What are the differential diagnoses for chest pain after acute coronary syndrome has been excluded?

Differential Diagnosis for Chest Pain After Excluding Acute Coronary Syndrome

After ruling out ACS, the most common cause of chest pain is musculoskeletal (particularly costochondritis), accounting for approximately 43% of cases in primary care settings, followed by gastrointestinal causes (especially GERD), pulmonary conditions, and psychiatric disorders. 1

Life-Threatening Causes That Must Still Be Excluded

Even after ACS is ruled out, several potentially fatal conditions require immediate consideration:

• Aortic dissection presents with sudden-onset "ripping" or "tearing" chest or back pain, pulse differentials between extremities (present in 30% of cases), blood pressure differentials, or new aortic regurgitation murmur. 1, 2

• Pulmonary embolism manifests with acute dyspnea and pleuritic chest pain, with tachycardia present in over 90% of patients and associated risk factors for thromboembolism. 3, 1, 2

• Tension pneumothorax causes severe dyspnea with unilateral absence of breath sounds and hemodynamic compromise. 1

• Esophageal rupture is rare but catastrophic, presenting with severe chest pain after vomiting or instrumentation. 1

Common Musculoskeletal Causes (Most Prevalent)

Musculoskeletal chest pain represents the leading non-cardiac etiology, present in 43% of general practice presentations. 1

• Costochondritis/Tietze syndrome is characterized by tenderness of costochondral joints on palpation, with pain reproducible by chest wall pressure and affected by palpation, breathing, turning, twisting, or bending. 3, 1, 2

• Chest wall pain is localized to a very limited area and worsens with specific movements or positions. 1

• Cervical radiculopathy causes pain radiating from the cervical spine into the chest. 2

Gastrointestinal Causes

Gastrointestinal disorders account for 10-20% of chest pain presentations among outpatients. 3

• Gastroesophageal reflux disease (GERD) is the most common esophageal cause, presenting with burning retrosternal pain that occurs after meals or at night, worsens with stress, and may be relieved by antacids. 3, 1, 2

• Esophageal motility disorders (achalasia, distal esophageal spasm, nutcracker esophagus) cause squeezing retrosternal pain or spasm, often accompanied by dysphagia. 3

• Peptic ulcer disease may present with epigastric pain radiating to the chest. 3, 2

• Esophagitis from medications (NSAIDs, potassium supplements, iron, bisphosphonates), infections (candidiasis), or eosinophilic causes can mimic cardiac pain. 3, 2

Pulmonary Causes

• Pneumonia presents with localized pleuritic chest pain, fever, productive cough, and may show egophony on examination; chest radiography is diagnostic. 3, 2

• Pleuritis causes sharp pain that worsens with deep breathing. 3, 2

• Pneumothorax manifests as pleuritic chest pain with unilateral decreased or absent breath sounds. 3, 2

Cardiac Causes Other Than ACS

• Pericarditis is characterized by sharp, pleuritic chest pain that worsens when supine and improves when leaning forward, with a friction rub on examination and often accompanied by fever. 3, 1, 2

• Myocarditis presents with chest pain, fever, signs of heart failure, and S3 gallop. 1

• Valvular disease (particularly aortic stenosis, aortic regurgitation, and hypertrophic cardiomyopathy) can cause chest pain even without acute coronary occlusion. 1, 2

Psychiatric Causes

Psychiatric disorders account for 11% of chest pain in general practice and 8% in emergency departments. 1

• Panic disorder and anxiety are often associated with other somatic symptoms including dyspnea, palpitations, and diaphoresis. 3, 2

• Somatoform disorders present as physical symptoms without identifiable organic cause and are diagnoses of exclusion. 2

Other Causes

• Herpes zoster causes painful rash in a dermatomal distribution, which may precede the visible rash. 3, 2

• Sickle cell crisis with acute chest syndrome requires emergency evaluation. 3, 2

Algorithmic Approach to Evaluation

When ACS has been excluded through negative cardiac biomarkers and appropriate testing, proceed systematically: 3

1. Obtain detailed pain characteristics: Sharp and pleuritic suggests pericarditis or pulmonary causes; burning and meal-related suggests GERD; reproducible with palpation suggests musculoskeletal origin. 3, 1

2. Perform targeted physical examination: Check for chest wall tenderness (costochondritis), friction rub (pericarditis), unilateral breath sounds (pneumothorax), pulse/BP differentials (aortic dissection). 1, 2

3. Consider chest radiography if pulmonary causes are suspected or if the diagnosis remains unclear. 3, 4

4. For suspected GERD: Trial of empiric proton pump inhibitor therapy is reasonable, though this was prescribed in only 20% of appropriate cases in one study. 3, 5

5. For suspected musculoskeletal pain: NSAIDs (ibuprofen 600-800 mg three times daily) provide symptom relief. 1

6. For recurrent unexplained chest pain: Evaluation for gastrointestinal causes with upper endoscopy, esophageal function testing, or pH monitoring is reasonable. 3, 2

Critical Pitfalls to Avoid

• Do not use nitroglycerin response as a diagnostic criterion, as esophageal spasm and other noncardiac conditions also respond to nitroglycerin. 3, 1

• Do not assume all non-cardiac chest pain is benign—pulmonary embolism and aortic dissection are life-threatening and must be excluded. 2

• Do not dismiss chest pain in women, elderly patients, or those with diabetes, as they frequently present with atypical symptoms. 3, 1

• Do not overlook psychological factors, which are common but frequently missed in clinical practice. 2, 5

• Do not ignore medication-related causes of esophageal irritation. 2

• Recognize that up to 15% of patients may have coexisting musculoskeletal tenderness even with myocardial infarction, so reproducible chest wall pain does not definitively exclude cardiac causes in all contexts. 1