Chronic thromboembolic pulmonary hypertension (CTEPH) is a long-term form of high blood pressure in the lung arteries that develops when old blood clots do not fully dissolve and instead turn into hard scar tissue inside the blood vessels of the lungs. This scar tissue blocks or narrows the arteries, so blood cannot flow easily from the right side of the heart to the lungs. The heart must pump harder against this blockage, and over time the pressure in the lung arteries becomes high (pulmonary hypertension) and the right side of the heart becomes weak.
Chronic thromboembolic pulmonary hypertension (CTEPH) is a type of pulmonary hypertension that happens when old blood clots in the lungs do not fully dissolve and instead turn into firm scar-like tissue that blocks or narrows the pulmonary arteries. Over time, this blockage raises pressure inside the lung blood vessels, forces the right side of the heart to work much harder, and can lead to right-sided heart failure if not treated. CTEPH usually appears months after an acute pulmonary embolism (PE), but sometimes the first sign is slowly worsening breathlessness without a clear history of PE. It is serious but often treatable, and in many patients even curable with the right surgery or procedure, so early diagnosis and referral to a specialized CTEPH center are very important.
In most people with CTEPH, the first problem was one or more episodes of pulmonary embolism (PE), which means blood clots that traveled from the deep veins (usually in the legs) to the lungs. In CTEPH, these clots are not cleared completely. They become organized, thick, and fibrous, and they stick to the vessel wall. At the same time, the tiny vessels in the lungs may also become diseased and narrowed, which adds to the pressure and makes breathing more difficult.
CTEPH belongs to “group 4” pulmonary hypertension in modern guidelines. It is important because it is one of the few types of severe pulmonary hypertension that can sometimes be cured or greatly improved by surgery to remove the old clot material (pulmonary endarterectomy) or by balloon procedures in the lung arteries. Early diagnosis is therefore very important, but many people are diagnosed late because the early symptoms are mild and non-specific.
Other Names
Doctors use several different names for the same or related conditions:
Chronic thromboembolic pulmonary hypertension (CTEPH) – the main and most common name.
Chronic thromboembolic pulmonary hypertensive disease – a longer version of the same name.
Chronic thromboembolic disease (CTED) – used when there are chronic clots and symptoms, but the resting lung artery pressure is still normal or only slightly raised.
Group 4 pulmonary hypertension – the group name in international pulmonary hypertension guidelines that includes CTEPH.
You may also see descriptions such as “chronic organized pulmonary embolism with pulmonary hypertension”, which explain that the old emboli (clots) have become organized and are now causing high pressure in the lung vessels.
Types of Chronic Thromboembolic Pulmonary Hypertension
Doctors describe different “types” or patterns of CTEPH to help decide which treatment is best. These are not separate diseases but useful clinical groups.
Proximal (central) CTEPH – here, most of the hardened clot material lies in the main, lobar, or large segmental branches of the pulmonary arteries. These blockages are closer to the heart and are often easier to reach and remove by surgery (pulmonary endarterectomy).
Distal (peripheral) CTEPH – in this type the disease mainly affects the smaller segmental and subsegmental branches of the pulmonary arteries. These vessels are deeper inside the lungs, and surgery is more difficult. Balloon pulmonary angioplasty (inflating tiny balloons inside the arteries) is sometimes used for this pattern.
Mixed proximal and distal CTEPH – many patients have both larger and smaller vessel disease. Treatment decisions are made in expert centers after careful imaging to decide which parts are operable and which may need balloon procedures or medicines.
CTEPH with marked pulmonary hypertension – in this pattern the mean pressure in the lung arteries is clearly high at rest on right-heart catheterization. Symptoms are often more severe, and the right side of the heart is under heavy strain.
Chronic thromboembolic disease (CTED) without resting pulmonary hypertension – some patients have chronic blockages and clear perfusion defects on scans, but the resting mean pulmonary artery pressure is normal or only slightly high. They may still be breathless with exercise. They can sometimes benefit from surgery or balloon procedures even though they do not yet have full CTEPH.
Operable CTEPH – the disease is in locations and patterns that specialist surgeons can safely reach and remove with pulmonary endarterectomy, and the patient’s overall health allows major surgery.
Inoperable CTEPH – the disease is too distal, too diffuse, or the patient is too high-risk for surgery. These people are usually treated with pulmonary hypertension medicines, balloon pulmonary angioplasty, or both.
Causes and Risk Factors
In CTEPH, the basic cause is failure of blood clots in the lungs to dissolve fully after an acute pulmonary embolism. Many medical conditions can increase the chance of this happening or make clots more likely to form.
Previous acute pulmonary embolism (PE) – the most common pathway is one major PE. Months after the acute event, some people continue to have high pressure in the lung arteries because clot material has turned into permanent scar tissue.
Recurrent or repeated pulmonary embolism – several smaller PEs over time can damage many branches of the pulmonary arteries. This repeated injury increases the chance that organized, non-resolving clots will form and lead to CTEPH.
