Andrew Hubbard, BSc (Hons)
Ellen Wong, BSc (Hons), ND

Student Scholarship – First Place Research Review

Atrial Fibrillation (AF) is the most commonly diagnosed heart arrhythmia in America.^1,2 Most causes are of cardiovascular origin and include hypertension, coronary artery disease, and cardiac valve disorders; however, the list of non-cardiac causes, such as obstructive sleep apnea, chronic obstructive pulmonary disease (COPD) and electrolyte imbalances, appears to be increasing.² Most recently, gastroesophageal reflux disease (GERD) has emerged as a significant non-cardiac contributor to AF.^3,4,5 Equally, AF and its subsequent treatment may also play a role in the development of GERD, further strengthening suspicions of a bi-directional phenomenon.^6,7 Additionally, a large body of research has been conducted investigating the potential gastric-cardiac connection with respect to GERD and AF. Despite this, the topic remains rather elusive in both conventional and alternative healthcare discussions. Thus, the aim of this paper is to review these conditions and shed light on their connection, discuss what mechanisms might be involved, and to evaluate effectiveness and suitability of the current medical treatments. We will also discuss how the naturopathic doctor can play a vital role in identifying and treating patients affected with these conditions using non-pharmacologic means.

Atrial Fibrillation

Atrial fibrillation is an irregular heart rhythm that stems from an uncoordinated contraction, or “quiver,” of the atrial chambers. This leads to ineffective blood pumping within the heart, which puts additional stress on the ventricles.² As clot formation often occurs in the setting of stagnant and inefficient blood pumping within the heart, patients with AF are at an increased risk of thromboembolic events such as stroke, and are often thus relegated to life-long treatment with anticoagulant medications.⁸ AF is associated with heart failure, is an independent risk factor for early death, and is a significant detriment to quality of life.⁸

The prevalence of AF in the general population is estimated at 1-2% but increases in patients over the age of 60.² Risk factors for AF include but are not limited to: age, male gender, smoking, hypertension, obesity, obstructive sleep apnea (OSA), and cardiac valve defects.⁵

Patients with AF may be asymptomatic, or they may have brief (paroxysmal) episodes of fatigue and an irregular heartbeat. They may also present to the ER with more alarming features, such as syncope, tachycardia, and chest pain.² Patients are often treated with antiarrhythmic and anticoagulant drugs or undergo radiofrequency catheter ablation in persistent cases where drug treatment has failed.²

The pathophysiology of AF is complex and uncertain; however, it is generally accepted that changes to cardiac muscle cells (myocytes) take on different electrical properties and begin disrupting the pace-making ability of the sino-atrial node (SA), which leads to uncoordinated atrial contractions.¹ As this progresses over time, a process of remodeling takes place in which irreversible changes to atrial tissue occur that lead to permanent AF. It is unclear what initiating factor causes myocytes to misfire and AF to initially develop, but it is suggested that local inflammation and mechanical stress are likely involved.¹

Gastroesophageal Reflux Disease

GERD is highly prevalent in North America and is one of the most common reasons for visits to primary care providers.³ The disease is characterized by the sensation of “heartburn” and regurgitation of acid from the stomach up into the esophagus. Reflux can present as erosive or non-erosive, the former being associated with esophagitis and dysplastic tissue changes, such as Barrett’s esophagus, which increases the risk of esophageal adenocarcinoma. Significant risk factors include smoking, obesity, OSA, and aging.⁷ Acid reflux symptoms are induced when sustained increases in intra-abdominal pressure (as seen in obesity) and consumption of large meals decrease lower esophageal sphincter (LES) tone. Increased visceral sensitivity and delayed gastric emptying may also be present.⁹ First-line treatment of GERD consists of an initial therapeutic trial of a proton-pump inhibitor, eg, omeprazole, and lifestyle modification.¹⁰

The Small Bridge Between

Based on the close anatomical relationship between the esophagus and the left atrium, it would seem plausible that a disturbance in one tissue might affect the other. Indeed, only 2 mm separate the esophagus from the left atrium.¹¹ Interestingly, cardio-gastric interactions are not new. A rare and fatal complication of left atrial catheter ablation is the development of an atrio-esophageal fistula.¹¹ More commonly, however, patients will develop GERD or esophagitis after this procedure, demonstrating the potential impact of an inflammatory insult on proximal tissues.¹²

