This is a prospective randomised clinical trial performed in a single center at Hospital Universiti Sains Malaysia (USM), Kelantan, Malaysia. Participants will be randomly allocated into either the empirical group or guided group for 8 weeks.The effectiveness in relieving chest pain (frequency and severity) will assessed after 2 weeks and 8 weeks of therapy with Gastroesophageal Reflux Disease Questionnaire (GERDQ) and Quality of Life Reflux and Dyspepsia (QOLRAD) questionnaire, and visual analogue scale (VAS) (score 1-10).

Non-cardiac chest pain (NCCP) is very common in the general population but symptom alone or patient's characteristics do not adequately differentiate cardiac and esophageal cause. Cardiologists are usually consulted first to exclude life-threatening acute coronary syndrome. Tests that are performed to exclude ischemic heart disease include exercise stress test and the more invasive coronary angiography. A negative stress test or angiogram or the presence of mild blockage of a single vessel disease will usually be adequate to exclude significant ischemia as a cause for chest pain.

The next most important cause of unexplained chest pain would be gastro-esophageal reflux disease (GERD). GERD and its complications of Barrett's oesophagus and oesophageal adenocarcinoma have increased markedly in recent decades, not just in the developed countries but also in Asia. Although relatively less common among populations in Malaysia, there are data to suggest an increasing prevalence of reflux disease largely a result of obesity and increased intra-abdominal pressure.

Dexlansoprazole (Takeda Pharmaceuticals, Japan) is a novel dual delayed release system recently approved by the FDA for treatment of heartburn associated with non-erosive and erosive reflux disease. It is unknown if dexlansoprazole is effective as an empirical therapy for NCCP.

Another approach would be therapy guided by investigations including high resolution (HR) esophageal impedance manometry and 24-hour pH-impedance studies. Study of esophageal function has greatly evolved with the recent availability of high resolution multi-channel solid state manometer and impedance. Water swallows are commonly used in esophageal manometric studies to evaluate for peristaltic abnormalities. Esophageal pH monitoring does not detect all gastroesophageal reflux (GER) events but with the combination of impedance, this technique allows detection of GER of gas and acid or non-acid liquids. These tests would enable diagnosis of GERD and functional chest pain and thereby allow targeted therapy.

For treatment of GERD, dexlansoprazole is effective and for functional chest pain, nonspecific adenosine antagonist, theophylline is proven to improve symptoms in patient with hypersensitive esophagus. A selective serotonin reuptake inhibitor (SSRI) is also effective for functional chest pain , however it is not known if theophylline is more effective than any other SSRIs.It is unknown about the response rates based on the guided therapy approach compared to the empirical PPI therapy.

Therefore, the aim of the intervention is to evaluate the effectiveness of empirical therapy vs. guided therapy on symptoms unexplained non-cardiac chest pain.

Inclusion Criteria: Participants with chest pain but normal angiogram or a negative stress test or normal electrocardiogram and cardiac enzyme.

Exclusion Criteria:

1. Participants with any medications that might affect the upper GI tract, previous surgeries of the upper GI tract and a negative endoscopic examination for peptic ulcer disease and upper GI tract malignancies
2. Participants with chronic, debilitating or life-threatening medical conditions and presence of overt psychiatric or psychological disturbances.

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