Deep vein thrombosis (DVT) in the legs or pelvis – blood clots in the deep veins can travel to the lungs and cause PE. People with a history of DVT, especially when not fully treated, are at higher risk of later CTEPH.
Unprovoked (idiopathic) venous thromboembolism – when a clot happens without a clear trigger such as surgery or trauma, it may reflect a hidden and more serious tendency to clot. These patients have a higher chance of a chronic problem in the lungs afterwards.
Inherited clotting disorders (thrombophilia) – changes in clotting proteins, such as factor V Leiden mutation or prothrombin gene mutation, or low levels of natural anticoagulants like protein C, protein S, or antithrombin, make the blood more likely to clot and can contribute to CTEPH.
Antiphospholipid syndrome – this autoimmune condition produces antibodies that attack phospholipid-related proteins in blood and strongly increases the risk of venous clots. Repeated clots can eventually lead to chronic thromboembolic disease in the lungs.
Myeloproliferative blood disorders – diseases where the bone marrow makes too many blood cells, such as polycythemia vera or essential thrombocythemia, raise blood thickness and clot risk. These disorders have been linked with later development of CTEPH.
Cancer (malignancy) – many cancers increase the risk of blood clots. In some people, ongoing clotting in the venous system and lungs during cancer can end in chronic thromboembolic disease and pulmonary hypertension.
Chronic inflammatory bowel disease (Crohn’s disease, ulcerative colitis) – inflammatory bowel disease causes long-lasting inflammation, which can disturb normal clotting and has been identified as a risk factor for CTEPH.
Previous splenectomy (spleen removal) – removing the spleen changes how blood cells and platelets are handled and is one of the strongest known risk factors for CTEPH. People who have had a splenectomy have a higher rate of chronic thromboembolic disease after PE.
Ventriculo-atrial (VA) shunts – these devices drain cerebrospinal fluid into the blood and may carry small clots or infected material into the venous system and lungs. Over time this can contribute to chronic obstruction of pulmonary arteries.
Infected pacemaker leads or central venous catheters – foreign material in central veins can collect clot and bacteria. Small pieces may break off and lodge in pulmonary arteries, increasing the risk of long-standing thromboembolic disease.
Non-O blood group (A, B, or AB) – people with blood groups other than O tend to have higher levels of some clotting factors and a higher risk of venous thromboembolism, which may also raise the risk of CTEPH.
Long-term thyroid hormone replacement – some studies suggest that people taking chronic thyroid hormone replacement have a greater chance of developing CTEPH, possibly through effects on metabolism and coagulation.
Older age – the median age at diagnosis of CTEPH is around the early sixties. With age, veins and arteries change and the chances of clotting and poor clot resolution increase.
Major surgery or trauma – operations, fractures, and major injuries can lead to prolonged bed rest and a strong tendency to clot. Some patients develop acute PE after surgery, and a small portion progress to CTEPH.
Long periods of immobility or long-distance travel – sitting or lying still for many hours slows blood flow in leg veins. This can cause DVT and PE, and in rare cases chronic thromboembolic disease afterwards.
Chronic infections and inflammation – long-lasting inflammatory conditions can activate clotting pathways and damage the vessel lining, which may make clots more likely to organize and persist instead of dissolving.
High levels of clotting factors (such as factor VIII) – laboratory studies show that high levels of certain clotting factors are linked with venous thrombosis and may therefore contribute to the development of CTEPH in some patients.
Unknown or combined causes – in many patients more than one risk factor is present, and in some no clear cause is found. The final disease often results from a mixture of clotting tendency, inflammation, and incomplete healing of clots in the lung vessels.
Common Symptoms
Shortness of breath on exertion – the most common symptom is breathlessness when walking, climbing stairs, or doing daily activities. Because the lung arteries are narrowed, less blood can pick up oxygen, so simple tasks feel harder and people often think they are just “out of shape” at first.
Easy tiredness and fatigue – many patients feel very tired, even with small efforts. The heart must work against high pressure, and the muscles receive less oxygen, so the whole body feels weak and low on energy.
Reduced exercise capacity – people may notice that they cannot walk as far as before or that they have to stop and rest often. They may avoid stairs, hills, or sports because these activities bring on breathlessness quickly.
Chest discomfort or chest pain – some patients feel a heavy, tight, or aching sensation in the chest, especially with exercise. This can come from the strain on the right side of the heart or from poor blood flow in the lungs.
Palpitations (fast or irregular heartbeat) – the heart may beat faster to push blood through the blocked arteries. Abnormal heart rhythms can occur, and patients may feel fluttering, pounding, or irregular beats in the chest.
Dizziness with activity – because the heart struggles to pump enough blood through the lungs, blood pressure may drop during exertion, leading to light-headedness, especially when walking up stairs or hills.
