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The link between pulmonary embolism and CTEPH

Approximately 2–4% of people with pulmonary embolism develop CTEPH, which remains a relatively rare disease. This article discusses the link between the two conditions

George Giannakoulas MD Cardiology Department, AHEPA University Hospital, Aristotle University of Thessaloniki, Greece

Incomplete resolution of pulmonary embolism (PE) is not uncommon. In fact, despite effective therapeutic anticoagulation, more than 50% of patients have residual perfusion defects six months after diagnosis of PE.1 After 4.5 months of anticoagulation, residual pulmonary thromboemboli – as diagnosed with computed tomography (CT) angiography – persist in 26% of patients.2

Table 1: Reported incidence of CTEPH after PE First author, year n Marti et al, 20104 Dentali et al, 20095 Guerin et al, 20146 Pengo et al, 20047 Surie et al, 20108 Miniati et al, 20069

110 91

146 223 110

Becattini et al, 200610

Klok et al, 201011 Poli et al, 201012

320 259

866 239

A recent safety analysis of the Einstein PE study with an early CT scan at three weeks after the index PE episode showed that rivaroxaban resulted in complete clot resolution in 44% of the patients with acute PE, and in partial clot resolution in 45%; no relevant change was observed in 11%.3

Incidence of CTEPH 38

Chronic thromboembolic pulmonary hypertension (CTEPH) has been reported to be a long-term complication of PE. However, although there is a definite link between the two conditions, the true incidence of CTEPH after an episode of acute PE is currently unknown. There is a wide variation of reported frequencies (Table 1), which can be explained by differences in inclusion criteria and screening methods, as well as by the inherent difficulty of differentiating a true episode of acute PE from a superimposed acute PE on pre-existing CTEPH. The cumulative incidence of symptomatic

Median follow-up (months) 24

NA 26

94.3 36

25.2 46

34 36

CTEPH was approximately 1%, 3% and 4% at six months, one year and two years, respectively, in a prospective study of 223 patients who presented with acute PE.7

In patients with a prior

episode of deep vein thrombosis the incidence was 5.2%, and 33% in patients with a prior episode of PE. However, up to one-quarter of patients of CTEPH have no known history of PE and, therefore, defining the true incidence of the disease remains a difficult task.13 This is the reason why CTEPH is often identified during diagnostic workup in patients with unexplained PH and an unremarkable past history of venous thromboembolism or PE. A history of acute PE is less common in patients with non-operable distal disease.14 The risk of developing CTEPH is increased in patients who have recurrent episodes of venous thromboembolism, large perfusion defects, younger age and echocardiographic signs of PH at the initial presentation. It is noteworthy that the normal right ventricle can maintain acutely a systolic arterial pressure of

RHC performed CTEPH prevalence (%) N N Y Y Y Y Y

9.1 8.8 4.8

3.8 at 2 years 2.7 1.3 0.8


0.57 0.4

approximately 40mmHg. Therefore, whenever patients present with seemingly acute PE and echocardiographic signs of severe PH, CTEPH is likely already to have been present.


Non-resolving acute or recurrent episodes of PE are the most common causes of CTEPH. These thrombotic events may be symptomatic or silent. Perfusion defects on lung perfusion VQ scan appear identical for either PE or CTEPH and, therefore, differential diagnosis is practically impossible. However, with the use of CT pulmonary angiography, the defects in chronic disease usually have a different appearance from PE and require training to detect such differences.15

The pathway from acute PE to CTEPH encompasses the progression from acute thrombus, composed primarily of fibrin and erythrocytes, to organised obstructive fibrotic material and finally to precapillary PH. Although CTEPH has

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