Every clinician who has worked in an emergency department, urgent care, or inpatient unit has felt it: a patient walks in with chest pain, and your brain immediately starts running through a list of diagnoses that can kill. That instinct is correct. Chest pain demands a systematic approach because the consequences of missing ACS, aortic dissection, or PE are catastrophic.
Here's the framework — built around the six diagnoses you can never afford to miss.
⚠️ The Six Must-Not-Miss Diagnoses
Before any chest pain workup, these six diagnoses must be on your differential and actively evaluated: ACS/STEMI, Aortic Dissection, Pulmonary Embolism, Tension Pneumothorax, Cardiac Tamponade, Esophageal Rupture. Missing any of these can be fatal.
Step 1: Immediate Risk Stratification
Before taking a detailed history, a 10-second assessment answers: is this patient dying right now? Look at vital signs, general appearance, and level of distress. Hypotension + chest pain = immediate action. Diaphoresis + chest pain = high suspicion for serious etiology. Oxygen saturation drop = consider PE or tension pneumothorax.
If the patient is hemodynamically unstable, your approach changes entirely — you're managing simultaneously while diagnosing. The detailed history comes after you've stabilized.
Step 2: The Discriminating History
For chest pain, these are the history features with the highest likelihood ratios for serious diagnoses:
| Feature | Points Toward | Risk |
|---|---|---|
| Sudden onset, tearing/ripping quality, radiating to back | Aortic dissection | HIGH |
| Pressure/squeezing, radiation to jaw or left arm, diaphoresis | ACS | HIGH |
| Pleuritic (worse with inspiration), recent immobility or travel | Pulmonary embolism | HIGH |
| Sudden severe dyspnea, unilateral breath sounds absent | Tension pneumothorax | HIGH |
| Positional (worse supine, better leaning forward) | Pericarditis | Moderate |
| Reproducible with palpation | Musculoskeletal | Low |
| Associated with meals, relieved by antacids | GERD / esophageal | Low |
Clinical Pearl
The classic "tearing pain radiating to the back" of aortic dissection is present in only 50-70% of cases. Don't rule it out without checking bilateral blood pressures and a widened mediastinum on CXR.
Step 3: Targeted Physical Exam
The physical exam in chest pain should be directed by your differential, not a head-to-toe checklist. Key findings to specifically look for:
- Blood pressure both arms — difference >20 mmHg suggests aortic dissection
- JVD + muffled heart sounds + hypotension — Beck's triad for cardiac tamponade
- Absent breath sounds + tracheal deviation — tension pneumothorax (treat before imaging)
- Friction rub — pericarditis
- New murmur — valvular pathology, papillary muscle rupture in ACS
- Unilateral leg swelling — DVT supporting PE
Step 4: ECG First, Everything Else Second
The ECG should be obtained within 10 minutes of presentation for any chest pain. It is the fastest test that most changes your management. ST elevation = activate the cath lab. Right heart strain pattern (S1Q3T3, new RBBB) increases probability of PE. Diffuse ST elevation with PR depression = pericarditis. Normal ECG does not rule out ACS — up to 6% of MIs have normal initial ECG.
Step 5: Risk Stratify with a Score
For undifferentiated chest pain after initial evaluation, validated scores guide disposition:
HEART Score
History + ECG + Age + Risk Factors + Troponin
Score 0-3: Low risk — consider discharge with outpatient follow-up. Score 4-6: Moderate — observation, serial troponins. Score 7-10: High — early invasive strategy.
Wells Score for PE
Clinical probability of pulmonary embolism
Score ≤4 (low probability) + negative D-dimer effectively rules out PE. Score >4 or high clinical suspicion → CT pulmonary angiography.
Step 6: The One-Liner Synthesis
Before ordering anything, synthesize what you know into one sentence: "This is a 58-year-old male smoker with hypertension presenting with acute pressure-like chest pain radiating to the left arm with diaphoresis and ST elevations in V1-V4." That one sentence drives everything that follows — it defines your leading diagnosis, your must-not-miss diagnoses, and your immediate management priorities.
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Start Practicing Free →Frequently Asked Questions
What are the must-not-miss causes of chest pain?
The six must-not-miss causes are: STEMI/ACS, aortic dissection, pulmonary embolism, tension pneumothorax, cardiac tamponade, and esophageal rupture. These are life-threatening and require immediate identification.
What history questions are most important in chest pain?
The most discriminating features are onset (sudden vs gradual), quality (pressure suggests cardiac; tearing suggests dissection; pleuritic suggests PE), radiation (to jaw/arm for ACS; to back for dissection), and associated symptoms (diaphoresis, dyspnea, syncope).
How do you use the HEART score for chest pain?
The HEART score stratifies chest pain into low (0-3), moderate (4-6), and high (7-10) risk for major adverse cardiac events. Low-risk patients can often be safely discharged; high-risk patients warrant urgent cardiology evaluation.