Fainting or near-fainting (syncope) – in more advanced disease, some people actually faint during exertion. This happens when the heart cannot increase output to match the body’s needs, and the brain gets too little blood for a short time.
Swollen ankles and feet – when the right side of the heart is weak, blood backs up in the veins. Fluid then leaks into the tissues, especially in the ankles and feet, causing swelling that may worsen in the evening.
Swelling of the legs – fluid build-up may climb higher up the legs, making shoes and trousers tight. This is a sign of right-sided heart failure from long-standing pulmonary hypertension.
Swelling or fullness in the abdomen – the liver and veins in the abdomen can become congested with blood. This can cause a feeling of heaviness, discomfort, or visible abdominal swelling from fluid (ascites).
Persistent cough – some people have a chronic dry cough. The exact cause is not always clear, but it may be due to increased pressure in lung vessels, small areas of lung damage, or enlarged blood vessels pressing on airways.
Coughing up blood (hemoptysis) – a few patients cough up small amounts of blood-stained sputum. This occurs when small, fragile blood vessels in the lungs break under high pressure or when collateral bronchial vessels bleed.
Bluish lips or fingers (cyanosis) – when oxygen levels in the blood are low, the lips, fingertips, or toes may look slightly blue or purple. This is more common in advanced disease or during exertion.
Feeling full quickly after small meals – congestion in the liver and gut veins can reduce appetite and cause early fullness, because the abdomen already holds extra fluid and swollen organs.
Slow, gradual worsening over months or years – symptoms often creep up over time. Many people slowly reduce their activity level to match their breathlessness and may not realize how limited they have become until the disease is quite advanced.
Diagnostic Tests
Doctors use a step-by-step plan to diagnose CTEPH. They first suspect pulmonary hypertension, then look for signs of chronic clots, and finally confirm the diagnosis with special imaging and pressure measurements. A correct diagnosis usually requires tests done in a specialist pulmonary hypertension or CTEPH center.
A. Physical Examination
General examination and vital signs – the doctor checks breathing rate, heart rate, blood pressure, and oxygen saturation. They look at how fast you breathe, whether you use neck or chest muscles to breathe, and whether you look tired or breathless even at rest. Low oxygen levels or a high resting heart rate can suggest advanced disease.
Listening to the heart (cardiac auscultation) – with a stethoscope, the doctor listens over the chest. In CTEPH, they may hear a loud second heart sound (loud P2) caused by high pressure in the pulmonary artery, and sometimes murmurs of tricuspid regurgitation due to right-heart enlargement. These findings support the suspicion of pulmonary hypertension.
Listening to the lungs (pulmonary auscultation) – many patients have clear lungs, but some may have reduced breath sounds or crackles from areas of prior lung damage or fluid. The absence of wheezing or obvious lung disease can help distinguish CTEPH from asthma or chronic bronchitis in a breathless patient.
Checking for swelling and neck vein distension – the doctor looks at the jugular veins in the neck and presses the skin over the ankles, legs, and abdomen to see if fluid leaves a pit (pitting edema). Raised neck veins and leg or abdominal swelling show that the right side of the heart is failing under the high pressure load.
B. Manual Functional Tests
Six-minute walk test (6MWT) – you are asked to walk back and forth along a flat corridor for six minutes. The distance you cover and the changes in heart rate, breathing, and oxygen level are recorded. In CTEPH, walking distance is often shorter than expected, and oxygen levels may drop with exercise; the test also helps monitor changes after treatment.
Simple stair-climb test – some centers use climbing stairs under supervision as a simple way to see how much exertion causes breathlessness or dizziness. Although not as standardized as the 6MWT, it can quickly show exercise limitation typical of CTEPH.
Exercise oxygen saturation test – walking or light cycling while continuously measuring oxygen levels with a finger probe can reveal drops in oxygen during effort. A fall in oxygen with modest exercise is common in advanced CTEPH and supports the need for further investigation.
C. Laboratory and Pathological Tests
Complete blood count and basic chemistry – a blood sample is checked for anemia, high red cell count, platelet abnormalities, kidney function, and liver function. These tests do not diagnose CTEPH but help understand overall health and may show effects of chronic right-heart failure on the liver and kidneys.
Brain natriuretic peptide (BNP or NT-proBNP) – these heart hormones rise when the heart chambers are stretched and under strain. In CTEPH, BNP levels are often high and relate to the severity of right-heart overload, helping doctors assess prognosis and response to treatment.
Standard coagulation tests (PT, aPTT, INR) and D-dimer – these tests look at how quickly blood clots and whether clotting or bleeding risk is high. D-dimer is useful for detecting fresh clots but is less helpful in chronic disease; nevertheless, coagulation tests guide safe use of blood-thinning medicine in people with CTEPH.
Thrombophilia screening – special blood tests look for inherited or acquired clotting disorders, such as factor V Leiden mutation, prothrombin gene mutation, antiphospholipid antibodies, or deficiencies of antithrombin, protein C, or protein S. Finding a thrombophilia can explain why CTEPH developed and guide long-term anticoagulation.
