Yield of upper endoscopy and predictors of clinically relevant outcomes in patients with proton pump inhibitor–refractory heartburn

Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder, with heartburn as its hallmark symptom. While proton pump inhibitors (PPIs) remain the cornerstone of GERD management, a significant subset of patients exhibits refractory symptoms, necessitating further diagnostic evaluation. The utility and predictors of clinically significant findings (CSFs) during gastroscopy in PPI-refractory patients remain underexplored. We aimed to evaluate the diagnostic yield of gastroscopy in patients with PPI-refractory heartburn and identify predictors of CSFs. This retrospective multi-center cohort study included 6488 patients undergoing gastroscopy at two teaching hospitals between 2012 and 2022. Patients were stratified into three groups based on treatment status: PPI therapy, H2 receptor antagonists (H2RAs), and no pharmacological treatment. Demographic, clinical, and procedural data were extracted from electronic medical records. CSFs were defined as moderate-to-severe esophagitis, esophageal stricture, histologically confirmed Barrett’s esophagus, upper GI malignancies, or gastric and duodenal ulcers. Diagnostic yield and the number needed to investigate (NNI) were calculated. Multivariate logistic regression identified predictors of CSFs. The mean age was 51.7±12.3 years. Most patients (n=5168) had received PPI therapy, while 837 were on H2RAs and 434 were untreated. CSFs were most frequent among untreated patients (27.9%), followed by H2RA users (18.2%), and were lowest in the PPI group (11.5%) (P <0.01 for all comparisons). In the PPI subgroup, multivariate analyses identified older age, Arab ethnicity, hiatal hernia, shorter PPI duration (< 8 weeks), and low-dose PPI therapy as independent predictors of CSFs. The prevalence of upper GI malignancy was low: 0.04% in patients <50 years (NNI=2290) and 0.17% in those ≥50 years (NNI=585). The diagnostic yield of gastroscopy in patients with persistent heartburn is modest. CSF detection was more strongly associated with treatment duration and PPI dose, rather than frequency. Given the low yield in younger patients and those adequately treated, clinical strategies should prioritize adherence to optimized therapy and lifestyle measures prior to endoscopy referral.