What are the differential diagnoses and initial emergency work‑up for a patient presenting with chest pain, dyspnea, fatigue, and generalized paresthesias?

Differential Diagnosis and Emergency Work‑Up for Chest Pain, Dyspnea, Fatigue, and Generalized Paresthesias

Obtain a 12‑lead ECG within 10 minutes of arrival and draw a high‑sensitivity cardiac troponin immediately, because this constellation of symptoms—chest pain, dyspnea, fatigue, and whole‑body paresthesias—can represent acute coronary syndrome, pulmonary embolism, aortic dissection, or hyperventilation syndrome, all of which require urgent exclusion. 1

Immediate Life‑Threatening Diagnoses to Exclude (First 10 Minutes)

Acute Coronary Syndrome (ACS)

• Typical presentation: retrosternal pressure, squeezing, or heaviness that builds over minutes, often radiating to the left arm, neck, or jaw; associated symptoms include diaphoresis, dyspnea, nausea, or syncope. 1, 2
• Atypical presentations are common: women, older adults (≥75 years), and patients with diabetes frequently present with fatigue, dyspnea, jaw pain, nausea, or epigastric discomfort rather than classic chest pressure. 1
• Paresthesias as an anginal equivalent: bilateral hand numbness or whole‑body tingling may represent an atypical manifestation of myocardial ischemia, particularly in women. 1
• A normal initial ECG does not exclude ACS: 30–40 % of acute myocardial infarctions present with a normal or nondiagnostic first ECG. 1, 2
• Physical examination may be entirely normal in uncomplicated myocardial infarction; absence of findings does not rule out ACS. 1, 2

Pulmonary Embolism (PE)

• Classic presentation: sudden dyspnea with pleuritic chest pain that worsens on inspiration; tachycardia occurs in >90 % of patients and tachypnea in ≈70 %. 1, 2, 3
• Paresthesias may occur secondary to hyperventilation triggered by acute dyspnea and hypoxemia. 3
• Right ventricular strain on ECG (S1Q3T3 pattern, right bundle‑branch block, or T‑wave inversions in anterior leads) suggests PE. 1, 4
• Bedside echocardiography can reveal right ventricular free‑wall akinesia with apical sparing (McConnell's sign), which is highly specific for PE and helps differentiate it from ACS. 4, 5

Acute Aortic Dissection

• Hallmark presentation: sudden "ripping" or "tearing" chest or back pain that is maximal at onset and radiates to the upper or lower back. 1, 2
• Pulse differential between extremities occurs in ≈30 % of cases; a systolic blood‑pressure difference >20 mm Hg between arms is a key diagnostic clue. 1, 2
• New aortic‑regurgitation murmur is present in 40–75 % of type A dissections. 1, 2
• If dissection is suspected, withhold aspirin, heparin, and all antithrombotic agents and arrange immediate transfer to a center with 24/7 aortic imaging (CT angiography, MRI, or transesophageal echocardiography) and cardiac‑surgery capability. 1

Hyperventilation Syndrome / Panic Attack

• Presentation: chest tightness, dyspnea, perioral and acral paresthesias (hands, feet, face), light‑headedness, and carpopedal spasm triggered by respiratory alkalosis from hyperventilation. 2
• Whole‑body paresthesias are characteristic of hypocapnia‑induced ionized hypocalcemia. 2
• This is a diagnosis of exclusion: cardiac and pulmonary causes must be ruled out first with ECG, troponin, and imaging before attributing symptoms to anxiety. 1, 2

Tension Pneumothorax

• Presentation: dyspnea and sharp chest pain that intensifies with inspiration; unilateral absent or markedly reduced breath sounds, hyperresonant percussion, tracheal deviation, and hemodynamic instability. 1, 2, 6

Cardiac Tamponade

• Presentation: pleuritic chest pain that worsens when lying supine, jugular venous distension, hypotension, muffled heart sounds (Beck's triad), and pulsus paradoxus >10 mm Hg. 1, 2

Mandatory Initial Diagnostic Testing

• 12‑lead ECG within 10 minutes: identify ST‑elevation myocardial infarction (≥1 mm in contiguous leads), ST‑depression, T‑wave inversions, new left bundle‑branch block, or right ventricular strain patterns (S1Q3T3, right bundle‑branch block, anterior T‑wave inversions). 1, 2, 6
• High‑sensitivity cardiac troponin immediately: it is the most sensitive and specific biomarker for myocardial injury; repeat at 1–3 hours (or 3–6 hours with conventional assay) because a single normal result does not exclude ACS. 1, 2
• Vital signs in both arms: measure heart rate, respiratory rate, oxygen saturation, and bilateral arm blood pressures to detect pulse/pressure differentials suggestive of aortic dissection or tachycardia/tachypnea indicative of PE. 1, 2, 3
• Focused cardiovascular examination: assess for diaphoresis, tachypnea, pulmonary crackles, S3 gallop, new murmurs (mitral or aortic regurgitation), pericardial friction rub, unilateral absent breath sounds, pulse differentials, jugular venous distension, and subcutaneous emphysema. 1, 2, 6
• Arterial blood gas (ABG): obtain in patients with respiratory distress, suspected PE, or hemodynamic instability to assess oxygenation, acid‑base balance, and detect respiratory alkalosis (hyperventilation syndrome). 1, 3
• Chest radiography: evaluate for pneumothorax, pneumonia, pleural effusion, widened mediastinum (aortic dissection), or pulmonary edema. 1, 6