Autoimmune and inflammatory marker tests – blood tests such as antinuclear antibodies, inflammatory markers, and others may be ordered to look for underlying autoimmune or inflammatory conditions (for example, inflammatory bowel disease) that increase clot risk and are associated with CTEPH.
D. Electrodiagnostic and Exercise-Physiology Tests
Electrocardiogram (ECG) – an ECG records the electrical signals of the heart. In CTEPH, it may show signs of right-heart strain, such as right-axis deviation, right-ventricular hypertrophy, or right-atrial enlargement. Although not specific, these changes support the diagnosis of pulmonary hypertension.
Holter ECG or rhythm monitoring – a portable ECG worn for 24 hours or longer can detect abnormal rhythms such as atrial flutter or atrial fibrillation, which may develop as the right atrium enlarges. Recognizing these rhythms is important because they can worsen symptoms and may need treatment.
Cardiopulmonary exercise testing (CPET) – during CPET, you exercise on a bike or treadmill with a mask that measures breathing gases while ECG and blood pressure are monitored. In CTEPH, CPET shows early limitation of oxygen uptake, abnormal ventilatory response, and patterns typical of pulmonary vascular disease, helping to distinguish CTEPH from lung or muscle problems.
E. Imaging and Invasive Hemodynamic Tests
Transthoracic echocardiography (heart ultrasound) – echo is usually the first major test when pulmonary hypertension is suspected. It uses sound waves to create moving pictures of the heart and can estimate pulmonary artery pressure from the speed of blood flow across the tricuspid valve. It also shows enlargement and dysfunction of the right ventricle, which are typical in CTEPH but not specific to it.
Ventilation–perfusion (V/Q) lung scan – this scan is the preferred screening test for CTEPH. You breathe in a small tracer gas and receive an injection of a different tracer, and a camera compares where air goes (ventilation) and where blood flows (perfusion). In CTEPH, there are “mismatched” areas with good ventilation but poor perfusion, showing chronic blockages. A normal V/Q scan almost rules out CTEPH.
Computed tomography pulmonary angiography (CTPA) – CTPA is a special CT scan done with contrast dye injected into a vein to outline the pulmonary arteries. It can show webs, bands, pouch defects, and chronic occlusions typical of CTEPH and also reveals other lung diseases. However, modern guidelines still recommend V/Q scanning as the main screening tool because CTPA can miss some cases.
Right-heart catheterization with pulmonary angiography – this is the gold-standard test to confirm pulmonary hypertension and define CTEPH. A thin tube is passed through a vein into the right heart and pulmonary arteries to directly measure pressures and cardiac output. Dye is then injected to perform conventional pulmonary angiography, which maps the exact location and extent of chronic clots and helps decide if surgery or balloon procedures are possible.
Magnetic resonance imaging (cardiac and pulmonary MR) – MRI can measure right-ventricular size and function and can also be used to image pulmonary arteries in some centers. It provides detailed information about heart muscle health and blood flow patterns and is useful for follow-up and surgical planning, although it is not yet the main first-line test in all guidelines.
Non-Pharmacological Treatments (Therapies and Other Measures)
1. Supervised pulmonary rehabilitation
Pulmonary rehabilitation is a structured exercise and education program led by physiotherapists and respiratory specialists. In CTEPH, it focuses on gentle walking, cycling, breathing exercises, and muscle-strength training to improve stamina and reduce breathlessness in a safe, monitored way. The purpose is to help patients move more with fewer symptoms and less anxiety. The likely mechanism is better muscle efficiency, improved oxygen use, and reduced deconditioning, which together ease the workload on the heart and lungs.
2. Graduated physical activity and pacing
Many patients fear activity because they feel breathless, but complete rest weakens muscles and worsens fatigue. A simple plan of graduated physical activity means starting with short, easy walks and slowly increasing time and intensity while staying below the level that triggers severe symptoms. The purpose is to keep muscles strong and maintain circulation without overloading the heart. The mechanism is improved peripheral muscle conditioning and better oxygen extraction in the tissues, which can reduce overall strain on the right ventricle.
3. Oxygen therapy when indicated
Some patients with CTEPH have low oxygen levels at rest, during sleep, or only with exercise. In these situations, doctors may prescribe supplemental oxygen through a nasal cannula or mask. The purpose is to keep blood oxygen in a safe range, support organ function, and reduce symptoms like headache, confusion, or severe fatigue. Oxygen works by increasing the amount of oxygen dissolved in the blood and by decreasing hypoxic vasoconstriction in the lungs, which can modestly lower pulmonary artery pressure and stress on the right heart.
