**2. Epidemiology of CTEPH**

Pulmonary embolism (PE) is a common condition with an annual incidence estimated at 50 per 100,000 persons [12]. This is an acute disease and usually reversible after anticoagulation and / or after thrombolysis. Patients are frequently deemed to be "cured" after treatment. However, studies based on V/Q lung or computed tomography pulmonary angiogram (CTPA) reported the presence of residual perfusion disorders after acute pulmonary embolism [13]. Other echocardiographic studies have also shown that 30% of patients with PAH have residual or impaired right ventricular wall motion abnormalities and functional impairment after acute pulmonary embolism [14]. These data suggest that a significant proportion of patients with acute symptomatic PE develop persistent pulmonary vascular sequelae with serious long-term consequences [14.15]. Initial estimates of the frequency of CTEPH are of the order of 0.1% to 0.5% of patients surviving an episode of acute pulmonary embolism [16, 17]. More recent data suggest that 1% to 4% of patients may develop CTEPH after a first episode of pulmonary embolism [18, 19]. This frequency is even higher after recurrent thromboembolic events [20].

**3. Risk factors for CTEPH**

after an acute pulmonary embolism [30, 32].

• Indwelling central venous catheters (e.g. Port, Hickman catheter) • Chronic inflammatory diseases (osteomyelitis, inflammatory bowel

Independent clinical risk factors for CTEPH

• Thyroid hormone replacement therapy

Plasmatic risk factors associated with CTEPH • Elevated factor VIII levels *"/>*250%

• Previous pulmonary embolism

• Combined coagulation defects

**Table 1.** Risk factors for CTEPH [23].

• Large perfusion defect • Idiopathic PE at presentation

• Fibrinogen mutations

Risk factors associated with CTEPH after symptomatic PE

APA, antiphospholipid antibodies; LAC, lupus anticoagulans.

• Ventriculo-atrial (VA) shunts

• Splenectomy

diseases)

• Young age

• APA/LAC

• Pacemaker leads

• Malignant diseases

To better identify patients with pulmonary embolism who are more likely to develop CTEPH, many studies have assessed the potential risk factors for CTEPH including demographic factors, the specific details of pulmonary embolism, the presence of co-morbidities and underlying thrombophilia (table 1) [23, 30]. An increased risk of CTEPH is associated with splenectomy, cancer, chronic inflammatory diseases (Crohn's disease and ulcerative colitis), hypothyroidism, an atrioventricular shunt and infected cardiac pacemaker [30, 31]. Compli‐ cations associated with pulmonary embolism such as acute perfusion defects, idiopathic, recurrent thromboemboli, massive pulmonary emboli, and delayed diagnosis may also predispose patients to CTEPH. Patients older than 70 years whose systolic pulmonary artery pressure is above 50 mmHg have a higher risk of persistent pulmonary hypertension one year

Chronic Thromboembolic Pulmonary Hypertension

http://dx.doi.org/10.5772/54749

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Thrombolytics are frequently used to treat acute pulmonary emboli. The rapid and complete recanalization of the pulmonary arteries may decrease the subsequent development of CTEPH [33]. 23 of 40 patients who had angiographically proven pulmonary embolism and who had initially been randomized to an IV infusion of heparin (n = 11) or a thrombolytic agent (urokinase or streptokinase, n = 12) were restudied after a mean follow-up of 7.4 years to

In a series of 866 patients with acute pulmonary embolism, all patients who had not previously been diagnosed with pulmonary hypertension (PH) and had survived until inclusion in the study were asked to undergo echocardiography. Patients suspected of having PH by echo‐ cardiogram underwent complete assessment to test chronic thromboembolic pulmonary hypertension. This procedure includes V/Q scintigraphy and right heart catheterization. The results showed the incidence of CTEPH to be about 0.5% [21, 22].

In a prospective study, after a first episode of symptomatic pulmonary embolism for pa‐ tients with unexplained persistent dyspnea, echocardiographic abnormality, a V/Q scan, pulmonary angiography, and right heart catheterization, the cumulative incidence of symptomatic CTEPH was 1.0% at six months, 3.1% at one year and 3.8% at two years [23]. In another study of 320 patients who presented with a symptomatic pulmonary em‐ bolism, V/Q scintigraphy results showed persistent perfusion defects 6 and 12 months af‐ ter pulmonary embolism. The cumulative incidence of CTEPH was 0.9% to 1.3% [24]. The true incidence of CTEPH may have been underestimated due to exclusion of pa‐ tients with a history of venous thromboembolism, thrombophilia or other potential caus‐ es of pulmonary hypertension. In addition, a significant proportion of patients with CTEPH have not shown any previous episode of symptomatic pulmonary embolism [25, 26]. The discrepancy between theoretical estimates and the number of patients diagnosed with CTEPH emphasizes that CTEPH is likely to be underdiagnosed. The time between an acute pulmonary embolism episode and the development of CTEPH is also a matter of debate. Most cases of CTEPH are diagnosed during the first two years after the acute symptomatic pulmonary embolism [23]. However, some patients may experience symp‐ toms of CTEPH many years later [27, 28]. This variability was attributed to progressive vasculopathy which affected the distal small pulmonary arteries [29].
