Symptoms associated to weakly acidic reflux and esophageal motility abnormalities are common findings in patients with Non-Cardiac Chest Pain non-responding to PPI therapy. A multicenter italian study

Introduction: Previous studies showed that both visceral hyperalgesia to esophageal distension or even chemostimulation provoked by gastro-esophageal reflux and esophageal motor dysfunction are frequently involved in the aetiology of non-cardiac chest-pain (NCCP). Moreover, proton pump inhibitor (PPI) therapy has been demonstrated to be less effective on symptom relief in NCCP patients than in those with heartburn. Data on the potential causes of this reduced response rate are lacking. Aim: To assess the frequency of esophageal motility abnormalities and reflux disease in NCCP non-responders patients. Methods: Consecutive NCCP patients non-responders to PPI (<50% symptom improvement at double doses) underwent conventional manometry and impedance-pH testing (MII-pH) while on or off-PPI therapy. Manometric pattern was defined as follows: Normal peristalsis (NP; normal wave amplitude and progression), Ineffective Esophageal Motility (IEM; lower distal wave amplitude in ≥30% of wet swallows), Distal Esophageal Spasm (DES; simultaneous wave progression in >10% of wet swallows with normal or high distal amplitude), Nutcracker Esophagus (NE; normal wave progression and high distal wave amplitude). We also measured distal esophageal acid exposure time (AET; % pH<4), reflux episodes (acid/weakly acidic) and symptom-reflux association using both symptom association probability (SAP + if ≥ 95%) and symptom index (SI + if ≥ 50%). Results: Ninety-seven NCCP patients (55F/ 42M, mean age 48) reporting chest-pain during the testing day were enrolled. At manometry testing, NP was found in 62 (64%) patients, 23 (24%) had DES, 9 (9%) had NE and 3 (3%) had IEM. As to impedance-pH monitoring, 44 patients were studied on- and 53 off- PPI treatment. We found 13 (13%) patients with an abnormal AET, although 4 (4%) of them were on-therapy. Out of the remaining 84 (87%) patients, 8 (8%) had a positive SAP/ SI to acid reflux only, 31 (32%) to weakly acidic reflux only and 11 (11%) to both acid and weakly acidic reflux (4 were positive considering both refluxes as a whole). Thirty-four (35%) patients had no association between reflux and symptoms and out of them 23 (23%) had NP (i.e. functional chest-pain patients). Thus, at manometry testing 35 (36%) patients had esophageal motility abnormalities, while at impedance-pH monitoring 13 (13%) had acid GERD, 8 (8%) had SI/SAP+ to acid (i.e. hypersensitive esophagus to acid), 31 (32%) had SI/SAP+ to weakly acidic (i.e. weakly acidic GERD) and 11 (11%) had SI/SAP+ to both reflux (i.e. mixed GERD). Conclusion: Symptoms related to weakly acidic reflux and esophageal motility abnormalities are very common in NCCP patients non-responding to PPI therapy and may be responsible for the persistence of symptoms in the majority of these patients. The impact of this findings on NCCP management remains to be investigated by outcome studies.