BACKGROUND: Gastroesophageal reflux disease (GERD) has been associated with increased incidence/recurrence of atrial fibrillation (AF). However, the impact of GERD and proton pump inhibitor (PPI) therapy on outcomes of AF catheter ablation remains unclear. We aimed to assess the association between the presence of GERD and risk of repeat AF ablation, stratified by PPI therapy.

METHODS: A retrospective cohort study was conducted on paroxysmal/persistent AF patients undergoing initial ablation in 1/2011-9/2015. GERD was defined by endoscopic findings, objective reflux testing, or clinical symptoms. The association between GERD/PPI use and time to repeat ablation was evaluated by time-to-event analysis with censoring at last clinic follow-up within one year.

RESULTS: 381 subjects were included. GERD patients (n=80) had a higher one-year repeat ablation rate compared to no GERD (25% vs 11.3%, p=0.0034). Stratifying by PPI use, untreated GERD patients (37.5%) more likely needed repeat ablation compared to reflux-free (11.3%, p=0.0003) and treated GERD (16.7%, p=0.035) subjects. On multivariable Cox regression analyses, GERD was an independent risk factor for repeat ablation (HR 3.30, CI:1.79-6.08, p=0.0001). Specifically, untreated GERD was associated with earlier repeat ablation compared to those with no GERD (HR 4.02, CI:1.62-12.05, p=0.0013). However, no significant difference in repeat ablation risk was noted between reflux-free and PPI-treated GERD groups.

CONCLUSION: GERD was an independent predictor for risk of repeat AF ablation within one year, even after controlling for major cardiovascular comorbidities and confounders. PPI therapy modulated this risk, as repeat ablation-free survival for PPI-treated GERD was non-inferior to reflux-free patients.

BACKGROUND AND AIMS: Fecal incontinence (FI) is highly prevalent with substantial impacts on quality of life and healthcare utilization. The impact of obesity on FI remains unclear, with differing conclusions using BMI as risk factor. We aimed to determine the association between obesity and FI, and whether this relationship is dependent on the distribution of adiposity (waist circumference-to-height ratio, WHtR).

METHODS: This was a population-based analysis of the National Health and Nutrition Examination Survey, including participants who responded to the bowel health survey in 2005-2010. FI was defined by the accidental bowel leakage of solid stool, liquid, or mucus at least once in the past month. Stepwise multivariable logistic regression models were constructed to assess risk factors for FI.

RESULTS: A total of 7,606 participants were included, with an overall FI prevalence of 9.2%. When stratified by quartiles of body measurements, FI was increasingly prevalent from 1st to 4th quartile for both WHtR (range: 5.3%-12.5%) and BMI (range: 7.1%-10.5%). WHtR was associated with FI and was a stronger predictor than BMI in all quartiles of body measurement. On multivariable analysis, WHtR remained a significant predictor of FI comparing the 4th to the 1st quartile of body measurements (OR:1.77, CI:1.11-2.80, p=0.017), whereas BMI was not. A WHtR cutoff of >0.592 optimized the Youden index in prediction of FI in the overall sample.

CONCLUSION: WHtR was independently associated with increased odds of FI in this nationally representative sample of US adults, whereas BMI was not consistently correlated. This suggests bowel continence may depend more on how body mass is distributed.

PURPOSE OF REVIEW: Symptoms/complications related to extraesophageal reflux (EER) are increasingly prevalent presentations and pose significant challenges for clinicians. We summarize and discuss clinical advances and developments in pathophysiology, testing and treatment algorithms of upper/lower airway manifestations of EER.

RECENT FINDINGS: Growing evidence supports likely multifactorial causes of laryngeal symptoms, including EER, oropharyngeal pathologies, allergic conditions, and cognitive-affective processes (brain-larynx interaction). Diagnostic paradigm for laryngopharyngeal reflux (LPR) is shifting towards a personalized approach with noninvasive strategies/prediction tools to risk-stratify patients for upfront reflux testing over empiric acid suppression trials. Management should be multipronged to include antireflux therapies and treatments targeting other causes. Lower airway complications of EER may result in lung dysfunction and poor transplant outcomes. Esophageal symptoms are often absent and routine esophageal/reflux testing to guide timely antireflux therapies may lead to improved outcomes. Modalities that leverage impedance technology may be important, given the potential role of nonacidic reflux. Novel impedance-based metrics such as mean nocturnal baseline impedance and postreflux swallow-induced peristaltic wave index may provide adjunctive diagnostic values.

SUMMARY: Standardized approach to diagnosis/management of EER should include multidisciplinary care teams and consider different phenotypes, nonreflux contributors, and the complex gut-airway relationships. Prompt antireflux therapies after careful candidate selection may improve outcomes of these airway complications.

INTRODUCTION: Divergent recommendations for periprocedural management of GLP-1 receptor agonist (GLP-1 RA) medications rely on limited evidence. We performed a systematic review and meta-analysis to provide quantitative measures of gastric emptying relevant to mechanisms of weight loss and to periprocedural management of GLP-1 RA. We hypothesized that the magnitude of gastric emptying delay would be low and of limited clinical significance to procedural sedation risks.

