What is the next best step in managing a 45-year-old woman with a three‑week history of sharp, non‑radiating chest pain occurring at night, lasting 5–10 minutes, not related to exertion, with a normal physical exam, normal sinus ECG, and a history of hypertension and chronic back pain?

Next Step: Empiric Proton Pump Inhibitor Trial

After excluding acute coronary syndrome with ECG and troponin, initiate a therapeutic trial of omeprazole 20–40 mg twice daily for 2–4 weeks to diagnose and treat gastroesophageal reflux disease (GERD), which is the most likely cause of this patient's nocturnal, non-exertional chest pain. 1

Immediate Cardiac Exclusion Required First

Before attributing symptoms to GERD, life-threatening cardiac causes must be ruled out:

• Obtain a 12-lead ECG immediately to detect ST-segment changes, T-wave inversions, or other ischemic patterns, even though the patient reports a normal ECG. 2, 1

• Measure high-sensitivity cardiac troponin to exclude silent myocardial injury, because up to 30–40% of acute myocardial infarctions present with a completely normal physical examination. 1

• Women with hypertension presenting with chest pain require heightened vigilance, as they frequently present with atypical symptoms (throat discomfort, nausea) rather than classic substernal pressure. 1

• Sharp chest pain does not exclude acute coronary syndrome; approximately 13% of patients with pleuritic-type pain still have acute myocardial ischemia. 1, 3

Why This Presentation Suggests GERD Rather Than Cardiac Ischemia

The clinical features strongly point away from ischemic heart disease and toward esophageal pathology:

• Nocturnal timing without exertional provocation is atypical for angina, which characteristically occurs with physical or emotional stress. 2

• Sharp quality and non-radiating pattern are unlikely related to myocardial ischemia; anginal pain is typically described as pressure, heaviness, or squeezing that radiates to the left arm, jaw, or neck. 2

• Spontaneous resolution within 5–10 minutes without nitroglycerin or rest is consistent with esophageal spasm or reflux rather than coronary ischemia. 2

• Three-week duration without progression or crescendo pattern makes unstable angina or acute coronary syndrome unlikely. 2, 1

• Absence of associated symptoms (diaphoresis, dyspnea, nausea, syncope) further reduces the probability of acute coronary syndrome. 2, 1

Evidence Supporting Empiric PPI Trial as the Next Step

Once cardiac causes are excluded, an empiric PPI trial is both diagnostic and therapeutic:

• GERD accounts for 10–20% of chest pain presentations in outpatient settings and is the most common esophageal cause of non-cardiac chest pain. 1, 3

• The PPI test has a pooled sensitivity of 80% and specificity of 74% for diagnosing GERD-related non-cardiac chest pain when compared with 24-hour pH monitoring and endoscopy. 4, 5

• In randomized controlled trials, 81% of patients with non-cardiac chest pain and documented GERD improved with omeprazole versus only 6% with placebo (P = 0.001). 6

• The number needed to treat is 3, meaning for every three patients treated with a PPI, one will experience symptom resolution who would not have improved with placebo. 4

• High-dose PPI (omeprazole 20–40 mg twice daily) for 14 days is the most commonly studied and effective regimen in the literature. 7, 4, 5

Recommended PPI Regimen

• Prescribe omeprazole 20 mg twice daily before meals for 2–4 weeks as the initial empiric trial. 8, 7, 4

• If symptoms improve by ≥50%, consider the test positive and continue PPI therapy for 4–8 weeks, then attempt to step down to once-daily dosing. 8, 7

• If symptoms persist despite 2–4 weeks of high-dose PPI, refer for upper endoscopy, esophageal manometry, and 24-hour pH monitoring to evaluate for esophageal motility disorders, eosinophilic esophagitis, or other pathology. 1, 9

Why Exercise Stress Testing Is Not the Immediate Next Step

Although this patient has cardiovascular risk factors (age 45, hypertension), stress testing is not indicated as the immediate next step:

• Pretest probability of obstructive coronary disease is low given the non-exertional, nocturnal, sharp quality of pain without radiation or associated symptoms. 2

• Stress testing is appropriate for intermediate-risk patients with exertional symptoms or those with atypical features who remain symptomatic after initial evaluation. 2

• If the PPI trial is negative and symptoms persist, outpatient stress testing or coronary CT angiography within 72 hours would then be reasonable given her age and hypertension. 1

Critical Pitfalls to Avoid

• Do not rely on nitroglycerin response to differentiate cardiac from esophageal chest pain, as esophageal spasm also responds to nitroglycerin. 2, 1, 3

• Do not dismiss cardiac causes in women based on atypical presentations; women frequently present with sharp, non-radiating pain rather than classic substernal pressure. 1

• Do not assume a normal physical examination excludes acute coronary syndrome; uncomplicated myocardial infarction can present with entirely normal findings. 1, 3

• Do not delay cardiac evaluation if any high-risk features emerge (diaphoresis, dyspnea, hemodynamic instability, ECG changes, elevated troponin). 2, 1

Algorithmic Management Pathway

1. Obtain ECG and high-sensitivity troponin immediately to exclude ACS. 2, 1

2. If ECG shows ischemic changes or troponin is elevated, activate emergency services and manage as acute coronary syndrome. 1

3. If ECG and troponin are normal, initiate omeprazole 20 mg twice daily before meals for 2–4 weeks. 8, 7, 4

4. Reassess symptoms at 2–4 weeks:

   • ≥50% improvement: Continue PPI for 4–8 weeks total, then attempt once-daily maintenance dosing. 8, 7
   • <50% improvement or no improvement: Refer for upper endoscopy, esophageal manometry, and 24-hour pH monitoring. 1, 9

5. If symptoms recur after PPI discontinuation, resume PPI therapy and consider long-term maintenance at the lowest effective dose. 8

6. If multimodality esophageal testing is negative, consider outpatient stress testing or coronary CT angiography to definitively exclude coronary disease. 2, 1