Essence of this Article

Pulmonary embolism (PE) occurs when a part of a thrombus, usually dislodged from a deep vein thrombosis (DVT), passes into the pulmonary circulation, occluding the pulmonary arteries. PE is a potentially life-threatening condition and is the most common reason for preventable hospital death. Rapid diagnosis is crucial, but a diagnosis of PE can often be missed because of its non-specific clinical symptoms. Long-term complications of PE include chronic thromboembolic pulmonary hypertension (CTEPH). The Wells’ score is one scoring system that is commonly used to predict the clinical probability of PE. Computed tomography (CT) pulmonary angiography has become the method of choice for diagnostic imaging in patients with suspected PE, although other diagnostic methods are now available. The 2014 update of the European Society of Cardiology (ESC) guidelines for the management of PE brings about new recommendations for prognosis and treatment.

Pulmonary embolism

Pulmonary Embolism - Signs and Symptoms

Pulmonary embolism. The pathway of a pulmonary embolus from the lower part of the body: inferior vena cava, to right atrium, to right ventricle, to the pulmonary artery. This might eventually obstruct blood flow to the lung. Patients with deep vein thrombosis are at risk of PE, a life-threatening event. PE, pulmonary embolism.

PE is a potential cardiovascular emergency that occurs when a part of a thrombus, usually dislodged from a DVT (and then called an embolus), passes into the pulmonary circulation, occluding the pulmonary arteries. Nearly four-fifths of patients with PE have evidence of DVT,144 and approximately half of those with proven proximal DVT have an associated PE and, like DVT, PE is often asymptomatic.145 However, approximately 20–30% of cases are unprovoked (idiopathic).146

Epidemiological data indicate that, of the more than 1.1 million cases of VTE that occur in the European Union (EU) each year, approximately one-third are PE cases.124 PE is the most common reason for preventable hospital death.119 Long-term complications of PE include CTEPH, which can have serious consequences.147, 148

Pulmonary Embolus with Haemorrhage

Pulmonary embolus with haemorrhage. Section of pulmonary parenchyma with middle right (round) blood vessel containing embolus. The surrounding lung parenchyma has undergone haemorrhagic infarction.

Diagnosis of PE

Signs and symptoms
PE is a potentially life-threatening condition and in severe cases the occurrence of circulatory collapse and cardiac arrest may result in sudden death. Early fatality occurs in up to 15% of patients,146 and thus rapid diagnosis is crucial. However, the diagnosis of PE may be missed because of its non-specific clinical symptoms.146

Common signs and symptoms of PE are:149

  • Dyspnoea
  • Pleuritic chest pain
  • Cough
  • Substernal chest pain
  • Fever
  • Haemoptysis
  • Syncope
  • Unilateral leg pain
  • Signs of DVT (unilateral extremity swelling)

These symptoms are not specifically diagnostic of PE. For this reason, the diagnostic process, and decisions regarding the need for imaging tests specifically designed to detect PE, should be based on a careful assessment of clinical probability.149 A clinician should maintain a high index of suspicion for this condition, because prompt treatment of PE can dramatically reduce the levels of morbidity and mortality associated with PE. The ESC guidelines recommends the use of a stepwise diagnostic algorithm that combines several evidence-based diagnostic strategies.149

European Society of Cardiology algorithm for patients with suspected high-risk PE.

European Society of Cardiology algorithm for patients with suspected high-risk PE.
Adapted from Konstantinides et al.149 aIncludes cases in which the patient’s condition is so critical that it only allows bedside diagnostic tests. bApart from the diagnosis of RV dysfunction, a bedside transthoracic echocardiogram may, in some cases, directly confirm PE by visualizing mobile thrombi in the right heart chambers. cThrombolysis; alternatively, surgical embolectomy or catheter-directed treatment.
CT, computed tomography; PE, pulmonary embolism; RV, right ventricular.