METHODS: A protocolized search identified studies on GLP-1 RA that quantified gastric emptying measures. Pooled estimates using random effects were presented as weighted mean difference with 95% confidence intervals (CI). Univariate meta-regression was performed to assess the influence of GLP-1 RA type, short- vs long-acting mechanism of action, and duration of treatment on gastric emptying.

RESULTS: Fifteen studies met inclusion criteria. Five studies (n=247) utilized scintigraphy (GES). Mean T1/2 was 138.4 minutes (CI:74.5-202.3) for GLP-1 RA versus 95.0 minutes (CI:54.9-135.0) for placebo, with pooled mean difference of 36.0 minutes (CI:17.0-55.0, p<0.01, I2=79.4%). Ten studies (n=411) utilized the acetaminophen absorption test (AAT), with no significant delay in gastric emptying measured by Tmax, AUC4hr, and AUC5hr with GLP-1 RA (p>0.05). On meta-regression, type of GLP-1 RA, mechanism of action, and treatment duration did not impact gastric emptying (p>0.05).

CONCLUSIONS: While a gastric emptying delay of ∼36 minutes is quantifiable on GLP-1 RA medications, it is of limited magnitude relative to standard periprocedural fasting periods. There were no substantial differences in gastric emptying on modalities reflective of liquid emptying (AAT), particularly at time points relevant to periprocedural care.

INTRODUCTION: Among patients with chronic laryngeal symptoms, ambulatory reflux monitoring off acid suppression is recommended to evaluate for laryngopharyngeal reflux (LPR). However, reflux monitoring systems are diverse in configuration and monitoring capabilities, which present a challenge in creating a diagnostic reference standard in these patients. This study aimed to compare diagnostic yield and performance between reflux monitoring systems in patients with chronic laryngeal symptoms.

METHODS: This multicenter, international study of adult patients referred for evaluation of LPR over a 5-year period (March 2018-May 2023) assessed and compared diagnostic yield of pathologic gastroesophageal reflux (GER+) on ambulatory reflux monitoring off acid suppression.

RESULTS: Of 813 patients, 296 (36%) underwent prolonged wireless pH, 532 (65%) underwent 24-hour pH-impedance monitoring, and 15 (2%) underwent both tests. Overall diagnostic yield for GER+ was 36% and greater for prolonged wireless pH compared with that for 24-hour pH-impedance monitoring (50% vs 27%; P < 0.01). Among 15 patients who underwent both prolonged wireless pH and 24-h pH-impedance monitoring, concordance between systems for GER+ was 40%. The most common source of discordance was strong evidence of GER+ across multiple days on prolonged wireless pH compared with no evidence of GER+ on pH-impedance.

DISCUSSION: In this multicenter international study of patients with chronic laryngeal symptoms referred for LPR evaluation, diagnostic yield of ambulatory reflux monitoring off acid suppression was 36% and rose to 50% when using wireless pH monitoring. In patients referred for chronic laryngeal symptoms, 24-hour pH-impedance monitoring may risk a low negative predictive value in patients with unproven GER+ disease.

OBJECTIVE: The objective of this work was to gather an international consensus group to propose a global definition and diagnostic approach of laryngopharyngeal reflux (LPR) to guide primary care and specialist physicians in the management of LPR.

METHODS: Forty-eight international experts (otolaryngologists, gastroenterologists, surgeons, and physiologists) were included in a modified Delphi process to revise 48 statements about definition, clinical presentation, and diagnostic approaches to LPR. Three voting rounds determined a consensus statement to be acceptable when 80% of experts agreed with a rating of at least 8/10. Votes were anonymous and the analyses of voting rounds were performed by an independent statistician.

RESULTS: After the third round, 79.2% of statements (N = 38/48) were approved. LPR was defined as a disease of the upper aerodigestive tract resulting from the direct and/or indirect effects of gastroduodenal content reflux, inducing morphological and/or neurological changes in the upper aerodigestive tract. LPR is associated with recognized non-specific laryngeal and extra-laryngeal symptoms and signs that can be evaluated with validated patient-reported outcome questionnaires and clinical instruments. The hypopharyngeal-esophageal multichannel intraluminal impedance-pH testing can suggest the diagnosis of LPR when there is >1 acid, weakly acid or nonacid hypopharyngeal reflux event in 24 h.

CONCLUSION: A global consensus definition for LPR is presented to improve detection and diagnosis of the disease for otolaryngologists, pulmonologists, gastroenterologists, surgeons, and primary care practitioners. The approved statements are offered to improve collaborative research by adopting common and validated diagnostic approaches to LPR.

LEVEL OF EVIDENCE: 5 Laryngoscope, 134:1614-1624, 2024.

