Noncardiac Chest Pain: Empiric PPI Trial or Further Esophageal Workup
A negative cardiac workup for recurring chest pain shifts the question toward the esophagus — and here the actual disagreement is whether an empiric PPI trial is a reasonable next step or whether it risks anchoring on reflux before ruling out the motility disorders that produce a genuinely similar presentation.
Linda O., 49, took over her late father's accounting practice five years ago and still keeps his framed diploma on the wall behind her desk, a detail she mentioned unprompted while describing how the chest pain first started — three months ago, during the stretch of long nights that always comes with tax season. The pain is substernal, occasionally radiates to her back, lasts anywhere from ten minutes to over an hour, and has no consistent relationship to exertion, meals, or position that she's been able to identify herself. A full cardiac workup, including ECG, troponin, and an exercise stress test, was entirely negative, and her cardiologist has confidently ruled out a cardiac cause.
Once cardiac causes are excluded, the two leading esophageal explanations for a presentation like hers — GERD and an esophageal motility disorder such as diffuse esophageal spasm — can look genuinely similar from the history alone, which is exactly why the empiric-PPI-trial approach has real appeal: it's noninvasive, and GERD-related noncardiac chest pain does frequently respond to acid suppression, with trial data supporting empiric PPI therapy as a reasonable first diagnostic-and-therapeutic step in this population specifically, unlike the more consistently negative data seen in laryngopharyngeal reflux and chronic cough. But her pain's inconsistent relationship to meals and position, together with its sometimes-prolonged duration, is at least as consistent with a motility disorder that a PPI trial wouldn't touch — and if it isn't reflux, an empiric trial only delays the manometry that would actually find the real cause. Noncardiac chest pain is the one setting where the empiric trial has real evidentiary footing. The ACG reflux guideline (Katz and colleagues) endorses it here, on placebo-controlled trials of a short, high-dose course — the so-called "PPI test" — showing meaningfully better sensitivity and specificity for identifying reflux-driven chest pain than symptom history alone, a genuinely stronger evidentiary footing than the parallel empiric-trial literature in LPR or chronic cough discussed elsewhere in this same topic. Linda was also asked directly whether stress specifically, rather than meals or position, seemed to track with her episodes — tax season's long nights were the common thread she named herself, a detail that doesn't distinguish between the two esophageal causes under discussion but that the team recorded anyway, since it may matter once a diagnosis is actually reached.
Two esophageal causes that look similar from the history alone
With cardiac causes fully excluded, I'd start an empiric PPI trial. This is one of the better-supported empiric-trial indications in reflux medicine — the evidence specifically for noncardiac chest pain is real and reasonably consistent, unlike the more disappointing data in laryngopharyngeal reflux or chronic cough. It's noninvasive, and a genuine fraction of patients with her presentation do respond.
I'd want us to be honest that her specific pain pattern doesn't fit the typical reflux profile as cleanly as it fits a motility disorder. No consistent relationship to meals or position, and episodes sometimes lasting over an hour — that's at least as suggestive of something like diffuse esophageal spasm as it is of GERD.
I'm not saying the empiric trial is wrong, I'm saying if it fails, we shouldn't have lost real time getting to the manometry that would actually find the cause.
I don't think this needs to be sequential. She's already been through one negative workup and a fair amount of uncertainty; I'd rather get both processes moving now than have her wait out a full empiric trial before manometry even gets scheduled. Start the PPI trial given the real supporting evidence in this specific indication, and refer for manometry today in parallel — if the trial works, we simply cancel the study rather than lose the weeks it would take to schedule it after the fact.
Agreed: an 8-week empiric PPI trial started today, with esophageal manometry referred and scheduled in parallel rather than held for after a failed trial — if the PPI trial resolves her symptoms, the manometry appointment is simply cancelled rather than needing to be scheduled from scratch afterward.