Risk Stratification and Serial Testing

• If ECG shows STEMI or new ischemic changes: activate STEMI protocol immediately; target door‑to‑balloon time <90 minutes for primary PCI or door‑to‑needle time <30 minutes for fibrinolysis. 1, 2
• If ST‑depression, T‑wave inversions, or elevated troponin without ST‑elevation: admit to a coronary‑care unit, start dual antiplatelet therapy (aspirin + P2Y12 inhibitor) and anticoagulation, and arrange urgent coronary angiography. 1, 2
• If initial ECG and troponin are normal: repeat troponin at 1–3 hours (high‑sensitivity) or 3–6 hours (conventional); obtain serial ECGs every 15–30 minutes if symptoms persist or recur. 1, 2
• Add posterior leads (V7–V9) when suspicion for ACS is intermediate‑to‑high and the standard ECG is nondiagnostic. 1, 2

Pulmonary Embolism Work‑Up

• Calculate a Wells score or revised Geneva score to estimate pre‑test probability of PE. 1, 3
• For low‑to‑intermediate probability: obtain an age‑ and sex‑adjusted D‑dimer; a negative result effectively rules out PE. 1, 2
• For high probability or positive D‑dimer: proceed directly to CT pulmonary angiography. 1, 2, 3
• Bedside echocardiography can identify right ventricular enlargement, hypokinesis, or McConnell's sign (right ventricular free‑wall akinesia with apical sparing), which is highly specific for PE and helps differentiate it from ACS. 4, 5

Hyperventilation Syndrome Assessment

• Clinical clues: perioral and acral paresthesias, carpopedal spasm, chest tightness, dyspnea, and light‑headedness in the setting of anxiety or emotional stress. 2
• ABG findings: respiratory alkalosis (elevated pH, low PaCO₂) with normal PaO₂ confirms hyperventilation. 3
• This is a diagnosis of exclusion: complete cardiac and pulmonary work‑up (ECG, troponin, chest X‑ray, and possibly CT pulmonary angiography) must be normal before attributing symptoms to hyperventilation. 1, 2

Special Population Considerations

• Women: higher risk of underdiagnosis; more likely to present with jaw/neck pain, nausea, fatigue, dyspnea, epigastric discomfort, or whole‑body paresthesias rather than classic chest pressure. Use sex‑specific troponin thresholds (>16 ng/L for women vs >34 ng/L for men) to avoid missing STEMI. 1, 2
• Older adults (≥75 years): may present atypically with isolated dyspnea, syncope, acute delirium, unexplained falls, or fatigue without classic chest pain. 1, 2
• Patients with diabetes: often have atypical symptoms including vague abdominal discomfort, confusion, or isolated dyspnea; higher risk for silent ischemia. 1

Critical Pitfalls to Avoid

• Do not dismiss ACS based on atypical symptoms: whole‑body paresthesias, fatigue, and dyspnea can represent anginal equivalents, particularly in women and older adults. 1, 2
• Do not rely on nitroglycerin response to differentiate cardiac from non‑cardiac chest pain; esophageal spasm and other conditions may also improve. 1, 2
• Do not assume a normal physical examination excludes ACS: uncomplicated myocardial infarction can present with entirely normal findings. 1, 2
• Do not delay EMS transport for troponin testing when ACS or other life‑threatening causes are suspected; immediate transfer is essential. 1, 2
• Do not attribute symptoms to anxiety without objective testing: hyperventilation syndrome is a diagnosis of exclusion after cardiac and pulmonary causes are ruled out. 1, 2
• A normal initial ECG does not rule out ACS: 30–40 % of acute myocardial infarctions present with a normal or nondiagnostic ECG. 1, 2

Pre‑Hospital and EMS Management

• Activate EMS immediately for any suspected life‑threatening chest pain; personal‑vehicle transport carries a 1.5 % risk of cardiac arrest en route. 1, 2
• Administer chewed aspirin 162–325 mg to alert adults without allergy or active gastrointestinal bleeding while awaiting EMS. 1, 2
• Give sublingual nitroglycerin unless systolic blood pressure <90 mm Hg or heart rate <50 bpm or >100 bpm. 1
• Provide intravenous morphine 4–8 mg (repeat 2 mg every 5 minutes as needed) for pain relief; uncontrolled pain increases sympathetic drive and myocardial workload. 1
• Supply supplemental oxygen 2–4 L/min only if the patient is breathless, shows heart‑failure features, or has low oxygen saturation; routine oxygen in normoxemic patients may be harmful. 1

Algorithmic Summary

1. First 10 minutes: 12‑lead ECG, high‑sensitivity troponin, vital signs (bilateral arm blood pressures), focused cardiopulmonary exam, arterial blood gas if respiratory distress. 1, 2, 6, 3
2. If ECG shows STEMI or new ischemic changes OR troponin ≥99th percentile: activate emergency services, start dual antiplatelet therapy and anticoagulation, arrange urgent coronary angiography. 1, 2
3. If ECG normal and troponin normal: repeat troponin at 1–3 hours; obtain serial ECGs if symptoms persist; calculate Wells score for PE; obtain D‑dimer (low‑to‑intermediate probability) or CT pulmonary angiography (high probability). 1, 2, 3
4. If cardiac and pulmonary work‑up is normal and ABG shows respiratory alkalosis: consider hyperventilation syndrome as a diagnosis of exclusion; provide reassurance and consider referral for anxiety management. 1, 2, 3
5. Bedside echocardiography should be performed to detect regional wall motion abnormalities (ACS), right ventricular strain (PE), pericardial effusion (tamponade), or aortic dissection. 4, 5