BACKGROUND: Defecation dysfunction may contribute to chronic constipation (CC), but the impact of obesity on anorectal physiology in CC remains unclear. We aimed to evaluate the relationship between obesity and anorectal function on physiologic testing in patients presenting with CC.

METHODS: This was a retrospective cohort study of consecutive adults who underwent high resolution anorectal manometry (HRAM) at a tertiary center for CC. Patient demographics, clinical history, surgical/obstetric history, medications, and HRAM results were reviewed. Patients were classified into obese (BMI > 30 kg/m2) vs non-obese (BMI < 30 kg/m2) groups at the time of HRAM. Fisher-exact/student t-test for univariate analyses and general linear regression for multivariable analysis were performed.

RESULTS: 383 adults (mean 50.3 years; 85.8% female) with CC were included. On HRAM, patients with obesity had lower anal sphincter resting tone (37.3 vs 48.5 mmHg, p = 0.005) and maximum squeeze pressure (104.8 mmHg vs 120.0 mmHg, p = 0.043). No significant differences in dyssynergia (61% vs 53%, p = 0.294) and failed balloon expulsion (18% vs 25%, p = 0.381) were found between obese and non-obese groups. On balloon distention testing, the maximum tolerated (163.5 vs 147.6 mL, p = 0.042) and urge sensation (113.9 vs 103.7 mL, p = 0.048) volumes were significantly increased among patients with obesity. After adjusting for potential confounders, obesity remained independently associated with increased maximum tolerated volume (β-coefficient 13.7, p = 0.049).

CONCLUSION: Obesity was independently associated with altered rectal sensitivity among patients with CC. Altered rectal sensation may play an important role in CC among patients with obesity. Anorectal physiology testing should be considered to understand the pathophysiology and guide management.

Acid reflux has been associated with allograft injury and rejection in lung transplant patients; however, the pathogenic role of non-acid reflux remains debated. We aimed to evaluate the impact of concurrent abnormal non-acid reflux with acid reflux on chronic rejection in lung transplant patients with acid reflux. This was a retrospective cohort study of lung transplant recipients who underwent pre-transplant combined impedance-pH study off acid suppression. Only subjects with acid exposure >4% were included. Non-acid reflux (pH > 4) episodes >27 was considered abnormal per prior normative studies. Chronic rejection was defined as chronic lung allograft dysfunction (CLAD) per International Society for Heart and Lung Transplantation criteria. Time-to-event analyses were performed using Cox proportional hazards and Kaplan-Maier methods, with censoring at death, anti-reflux surgery, or last follow-up. In total, 68 subjects (28 abnormal/40 normal non-acid reflux) met inclusion criteria for the study. Baseline demographic/clinical characteristics were similar between groups. Among this cohort of patients with increased acid exposure, subjects with concurrent abnormal non-acid reflux had significantly higher risk of CLAD than those without on Kaplan-Meier analysis (log-ranked P = 0.0269). On Cox multivariable regression analysis controlling for body mass index, age at transplantation, and proton pump inhibitor use, concurrent abnormal non-acid reflux remained independently predictive of increased CLAD risk (hazard ratio 2.31, confidence interval: 1.03-5.19, P = 0.04). Presence of concurrent abnormal non-acid reflux in lung transplant subjects with increased acid exposure is associated with additional risk of chronic rejection. Non-acid reflux may also contribute to pathogenicity in lung allograft injury/rejection, supporting a potential role for impedance-based testing in this population.

BACKGROUND AND AIMS: Heartburn symptoms contribute to healthcare-seeking among patients with gastroesophageal reflux disease (GERD). Despite clinical guidance, management is often dictated by insurance restrictions. Several potassium-competitive acid blockers (PCAB) are under development as a new class of therapy. We performed economic analyses to align GERD drug development with the needs of gastroenterologists, insurers and patients in a value-based environment.

METHODS: A decision-analytic model was constructed to compare vonoprazan 20mg daily (an example of a potassium-competitive acid blocker[PCAB]), common over-the-counter or prescription proton pump inhibitor (PPI) regimens, and no treatment over a one-year time horizon. Clinical responses were evaluated based on the proportions of heartburn-free days in a recent phase 3 multicenter trial. Healthcare utilization for persistent reflux symptoms was derived from national observational studies compared to healthy controls. Costs and quality-adjusted life years [QALY] were reported.

RESULTS: Without insurance coverage for appropriate therapy, patients spend $4,443 and insurers spend $3,784 on average per year for inadequately treated GERD symptoms. Our model estimates that PCABs could save at least $3,000 in annual costs to patients and insurers, could generate QALY gains (+0.06/year), and could be cost-saving to insurers as a covered option at a price up to $8.57/pill, if these drugs are able to demonstrate similar effectiveness to PPIs in future trials evaluating heartburn relief and erosive esophagitis healing to regulators. Threshold prices reflect pricing after all pharmacy benefits manager rebates and discounts.

DISCUSSION: We demonstrate that aiming GERD-related drug development toward heartburn relief appears critical to align cost-effective incentives for industry and insurers with those of patients and gastroenterologists.