How is pulmonary embolism (PE) classified and what are the criteria and lab markers used for its classification?

Pulmonary Embolism Classification, Criteria, and Lab Markers

Pulmonary embolism (PE) is classified into three main categories based on early mortality risk: high-risk, intermediate-risk, and low-risk, with treatment decisions guided by this risk stratification to reduce morbidity and mortality. 1

Classification of PE Severity

High-Risk PE (Massive PE)

• Defined by the presence of shock or persistent arterial hypotension 2, 1
• Clinical presentations include:
  • Cardiac arrest
  • Obstructive shock (systolic BP <90 mmHg or vasopressors required to achieve BP ≥90 mmHg despite adequate filling status)
  • Persistent hypotension (systolic BP <90 mmHg or a systolic BP drop ≥40 mmHg for >15 min not caused by arrhythmia, hypovolemia, or sepsis) 2
• Accounts for approximately 5% of hospitalized PE patients 2
• Associated with 30-day mortality rate of approximately 30% if untreated 2, 1

Intermediate-Risk PE (Submassive PE)

• Normotensive patients with evidence of RV dysfunction and/or myocardial injury 2, 1
• Further stratified into:
  • Intermediate-high risk: Both RV dysfunction and elevated cardiac biomarkers
  • Intermediate-low risk: Either RV dysfunction or elevated cardiac biomarkers (but not both) 2
• Accounts for approximately 30-40% of hospitalized PE patients 2
• Associated with 2-3% mortality rate in patients treated with anticoagulation alone 2

Low-Risk PE

• Hemodynamically stable patients without evidence of RV dysfunction or myocardial injury 2, 1
• Accounts for 40-60% of hospitalized PE patients 2
• Associated with 30-day mortality rate of approximately 1% 2, 1

Criteria and Tools for Risk Stratification

Clinical Prediction Rules

Pulmonary Embolism Severity Index (PESI)

• Validated tool to predict 30-day mortality 1
• Includes 11 differently weighted variables 2
• Classification:
  • Class I (≤65 points): Very low risk (30-day mortality ≤1.6%)
  • Class II (66-85 points): Low risk (30-day mortality 3.6%)
  • Class III (86-105 points): Intermediate risk
  • Class IV (106-125 points): High risk
  • Class V (>125 points): Very high risk 1

Simplified PESI (sPESI)

• Simplified version with 6 variables (age >80 years, cancer, chronic cardiopulmonary disease, heart rate ≥110 bpm, systolic BP <100 mmHg, and SaO₂ <90%) 2
• Score of 0 indicates low risk with 30-day mortality of approximately 1% 1
• Score of ≥1 indicates higher risk 2

Hemodynamic Assessment

• Systolic BP <90 mmHg or a drop of >40 mmHg for at least 15 minutes 2
• Need for vasopressor support 2
• Signs of end-organ hypoperfusion 2

Laboratory and Imaging Markers

Cardiac Biomarkers

• Troponin elevation: Indicates myocardial injury 2

  • Predictor of 30-day all-cause mortality 2

• B-type natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP):

  • NT-proBNP ≥600 ng/L indicates RV strain 2
  • Provides additional prognostic information 2

• Other biomarkers with prognostic value:

  • Heart-type fatty acid-binding protein (H-FABP) ≥6 ng/mL
  • Copeptin ≥24 pmol/L 2

Imaging Markers of RV Dysfunction

• Echocardiographic findings:

  • RV/LV diameter ratio >0.9 2
  • Hypokinesis of the RV free wall
  • Increased tricuspid regurgitation velocity
  • Decreased tricuspid annular plane systolic excursion (TAPSE)
  • 60/60 sign (RV acceleration time <60 ms with tricuspid insufficiency pressure gradient <60 mmHg) 2

• CT findings:

  • RV/LV diameter ratio >0.9 on CT pulmonary angiography 2
  • Reflux of contrast into the inferior vena cava
  • Interventricular septal flattening 2

Additional Risk Factors

• Concomitant DVT: Independent predictor of 30-day all-cause mortality (OR 1.9,95% CI 1.5-2.4) 2
• D-dimer: Useful for excluding PE in low-risk patients but not for risk stratification once PE is confirmed 2

Diagnostic Algorithm for PE

For Suspected High-Risk PE (with hemodynamic instability)

1. Bedside transthoracic echocardiography (TTE) to assess for RV dysfunction
2. If RV dysfunction present, consider PE confirmed and initiate treatment
3. If CTPA is immediately available, perform for definitive diagnosis 2

For Suspected Non-High-Risk PE

1. Assess clinical probability using validated prediction rules (Wells score, Geneva score)
2. Based on clinical probability:
   • Low/intermediate probability: D-dimer testing
     • Negative D-dimer: PE excluded
     • Positive D-dimer: Proceed to CTPA
   • High probability: Proceed directly to CTPA 2

Common Pitfalls in PE Classification

• Overreliance on a single parameter: Risk stratification should incorporate clinical, laboratory, and imaging findings 2
• Misinterpreting subsegmental PE: Clinical significance remains unclear, especially in isolation 2
• Neglecting concomitant DVT: Presence of DVT is an independent predictor of mortality 2
• Discrepancies between clinical scores and biomarkers/imaging: When PESI/sPESI suggests low risk but RV dysfunction or elevated biomarkers are present, patient should be classified as intermediate-risk 2

By accurately classifying PE severity using these criteria and markers, clinicians can guide appropriate treatment decisions, including the need for hospitalization, monitoring intensity, and consideration of advanced therapies such as thrombolysis or embolectomy.