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is an important cause of PH on a global scale.11

there are no specific drugs available for this particular form of PH.13

In a recent prospective study, 4.8% of acute pulmonary embolism patients were diagnosed with CTEPH after a subsequent median follow-up of 26 months.16

while a much lower percentage was found in a Dutch prospective cohort study.15


majority of CTEPH patients already had signs of pulmonary hypertension during the initial episode of acute pulmonary embolism, suggesting that a first clinical presentation of CTEPH may mimic acute pulmonary embolism. A total of 20–25% of CTEPH cases occur in patients without a history of venous thrombo-embolic disease.17,18

Drugs, toxins



Because organised pulmonary emboli are easily overlooked on a standard computed tomography (CT) angiography, ventilation/perfusion scintigraphy is still the central diagnostic procedure to confirm or exclude CTEPH in a patient with PH. CTEPH treatment is primarily surgical and consists of a pulmonary endarterectomy. During this procedure, thrombotic material is removed together with the inner layers of the pulmonary arteries, to allow reperfusion of previously obstructed segments of the pulmonary circulation.

For non-operable or residual/ persistence, there is a medical treatment available.


A diagnosis of PAH can only be made after the exclusion of significant heart or lung disease and chronic thromboembolism. PAH is characterised by an abnormal growth pattern of endothelial and smooth muscle cells in pulmonary arterioles, partially obstructing or occluding the vascular lumen. The hallmark lesion of PAH is the so-called plexiform lesion, which is a glomeruloid structure consisting of functionally and morphologically altered endothelial and smooth muscle cells. PAH

Idiopathic or heritable PAH

Figure 1: Diagnostic algorithm, Nice consensus.22

BGA = blood gas analysis; CTD = connective tissue disease; CHD = congenital heart disease; CTEPH = chronic thromboembolic PH; DLCO = diffusing capacity for carbon monoxide, % predicted; ECG = electrocardiogram; HR-CT = high-resolution computed tomography; PA = pulmonary angiography; PAPm = mean pulmonary arterial pressure; PAWP = pulmonary artery wedge pressure; PCH = pulmonary capillary hemangiomatosis; PEA = pulmonary endarterectomy; PFT = pulmonary function test; PH = pulmonary hypertension; PVOD = pulmonary veno-occlusive disease; PVR = pulmonary vascular resistance; RHC = right heart catheterisation; RV = right ventricular; V/Q = ventilation/perfusion; WU = Woods Units.

occurs in four forms: idiopathic, hereditary, drug-induced and associated with an underlying condition. A number of diseases are associated with the development of PAH, including systemic sclerosis, systemic lupus erythematosus, hepatic disease, HIV infections and the existence of congenital systemic to pulmonary shunts. Among the first pharmaceutical compounds known to induce PAH in susceptible subjects were appetite suppressants, such as Ponderal. Recently, a relationship was established between the development of PAH and the use of the tyrosine kinase inhibitor, dasatinib.19

When PAH occurs in a

hereditary form, it is mostly related to a mutation in the gene encoding the bone morphogenic protein receptor type II. In the absence of an underlying risk factor, idiopathic PAH is diagnosed, a condition that most frequently occurs in young women but can also develop in all age

groups and males (30% of all patients).20 Before 1997, PAH was untreatable, with a median survival after diagnosis of about three years. Currently, more than 12 drugs are available for the treatment of PAH and these drugs do improve survival.4,5

(group 5?)

Family history; consider genetic studies (expert centres only)


Chronic thromboembolic PH Chronic thromboembolic PH (CTEPH) is a rare but potentially deadly complication of pulmonary embolism. Pengo et al estimated that 4% of patients with a proven acute episode of pulmonary embolism developed CTEPH,14

Regardless of its underlying cause, the presence of PH in chronic lung disease is associated with a worse prognosis. Even so, it remains to be determined whether PH in chronic lung disease is a true cause of early death or merely a marker of more severe lung disease. While long-term oxygen therapy delays the progression of PH in COPD,12

Symptoms, signs, history suggestive of PH

Echocardiography compatible with PH?


Consider most common causes of PH (i.e. left heart disease, lung disease)

History, signs, risks, ECG, X-ray, PFT incl. DLCO, consider BGA, HR-CT


No signs of severe PH/ RV disfunction

Treat underlying disease

CT angiography, RHC plus PA (PEA expert centre)

YES Specific diagnosis tests CTD CHD pulmonary

Schistoso- miasis

Porto- PAH likely CTEPH likely NO PH unlikely Consider other causes or recheck

Diagnosis of heart disease or lung disease confirmed?

NO V/Q scintigraphy YES NO

PAPm ≥25 mmHg, PAWP ≤15 mmHg, PVR >3 WU

NO other causes Consider RHC YES

Signs of severe disfunction

Refer to PH expert centre


PAH is a rare disease requiring an elaborate diagnostic approach, including right heart catheterisation and because PAH treatment is complex, European guidelines advocate diagnosis and treatment of patients in expert centres.7,21

Despite recent

improvements in PAH treatment, the prognosis of this group of relatively young patients remains poor. Timely referral for lung transplantation is an essential aspect of the management of this disease.

Diagnostic algorithm To prevent unnecessary diagnostic procedures, a diagnostic algorithm for patients with suspected PH is incorporated


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