Atrial Flutter After Radiofrequency Ablation for Barrett’s Esophagus: A Case Report

Background

Barrett’s esophagus (BE) is a change in the epithelial lining of the esophagus and is a precursor condition for esophageal adenocarcinoma (EAC). BE develops as a result of chronic exposure to refluxed stomach acids, enzymes, and bile. It occurs when a patient’s lower esophageal sphincter or valve fails to close properly, thus not preventing acid backwash into the lower esophagus. This results in recurrent mucosal injury that is accompanied by inflammation, and ultimately meta-plasia to intestinal epithelium, associated with risk of cancer transformation. The steps between normal esophageal tissue and cancer are described as normal squamous epithelium – intestinal metaplasia – low-grade dysplasia – high-grade dysplasia – cancer (mainly adenocarcinoma) based on histological analysis [1] and classified according to Prague circumferential (C) length and maximal (M) length criteria [2] after endoscopic examination. Therefore, once diagnosed, the current recommendation is to establish endoscopic surveillance to identify early dysplasia and neoplasia that could be treated by endoscopic eradication therapy.

Focal radiofrequency ablation is a valid technique for BE treatment by inducing superficial and focal thermic destruction of metaplastic tissues [3]. The use of sizing balloons is required to determine the inner diameter of the targeted portion of the esophagus. This is followed by placement of a balloon-based electrode with a 3-cm-long treatment area incorporating tightly spaced bipolar electrodes that alternate in polarity. The electrode is then attached to a radiofrequency generator and a preselected amount of energy is delivered in less than 1 s at 350 W. The procedure drives focal mucosal destruction. New esophageal squamous tissue regenerates, decreasing the risk of cancer transformation. The technique has good long-term results, maintaining normal esophageal mucosa with no recurrence of BE in 75% to 92% of patients at 3 years [4,5].

The rate of adverse effects of RFA is low and mainly involves post-procedure chest discomfort or odynophagia, upper-gastrointestinal hemorrhage (<1%) [3], post-procedure nausea or vomiting, or late esophageal stricture endoscopically identified after 3 years (6–13.3%) [3,4,6]. Here, we report the case of 1 patient who had an atrial flutter that was an uncommon radiofrequency ablation-linked complication.

Case Report

The present case report was developed according to the Consensus-based Clinical Case Reporting Guideline (CARE checklist) [7]. A 74-year-old man was referred to Nouvel Hôpital Civil in Strasbourg (France) for a non-dated Barrett’s esophagus discovered in February 2021 during a gastroscopy, performed to investigate chronic anemia. His past medical history included pericarditis in 1994, type 2 diabetes treated with oral medications, prostate cancer treated by total prostatectomy in 2004, narcolepsy-cataplexy syndrome, and chronic angina pectoris cured by a mono-troncular stent in the right coronary artery in October 2015. There was no dysplasia when BE was discovered. The patient has been treated first with a high-dose proton pump inhibitor (esomeprazole 40 mg 2 times daily), and at an endoscopic control in May 2021 showed a BE of an 8-cm-long circular section (C), measured from the proximal cardial notch, and an additional short tongue of 1 cm, C8M9 according to Prague C&M classification [2], with no dysplasia. At 1-year endoscopic control in September 2021, a progression to C8M12 BE with a low-grade dysplasia was found. After a multidisciplinary meeting, we decided to perform radiofrequency ablation to achieve local control of the dysplastic area.

In December 2021, we performed a non-circumferential Barrx Halo90 (Barrx Medical, Sunnyvale, Calif) radiofrequency ablation (RFA 12 J/300 W). The endoscopic procedure was performed under general anesthesia with endotracheal intubation. Propofol was the sedative used to induce anesthesia. The esophageal epithelium was first irrigated with acetylcysteine (1%), a mucolytic agent, via a spray-tip catheter. The endoscope was removed, and the sizing balloon was calibrated and inserted over the guidewire to ensure uniform contact between the RFA electrode and the esophageal mucosa. A 22-mm ablation catheter was introduced under endoscopic control. The electrode was then activated with energy settings of 12 J/m2 and 300 W/cm2, thus completing the ablation procedure (Figure 1). After removing the balloon and endoscope and cleaning the electrode, the endoscope was reintroduced and used to remove adherent coagulum from the ablation zone (Figure 2). The procedure was then repeated once more.

The patient was monitored for 2 h after recovering from general anesthesia. A 12-lead electrocardiogram revealed a sawtoothed pattern of inverted F waves in the inferior leads II, III, and aVF associated with biphasic F waves in I and aVL, an upright F wave in V1, and an inverted F wave in V6 with an atrial cycle length of 200 ms. This electrocardiographic surface was diagnostic for a typical type I atrial flutter (Figure 3).

The episode was symptomatic but well tolerated with dyspnea but no chest pain or palpitations. Monitoring was performed with serial electrocardiograms and 24-h Holter monitor. Atrial flutter was first treated by intravenous amiodarone, a class III antiarrhythmic, at a dosage of 150 mg over a period of 10 min, followed by a 1 mg/min infusion for 6 h, and then by an infusion at 0.5 mg/min for 24 h. Intravenous therapy was finally switched to oral administration of amiodarone 400 mg daily. This management allowed us to regain sinus cardiac rhythm. We started a curative anticoagulation treatment by heparin. Two days after the procedure, on 10 December, a new atrial flutter episode occurred. This second event was characterized by more pronounced symptoms with palpitations, chest pain, and dyspnea. Medical treatments were not effective, and an external electrical cardioversion was necessary to induce return to sinus cardiac rhythm. The patient was discharged on 22 December 2021, with an antiarrhythmic treatment, including bisoprolol 10 mg/day and amiodarone 200 mg/day, and atrial flutter ablation was planned. After atrial flutter ablation, 2 more radiofrequency procedures were performed to treat BE, and both were free of adverse events. Endoscopic control in March 2022 found lower-esophageal ulceration, but no findings of BE. A laparoscopic Nissen fundoplication was performed. Endoscopic follow-ups in January and March 2023 were normal, with complete endoscopic and histologic eradication of BE after 12-month follow-up.

