What are the typical presentation, differential diagnosis (DDX), diagnostic investigations (INVX), management (MX), and complications of pulmonary embolism (PE)?

Pulmonary Embolism: Clinical Presentation, Diagnosis, Management, and Complications

Clinical Presentation (Signs and Symptoms)

Pulmonary embolism (PE) presents with a characteristic constellation of symptoms including dyspnea, chest pain, and syncope, which are present in 97% of patients with PE. 1

Common Symptoms:

• Dyspnea (80% of cases) - most frequent symptom 1
  • May be acute and severe in central PE
  • Can be mild and transient in peripheral PE
  • May be progressive over weeks in some cases
• Chest pain (52% of cases) 1
  • Pleuritic pain (caused by distal emboli with pleural irritation)
  • Substernal angina-like pain (may reflect RV ischemia in central PE)
• Syncope (19% of cases) - indicates severe hemodynamic compromise 1
• Hemoptysis (11% of cases) - associated with pulmonary infarction 1, 2

Common Signs:

• Tachypnea (>20 breaths/min) - present in 70% of cases 1
• Tachycardia (>100 beats/min) - present in 26% of cases 1
• Signs of DVT (15% of cases) - unilateral leg swelling 1
• Fever (7% of cases) 1
• Cyanosis (11% of cases) 1
• Hypoxemia - present in 75% of cases, though up to 40% may have normal arterial oxygen saturation 1, 2

Presentation Based on PE Severity:

• High-risk PE (massive): Presents with shock or persistent arterial hypotension 1
• Intermediate-risk PE (submassive): Hemodynamically stable but with RV dysfunction 1
• Low-risk PE: Hemodynamically stable without RV dysfunction 1

Important Clinical Caveat:

Approximately 10% of PE cases are "silent" and discovered incidentally during diagnostic workup for another disease 2. In patients with pre-existing heart failure or pulmonary disease, worsening dyspnea may be the only symptom indicative of PE 1.

Differential Diagnosis (DDX)

The differential diagnosis for PE is broad due to its non-specific symptoms:

1. Acute Coronary Syndrome

   • Differentiated by ECG changes, cardiac biomarkers, and coronary angiography
   • Central PE can cause angina-like chest pain requiring differentiation 1

2. Pneumonia

   • Typically presents with fever, productive cough, and focal consolidation on imaging
   • May coexist with PE

3. Acute Heart Failure

   • Presents with dyspnea, peripheral edema, and pulmonary congestion
   • Echocardiography helps differentiate

4. Pneumothorax

   • Sudden-onset dyspnea and pleuritic chest pain
   • Characteristic findings on chest X-ray

5. Aortic Dissection

   • Severe, tearing chest pain radiating to the back
   • Requires CT angiography for diagnosis

6. Pericarditis

   • Positional chest pain, pericardial friction rub
   • ECG shows diffuse ST elevation

7. Musculoskeletal Chest Pain

   • Pain reproduced by palpation
   • No respiratory or hemodynamic compromise

8. COPD/Asthma Exacerbation

   • History of obstructive lung disease
   • Wheezing, response to bronchodilators

Diagnostic Investigations (INVX)

Step 1: Clinical Probability Assessment

• Use validated clinical prediction rules:
  • Wells score or revised Geneva score 1
  • Categorizes patients into low, intermediate, or high probability of PE

Step 2: D-dimer Testing

• Indicated in patients with low or intermediate clinical probability 1
• High negative predictive value - normal D-dimer safely excludes PE in low/intermediate probability patients
• Not useful in high probability patients (proceed directly to imaging) 1, 3

Step 3: Imaging Studies

1. CT Pulmonary Angiography (CTPA)

   • First-line imaging test for suspected PE 1
   • High sensitivity (83-100%) and specificity (89-97%)

2. Ventilation-Perfusion (V/Q) Scan

   • Alternative when CTPA is contraindicated (renal failure, contrast allergy)
   • Interpreted as high, intermediate, or low probability

3. Echocardiography

   • Not diagnostic for PE but useful for risk stratification
   • Can detect RV dysfunction, suggesting more severe PE
   • May be first-line in unstable patients when CTPA is not immediately available

4. Lower Extremity Ultrasound

   • Can detect DVT as source of PE
   • Positive finding in proximal veins may obviate need for further testing