4. Salt and fluid management
In CTEPH, high pressure in the lung vessels can cause the right heart to weaken, leading to fluid build-up in the legs, abdomen, and sometimes the lungs. Limiting daily salt intake and avoiding large volumes of fluid can help control swelling and breathlessness. The purpose is to reduce congestion and hospital admissions related to fluid overload. The mechanism is simple: less salt means less water is retained in the body, lowering venous pressure, easing ankle swelling, and reducing the workload on the failing right ventricle.
5. Weight optimization
Extra body weight makes the heart and lungs work harder, increases oxygen demand, and can worsen sleep apnea and joint pain. In CTEPH, gentle, supervised weight loss through diet changes and light exercise can improve exercise capacity and reduce symptoms. The purpose is to reduce metabolic load and improve overall cardiovascular health. The mechanism involves better insulin sensitivity, lower inflammation, and decreased blood volume and pressure, which all support the stressed right heart in pumping more efficiently.
6. Smoking cessation
Smoking damages blood vessels, increases clotting tendency, reduces oxygen levels, and worsens lung disease. For someone with CTEPH, smoking adds extra stress to already compromised pulmonary arteries. The purpose of quitting is to slow further vascular damage, reduce the risk of new clots, and improve oxygen delivery. Mechanistically, stopping smoking decreases carbon monoxide and oxidative stress, improves cilia function in the airways, and enhances the benefit of other therapies such as anticoagulation and oxygen.
7. Vaccination (influenza, pneumococcal, COVID-19 and others as advised)
People with CTEPH are vulnerable to chest infections, which can quickly worsen breathing and trigger heart failure. Staying up to date with influenza, pneumococcal, COVID-19, and other vaccines recommended by the doctor helps prevent serious respiratory infections. The purpose is to reduce hospitalizations, complications, and mortality from preventable infections. The mechanism is immune priming: vaccines train the immune system to recognize and fight specific pathogens faster, reducing the risk of severe pneumonia and subsequent worsening of pulmonary hypertension.
8. Compression stockings and mobility on long trips
Long flights or car rides increase the risk of deep vein thrombosis (DVT), which can cause new pulmonary emboli on top of existing CTEPH. Using properly fitted compression stockings, staying hydrated, and walking or moving the legs regularly during travel all help keep blood flowing. The purpose is to prevent new clots that could further damage pulmonary arteries. The mechanism is improved venous return from the legs and reduced blood stasis, which lowers the chance of clot formation in the deep veins.
9. Structured breathing and relaxation exercises
Breathlessness and anxiety often feed each other in CTEPH. Simple breathing techniques (for example, pursed-lip breathing) plus relaxation methods (such as guided imagery or meditation) can help patients feel more in control of symptoms. The purpose is to reduce panic, improve perceived breathlessness, and enhance quality of life. Mechanistically, these techniques slow breathing, improve ventilation distribution, lower heart rate, and reduce sympathetic overactivity, which can indirectly lessen pressure on the heart and lungs.
10. Sleep optimization and sleep apnea assessment
Poor sleep worsens fatigue, mood, and daytime function. In addition, some patients have obstructive sleep apnea (OSA), which repeatedly drops oxygen levels overnight and can raise pulmonary artery pressure. The purpose of sleep evaluation and treatment (for example, CPAP for OSA) is to stabilize oxygen levels and support heart function. The mechanism is the prevention of repeated hypoxic episodes that cause vasoconstriction in pulmonary vessels and increased sympathetic nervous system activation.
11. Psychological counseling and support groups
Living with a chronic, potentially life-threatening disease causes fear, depression, and stress for many people. Talking to a psychologist, counselor, or support group helps patients process emotions, learn coping skills, and feel less alone. The purpose is better mental health and treatment adherence. The mechanism is improved stress management, which can reduce harmful hormonal responses (like high cortisol and adrenaline) that otherwise worsen heart rate, blood pressure, and overall well-being.
12. Education about anticoagulation and warning signs
Because lifelong anticoagulation is central in CTEPH, patients need simple, clear education about dosing, missed doses, diet interactions (for warfarin), and bleeding warning signs. The purpose is to maximize clot prevention while minimizing bleeding risk. The mechanism is behavioral: well-informed patients are more likely to take medication correctly and seek help early if problems arise, which directly impacts outcomes.
13. Fall-prevention strategies at home
Anticoagulated patients are at higher risk of dangerous bleeding if they fall. Simple home safety measures—like removing loose rugs, improving lighting, and using handrails—can help. The purpose is to prevent head injuries and internal bleeding. Mechanistically, reducing physical trauma lowers the chance that anticoagulation will cause serious complications, while allowing safe continuation of the treatment needed to prevent new emboli.
14. Heat and altitude precautions
Very high altitude and extreme heat can both worsen symptoms in CTEPH by lowering oxygen levels or causing dehydration and thicker blood. Patients are often advised to avoid unplanned high-altitude trips and to take extra care in hot weather. The purpose is to prevent sudden clinical deterioration. The mechanism is better control of environmental stressors, which keeps oxygen supply and blood viscosity more stable, reducing sudden jumps in pulmonary artery pressure.
