Anti-Reflux Mucosal Ablation (ARMA) is an innovative endoscopic intervention for managing PPI-refractory GERD by enhancing the structural integrity of the gastroesophageal junction (GEJ). Utilizing controlled thermal ablation, ARMA induces localized mucosal fibrosis to reinforce the anti-reflux barrier. Clinical studies demonstrate significant improvements in GERD symptoms, acid exposure time, and DeMeester scores, with over 70% clinical success in one year. The procedure is well-tolerated, with manageable complications such as transient stenosis treated via endoscopic dilation. ARMA offers advantages over surgical fundoplication due to its reduced procedural complexity and minimally invasive nature. While early outcomes are promising, larger multicenter trials are needed to validate long-term efficacy and define optimal patient selection, particularly in those with mild to moderate GEJ abnormalities.

Introduction

Gastroesophageal reflux disease (GERD) is a highly prevalent condition. GERD is characterized by the retrograde movement of gastric contents into the esophagus, leading to symptoms such as heartburn, regurgitation, and atypical presentations like cough, chest pain, hoarseness, and laryngitis. GERD affects an estimated 20% of adults in Western populations and incurs significant healthcare costs while impairing quality of life.^1,2

Despite the widespread use of proton pump inhibitors (PPIs) as the first-line therapy, 30–40% of patients continue to experience symptoms despite adequate acid suppression.^3,4 Surgical interventions such as laparoscopic Nissen fundoplication are highly effective but are associated with complications like dysphagia and gas bloat syndrome and have a significant failure rate, necessitating the exploration of less invasive alternatives.^5,6,7

Anti-reflux mucosal interventions, including Anti-Reflux Mucosectomy (ARMS) and Anti-Reflux Mucosal Ablation (ARMA), have emerged as innovative endoscopic procedures aimed at improving the anatomical and functional integrity of the gastroesophageal junction (GEJ). These techniques are gaining traction as viable options for managing PPI-refractory GERD.⁸ This article will review the current status of ARMS and ARMA. 

Pathophysiology of GERD and Role of the GEJ

The pathogenesis of GERD is multifactorial, involving structural and functional abnormalities of the GEJ.⁹ Key contributors include:

Impaired Lower Esophageal Sphincter (LES) Pressure: A hypotensive LES facilitates retrograde reflux.¹⁰

Hiatal Hernia: Alters the anatomical configuration of the GEJ and diaphragm, reducing its anti-reflux competency, and allowing acid-producing gastric mucosa above the diaphragm.¹¹

Transient LES Relaxations (TLESRs): Excessive, non-swallowing LES relaxations increase reflux events.¹²

Esophageal Clearance Dysfunction: Impaired peristalsis delays the clearance of refluxed material.¹³

Hill’s classification (grades I–IV) of the gastroesophageal flap valve provides a structural assessment of the GEJ, with grades II-IV associated with an increased risk of PPI-refractory GERD.^1,7 Endoscopic therapies like ARMA directly target the structural deficiencies of the GEJ, offering a minimally invasive alternative to surgical fundoplication 

Evolution of Endoscopic Therapies

Endoscopic approaches to GERD management have advanced significantly, offering effective alternatives to traditional medical and surgical treatments.¹⁴  These approaches can be categorized into several techniques, as shown in Table 1.

1. Reconstructive Therapies:

○ Transoral Incisionless Fundoplication (TIF):Creates full-thickness plications to mimic surgical fundoplication. While effective, it is technically demanding, time-consuming, and requires specialized training and equipment.¹⁵

○ Magnetic Sphincter Augmentation (LINX): Places a ring of magnetic beads around the LES via laparoscopy. It has shown promise but is limited by MRI incompatibility, specific anatomical requirements, and risk of adverse events including dysphagia and device breakage, among others.¹⁶

2. Ablative Therapies:

○ Radiofrequency Ablation (RFA): Remodels LES muscle fibers using devices like Stretta but has variable efficacy.¹⁷

○ ARMS: Involves partial mucosal resection at the gastric cardia to induce scar-mediated tightening of the GEJ.⁸

○ ARMA: Focuses on controlled thermal ablation of the gastric cardia mucosa, leading to scar formation and enhanced flap valve integrity.⁸

Technical Considerations of ARMA

ARMA is a minimally invasive endoscopic procedure aimed at reinforcing the GEJ by inducing targeted mucosal scarring to enhance the anti-reflux barrier.¹⁸

The procedure begins with the patient positioned in the left lateral decubitus position. General anesthesia is typically used to ensure patient comfort and procedural safety, although conscious sedation may suffice in select cases based on the patient’s clinical status and tolerance. A high-definition gastroscope fitted with a transparent hood enhances visualization and precision. Ablation zones are marked in a butterfly-shaped pattern along the gastric side of the cardia, leaving two non-ablated segments to avoid circumferential scarring and mitigate the risk of stenosis. This pattern is crucial for ensuring localized scar formation without excessive narrowing of the lumen. Submucosal injection of saline mixed with indigo carmine dye is performed to lift the mucosa and create a protective cushion, safeguarding deeper layers from thermal injury during ablation.^17,18

