Massive Acute Pulmonary Embolism

Pathophysiology

Obstruction of flow through the main pulmonary arteries results in increased afterload on the RV. In addition, release of vasoactive mediators, including thromboxane A2 and serotonin, results in pulmonary vasoconstriction and increased pulmonary vascular resistance. The resultant increase in RV wall tension results in displacement of the interventricular septum to the left and impaired left ventricular (LV) filling. If untreated, the RV outflow obstruction also results in reduced preload in the LV, reduced cardiac output, and, eventually, circulatory collapse and shock. Younger patients with otherwise normal underlying cardiac function may tolerate the hemodynamic stress placed by a large PE without developing RV dysfunction or shock. In patients with compromised cardiac function, however, the onset of RV failure and circulatory collapse may be more rapid. In addition, hypoxia may result from the low cardiac output entering the pulmonary circulation, ventilation–perfusion mismatch, and the presence of a right-to-left shunt (through a patent foramen ovale, opened by increased right-sided pressure).

Clinical Presentation

The clinical presentation of PE varies widely. Massive PE may present with severe dyspnea at rest, syncope, or even cardiac arrest, whereas nonmassive PE may be asymptomatic or have limited symptoms. Past medical history may include some risk factors for venous thromboembolism. Physical signs include tachycardia, tachypnea, systemic hypotension, and cyanosis. Clinical evidence of RV dysfunction includes distended neck veins, parasternal heave, accentuated pulmonary component of the second heart sound, and a systolic murmur consistent with tricuspid regurgitation. An RV gallop rhythm may also be heard. The presence of a pleural rub, in association with pleuritic chest pain, may be secondary to pleural irritation caused by pulmonary infarction. These clinical features may also be used for risk stratification.

Diagnosis and Risk Stratification

Clinical features and predisposing risk factors have been incorporated into clinical scoring systems that are used to predict the likelihood of PE and determining subsequent investigations. These include the Wells Score, Simplified Geneva Score, and Pulmonary Embolism Severity Index (PESI; Table 31.1 ). The most extensively validated and widely used clinical scoring system is the Wells score.

Investigations for Risk Stratification

The chest radiograph (CXR) is usually abnormal in patients with acute PE. Although mainly nonspecific, the absence of other features such as atelectasis or pleural effusion can be used to exclude other causes of dyspnea or chest pain. Arterial blood gas (ABG) analysis usually demonstrates hypoxemia (partial pressure of oxygen [PaO ₂ ] <80 mm Hg), with hypocapnia and respiratory alkalosis. In up to 20% of patients, a normal PaO ₂ and alveolar-arterial gradient may be found. Alternatively, hypercapnia with respiratory and metabolic acidosis may be seen in patients with massive PE requiring cardiopulmonary resuscitation (CPR). Following assessment of the clinical and hemodynamic status of the patient using a clinical scoring system, the patients are subdivided into different probabilities of PE.

High Clinical Probability

If the patient has a high clinical probability of PE as determined by the clinical scoring systems, then multidetector computed tomography pulmonary angiography (CTPA) is required to determine the presence of thrombus within the pulmonary arterial vasculature. CTPA has become the imaging of choice in patients with suspected PE because of its speed of scanning, widespread availability, and high sensitivity and specificity (>90%). It provides excellent visualization of the pulmonary arterial vasculature, including the main, lobar, and segmental pulmonary arteries along with characterization of extravascular structures ( Fig. 31.1 ).

An alternative imaging modality, such as VQ scintigraphy, may also be required in patients with a contraindication to CTPA, such as those with renal failure or contrast allergy. In hemodynamically unstable patients who cannot be transferred for CTPA, echocardiography may be required.

Low or Intermediate Clinical Probability

If the patient has been classified as having a low or intermediate clinical probability of PE, a D-dimer enzyme-linked immunoabsorbent assay (ELISA) should be performed as the first-line investigation (sensitivity 96% and specificity 39%). Serum D-dimer is a degradation product of cross-linked fibrin and acts as an indirect marker for thrombosis and subsequent fibrinolysis. As the D-dimer ELISA has a high negative predictive value (NPV), its absence effectively rules out acute PE and an alternative diagnosis should be sought. The positive predictive value (PPV) of elevated serum D-dimer levels, however, is low, as although D-dimer is very specific for fibrin, fibrin can be produced in a wide variety of conditions, including aortic dissection, cancer, inflammation, and infection. Hence, if positive, the patient should undergo a CTPA.

