**1.3 Pathophysiology**

Based on the occlusion of the pulmonary vasculature we can differentiate between mild: <25%, intermediate: 25-50% and severe: >50% PE types. The pathophysiology of PE runs on two parallel pathways:


#### **1.3.1 Risk stratification**

Based on the haemodynamic symptoms,PE can be either *massive*, characterised by systolic blood pressure lower than 90 mmHg or a systolic blood pressure decrease > 40 mmHg, or *non-massive* which includes *submassive* severity characterised by increased right ventricular pressure (Torbicki et al., 2000).

The most recent PE guideline changed the definitions of various risk groups, according: high risk and non-high risk categories.

*High risk definition:* Shock and/or hypotension (systolic blood pressure <90 mmHg or a drop in blood pressure greater than 40 mmHg within 15 min. excluding other causes of shock (e.g. arrhythmia, hypovolaemia, sepsis etc.).

All others can be listed under *non-high risk* PE. Based on right ventricular (RV) pressure overload and myocardial injury, we can differentiate a subgroup, the *intermediate risk* PE patients without shock.

activated protein C resistance (Dahlbäck, 1995), 20210A mutation of factor II (Poort et al., 1996), hyperhomocysteinaemia (den Heijer et al., 1996), antithrombin III, protein C and

*a/ Congenital risk factors:* Lack of anti-thrombin III (0.2%), lack of protein C (0.8%), lack of protein S (1.3%), Leiden point-mutation of factor V (3.0%), mutation of prothrombin G20210

*b/ Acquired risk factors*: DVT, phlebitis, immobilization, bed rest, post-traumatic and operative state, sepsis, diabetes, smoking, hypovolaemia, diuretic treatment, elevated plasma/blood viscosity, coagulation disorders (disseminated intravascular coagulation, heparin induced thrombocytopenia (HIT), drug induced coagulopathy (anticoncipient, oestrogen), obesity, sedentary lifestyle, pregnancy, postnatal state, cardiac insufficiency, heart valve disorders, artificial valves, central venous catheter, pacemaker electrode,

Based on the occlusion of the pulmonary vasculature we can differentiate between mild: <25%, intermediate: 25-50% and severe: >50% PE types. The pathophysiology of PE runs on

• *haemodynamic alterations*: The oxygen demand and workload on the right atrium increases with the afterload, while cardiac index decreases (even with normal arterial blood pressure and tachycardia) leading to systemic hypotension. The right intraatrial pressure increases and the pressure gradient between the right atrium and the aorta drops, pushing the intraventricular septa into the cavity of the left ventricle (LV) (D-

• *hypoxaemia*: Ventilation/perfusion (V/Q) disequilibrium rises. Areas with hypoperfusion have an increased V/Q, while it decreases on hypoventilated (atelectasis) or normally perfused regions. Low LV cardiac output results from shuntperfusion and hypoxaemia (Nowak et al., 2007). Platelet released vasoactive substances cause vaso- and bronchospasm in the affected regions (Stratmann & Gregory, 2003; Wood, 2002; Konstantinides, 2005). Surfactant production impairs in the early phase of pulmonary hypertension. Due to shunt-perfusion, global arterial hypoxaemia develops with a decrease of arterial oxygen saturation (Konstantinides & Hasenfuss, 2004).

Based on the haemodynamic symptoms,PE can be either *massive*, characterised by systolic blood pressure lower than 90 mmHg or a systolic blood pressure decrease > 40 mmHg, or *non-massive* which includes *submassive* severity characterised by increased right ventricular

The most recent PE guideline changed the definitions of various risk groups, according:

*High risk definition:* Shock and/or hypotension (systolic blood pressure <90 mmHg or a drop in blood pressure greater than 40 mmHg within 15 min. excluding other causes of shock

All others can be listed under *non-high risk* PE. Based on right ventricular (RV) pressure overload and myocardial injury, we can differentiate a subgroup, the *intermediate risk* PE

protein S deficiency (Demers et al., 1992). Aetiology can be divided into two groups:

tumour, old age, nephrosis syndrome (Goldhaber et al., 1997).

sign). A severe shock with global cardiac ischemia can develop.

A (2.3%) (Ageno et al., 2006).

**1.3 Pathophysiology** 

two parallel pathways:

**1.3.1 Risk stratification** 

patients without shock.

pressure (Torbicki et al., 2000).

high risk and non-high risk categories.

(e.g. arrhythmia, hypovolaemia, sepsis etc.).


(+) Presence of shock/hypotension it is not necessery confirm RV dysfunction

Table 1. Risk stratification according to the ESC 2008 guidelines.

The prognosis of the increased RV pressure (intermediate risk) group is worse than the normal RV pressure group (Torbicki et al., 2008).


Table 2. Clinical probability score

#### **1.4 Pulmonary embolism diagnostic strategy**

Acute PE, in the presence of shock/hypotension, RV dysfunction and myocardial injury causes high mortality risk. Rapid and clear diagnosis and appropriate therapy may help to improve survival of this critical condition.

Pathophysiology, Diagnosis and Treatment of Pulmonary

Embolism Focusing on Thrombolysis - New approaches 123

recommended in case of uncertain radiological imaging results. Non-invasive CT angiography offers comparable or better sensitivity (Wan et al., 2004; Agnelli et al., 2002).

The MDCT is a non-invasive approach, replacing angiography without the need of central venous access. It has a sensitivity of 83% and specificity of 96%. The negative predictive value of MDCT for PE is 89% in the intermediate and 96% in the low clinical risk groups. The cost-benefit and cost-life ratio increases significantly with the combination of MDCT and D-dimer assessment (Perrier et al., 2004; van Belle et al., 2006). With MDCT imaging one can visualise pulmonary vasculature up to the segmental level. An MDCT result showing a PE up to the segmental level could be taken as firm evidence (Eyer et al., 2005; Brunot et al.,

**1.4.6 Computed tomography, Multidetector Computed Tomography (MDCT)** 

2005; Righini et al., 2008; Ghaye et al., 2001; Perrier et al., 2004).

Fig. 1. Computed tomography image of acute pulmonary embolism.

**1.4.7 Echocardiography**  *Transthoracic echocardiography* 

(From authors own collection. A: aorta, TP: pulmonary trunk, F: thoracic effusion, Thr: clot)

Echocardiography is a useful bedside non-invasive procedure in the differential diagnosis of various conditions (acute myocardial infarction, aortic dissection, pericardial tamponade,