Algorithms for the diagnosis of PE

The 2014 ESC guidelines include algorithms for the diagnosis of PE that stratify patients according to their risk of early death based on clinical symptoms.149

High-risk PE in this context is usually suspected if shock and/or hypotension are present. Once stabilized, suspected ‘high-risk’ PE patients can undergo CT pulmonary angiography to confirm or dismiss the diagnosis of PE. If PE is not found to be the cause of haemodynamic instability, other causes (such as acute coronary syndrome) should be investigated.149

In the absence of shock and/or hypotension, patients are categorized to have suspected ‘low-to-intermediate’ risk PE. CT pulmonary angiography is not recommended as a first-line test in these patients, because most patients will be found not have the disease. Instead, the ESC guidelines recommend further risk stratification using clinical judgement or a clinical prediction rule such as the Wells’ score. Patients deemed to have a high clinical probability of PE after this assessment are recommended to undergo CT pulmonary angiography for confirmation of the diagnosis. Patients with a ‘low/intermediate’ clinical probability of PE should first undergo a plasma D-dimer test before imaging of the pulmonary vasculature.149

These algorithms have been validated in both the emergency ward and primary care settings.149

European Society of Cardiology algorithm for patients with suspected non-high-risk PE.

European Society of Cardiology algorithm for patients with suspected non-high-risk PE.
Adapted from Konstantinides et al.32 aTwo alternative classification schemes may be used for clinical probability assessment, i.e. a three-level scheme (clinical probability defined as low, intermediate or high) or a two-level scheme (PE unlikely or PE likely). bTreatment refers to anticoagulation treatment for PE. cCT pulmonary angiogram is considered to be diagnostic of PE if it shows PE at the segmental or more proximal level. dIn case of a negative CT pulmonary angiogram in patients with a high clinical probability, further investigation may be considered before withholding PE-specific treatment.
CT, computed tomography; PE, pulmonary embolism.

Clinical probability scores

Scoring systems used in clinical practice include several key risk factors and markers for PE based on patient history and presentation. The Wells’ score is one scoring system that is commonly used method to predict clinical probability of PE.149 This prediction rule has been revised several times since its development to make it simpler and more accurate.150

Wells score for prediction of PE.150 A total score >6 indicates a high probability of a PE, a score of 2−6 moderate probability and a score <2 low probability.149

Parameter Score
Clinically suspected DVT 3
Alternative diagnosis less likely than PE 3
Rapid heart rate 1.5
Immobilization within past 4 weeks 1.5
History of DVT 1.5
Haemoptysis 1
Malignancy 1
DVT, deep vein thrombosis; PE, pulmonary embolism.

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Imaging

CT pulmonary angiography has become the method of choice for diagnostic imaging in patients with suspected PE, and provides a high resolution image, which allows adequate visualization down to the last segmental level. This method is just as accurate and less invasive compared with pulmonary angiography, the previous ‘gold standard’. Ventilation-perfusion scintigraphy (V/Q scan) is another established diagnostic test for suspected PE. Patients undergoing a V/Q scan are exposed to significantly lower levels of radiation compared with those undergoing a CT pulmonary angiography; this may be preferential in pregnant patients, young patients or those with severe renal impairment. A V/Q scan indicating a high probability of PE provides sufficient evidence for the initiation of treatment, although it should be noted that a scan indicating a low probability of PE does not rule out the condition. Because V/Q scanning is not sufficient to diagnose PE alone, further diagnostic tests may be required.149

Prognostic assessment strategy

Haemodynamically unstable patients with shock or hypotension are immediately stratified as high-risk patients (owing to a high risk of in-hospital or 30-day mortality) prior to diagnosis of PE. In non-high-risk patients, further risk stratification is necessary once a PE diagnosis has been confirmed. Validated clinical risk stratification scores include the Pulmonary Embolism Severity Index (PESI) score and the simplified PESI (sPESI) score, which allow reliable identification of patients at low risk of 30-day mortality (PESI Class I and II; sPESI score of 0). The ESC guidelines recommend that low-risk patients should be considered for early discharge and home treatment providing proper outpatient care and anticoagulant treatment can be provided.149 Post hoc analysis of patients enrolled in the EINSTEIN PE study, stratified by sPESI score, reported a low incidence of major adverse outcomes during the first 30 days of treatment in low-risk patients, supporting the outpatient management of these patients.151