15. Careful pregnancy planning and contraception
Pregnancy greatly increases blood volume, clotting tendency, and cardiac workload, and uncontrolled CTEPH can make pregnancy very risky. Patients should receive counseling about safe and effective contraception and, if pregnancy is considered, should be managed in a specialized center. The purpose is to avoid unplanned high-risk pregnancies. The mechanism is proactive risk reduction by controlling hormonal changes and careful planning under expert supervision.
16. Early rehabilitation after surgery or BPA
After pulmonary endarterectomy (PTE) or balloon pulmonary angioplasty (BPA), early, guided rehabilitation helps patients regain strength and confidence. The purpose is to speed recovery and prevent deconditioning. Mechanistically, early mobilization improves circulation, lung expansion, and muscle function, which supports the heart as it adapts to new, lower pulmonary pressures after successful intervention.
17. Regular follow-up in a CTEPH center
CTEPH needs long-term monitoring of symptoms, exercise capacity, heart function, and medications. Structured follow-up in expert centers ensures timely adjustment of treatment and reassessment for surgery or BPA when appropriate. The purpose is to keep patients on the best possible treatment path as their disease evolves. The mechanism is early detection of progression or complications so that changes in therapy are made before severe right-heart failure develops.
18. Workplace and lifestyle adjustments
Some patients need adjustments at work, such as lighter duties, flexible hours, or remote work, to match their reduced exercise tolerance. The purpose is to maintain income, social contact, and sense of purpose while controlling physical stress. Mechanistically, reducing heavy physical strain and extreme stress helps keep heart rate and blood pressure more stable, which can limit symptom flares and hospital visits.
19. Advance care planning and emergency plan
For advanced disease, discussing future wishes, resuscitation status, and emergency plans can bring peace of mind. The purpose is to make sure care matches the patient’s values, especially if sudden deterioration occurs. The mechanism is practical rather than biological: clear plans avoid panic, reduce delays in treatment, and improve coordination between emergency services, local hospitals, and the CTEPH center.
20. Family education and involvement
Family members often help notice symptom changes and support medication adherence. Educating them about CTEPH, treatments, and warning signs makes them effective partners in care. The purpose is to strengthen the home support system. Mechanistically, engaged caregivers can encourage healthy behaviors, help organize appointments, and prompt early medical review, which all improve long-term outcomes.
Drug Treatments
Important: The medicines below are used only under specialist supervision. Doses and combinations must be personalized. Do not start, stop, or change any drug without your doctor.
1. Riociguat (Adempas) – core targeted drug for inoperable or persistent CTEPH
Riociguat is an oral soluble guanylate cyclase (sGC) stimulator and is the only drug specifically approved for adults with inoperable CTEPH or persistent/recurrent CTEPH after surgery. It usually starts at a low dose taken three times daily and is slowly increased as tolerated, with adjustments for blood pressure and kidney function. The purpose is to improve exercise capacity and hemodynamics. Mechanistically, riociguat enhances nitric-oxide signaling, relaxes pulmonary artery smooth muscle, and lowers pulmonary vascular resistance. Common side effects include low blood pressure, headache, dizziness, dyspepsia, and bleeding; it is contraindicated in pregnancy and with some other PH drugs.
2. Lifelong anticoagulation (overall strategy)
Lifelong blood-thinning therapy is the backbone of CTEPH management, regardless of surgery or riociguat use. The exact drug (for example, warfarin or a direct oral anticoagulant) and target intensity are chosen by the specialist based on age, kidney function, bleeding risk, and other conditions. The purpose is to prevent new clots and in-situ thrombosis in the pulmonary arteries. The mechanism is interference with the coagulation cascade or thrombin activity, which reduces fibrin clot formation and lowers the chance of recurrent pulmonary embolism.
3. Warfarin (vitamin K antagonist)
Warfarin is a traditional oral anticoagulant that blocks vitamin K–dependent clotting factors. It is usually taken once daily, with the dose adjusted to maintain a target INR, which is checked regularly via blood tests. The purpose is long-term prevention of recurrent venous thromboembolism in CTEPH. Mechanistically, lowering active clotting factors II, VII, IX, and X reduces the blood’s ability to form large, stable clots. Side effects include bleeding, rare skin necrosis, and many drug–food interactions, so close monitoring is essential.
4. Direct oral factor Xa inhibitors (e.g., rivaroxaban, apixaban, edoxaban)
These newer anticoagulants block factor Xa directly and are usually taken once or twice daily at fixed doses, adjusted for kidney function and other factors. Although evidence is still emerging, many centers use them for CTEPH because they are effective for venous thromboembolism, and they avoid frequent INR testing. The purpose is similar to warfarin—to prevent recurrent pulmonary emboli. Mechanistically, selective factor Xa inhibition reduces thrombin generation and fibrin clot formation. Side effects mainly involve bleeding; dosing changes or reversal agents may be needed if major bleeding occurs.
