What is CTEPH?

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, long-term disease caused by blockages in the blood vessels that deliver blood from the heart to the lungs (the pulmonary arterial tree). Most patients have a combination of microvascular (small vessel) and macrovascular (large vessel) obstructions. CTEPH is defined as pulmonary hypertension in the presence of an organized thrombus within the pulmonary vascular bed that persists at least 3 months after the onset of anticoagulant therapy.¹

What are the symptoms of CTEPH?

The most commonly reported symptoms of CTEPH include exercise intolerance, fatigue, and dyspnea. Patients may subsequently report chest discomfort, syncope, hemoptysis, light-headedness, or peripheral leg edema.²

Is CTEPH curable?

CTEPH is potentially curable by a type of surgery called pulmonary endarterectomy (PEA). PEA surgery is the recommended first option for patients with CTEPH.³ Patients who have operable CTEPH should be referred for surgery without delay.⁴ However, surgery is not an option for many patients – in an international prospective registry of over 679 patients newly diagnosed with CTEPH, approximately 37% of patients were deemed inoperable.⁵ Even after PEA surgery, up to 35% of patients develop persistent or recurrent CTEPH and therefore require further treatment.^6–8

What is the difference between CTEPH and PAH?

CTEPH and PAH (pulmonary arterial hypertension) have similar clinical presentations, but there are key differences in the cause and treatment of these conditions. CTEPH is caused by macrovascular obstructions in the pulmonary arteries, which can be removed during pulmonary endarterectomy (PEA) surgery. In appropriate surgical candidates, PEA surgery is potentially curative and is therefore the first-line recommended treatment for CTEPH.^2,3 By contrast, PAH is not caused by thromboembolic obstructions and so cannot be treated with PEA surgery.⁹  It is therefore important to differentiate CTEPH from PAH, as CTEPH is the only potentially curable form of pulmonary hypertension (PH).⁴ A ventilation/perfusion (V/Q) scan can distinguish patients with CTEPH from those with PAH.¹⁰

What are the risk factors for CTEPH?

CTEPH is an infrequent, but feared, potential long-term complication of acute pulmonary embolism (PE). Around 2.8–3.2% of patients may go on to develop CTEPH after surviving an acute PE.^11,12  Multiple factors related to PE can increase the risk of developing CTEPH, such as recurrent, unprovoked, or idiopathic PE, or large perfusion defects at the time that PE was detected.^2,13 In addition, some medical conditions are associated with increased risk of CTEPH in post-PE patients, such as splenectomy, history of malignancy, or inflammatory bowel disease.^2,,13

How is CTEPH diagnosed?

CTEPH diagnosis can be challenging, due to non-specific symptoms in the early stages of disease progression.¹⁴ However, diagnostic guidelines outline the key steps and clinical tests required to confirm CTEPH diagnosis.¹⁰

Imaging plays an important role in CTEPH diagnosis. Echocardiography is used in the initial assessment of suspected pulmonary hypertension (PH).^10,15 For those with high or intermediate probability of PH, ventilation/perfusion (V/Q) scans are the preferred and recommended screening test for CTEPH.^4,10 Following V/Q scanning, patients with mismatched perfusion defects should be referred to specialized CTEPH centers to confirm CTEPH diagnosis and provide prognostic information.^2,10

What is a V/Q scan?

A ventilation perfusion (V/Q) scan is the preferred and recommended screening test for CTEPH, with a sensitivity of over 96%.^2,10,16 The V/Q scan has two parts: the ventilation scan detects radioactive gas inhaled by the patient and shows the distribution of ventilation in the lungs, while the perfusion scan detects a radioactive tracer (intravenously injected prior to the scan) and shows the distribution of pulmonary perfusion. Mismatched ventilation and perfusion is suggestive of CTEPH, meaning any patient with an abnormal V/Q scan should be referred for further testing according to the diagnostic algorithm.^10,16

What is right heart catheterization?

Right heart catheterization (RHC) is used to evaluate key hemodynamic parameters relevant to CTEPH diagnosis, such as mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR). Assessment of mPAP by RHC is required for pulmonary hypertension (PH) diagnosis (PH is defined as an increase in mPAP ≥25 mmHg at rest), while PVR is an important determinant of prognosis in CTEPH and risk associated with pulmonary endarterectomy (PEA) surgery.^10,15

How is CTEPH severity assessed?

Assessing disease severity is important when considering treatment options for patients with CTEPH. Hemodynamic parameters – such as pulmonary vascular resistance (PVR) – may be useful predictors of prognosis in CTEPH.¹⁵ Clinical parameters may also be used to assess CTEPH severity or treatment response. The World Health Organization functional class (WHO FC) system is used to assess the impact of pulmonary hypertension (PH) symptoms on patients’ day-to-day activities, while exercise capacity can be assessed by measuring six-minute walk distance (6MWD).¹⁰

What treatment options are available for patients newly diagnosed with CTEPH?