Intermediate-risk patients are identified as PESI Class III or higher or an sPESI score of ≥1, and should be further stratified by assessment of right ventricular (RV) function and cardiac biomarker levels. Patients with normal RV function and/or normal cardiac biomarkers are stratified as intermediate-low risk, whereas those patients with evidence of RV dysfunction and elevated cardiac biomarkers (especially elevated cardiac troponin levels) should be classified as intermediate-high risk. These intermediate-high-risk patients should be monitored closely to permit rescue reperfusion therapy if clinical signs of haemodynamic decompensation appear.149

Risk stratification using PESI and sPESI scores149

Parameter PESI sPESI
Age Points = age in years If aged >80 years old = 1 point
Male sex +10 points
Cancer +30 points 1 point
Chronic heart failure +10 points 1 point
Chronic pulmonary disease +10 points 1 point
Pulse rate ≥110 bpm +20 points 1 point
Systolic blood pressure <100 mmHg +30 points 1 point
Respiratory rate >30 breaths/min +20 points -
Temperature <36°C +20 points -
Altered mental status +60 points -
Arterial oxyhaemoglobin saturation <90% +20 points 1 point
Class I: ≤65 points
Very low 30-day mortality risk (0–1.6%)
Class II: 66–85 points
Low mortality risk (1.7–3.5%)
0 points = low risk
Low 30-day mortality risk (1.0%)
(95% CI 0–2.1%)
Class III: 86–105 points
Moderate mortality risk (3.2–7.1%)
Class IV: 106–125 points
High mortality risk (4.0–11.4%)
Class V: >125 points
Very high mortality risk (10.0–24.5%)
≥1 point(s) = not low risk
30-day mortality risk (10.9%)
(95% CI 8.5–13.2%)

bpm, beats per minute; CI, confidence interval; PESI, Pulmonary Embolism Severity Index; sPESI, simplified Pulmonary Embolism Severity Index.

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Classification of patients with acute PE based on early mortality risk149

Early mortality risk Risk parameters and scores
Shock or hypotension PESI class III–V or sPESI >1a Signs of RV dysfunction on an imaging test Elevated cardiac biomarkers
High + (+)b + (+)b
Intermediate high - + Both positive
Intermediate low - + Either one (or none) positivec
Low - - Assessment optional; if assessed, both negativec

aPESI Class III–V: moderate to very high 30-day mortality risk; sPESI ≥1 point(s): high 30-day mortality risk. bNeither calculation of PESI (or sPESI) nor laboratory testing are considered necessary in patients with hypotension or shock. cPatients with PESI Class I–II/sPESI of 0, and elevated cardiac biomarkers/signs of RV dysfunction, are to be considered as intermediate-low risk.
PE, pulmonary embolism; PESI, Pulmonary Embolism Severity Index; RV, right ventricular; sPESI, simplified Pulmonary Embolism Severity Index.

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Risk factors for recurrence

As with DVT, the risk of recurrent PE appears to be higher in patients with an initial unprovoked PE and/or persistent risk factors than in those with transient risk factors.152

Persistent risk factors include:152

  • Active cancer
  • Elevated levels of antiphospholipid antibodies
  • Elevated D-dimer concentration after discontinuation of therapy

Several studies have indicated that patients with an initial PE are at high risk of recurrent PE, and one meta-analysis suggested that the risk for recurrent PE is 3.1-fold greater in patients who have had an initial symptomatic PE than in those with initial proximal DVT.153