Can acid reflux trigger afib?

can acid reflux trigger afib?

Can acid reflux trigger afib, aka atrial fibrillation? Like most people, you may have never considered a connection between these two diagnoses. But some research points to a relationship between GERD and afib. On top of this possible association, there is a fascinating connection between the drugs used to treat afib, acid reflux, and melatonin. If you want to learn more, strap in tight because, as Dr. Mike T. Nelson likes to say, we’re about to go hard down the nerd chute!

Can acid reflux trigger afib?

Sotalol hydrochloride is commonly prescribed as an anti-arrhythmic drug for those with atrial fibrillation. It non-selectively inhibits beta-adrenoreceptors and exerts its anti-arrhythmic properties via cardiac action potential duration prolongation. However, the pharmacodynamic beta-receptor inhibition is not cardio-selective (Bayer, 2011). Sotalol and other specific beta1-blockers such as propranolol and atenolol have the ability to decrease endogenous melatonin production.

Melatonin is synthesized and produced from norepinephrine’s stimulation of beta1-adrenoreceptors, primarily in the pineal gland (Stoschitzky et al., 1999). A 2004 cell study by Carillo-Vico et al. found that lymphocytes may also produce melatonin, and its presence is linked to proper immune function via regulation of IL-2 (T cell growth factor). Additionally, melatonin has been shown to act as a powerful antioxidant in vitro, with higher relative oxygen radical absorbing capacity than water-soluble vitamin E analogue Trolox, vitamin C, and reduced glutathione (Pieri, Marra, Moroni, Recchioni, and Marcheselli, 1994). Melatonin was also found to be an effective antioxidant in animal models of mucosal damage that mimic the damage induced by chronic gastroesophageal reflux disease (GERD) (Bilici et al., 2002).

This review of sotalol’s possible interference in melatonin synthesis and physiological influence is viewed in the context of a case study in order to investigate the possible interactions between GERD, use of beta-blockers, and atrial fibrillation.

The patient is a 69-year-old male with a long-term history of GERD who developed spontaneous atrial fibrillation one and a half years ago in the absence of structural heart disease, “lone atrial fibrillation.” At the time of atrial fibrillation occurrence, the patient had a BMI of 33% and was taking 25 mg once per day metoprolol, 20 mg twice per day esomeprazole, and possibly 10 mg once per day atorvastatin—patient reported that he frequently started and stopped atorvastatin due to muscle soreness and cramping. He suffered from GERD for over 40 years and had been treated with antibiotics to address H. pylori infection found via biopsy. However, the GERD continued to the time of atrial fibrillation and continues to the present day. He reports a burning sensation due to GERD at the xiphoid process, sometimes accompanied by the symptom of aching ear pain. He recently underwent successful surgical ablation to correct the atrial fibrillation and currently takes 40 mg twice per day sotalol and 5 mg twice per day apixaban.

According to Roman, des Varannes, Muresan, Picos, and Dumitrascu (2014), there is evidence of a relationship between GERD and atrial fibrillation. Their review of seven epidemiological studies and one human randomized controlled trial determined that inflammation and/or vagal stimulation may be the underlying mechanisms of this correlation. The inflammatory profile of reflux esophagitis—esophageal inflammation due to acid reflux—may be particularly important due to the proximity of the esophagus to the heart’s left atrium. The inflammatory profile of atrial fibrillation is predictably similar to that of reflux esophagitis, including macrophage recruitment and IL-6 expression (Yamashita et al., 2010). Though controversial due to the possibility of interference in calcium and magnesium levels (Iqbal & Anwar, 2018), proton pump inhibiting drugs may help reduce symptoms of atrial fibrillation (Weigl, Gschwantler, Gatterer, Finsterer, & Stollberger, 2003) as they reduce the levels of hydrochloric acid available to enter the esophagus. The repeated esophageal exposure to the highly acidic gastric reflux may elicit the aforementioned inflammatory or vagal response.

Additionally, melatonin effectively protects the gastric mucosa against free radicals and relieves epigastric pain with or without the use of omeprazole in patients with GERD (Kandil, Mousa, El-Gendy, & Abbas, 2010). In combination with l-tryptophan, vitamin B6, folic acid, vitamin B12, methionine, and betaine, melatonin was shown to work better than omeprazole in relief of GERD symptoms (Pereira, 2006). This is promising information for patients with atrial fibrillation and/or GERD, and especially those with a combination of both diagnoses due to possible pathophysiological cross-talk. Levels of melatonin must be maintained to protect mucosa and the shared local and systemic inflammatory profile of these diseases.

The beneficial effect of melatonin on heart rhythm may be another exciting therapeutic action for those with atrial fibrillation. A 2016 study by VanKirk, Powers, and Dowse on the influence of melatonin on Drosophila with cardiac rhythmicity mutations found that injections of melatonin increased regularity of the heartbeat. More intriguing still, Benova et al. (2015) found that they could not induce ventricular fibrillation, even by the most substantial available stimulus (50 mega amperes of electrical current) in guinea pig hearts pre-treated with melatonin.