Reflux, Inflammation, & Vagal Stimulation

It is postulated that reflux symptoms leading to esophageal inflammation may disturb neighboring vagus nerve fibers, which then causes a cardiac reflex. This can in turn upset the heart rhythm, leading to episodes of AF.¹³ The heart receives input from both sympathetic and parasympathetic (vagal) signals, and this balance is crucial for maintaining normal conductivity. The following studies reveal that this balance is altered in patients with reflux symptoms and with AF. In many cases, lowering esophageal acid exposure via proton-pump inhibitors (PPIs) results in the resolution of AF symptoms.^14,15 So, let’s examine this relationship a little closer.

Exploring the Evidence

A 2014 systematic review revealed a prevalence of AF ranging from 0.62% to 14% in those patients with GERD as compared to those without GERD.³ The authors also found that patients experiencing more severe GERD symptoms had higher rates of AF.

Several large population-wide studies have examined prevalence rates of GERD with AF.^4,5 In 2009, Kunz et al reported the relative risk (RR) of developing AF in those with pre-existing GERD to be 1.39. After adjusting for cardiovascular risk factors, this association fell to 1.19 but remained significant. Other risk factors reported in this study included hypertension (RR 1.75), smoking (RR 1.47), and diabetes (RR 1.21).⁵

Smaller studies, such as those conducted by Bunch et al,¹⁶ have shown no association between GERD and AF risk, although patients with a higher frequency of reflux symptoms reportedly had a slightly elevated risk of AF. Bunch et al also concluded that patients with esophagitis were at a significantly higher risk of developing AF (RR 1.94),¹⁶ supporting the local inflammatory hypothesis.

Hwang et al⁷ and Kubota et⁶ al have both reported a significantly increased risk of developing GERD in patients with newly diagnosed AF. Those experiencing an increased severity of arrhythmia, which progressed from paroxysmal AF to permanent AF, reported higher reflux scores.⁶ This supports a potential bi-directional relationship.

To summarize, the research thus far has revealed a consistent upward trend for the prevalence of AF in patients with GERD and suggests that this association increases with a worsening of reflux symptoms and even more so in the presence of esophagitis. Conversely, AF appears to increase the risk of developing GERD and this risk is further increased with worsening AF.

Does Suppressing Acid Suppress AF?

Two important studies have used unique approaches for evaluating the effects of GERD in AF and the subsequent effects of PPI therapy.

The first study used esophageal manometry (a technique for measuring acidity in the esophagus) and heart rate variability (a reliable and accurate way of measuring sympathetic and vagal activity) to correlate GERD and arrhythmic sequences.¹⁴ A significant number of patients demonstrated increased vagal responses corresponding with increased esophageal acid exposure. These patients then underwent PPI therapy, and both reflux and arrhythmic symptoms were significantly reduced.¹⁴

In the second study, 24-hour esophageal pH monitoring and simultaneous ambulatory ECG (Holter) monitoring were used to assess 3 cases of GERD and atrial arrhythmias.¹⁵ Reflux episodes were strongly correlated with episodes of AF in these patients, which resolved with acid-suppressive therapy. These studies, although small, provide the first real-time evidence regarding reflux events and atrial arrhythmias and their symptomatic resolution through PPI therapy.

While treatment of AF with PPIs in patients who have significant reflux symptoms has been shown to be effective at reducing AF events,^14,15 these studies were of short duration and had small sample populations. Furthermore, the use of PPIs has been demonstrated to negatively impact nutrient and mineral absorption, including B12, calcium, vitamin D, and magnesium¹⁷; some studies suggest that low magnesium status could potentiate moderate-to-severe arrhythmias.¹⁸ Aside from patients with erosive esophagitis or Barrett’s esophagus, patients who are using PPIs to control reflux symptoms and potential arrhythmias should be treated for a short duration, and medications should be discontinued once symptoms have resolved.