Table 1. Comparative Analysis of Endoscopic Therapies for GERD

 Mucosal ablation is typically conducted using electrocautery in spray coagulation mode. The generator settings commonly used for electrocautery include effect 2 and 50 W power, which deliver controlled thermal energy for uniform ablation. In some studies, argon plasma coagulation (APC) has been employed as an alternative, providing effective mucosal ablation while reducing the risk of deep thermal injury. When APC is used, the same generator settings are often applied to ensure consistent outcomes. While radiofrequency ablation (RFA) devices may be considered, APC remains the preferred method based on safety, availability, and efficacy data in the literature.^18,21 (Figure 1)

A crucial patient selection criterion is the presence and size of a hiatal hernia. ARMA is most effective in patients with small hernias (<2 cm). Larger hernias (>2 cm) typically require surgical repair, as ARMA does not address the anatomical displacement of the GEJ associated with larger hernias. Thus, a pre-procedure assessment, including endoscopy and esophageal manometry, is essential.  Post-procedurally, patients are prescribed PPI therapy for 4 – 6 weeks to promote mucosal healing, minimize inflammation, and reduce the risk of complications such as ulcers or delayed bleeding. Follow-up includes reassessment of symptoms using validated GERD questionnaires, endoscopic examination, and, if indicated, 24-hour pH monitoring.¹⁸

Clinical Outcomes

ARMA has shown significant efficacy in improving GERD-related symptoms and objective reflux control. A 2024 international bi-center study reported a reduction in median GERD-HRQL scores from 26 to 11 at six months (P < 0.001), Acid Exposure Time (AET) fell from 5.3% to 0.7% (P = 0.003), alongside significant improvements in DeMeester scores. Follow-up data at 12 months indicated a clinical success rate of 70%, defined as a greater than 50% reduction in validated GERD questionnaire scores, suggesting durable symptomatic and reflux improvements over time.²³

A meta-analysis of 15 nonrandomized studies (n = 461) demonstrated a technical success rate of 100% and clinical success rates of 78% at six months, 72% at one year, and 73% at three years, with consistent outcomes across ARMS and ARMA. At one year, 64% of patients were off PPIs, with significant improvements observed in symptom scores, esophagitis resolution, and acid exposure time (P < 0.01). These findings underscore ARMA’s ability to potentially deliver durable symptom relief and effective reflux control, offering a promising therapeutic option for refractory GERD.⁸

Safety and Adverse Events

The safety profile of ARMA, while promising, reflects the early stages of adoption and ongoing evaluation of this emerging technology. In clinical studies, transient stenosis was observed in 13.2% of cases, all of which were effectively managed with endoscopic balloon dilation. Other adverse events included minor bleeding and mucosal ulceration, both of which resolved with conservative management, including short-term PPI therapy. Importantly, no perforations or severe adverse events, such as significant bleeding requiring transfusion or long-term complications, were reported in the available data. These findings highlight the need for ongoing studies to validate the long-term safety and risk profile of ARMA while acknowledging its manageable short-term complications.^23,24

Comparative Effectiveness of ARMA

Compared to ARMS and other endoscopic therapies, ARMA offers distinct clinical advantages. Its controlled thermal ablation approach avoids full-thickness mucosal resection, resulting in lower technical complexity, significantly shorter procedure times, and a reduced risk of perforation. This makes ARMA more accessible and less invasive for a broader range of patients. The procedure is particularly effective in patients with prior gastric cardia fibrosis (e.g., due to previous interventions or inflammation) or anatomical modifications, such as post-bariatric surgery anatomy or hiatal hernias smaller than 2 cm, thereby broadening its applicability.^{17, 21}

In a randomized trial comparing ARMA to PPI therapy, ARMA demonstrated superior symptom control, improved mucosal integrity, and significant reductions in acid reflux parameters, including acid exposure time and DeMeester scores. These findings support its role as an effective treatment for GERD refractory to pharmacological therapy. While short-term PPI therapy (approximately 4 – 6 weeks) is typically recommended post-procedure to promote mucosal healing, many patients experience reduced long-term dependence on PPIs due to the durable improvements provided by ARMA.

Limitations and Future Directions

While ARMA has shown promising short-term outcomes, several limitations remain. Most studies provide data for up to 12 months, leaving long-term durability uncertain. Additionally, the majority of evidence comes from single-center and small-scale trials, necessitating larger, multicenter randomized controlled trials to validate findings. Current studies also focus primarily on PPI-refractory GERD in patients with mild to moderate anatomical abnormalities, limiting generalizability. Future research should explore ARMA’s long-term durability, comparative efficacy with surgical fundoplication, emerging endoscopic techniques such as antireflux mucosal valvuloplasty (ARMV), and its cost-effectiveness in routine clinical practice.²⁷ Optimization of patient selection criteria, particularly anatomical and functional predictors of success, is crucial to further refine its role in GERD management.²⁵

Conclusion

ARMA is a novel endoscopic technique that is promising in the minimally invasive management of GERD. By targeting the gastroesophageal junction (GEJ) to enhance its structural integrity, ARMA has demonstrated effectiveness in reducing GERD symptoms, particularly in patients with PPI-refractory disease. However, as a relatively new intervention, its long-term efficacy and safety profile require further validation through robust, multicenter studies. While early evidence suggests ARMA may serve as a valuable addition to the therapeutic arsenal for GERD, its role relative to established medical and surgical treatments will be further defined as additional studies and data emerge. 

References

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