**3. Diagnostic studies**

**2.1. Clinical presentation**

118 Pulmonary Hypertension

development of venous thrombosis and subsequent PE.

Trauma ≤ 3 months Lower extremity

Travel

Matta 2010)

**2.2. Clinical manifestations**

>4 hr in past month

Risk factors for PE are summarized in table 1 (Stein and Matta Curr Probl Cardiol 2010). Conditions predisposing to the development of deep venous thrombosis (DVT) include malignancy (especially pancreatic and brain cancers), chronic obstructive pulmonary disease, stroke, pregnancy, obesity, and immobilization, especially after lower extremity trauma or after surgery (hip and knee replacement). Hypercoagulable states may be acquired or inher‐ ited. Deficiencies in antithrombin, protein C, or protein S, factor V Leiden mutation, pro‐ thrombin gene 20210 mutation, and antiphospholipid antibodies predispose individuals to the

**Condition Prevalence (%)**

11

4

Immobilization 44 Surgery ≤ 3 month 35 Malignancy 18 Thrombophlebitis 16 Myocardial infarction 13

Heart failure 9 Asthma 9 COPD 8 Stroke, paresis, or paralysis 8 Prior PE 5

Collagen vascular disease 4 Pneumonia (current) 1

**Table 1.** Predisposing conditions in patients with PE (based upon data from PIOPED I and II; (adapted from Stein and

The clinical manifestations and presentation of acute PE are not specific and range from mild breathlessness to hemodynamic collapse. Dyspnea either at rest or with exertion occurs in approximately three quarters of patients diagnosed with PE (Stein 2010). Pleuritic or non‐ pleuritic chest discomfort occurs less frequently. Hemoptysis occurs in 5-15% of patients with PE. Approximately one third of patients with DVT have clinically asymptomatic PE (Stein 2010). The clinical presentation of PE has been classified recently into three categories: 1)

Because the clinical presentation and manifestations of PE are not specific, further diagnostic testing is required to establish the diagnosis definitively. Patients are usually categorized by the clinical probability, either high or intermediate/low, based upon the clinician's suspicion for the presence of PE. Several evaluation systems have been developed to assess the clinical probability for the presence of PE and the most widely used algorithms are the Wells score and the revised Geneva score (Wells 2000, LeGal 2006). If the suspicion for PE is intermediate or low, a D-dimer assay is performed. D-dimer is formed during the degradation of crosslinked fibrin and its presence is very sensitive for intravascular thrombosis due to either venous thrombosis or PE. The threshold value for D-dimer testing depends upon the assay but a value below the threshold indicates a very low risk for the presence of thrombosis. However, a value above the threshold is not specific for thrombosis and further evaluation is required. Com‐ pression ultrasonography is the currently preferred evaluation for suspected DVT and chest computed tomographic pulmonary angiography (CTPA) is used to diagnose PE.

#### **3.1. Laboratory abnormalities**

Troponin I and T and brain natriuretic peptide (BNP) are cardiac biomarkers that are released into the circulation when cardiac myocytes are stretched or injured as may occur during right ventricular dysfunction after an acute pulmonary embolism (Samama 2006). Elevation of these biomarkers identifies patients who are normotensive but have an increased risk of mortality (Pruszcyk 2003). Neither biomarker is a sensitive assay for the diagnosis of pulmonary embolism (Meyer 2003).

Measurement of PaO2 and PaCO2 are routinely performed in patients presenting with breath‐ lessness or pleurisy. In patients suspected to have PE, the sensitivity and specificity of a PaCO2<36 mmHg are 45% and 60%, respectively, and a PaO2<80 mmHg are 57% and 53%, respectively (Rodger 2000).

#### **3.2. Electrocardiogram**

The electrocardiographic manifestations of pulmonary embolism vary greatly from sinus tachycardia to conduction delays to patterns of RV strain (Panos 1988). Up to one quarter of patients with acute PE have normal electrocardiograms. Rhythm disturbances include tachycardia which is most common, atrial fibrillation, and atrial flutter. Conduction abnor‐ malities include first degree AV block, and left and right bundle branch block. The S1Q3T3 pattern may occur in 25-50% of patients.

paradoxical septal motion, pulmonary arterial hypertension, and patent foramen ovale

Acute Thromboembolic Pulmonary Hypertension

http://dx.doi.org/10.5772/56719

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ECHO may be used to risk stratify hemodynamically stable patients with acute PE. In a metaanalysis, Sanchez and colleagues found the unadjusted relative risk of RV dysfunction for predicting death in patients with acute PE and normal hemodynamics was 2.4 (95% CI 1.3-4.4) (Sanchez 2008). In a prospective study of patients with acute PE, RV dysfunction determined by ECHO had an odds ratio of 1.2 (95% CI 1.1-1.4) for adverse events including death,

The response of the RV to acute PE depends upon its pre-existing level of function and hemodynamic relationship with the LV, the extent of pulmonary artery bed occlusion, and the degree of pulmonary arterial vasoconstriction caused by hypoxemia, release of vasoactive and bronchoactive mediators from platelets and vascular endothelial cells, and neural responses.

Approximately half of patients with acute PE have RV dysfunction at presentation and 14-17% have persistently reduced RV function six months later (Klok 2011, Stevinson 2007). Serial echocardiograms show that the PA pressure declines and RV dysfunction improves rapidly over the 30 days after presentation in approximately 90% of patients with acute PE and that age greater than 70 years and PAP greater than 50 mmHg are associated with persistent PH

In a series of 690 patients diagnosed with PE, the number of occluded pulmonary artery segments ranged from 1 to 17 and was normally distributed with a mean of 9.2 segments representing 51.2% of the pulmonary arterial bed (Guintini 1995). Because the pulmonary vasculature is a high capacitance system, earlier studies suggested that occlusion of 70% or more of the pulmonary vasculature is required for the elevation of pulmonary pressures (Sabiston 1965, Wagenvort 1995). Subsequent studies using measures of pulmonary vascular bed occlusion such as the Miller index, the Walsh score, or the Qanadli index suggested that obstruction of at least 30-40% identifies greater than 90% of patients with RV dilation (Qanadli 2001). However, further studies have shown that the RV ejection fraction determined with or without electrocardiographic synchronization and the RV/LV ratio are better predictors of

clinical outcome than the pulmonary artery obstruction index (van der Bijl 2011)

cardiogenic shock, and recurrent venous thromboembolism (Sanchez 2010).

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

(Goldhaber 2002).

**5.1. RV response to Acute PE**

**5.2. Baseline cardiopulmonary status**

and RV dysfunction ( Ribeiro 1999).

**5.3. Extent of pulmonary vascular occlusion**