Naturopathic Tools

Based on mechanisms discussed thus far, naturopathic doctors and other clinicians should start by first identifying and addressing the underlying factors that might be contributing to GERD and AF. As discussed previously, these could include obesity, OSA, inflammation, and smoking.

Overwhelming benefits of weight management, observed in intervention trials for both GERD and AF, suggest this may be an effective first step in the appropriate patient.¹⁹ It is worth mentioning that adherence to a Mediterranean diet has been shown to reduce cardiovascular events in AF and may be well suited to these patients.²⁰

Gastric motility, vagus nerve, and LES function may be improved by encouraging stress reduction and deep breathing exercises prior to and following mealtime.²¹ No studies to date have explored the potential benefits of adopting mindful eating habits such as appetite awareness and chewing food thoroughly; however, this seems like a reasonable approach in the patient with AF and reflux symptoms.

If esophageal inflammation is predominant, then herbal medicines with anti-inflammatory, demulcent, and mucosal healing properties, such as Glycyrrhiza, Filipendula, Althea, and Ulmus, could be helpful.²² If LES function is compromised, or gastric emptying is delayed, clinicians may want to consider bitter and prokinetic herbs such as Angelica, Zingiber, Gentiana, and Coleus.²² As nicotine is a strong LES relaxant, smoking cessation should be strongly encouraged.

Structurally similar to PPIs, melatonin has been investigated for its potential benefits in the treatment of GERD. Studies have been promising thus far, suggesting that melatonin may be as effective as PPIs for controlling symptoms of GERD.²³ Melatonin might thus be an attractive, cost-effective option for patients who decline or do not respond to initial PPI therapy.

Lastly, acupuncture represents a promising strategy to treat the patient who presents with both AF and reflux symptoms. In fact, a recent meta-analysis concluded that acupuncture was at least as effective as drug therapy for treating arrhythmias and that a further benefit was observed when acupuncture was combined with drug therapy as compared with drug therapy alone.²⁴ The most commonly used acupuncture points reported in this study were Pericardium 6 (PC6), Heart 7 (HT7) and Urinary Bladder 15 (UB15). Acupuncture represents an ideal individualized treatment, as it can target both reflux symptoms²⁵ and the heart rhythm disturbances seen in these patients.

Closing Thoughts

Although still controversial, it appears that GERD and AF impact one another. While the prevalence of patients suffering from both GERD and AF ultimately remains low, there appears to be a significant clinical correlation between the two. The strength of this relationship increases when esophageal damage is present or when reflux symptoms increase, and is dependent on the type and severity of arrhythmia. Being aware of this clinical correlation may present clinicians with an opportunity to substantially improve patients’ quality of life and potentially prevent lifelong consequences of AF and side-effects of long-term drug use. Much can be gained by utilizing diet and lifestyle interventions such as healthy weight management, giving patients tools to manage stress, and fostering mindful eating behaviors.

References:

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21. Frøkjaer JB, Bergmann S, Brock C, et al. Modulation of vagal tone enhances gastroduodenal motility and reduces somatic pain sensitivity. Neurogastroenterol Motil.2016;28(4):592-598.
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Andrew Hubbard, BSc (Hons), is currently studying in his 4^th year at CCNM in Toronto. He has a passion for researching, writing, and speaking on topics that include gastrointestinal, neurological, and endocrine health. Andrew plans on opening an integrative clinic with a special interest in digestive wellness and is fascinated with designing future nutraceutical products. In between the clinic and the late-night PubMed searches, Andrew can usually be found sprinting out on the trails or at the gym re-inventing exercise to be more fun and enjoyable.

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Ellen Wong, BSc (Hons), ND, is an associate professor at the Canadian College of Naturopathic Medicine (CCNM), where she graduated in 2009 and completed an accredited clinical residency in 2011. Currently, Dr Wong teaches an evidence-informed therapeutics class, as well as supervises interns at the Robert Schad Naturopathic Clinic (teaching clinic of CCNM). She practices in Ontario, Canada, with a focus on cardiovascular disease, its comorbidities, and geriatric care. In her spare time, Dr Wong explores the culinary scenes of Toronto, is an avid reader, and tries to squeeze in some time for exercise.