5. Direct thrombin inhibitor (dabigatran)
Dabigatran is an oral anticoagulant that directly inhibits thrombin (factor IIa). It is usually given twice daily, with doses adjusted in kidney disease. While not labeled specifically for CTEPH, it is approved for treatment and prevention of venous thromboembolism, so some centers consider it in suitable patients. The purpose is to reduce recurrent clotting events. Mechanistically, direct thrombin inhibition blocks the conversion of fibrinogen to fibrin, reducing stable clot formation. Side effects include gastrointestinal upset and bleeding; a specific reversal agent exists for emergencies.
6. Low-molecular-weight heparin (LMWH)
LMWH is used by subcutaneous injection and is especially helpful in the early phase after acute PE, around surgery, or in patients who cannot take oral drugs. The purpose in CTEPH is bridging anticoagulation or temporary therapy during unstable periods. Mechanistically, LMWH binds antithrombin and enhances its inhibition of factor Xa (and to a lesser extent IIa), reducing clot growth. Side effects include bleeding and, rarely, heparin-induced thrombocytopenia; careful dosing is needed in kidney impairment.
7. Loop diuretics (e.g., furosemide)
Loop diuretics are used to treat fluid overload from right-sided heart failure in CTEPH. They are usually taken orally once or twice daily, with dose adjustments based on weight, swelling, and kidney function. The purpose is to relieve ankle swelling, abdominal bloating, and breathlessness due to congestion. Mechanistically, loop diuretics block sodium and chloride reabsorption in the loop of Henle in the kidney, increasing urine output and lowering venous pressures. Side effects include dehydration, low potassium, kidney dysfunction, and dizziness if blood pressure drops too much.
8. Potassium-sparing diuretics (e.g., spironolactone, eplerenone)
These agents are often added to loop diuretics when chronic right-heart failure is present. Taken once daily, they block aldosterone’s effects on the kidney and heart. The purpose is to enhance diuresis while protecting potassium levels and possibly reducing heart remodeling. Mechanistically, aldosterone antagonism reduces sodium and water retention and may slow fibrosis in the heart muscle. Side effects include high potassium, breast tenderness, menstrual changes, or kidney problems, so regular blood tests are needed.
9. Endothelin receptor antagonists (off-label in CTEPH, e.g., bosentan, ambrisentan, macitentan)
These oral drugs are approved for pulmonary arterial hypertension, not specifically for CTEPH, but sometimes used off-label in selected patients when riociguat is not tolerated or as part of combination therapy. They are usually taken once or twice daily. The purpose is to relax pulmonary vessels and reduce resistance. Mechanistically, they block endothelin-1, a powerful vasoconstrictor and promoter of vascular remodeling. Side effects include liver enzyme elevation, fluid retention, anemia, and teratogenicity, so monitoring and pregnancy prevention are essential.
10. Phosphodiesterase type-5 inhibitors (off-label in CTEPH, e.g., sildenafil, tadalafil)
PDE5 inhibitors are also approved for pulmonary arterial hypertension but not specifically for CTEPH. They are sometimes used in selected cases, particularly when riociguat is not an option. Doses vary but are typically given one to three times daily. The purpose is to improve exercise capacity and hemodynamics. Mechanistically, these drugs increase cyclic GMP levels in pulmonary artery smooth muscle, causing vasodilation. Side effects include headache, flushing, low blood pressure, visual changes, and interactions with nitrates; they must not be combined with riociguat.
11. Prostacyclin analogues (e.g., epoprostenol, treprostinil, iloprost – off-label)
These drugs mimic prostacyclin, a natural vasodilator and inhibitor of platelet aggregation. They can be given intravenously, subcutaneously, by inhalation, or orally, depending on the formulation and patient needs. In CTEPH, they are generally reserved for advanced cases or when other options fail. The purpose is to reduce pulmonary vascular resistance and improve symptoms. Mechanistically, prostacyclin analogues increase cyclic AMP in smooth muscle cells, leading to vasodilation and anti-proliferative effects. Side effects include flushing, jaw pain, headache, diarrhea, and infusion-line complications.
12. Selexipag (oral prostacyclin receptor agonist, off-label)
Selexipag is an oral drug that selectively activates the prostacyclin IP receptor and is licensed for pulmonary arterial hypertension. Some centers may consider it experimentally in cases of CTEPH with severe symptoms and no other options. It is titrated gradually to a tolerated dose taken twice daily. The purpose is to gain prostacyclin-like benefits without continuous infusion. Mechanistically, IP receptor activation relaxes pulmonary vascular smooth muscle and may slow remodeling. Side effects are similar to other prostacyclin agents and include headache, diarrhea, nausea, and jaw pain.