Once the diagnosis of acute PE has been made, the patients are stratified into low-risk (nonmassive), intermediate-risk (submassive), and high-risk (massive) groups, according to the presence of hypotension, shock and/or RV dysfunction. The clinical status of the patient will differentiate the high-risk (massive) PE from non-high-risk PE patients. Echocardiography can then be used to further delineate non-high-risk PE patients into intermediate-risk PE (with evidence of RV dysfunction) or low-risk PE (with no RV dysfunction) groups. Surrogate markers of RV dysfunction include RV dilatation (RV end-diastolic dimension >30 mm), interventricular septal flattening with paradoxical motion, increased RV/LV ratio (>0.9), RV hypokinesis, pulmonary hypertension (pulmonary artery systolic pressure >30 mm Hg), and increased tricuspid regurgitation jet velocity (>2.6 m/s), which are found in approximately 25% of patients with acute PE ( Fig. 31.2 ).

Echocardiography can also be used to exclude other important causes of acute circulatory collapse, including acute myocardial infarction (MI), pericardial tamponade, or type A aortic dissection. Normal RV size and function on echocardiography in a patient with shock or hypotension virtually rules out acute PE as a cause of hemodynamic instability. The McConnell sign, a distinct echocardiographic feature of acute massive pulmonary embolism, is a regional pattern of RV dysfunction, with akinesia of the mid–free wall and hypercontractility of the apical wall ( Video 31.1 ). Transesophageal echocardiography can provide excellent imaging of the RV and proximal pulmonary vasculature to identify thrombus and can assess RV function and size. In patients with suspected PE with evidence of RV dysfunction, it has a sensitivity of 80% and specificity of 97%. However, it should not be undertaken in hypoxic patients with hemodynamic instability except in special circumstances (i.e., the patient is already intubated and ventilated).

Biomarkers, including serum troponin I or T and brain natriuretic peptide (BNP), may be indirect evidence of RV dysfunction in patients with acute PE. Troponin levels—including troponin I and troponin T rise in PE secondary to increased RV wall tension and end-diastolic pressure—reduced right coronary artery flow, increased RV myocardial oxygen demand, RV myocardial ischemia (even in the presence of normal coronary arteries), and subsequent leakage of the enzymes from the RV myocytes into the bloodstream. They can be used to risk stratify patients with non-high-risk PE into intermediate-risk PE (with elevated troponin levels) or low-risk PE (normal troponin levels). Similarly, plasma B-type natriuretic peptide (BNP) is released from the RV in response to increased pressure and stretch and has been shown to correlate with the presence of RV dysfunction. Elevated levels of both troponin and BNP have been shown to be associated with adverse prognosis and short-term outcomes in patients with acute PE. Raised levels of both biomarkers, however, are not specific to PE.

Electrocardiography (ECG) is normal in up to 30% of patients but often demonstrates nonspecific changes, such as sinus tachycardia, atrial fibrillation, or ST/T wave changes. Despite having a low sensitivity and specificity, the ECG may demonstrate evidence of right heart strain, such as T-wave inversion in leads V ₁ to V ₄ , P pulmonale, right axis deviation, incomplete or complete right bundle branch block, or the combination of a prominent S wave in lead I, Q wave in lead III, and T-wave inversion in lead III (the classical S ₁ Q ₃ T ₃ pattern, which is present in only 2% to 15% of patients with PE).

As massive PE has a high mortality in the first 6 hours following the onset of symptoms, early diagnosis is paramount in order to instigate timely management. Unfortunately, the diagnosis is frequently first made at autopsy.

Management

The primary cause of death in patients with massive PE is low cardiac output. Massive PE should be suspected in patients with major hemodynamic instability accompanied by an elevated central venous pressure, which is not otherwise explained by pericardial tamponade, acute MI, or tension pneumothorax. As the short-term mortality increases depending on the degree of hemodynamic insult caused by obstruction to RV outflow, the choice of initial therapy will also depend on the severity of the hemodynamic insult.