**2. Hemodynamic consequences of acute pulmonary embolism**

Anatomically massive PE has been defined as having more than 50% obstruction of the pulmonary vasculature or the occlusion of two or more lobar arteries (Urokinase Pulmonary Embolism Study Group, 1970). In a unique situation, a large embolus may lodge at the bifurcation of the main pulmonary artery, i.e. saddle embolus. Although it was once regarded as a severe form of PE, a saddle PE shares a similar clinical course with a non-saddle PE, and low in-hospital mortality (Pruszczyk et al., 2003; Kaczyńska et al., 2005; Ryu et al., 2007).

An anatomically massive PE in a patient with adequate cardiopulmonary reserve and a submassive PE in a patient with poor reserve may manifest similar hemodynamic outcomes. The hemodynamic response to an acute PE depends not only the size of the embolus and the degree of pulmonary vasculature obstruction, but also on the physiologic reaction to the neurohumoral factors released and the underlying cardiopulmonary status of the patient.

Normally, the RV faces low resistance as it empties into a low-pressure system of the pulmonary vasculature. In acute PE, both mechanical obstruction and hypoxic vasoconstriction increase pulmonary vascular resistance, and this initiates a series of hemodynamic derangements leading to RV dysfunction (Figure 1). The release of humoral factors, such as serotonin from platelets, thrombin from plasma and histamine from tissue also contribute to pulmonary artery vasoconstriction. As a consequence of the elevated pulmonary resistance, the highly compliant RV dilates acutely.

Initially, compensatory maintenance of cardiac output is achieved by catecholamine-driven tachycardia and vasoconstriction. The left atrial contraction also contributes more than usual to

Risk Stratification of Patients with Acute Pulmonary Embolism 21

mortality risk of > 15%. Non high-risk patients are more heterogenous and are further stratified into intermediate risk (short term mortality risk of 3 to 15%) and low risk (short

Fig. 2. Risk stratification based on pulmonary embolism-related adverse outcomes

The presence of co-morbidities increases the risk of adverse events, even with a small PE. Advanced age (more than 70 years old), congestive heart failure, cancer, or chronic lung disease were identified as independent predictors of 3-month mortality from PE

The clinical manifestations of acute PE are non-specific and often overlap with other cardiac and pulmonary conditions. Chest pain is one of the most frequent presentations of PE. Pleuritic chest pain, with or without dyspnea, is usually caused by pleural irritation due to distal emboli which may be associated with pulmonary infarction. Individuals may also present with retrosternal angina-like chest pain, reflecting right ventricular ischemia. Isolated dyspnea of a rapid onset is suspicious of a more central and hemodynamically significant PE. Occasionally, the onset of dyspnea is more insidious especially in patients

Cardiogenic shock occurs in less than 5% of acute PE, and these patients have a high risk of death. Conversely, patients with non-massive PE present with stable blood pressure and have a lower risk of death. In the International Cooperative Pulmonary Embolism Registry,

**4. Risk assessment based on clinical parameters and risk models** 

with co-existing heart failure or pulmonary disease.

term mortality risk of less than 1%) (Figure 2).

(Goldhaber, 1999).

left ventricular filling. Eventually, with persistent pressure overload and wall stress, RV systolic function begins to fall. Cardiac output is decreased further by impaired distensibility of the left ventricle (LV) from the leftward shift and flattening of the interventricular septum during systole/early diastole, and impaired LV filling during diastole.

Myocardial ischemia also worsens RV function by increased oxygen demands due to elevated wall stress and decreased oxygen supply from elevated right-sided pressures (Goldhaber et al., 2003; Wood, 2002).

The hemodynamic cascade provides an appreciation in understanding the roles the various imaging modalities and biomarkers play in the risk assessment of patients with acute PE.

Fig. 1. Hemodynamic consequences due to acute pulmonary embolism and mechanism of biomarkers detection (PA, pulmonary artery; RV, right ventricle; LV, left ventricle; BNP, brain natriuretic peptide; NT-proBNP, NT-pro brain natriuretic peptide; H-FABP, heart-type fatty acid binding protein)

#### **3. Classification of risk**

The prognosis of acute PE correlates most directly with the degree of hemodynamic compromise and RV dysfunction.

The European Society of Cardiology recommends an individual risk assessment of early PErelated deaths (Torbicki et al, 2008). Based on the clinical presentation, presence of RV dysfunction and elevated biomarkers, high-risk PE has a short-term (in-hospital or 30-day)

left ventricular filling. Eventually, with persistent pressure overload and wall stress, RV systolic function begins to fall. Cardiac output is decreased further by impaired distensibility of the left ventricle (LV) from the leftward shift and flattening of the interventricular septum

Myocardial ischemia also worsens RV function by increased oxygen demands due to elevated wall stress and decreased oxygen supply from elevated right-sided pressures

The hemodynamic cascade provides an appreciation in understanding the roles the various imaging modalities and biomarkers play in the risk assessment of patients with acute PE.

Fig. 1. Hemodynamic consequences due to acute pulmonary embolism and mechanism of biomarkers detection (PA, pulmonary artery; RV, right ventricle; LV, left ventricle; BNP, brain natriuretic peptide; NT-proBNP, NT-pro brain natriuretic peptide; H-FABP,

The prognosis of acute PE correlates most directly with the degree of hemodynamic

The European Society of Cardiology recommends an individual risk assessment of early PErelated deaths (Torbicki et al, 2008). Based on the clinical presentation, presence of RV dysfunction and elevated biomarkers, high-risk PE has a short-term (in-hospital or 30-day)

during systole/early diastole, and impaired LV filling during diastole.

(Goldhaber et al., 2003; Wood, 2002).

heart-type fatty acid binding protein)

**3. Classification of risk** 

compromise and RV dysfunction.

mortality risk of > 15%. Non high-risk patients are more heterogenous and are further stratified into intermediate risk (short term mortality risk of 3 to 15%) and low risk (short term mortality risk of less than 1%) (Figure 2).

Fig. 2. Risk stratification based on pulmonary embolism-related adverse outcomes
