E, Finsterer J, Stöllberger C. Reflux esophagitis in the pathogenesis of paroxysmal atrial fibrillation: results of a pilot study. South Med J. 2003;96(11):1128-32.

Gerson LB, Friday K, Triadafilopoulos G. Potential relationship between gastroesophageal reflux disease and atrial arrhythmias. J Clin Gastroenterol. 2006;40(9):828-32.

DeCicco AE, Finkel JB, Greenspon AJ, Frisch DR. Clinical significance of atrial fibrillation detected by cardiac implantable electronic devices. Heart Rhythm. 2014;11(4):719-24.

Marcus GM, Smith LM, Scheinman MM, Badhwar N, Lee RJ, Tseng ZH, et al. Proton pump inhibitors are associated with focal arrhythmias. J Innov Card Rhythms Manage. 2010;1:85-9.

Hoorn EJ, van der Hoek J, de Man RA, Kuipers EJ, Bolwerk C, Zietse R. A case series of proton pump inhibitor-induced hypomagnesemia. Am J Kidney Dis. 2010;56:112-6.

Cuomo R, De Giorgi F, Adinolfi L, Sarnelli G, Loffredo F, Efficie E, et al. Oesophageal acid exposure and altered neurocardiac function in patients with GERD and idiopathic cardiac dysrhythmias. Aliment Pharmacol Ther. 2006;24:361-70.