There is a high and growing prevalence of both GERD—27% in the western population (Yamasaki, Hemond, Eisa, Ganocy, & Fass, 2018)—and atrial fibrillation—approximately 9% of westerners over 65 years of age (CDC, 2017). The common use of beta1-blocking medications to address atrial fibrillation and their subsequent interference with melatonin synthesis, melatonin’s systemic antioxidant capacity, and the connection between GERD and atrial fibrillation with the possible shared mechanism of inflammatory mediators, as mirrored in this case study, warrants a closer look via larger-scale, controlled studies. These connections strongly point toward the recommendation of melatonin to patients with atrial fibrillation who are prescribed a beta1-blocker, patients with GERD for possible prevention of atrial fibrillation, and patients with evidence of both, or possibility of both, pathophysiologies.

References

Bayer HealthCare Pharmaceuticals Inc. Betapace (sotalol) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021151s010lbl.pdf. Revised June 2011. Accessed November 13, 2019.

Benova, T., Knezl, V., Viczenczova, C., Bacova, B. S., Radosinska, J., & Tribulova, N. (2015). Acute anti-fibrillating and defibrillating potential of atorvastatin, melatonin, eicosapentaenoic acid and docosahexaenoic acid demonstrated in isolated heart model. Journal Of Physiology And Pharmacology: An Official Journal Of The Polish Physiological Society66(1), 83–89.

Bilici, D., Süleyman, H., Banoğlu, Z. N., Kiziltunç, A., Avci, B., Ciftçioğlu, A., & Bilici, S. (2002). Melatonin prevents ethanol-induced gastric mucosal damage possibly due to its antioxidant effect. Digestive Diseases And Sciences47(4), 856–861.

Carrillo-Vico, A., Calvo, J. R., Abreu, P., Lardone, P. J., García-Mauriño, S., Reiter, R. J., & Guerrero, J. M. (2004). Evidence of melatonin synthesis by human lymphocytes and its physiological significance: possible role as intracrine, autocrine, and/or paracrine substance. FASEB Journal: Official Publication Of The Federation Of American Societies For Experimental Biology18(3), 537–539.

Centers for Disease Control and Prevention (CDC). Atrial Fibrillation Fact Sheet. (2017).

Iqbal, U., & Anwar, H. (2018). Proton Pump Inhibitors (PPIs) are inhibitors or risk factor for Atrial Fibrillation? JPMA. The Journal Of The Pakistan Medical Association68(7), 1141.

Kandil TS, Mousa AA, El-Gendy AA, Abbas AM. The potential therapeutic effect of melatonin in Gastro-Esophageal Reflux Disease. BMC Gastroenterology. 2010;10:7. doi:10.1186/1471-230X-10-7. 

Pereira, R. de S. (2006). Regression of gastroesophageal reflux disease symptoms using dietary supplementation with melatonin, vitamins and aminoacids: comparison with omeprazole. Journal of Pineal Research41(3), 195–200.

Pieri, C., Marra, M., Moroni, F., Recchioni, R., & Marcheselli, F. (1994). Melatonin: a peroxyl radical scavenger more effective than vitamin E. Life Sciences55(15), PL271-PL276.

Roman, C., Bruley des Varannes, S., Muresan, L., Picos, A., & Dumitrascu, D. L. (2014). Atrial fibrillation in patients with gastroesophageal reflux disease: a comprehensive review. World Journal Of Gastroenterology20(28), 9592–9599.

Stoschitzky, K., Sakotnik, A., Lercher, P., Zweiker, R., Maier, R., Liebmann, P., & Lindner, W. (1999). Influence of beta-blockers on melatonin release. European Journal Of Clinical Pharmacology55(2), 111–115.

Yamasaki, T., Hemond, C., Eisa, M., Ganocy, S., & Fass, R. (2018). The Changing Epidemiology of Gastroesophageal Reflux Disease: Are Patients Getting Younger? Journal of Neurogastroenterology & Motility24(4), 559–569.

Weigl, M., Gschwantler, M., Gatterer, E., Finsterer, J., & Stöllberger, C. (2003). Reflux esophagitis in the pathogenesis of paroxysmal atrial fibrillation: results of a pilot study. Southern Medical Journal96(11), 1128–1132.

VanKirk, T., Powers, E., & Dowse, H. B. (2017). Melatonin increases the regularity of cardiac rhythmicity in the Drosophila heart in both wild-type and strains bearing pathogenic mutations. Journal Of Comparative Physiology. B, Biochemical, Systemic, And Environmental Physiology187(1), 63–78.

Yamashita, T., Sekiguchi, A., Iwasaki, Y., Date, T., Sagara, K., Tanabe, H., … Aizawa, T. (2010). Recruitment of immune cells across atrial endocardium in human atrial fibrillation. Circulation Journal: Official Journal Of The Japanese Circulation Society74(2), 262–270.

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