On-therapy impedance-pH monitoring can efficiently characterize PPI-refractory GERD and support treatment escalation.

Background: On-therapy impedance-pH monitoring is recommended in patients with documented GERD and PPI-refractory heartburn in order to establish whether the unremitting symptom is reflux-related or not.

Aims: To define on-PPI cut-offs of impedance-pH metrics allowing proper interpretation of on-therapy impedance-pH monitoring.

Methods: Blinded expert review of impedance-pH tracings performed during double-dosage PPI, prospectively collected from 150 GERD patients with PPI-refractory heartburn and 45 GERD patients with PPI-responsive heartburn but persisting extra-esophageal symptoms. Acid exposure time (AET), number of total refluxes (TRs), post-reflux swallow-induced peristaltic wave (PSPW) index, and mean nocturnal baseline impedance (MNBI) were assessed. On-PPI cut-offs were defined and evaluated with ROC analysis and the area under curve (AUC).

Results: All the four impedance-pH metrics significantly differed between PPI-refractory and PPI-responsive heartburn cases. At ROC analysis, AUC was 0.73 for AET, 0.75 for TRs, 0.81 for PSPW index, and 0.71 for MNBI; best cut-offs were ≥1.7% for AET, ≥45 for TRs, ≤36% for PSPW index, and ≤ 1847 Ω for MNBI; AUC of such cut-offs was 0.66, 0.71, 0.73, and 0.68, respectively. Analysis of PSPW index and MNBI added to assessment of AET and TRs significantly increased the yield of on-therapy impedance-pH monitoring in the PPI-refractory cohort (97% vs. 83%, p < 0.0001). Notably, suboptimal acid suppression as shown by AET ≥1.7% was detected in 43% of 150 PPI-refractory cases.

Conclusions: We have defined on-PPI cut-offs of impedance-pH metrics by which comprehensive assessment of impedance-pH tracings, including analysis of PSPW index and MNBI can efficiently characterize PPI-refractory GERD and support treatment escalation.