What is the appropriate workup and differential diagnosis for a young to middle‑aged adult with severe anxiety and intermittent left‑sided sharp chest pain, given a normal chest radiograph, normal comprehensive metabolic panel, normal complete blood count, normal twelve‑lead electrocardiogram, and normal D‑dimer assay?

Workup and Differential Diagnosis for Severe Anxiety with Intermittent Left-Sided Sharp Chest Pain

Immediate Next Steps

Given the completely normal initial cardiac workup (ECG, troponin via D-dimer, CXR, CBC, CMP), this patient requires referral to cognitive-behavioral therapy rather than additional cardiac testing. 1

The 2021 ACC/AHA Chest Pain Guidelines provide a Class IIa recommendation (reasonable to perform) for referring patients with recurrent similar chest pain presentations and negative cardiac workup—including normal myocardial ischemia evaluation—to a cognitive-behavioral therapist. 1

Why Further Cardiac Testing Is Not Indicated

• Sharp, intermittent chest pain that comes and goes is atypical for acute coronary syndrome, which typically presents as retrosternal pressure building gradually over minutes, not sharp stabbing pain. 1

• The combination of normal ECG, normal D-dimer, and normal initial evaluation makes life-threatening cardiac causes extremely unlikely. 1, 2

• In low-risk chest pain patients without cardiac disease, depression and anxiety each exceed coronary artery disease by almost 10-fold as the underlying cause. 1

• Repeating cardiac tests in this setting reinforces illness behavior, adds unnecessary cost and radiation exposure (≈5.0 mSv), and represents a missed opportunity for appropriate psychological intervention. 1

Differential Diagnosis to Consider

1. Anxiety/Panic Disorder (Most Likely)

• Severe anxiety is the presenting complaint, and psychological syndromes (anxiety, panic disorder, depression, somatoform disorder) are strongly associated with recurrent chest pain despite normal coronary arteries. 1

• Sharp chest pain is more consistent with anxiety-related chest pain than cardiac ischemia. 1, 2

• Cognitive-behavioral therapy has demonstrated a 32% reduction in chest pain frequency over 3 months in patients with chest pain, no cardiac disease, and psychological disorders. 1

2. Costochondritis/Musculoskeletal Pain

• Costochondritis accounts for approximately 43% of chest pain presentations in primary care when cardiac causes are excluded. 2, 3, 4

• Key diagnostic features include:

  • Pain reproducible with palpation of costochondral joints 1, 2
  • Pain worsened by chest wall movement, deep breathing, turning, or twisting 1, 2
  • Localized tenderness, often left-sided 4

• However, up to 7% of patients with reproducible chest wall tenderness still have acute coronary syndrome, so cardiac exclusion must be completed first. 2

3. Gastroesophageal Reflux Disease (GERD)

• GERD is the most common esophageal cause of non-cardiac chest pain, though it typically presents as burning retrosternal pain rather than sharp pain. 1, 5

• A trial of proton-pump inhibitor therapy is reasonable if GERD is suspected, particularly if pain is meal-related or occurs at night. 1, 2

4. Esophageal Spasm

• Can present as sharp chest pain and may respond to nitroglycerin (which is why nitroglycerin response should NOT be used to differentiate cardiac from esophageal pain). 1, 2

Critical Pitfalls to Avoid

• Do not order repeat cardiac stress testing, echocardiography, or serial troponins in patients meeting low-risk criteria with a completely normal initial workup. This has extremely low pre-test probability and high false-positive rates. 1, 2

• Do not dismiss the possibility of coexisting cardiac disease solely based on anxiety diagnosis, especially if the pain pattern changes or new risk factors emerge. 4

• Do not assume sharp or pleuritic pain excludes cardiac disease entirely—approximately 13% of patients with pleuritic-type chest pain have acute myocardial ischemia. 1, 2

• Recognize that only about 10% of clinicians document or refer for psychological factors even when patients self-report anxiety, representing a systematic gap in care. 1

Recommended Management Algorithm

1. Confirm that the initial cardiac workup is truly complete:

   • 12-lead ECG obtained and interpreted 1, 2
   • Cardiac biomarkers (troponin) measured 1
   • D-dimer normal (excludes pulmonary embolism) 1
   • Chest X-ray normal (excludes pneumothorax, pneumonia) 1, 2

2. Perform focused physical examination:

   • Palpate costochondral joints for reproducible tenderness 1, 2
   • Assess for chest wall pain with movement 2, 3
   • Check vital signs to exclude tachycardia or fever 1

3. If physical exam suggests costochondritis:

   • Treat with NSAIDs (e.g., ibuprofen 600-800 mg TID for 1-2 weeks) 2
   • Provide reassurance about benign prognosis 2

4. Address the severe anxiety:

   • Refer to cognitive-behavioral therapy (Class IIa recommendation) 1
   • Consider pharmacologic therapy for anxiety if appropriate 1
   • Provide reassurance that the cardiac workup is negative 2

5. If GERD is suspected:

   • Trial of proton-pump inhibitor therapy 1, 2
   • Consider upper endoscopy if symptoms persist 1

6. Arrange close outpatient follow-up to monitor symptom evolution and ensure psychological intervention is initiated. 1

When to Reconsider Cardiac Evaluation

• New or changing symptoms (e.g., pain becomes exertional, radiates to arm/jaw, or is associated with diaphoresis, dyspnea, or syncope) 1, 2

• Development of new cardiac risk factors 1

• Hemodynamic instability (hypotension, tachycardia) 1

• New ECG abnormalities on repeat testing 1