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Circulation. 2021;144:e368–e454. DOI: 10.1161/CIR.0000000000001029 November 30, 2021 e405 CLINICAL STATEMENTS AND GUIDELINES Recommendation-Specific Supportive Text 1. If acute myocardial injury is ruled out, alternative diagnoses merit consideration in patients with persistent or recurrent symptoms. Clinical risk assessment, with implementation of CDPs when appropriate, is the key to selecting patients for further diagnostic evaluation and also to choosing among potential diagnostic modalities. 4.3.1 Evaluation of Acute Chest Pain With Suspected Gastrointestinal Syndromes Recommendation for Evaluation of Acute Chest Pain With Suspected Gastrointestinal Syndromes COR LOE Recommendation 2a C-LD 1. In patients with recurrent acute chest pain without evidence of a cardiac or pulmonary cause, evaluation for gastrointestinal causes is reasonable. Synopsis Among outpatients who present with chest pain, approximately 10% to 20% have a gastrointestinal cause.1 Gastrointestinal pain may result from stimulation of chemoreceptors by acid or hyperosmolar substances, of mechanoreceptors by abnormal contraction or distention, or of thermoreceptors.2 Some patients have abnormal perceptions of otherwise normal stimuli. Gastroesophageal reflux disease is the most likely cause for recurring unexplained chest pain of esophageal origin.3 Chest pain caused by gastroesophageal reflux disease can mimic myocardial ischemia and may be described as squeezing or burning. The duration can be minutes to hours, often occurs after meals or at night, and can worsen with stress. Depending on the severity, it may or may not resolve spontaneously or with antacids. Esophagitis not related to reflux may be caused by medications, underlying infections such as candidiasis, or radiation injury. Allergic conditions are associated with eosinophilic esophagitis, which is diagnosed by biopsy. Esophageal motility disorders such as achalasia, distal esophageal spasm, and nutcracker esophagus are less common but can present as squeezing retrosternal pain or spasm, often accompanied by dysphagia. Recommendation-Specific Supportive Text 1. The first step in evaluation of potential esophageal chest pain is a careful history. Although the clinical presentation often does not provide adequate clues to distinguish cardiac from esophageal pain, some symptoms may be suggestive of an esophageal cause, such as heartburn, regurgitation, or dysphagia, and relief with antacid or antisecretory agents. These symptoms, however, are not sufficiently specific to be fully diagnostic. A history of use of medications such as nonsteroidal anti-inflammatory agents, potassium supplements, iron, or bisphosphonates should be sought. Physical examination is often unrevealing. When an esophageal cause of chest pain is suspected, upper endoscopy should be considered.4 Symptoms and signs that merit early evaluation (usually within 2 weeks) include dysphagia, odynophagia, gastrointestinal bleeding, unexplained iron deficiency anemia, weight loss, and recurrent vomiting. Patients without these symptoms may merit a trial of empiric acid suppression therapy.5 If an upper endoscopy is normal and the symptoms persist despite a trial of acid suppression, consideration should be given to additional evaluation, such as esophageal function testing and pH monitoring, to exclude other esophageal causes.6 4.3.2. Evaluation of Acute Chest Pain With Suspected Anxiety and Other Psychosomatic Considerations Recommendation for Evaluation of Acute Chest Pain With Suspected Anxiety and Other Psychosomatic Considerations Referenced studies that support the recommendation are summarized in Online Data Supplement 25. COR LOE Recommendation 2a B-R 1. For patients with recurrent, similar presentations for acute chest pain with no evidence of a physiological cause on prior diagnostic evaluation including a negative workup for myocardial ischemia, referral to a cognitive-behavioral therapist is reasonable.1-14 Synopsis Although the heart-brain relationship is well established,15-17 its clinical relevance has been enhanced by recognition of stress cardiomyopathy.18,19 Less dramatic than the latter syndrome but highly prevalent is recurrent chest pain despite angiographically normal coronary arteries and no definable cardiac disease, including an assessment for INOCA.1-14 Chest pain in these patients has been variously labeled angina, angina-like, “atypical” angina, or noncardiac chest pain based on its deviation from characteristic ischemic cardiac discomfort. Prognosis of patients with noncardiac chest pain is largely devoid of cardiac complications.4,9,20-23 The close association of this symptom with psychological syndromes such as anxiety, panic attack, depression, somatoform disorder, and cardiophobia suggests that there may be a psychogenic origin in many patients. These factors have also raised consideration of mechanisms for noncardiac chest pain such as central nervous system-visceral inter- Downloaded from http://ahajournals.org by on October 7, 2026