Pulmonary endarterectomy (PEA) surgery is the first-line treatment of choice for patients with CTEPH.¹⁰ This potentially curative surgery allows for the removal of central obstructing lesions from the pulmonary vasculature, resulting in improved pulmonary hemodynamics for many patients.^2,10

However, up to 35% of patients develop persistent or recurrent CTEPH following PEA (whereby symptoms remain following PEA, or return after a symptom-free period).^6–8,17 In addition, PEA is not suitable for every patient with CTEPH, with around 4 in 10 newly diagnosed patients considered inoperable.⁵

Riociguat is the only approved oral medical therapy for patients with inoperable CTEPH, based on evidence from large, randomized controlled trials and real-world studies demonstrating the long-term benefits.^20–25 Riociguat is therefore recommended for the treatment of inoperable CTEPH by clinical practice guidelines.^4,10

Another treatment option for inoperable CTEPH, which may be considered in appropriate patients, is  balloon pulmonary angioplasty (BPA) – an interventional technique that should be performed in an expert center.^10,18

What is PEA surgery?

Pulmonary endarterectomy (PEA) surgery is the only potentially curative treatment for CTEPH, and is therefore the recommended first-line treatment option for all eligible patients.^3,9,19 PEA surgery is a complex and invasive procedure that allows for the removal of central obstructing lesions from the pulmonary vasculature.^2,4,19 In up to two-thirds of operated patients, the procedure results in normalization of hemodynamics and greatly increases survival, with a 5-year survival rate of 76%.⁸ However, 1 in 3 operated patients may have residual pulmonary hypertension (PH), and require further treatment, such as approved medical therapy or balloon pulmonary angioplasty.^8,10

How is PEA operability determined?

Pulmonary endarterectomy (PEA) surgery is a complex and invasive procedure – every patient diagnosed with CTEPH should therefore be evaluated by an expert CTEPH team to assess their suitability for PEA.^4,10,19 Three types of angiography may be used for PEA assessment: pulmonary, computer tomography (CT) and magnetic resonance imaging (MRI) angiography.¹⁵ These techniques can identify the extent and distribution of disease to identify appropriate surgical candidates, such as those with proximal, accessible lesions and an appropriate risk:benefit profile.^10,17

What treatment options are available for patients with inoperable CTEPH?

Around 40% of newly diagnosed patients with CTEPH are not eligible for pulmonary endarterectomy(PEA) surgery and are therefore considered inoperable.¹⁹ For these patients, treatment guidelines recommend medical therapy with or without balloon pulmonary angioplasty (BPA).^4,10

Riociguat is the only approved oral medical therapy for patients with inoperable CTEPH and is indicated for the treatment of adult patients with World Health Organization (WHO) functional class II and III to improve exercise capacity.¹⁰

For patients with inoperable CTEPH, BPA, an interventional technique which may clear fibrotic material in the pulmonary arteries and improve pulmonary hemodynamics, may also be considered.^10,18 BPA should only be performed in an expert center due to the risks associated with this complex procedure.¹⁸

What treatment options are available for patients with persistent or recurrent CTEPH?

Up to 1 in 3 patients may have residual pulmonary hypertension (PH) following pulmonary endarterectomy (PEA) surgery, and therefore require further treatment. For these patients, treatment guidelines recommend medical therapy with or without balloon pulmonary angioplasty (BPA).^4,10

Riociguat is the only approved oral medical therapy for patients with persistent or recurrent CTEPH after PEA surgery, and is indicated for the treatment of adult patients with World Health Organization (WHO) functional class II and III to improve exercise capacity.¹⁰ A large body of evidence – including randomized controlled trials and real world studies – suggests that riociguat is associated with long-term benefits for patients with CTEPH, including improved exercise capacity and WHO functional class.^20–25

What is BPA?

Balloon pulmonary angioplasty (BPA) is an interventional “keyhole” technique which involves insertion of a small balloon into the pulmonary arteries. The balloon is positioned within the fibrotic material using a catheter and guidewire, and the balloon is then inflated to rupture the lesions and restore pulmonary blood flow. Multiple sessions may be required to achieve therapeutic benefits and this complex procedure should only be performed in an expert center due to the associated risks.¹⁸ Treatment guidelines recommend consideration of BPA for patients with inoperable, persistent or recurrent CTEPH.^4,10

Can different treatment options be combined?

Pulmonary endarterectomy (PEA) is the first line treatment of choice for all eligible patients with CTEPH.⁹ However, for patients who are considered inoperable or experience persistent or recurrent CTEPH after PEA, guidelines recommend medical therapy with or without balloon pulmonary angioplasty (BPA). Medical therapy and BPA may be used sequentially in clinical practice, with real world data suggesting some patients may benefit from a combination approach.²⁶ Upcoming data from the RACE (Riociguat versus balloon pulmonary Angioplasty in non-operable Chronic thromboEmbolic pulmonary hypertension) extension study (NCT 02634203) will provide further information about the safety and efficacy of medical therapy combined with BPA.²⁷

How can I support my patients living with CTEPH?

Due to the rapid progression of the disease, any patient with suspected CTEPH should be referred to an expert center as soon as possible.¹⁰ Following referral, patients will receive care from a multidisciplinary team of specialists, who will decide on the best treatment option and assess operability for pulmonary endarterectomy (PEA) surgery. You may also want to give your patients guidance on tracking symptoms, when and how to get in touch with their healthcare team, and how to access to psychological and social work support where needed. The resources page includes a ‘Living with CTEPH’ poster that you can share with your patients, and a ‘Get the facts’ poster that you can use to talk your patient through what CTEPH is and what to expect. There are also videos from patients giving their perspectives on living with CTEPH.