Step 4: Additional Tests

• ECG - May show signs of RV strain: 1, 2

  • S1Q3T3 pattern
  • Right bundle branch block
  • T-wave inversions in leads V1-V4
  • Normal in up to 30% of cases

• Chest X-ray

  • Often abnormal but findings are non-specific 1
  • Useful for excluding other causes of symptoms
  • May show:
    • Pleural effusion (46%)
    • Atelectasis or infiltrate (49%)
    • Elevated diaphragm (36%)
    • Decreased pulmonary vascularity (36%)

• Arterial Blood Gas

  • May show hypoxemia and respiratory alkalosis
  • Normal values don't exclude PE (up to 20% have normal PaO2) 1

Management (MX)

Initial Stratification

• High-risk PE (with shock/hypotension): Requires immediate aggressive intervention
• Non-high-risk PE (without shock/hypotension): Further risk stratification needed 1

Anticoagulation

• Cornerstone of PE treatment for all objectively confirmed cases 3
• Options include:

  1. Direct Oral Anticoagulants (DOACs):

     • Preferred first-line therapy (apixaban, rivaroxaban, edoxaban, dabigatran) 3
     • Associated with 0.6% lower bleeding rate compared to traditional therapy 3
     • Rivaroxaban demonstrated non-inferiority to standard therapy in EINSTEIN PE study 4

  2. Low Molecular Weight Heparin (LMWH):

     • Initial parenteral anticoagulation (typically for 5-10 days)
     • Can be used as bridge to oral anticoagulation

  3. Unfractionated Heparin (UFH):

     • Preferred in severe renal impairment or if rapid reversal may be needed
     • Requires aPTT monitoring

  4. Vitamin K Antagonists (e.g., warfarin):

     • Target INR 2.0-3.0
     • Requires bridging with parenteral anticoagulation

Duration of Anticoagulation:

• Minimum 3 months for all PE cases 4, 5
• Extended/indefinite therapy considered for:
  • Unprovoked PE
  • Recurrent VTE
  • Active cancer
  • Persistent risk factors

Thrombolytic Therapy

• Indicated for high-risk PE with hemodynamic instability (systolic BP <90 mmHg) 3
• Associated with 1.6% absolute reduction in mortality 3
• Contraindicated in patients with high bleeding risk

Inferior Vena Cava (IVC) Filter

• Consider only when anticoagulation is contraindicated or has failed
• Temporary filters preferred when possible

Complications

Acute Complications:

1. Death - PE has a mortality rate of approximately 8-15% in the first 3 months 1
2. Cardiogenic shock - Due to RV failure in massive PE
3. Hypoxemic respiratory failure
4. Cardiac arrest

Long-term Complications:

1. Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

   • Occurs in 2-4% of PE survivors 1, 2
   • Presents with progressive dyspnea and exercise limitation
   • Usually fatal within 2-3 years if untreated 1

2. Post-PE Syndrome

   • Persistent dyspnea and exercise limitation
   • Affects up to 47% of patients at 1-year follow-up 2

3. Recurrent VTE

   • Risk is highest after discontinuation of anticoagulation
   • Approximately 30% risk of recurrence at 10 years for unprovoked PE 1

4. Pulmonary infarction

   • Relatively rare complication 1
   • May lead to pleural effusion and scarring

Prevention of Complications:

• Appropriate duration of anticoagulation
• Regular follow-up at 3-6 months after acute PE 2
• Consider thrombophilia testing in selected cases (young patients, family history, recurrent events)
• Evaluate for CTEPH in patients with persistent dyspnea

Key Pitfalls to Avoid

1. Dismissing PE in patients with normal oxygen saturation - Up to 40% of PE patients have normal SaO2 2
2. Relying solely on clinical features - No single symptom or sign can reliably confirm or exclude PE
3. Overlooking PE in patients with pre-existing cardiopulmonary disease - May present only as worsening of baseline symptoms
4. Failing to consider PE in syncope - PE accounts for up to 17% of syncope cases 1
5. Inappropriate use of D-dimer in high probability patients - Proceed directly to imaging
6. Delaying treatment while awaiting confirmation - Start anticoagulation if clinical suspicion is high and no contraindications exist