Chicago Classification Version 4.0 Improves Stratification of Ineffective Esophageal Motility Patients into Clinically Meaningful Subtypes: A Two-Center International Study

: The 4th iteration of the Chicago Classification (CC v4.0) for esophageal motility disorders offers more restrictive criteria for the diagnosis of Ineffective Esophageal Motility (IEM) compared to version 3.0 (CC v3.0). In light of the updated criteria for IEM, we aimed to characterize and compare the patients who retained their IEM diagnosis to those who were reclassified as normal motility, and to evaluate the clinical impact of the newly introduced CC v4.0. We performed a retrospective case-control study. We included all individuals who underwent a high-resolution manometry (HRM) between 2020 and 2021 at two centers. Consecutive studies reported as IEM according to the CC v3.0 were reanalyzed according to the CC v4.0. We compared demographics, clinical, manometry, and pH-monitoring parameters. Out of 452 manometry studies, 154 (34%) met criteria for IEM as per the CC v3.0 (CC v3.0 IEM group). Of those, 39 (25%) studies were reclassified as normal studies according to the CC v4.0 (CC v4.0 normal group), while the remaining 115 studies (25% of the overall cohort) retained an IEM diagnosis (CC v4.0 IEM group). The CC v4.0 normal group had more recovered contractions during solid swallows (p = 0.01), less ineffective swallows (p = 0.04), and lower acid exposure time (p = 0.02) compared to the CC4.0 IEM group. Under CC v4.0 criteria, fewer patients are diagnosed with IEM. Those diagnosed with IEM had worse esophageal function and higher acid burden. Though further studies are needed to confirm these findings, our results indicate that CC v4.0 criteria restrict the IEM diagnosis to a more clinically meaningful population.