Discussion

AUTONOMIC ACTIVATION:

Several stimuli (chemical, electrical, or mechanical) can modify sympathovagal balance causing arrhythmogenic substrates for re-entry, promoting atrial arrhythmias susceptibility [12]. In particular, the autonomic nervous system with adrenergic activation may start focal activity by 3 main principal cellular mechanisms: enhanced automaticity, early afterdepolarization, or delayed afterdepolarization-associated triggered activity. A link between cardiac arrhythmias and gastro-enteric stimuli (RFA included) involving the distal esophagus has been proven, given the close anatomical proximity between the esophagus and the left atrium. Acid reflux increases vagal activity, causing local inflammation directly entering the esophageal wall. This stimulates the adjacent vagal nerves, creating an arrhythmogenic substrate for re-entry circuits and increasing susceptibility to AF [13].

INFLAMMATION:

An inflammatory reaction resulting from radiofrequency ablation could involve anatomical structures by contiguity, propagating from the esophageal wall to the pericardium, to the atrial myocardium. Moreover, inflammatory cytokines may induce afferent-efferent reflex mechanisms, changing atrial electrophysiology and structural substrates, thereby leading to increased vulnerability to atrial fibrillation [14].

In particular, presence of systemic inflammation with elevations in C-reactive protein (CRP) and interleukin 6 (IL-6) is linked to a significant risk for future development of AF. An increase in inflammatory cytokines in the atrial tissue results in a local complement system activation leading to „atrial myocarditis„. The exact underlying mechanism is the cellular membrane dysfunction caused by CRP binding to phosphatidylcholine in the presence of Ca2+ ions. This generates a transmembrane ion transport malfunction with consequent electrical changes in the atrium [15].

Not only CRP, but also high plasma IL-6 levels are associated with AF occurrence and duration and an increased left atrial diameter. Furthermore, a genetic susceptibility could explain an enhanced inflammatory response with subsequent development of AF [16]. This theory is supported by evidence of a link between inflammatory bowel disease and the presence of electrocardiographic P-wave dispersion that is a risk factor for cardiac arrhythmias [17].

MYOCARDIAL INJURY:

In addition to the possible direct action of radiofrequency ablation, esophageal stimulation can cause anginal attacks and significantly reduce coronary blood flow in patients with coronary artery disease. The lack of this effect in heart transplant recipients with complete heart denervation suggests the involvement of a neural reflex [18]. This can be understood in the context of the „esophagocardiac reflex,„ which describes how esophageal chemical and mechanical stimulation in patients with documented coronary artery disease results in typical chest discomfort and a significant reduction in coronary blood flow. Reduced cardiac perfusion, increased microvascular resistance, and enhanced vasoconstrictor response may affect the atria, leading to substrates for atrial arrhythmias.

A high level of suspicion is needed for early diagnosis of cardiac arrhythmia after radiofrequency ablation for BE, as it is a rare complication. It seems reasonable to not propose radiofrequency ablation to patients with either history or high risk of heart rhythm disorder (heart failure, dilated cardiomyopathy, mitral valvular disease). Indeed, there are many other effective techniques to treat BE without using focal energy or electric current (eg, cryotherapy, endoscopic mucosectomy, dynamic phototherapy, and argon coagulation). Another important aspect to consider is the clinical effect of sedation-related adverse events (SRAE) during RFA. An interesting report focused on this topic found that the occurrence of an SRAE was a stronger predictor of increased RFA sessions than either Barrett’s length or hiatal hernia, which are the 2 most important factors for predicting response to treatment [18]. Moreover, it has been widely proven that propofol, the most commonly used sedative drug for induced anesthesia, has arrhythmogenic features due to its effects on cardiac electrical activity. Tascanov et al [19] investigated the effect of propofol on myocardial depolarization and repolarization during sedation induced for colonoscopy. The study showed that propofol significantly prolonged the frontal QRS-T angle, which had important prognostic value in predicting cardiovascular arrhythmias and is also associated with increased risk of ar-rhythmic death.

It is therefore clear how radiofrequency ablation used for BE treatment requires close supervision of heart rhythm during the entire hospital stay. In our patient, the atrial flutter occurred a few hours after the procedure and relapsed 2 days after. To prevent this type of complication, we could suggest to patients that they receive continuous heart monitoring after this procedure until they leave the hospital. The exact details of heart supervision after radiofrequency ablation remains unknown because of the small number of reported cases and the only hypothetical physiopathology of the electrical process induced by radiofrequency ablation in atrial flutter.

Conclusions

RFA with the Barrx™ catheter system is widely used for the treatment of BE. To the best of our knowledge, this is the first case of symptomatic atrial flutter reported in the literature after RFA with the Barrx™ system. Although cardiac rhythm disturbances are an extremely rare complication of the procedure, endoscopists should be aware of the possibility of this occur-rence and a category of high-risk patients should be identified based on the underlying mechanisms for whom RFA would be contraindicated.