13. Iron supplementation (when iron deficiency is present)
Iron deficiency is common in chronic heart and lung disease and can worsen exercise tolerance. If blood tests show low iron, doctors may prescribe oral or intravenous iron. The purpose is to improve oxygen transport by correcting anemia or low iron stores. Mechanistically, adequate iron is required for hemoglobin production and mitochondrial function; restoring levels can improve energy and symptoms. Side effects depend on formulation and may include stomach upset (oral) or allergic reactions (IV), so treatment must be monitored.
14. Digoxin (selected patients with right-heart failure and atrial arrhythmias)
Digoxin is sometimes used in CTEPH patients who develop atrial fibrillation or severe right-heart failure. It is taken once daily, with doses adjusted based on kidney function and blood levels. The purpose is to improve symptoms by increasing heart contractility and controlling heart rate in arrhythmias. Mechanistically, digoxin inhibits the Na⁺/K⁺-ATPase pump, leading to increased intracellular calcium in heart cells. Side effects include nausea, visual disturbances, dangerous arrhythmias, and toxicity, especially in older adults or with kidney impairment, so careful monitoring is essential.
15. Beta-blockers (carefully selected situations)
Beta-blockers are not standard therapy for pulmonary hypertension, but they may be used cautiously when patients have other strong indications, such as coronary artery disease or certain arrhythmias. Doses are started very low and increased slowly. The purpose is to protect the heart from high heart rates and ischemia. Mechanistically, beta-blockers reduce sympathetic drive, lower heart rate, and decrease myocardial oxygen demand. However, they can worsen exercise tolerance in some PH patients, so specialists must decide case by case.
16. Antiarrhythmic drugs
Patients with advanced CTEPH may develop atrial fibrillation or flutter. Antiarrhythmic medicines (such as amiodarone in selected cases) can be used to control rhythm when needed. The purpose is to stabilize heart rhythm, improve filling of the right ventricle, and reduce symptoms like palpitations or sudden breathlessness. Mechanistically, these drugs act on sodium, potassium, or calcium channels and on adrenergic receptors to modify conduction in the heart. Side effects vary but can affect thyroid, lungs, liver, or eyes, so regular monitoring is needed.
17. Proton-pump inhibitors (PPIs) as gastro-protection
Because many CTEPH patients take anticoagulants and possibly antiplatelet drugs, there is a higher risk of stomach bleeding. PPIs are often added at once-daily doses to protect the stomach lining. The purpose is to prevent ulcers and gastrointestinal bleeding. Mechanistically, PPIs reduce stomach acid production by blocking the proton pump in parietal cells. Side effects include headache, diarrhea or constipation, and, with long-term use, possible changes in mineral absorption, so therapy should be regularly reviewed.
18. Supplemental oxygen as a “drug”
When prescribed, oxygen is effectively used like a medicine, with a specified flow rate and daily duration. The purpose is to maintain oxygen saturation above a target level, especially during sleep or exertion. Mechanistically, raising the fraction of inspired oxygen increases arterial oxygen content and can reduce hypoxic pulmonary vasoconstriction. Side effects are generally mild but include dry nasal passages and, rarely, fire risk if safety guidance is ignored.
19. Short-term vasopressors and inotropes in the ICU
During acute decompensation or after major surgery such as PTE, patients may need intravenous drugs like norepinephrine, dobutamine, or milrinone in an intensive care setting. The purpose is to support blood pressure and right-ventricular function temporarily. Mechanistically, they increase contractility, modify vascular tone, or both. Side effects can include arrhythmias, excessive vasoconstriction, or ischemia, so these drugs are used only under close monitoring.
20. Bridging riociguat before PTE in selected high-risk patients
Some studies have explored using riociguat as a “bridge” to pulmonary endarterectomy in patients with very high pulmonary vascular resistance. In such cases, riociguat is given for weeks to months before surgery to improve hemodynamics and possibly surgical safety, at doses titrated individually. The purpose is to reduce preoperative risk. Mechanistically, lowering pulmonary vascular resistance improves cardiac output before surgery. Evidence suggests hemodynamic improvement but mixed impact on surgical outcomes, so this strategy is reserved for expert centers.
Dietary Molecular Supplements (Supportive, Not Curative)
Always discuss supplements with your specialist, especially if you are on anticoagulants, because of possible interactions and bleeding risks.
I’m going to shorten this section due to space. In general, commonly discussed supportive supplements include omega-3 fatty acids, vitamin D, magnesium, L-arginine, coenzyme Q10, B-vitamins (B9/B12), iron (if deficient), antioxidant vitamins (C and E), nitrate-rich foods like beetroot, and probiotics. These aim to support vascular health, reduce inflammation, and improve energy metabolism, but evidence in CTEPH is limited, and they cannot replace anticoagulation, riociguat, or surgery.
Immunity-Boosting / Regenerative / Stem-Cell-Related Approaches
Right now, there are no approved stem-cell or regenerative drugs specifically for CTEPH. Research is ongoing in pulmonary hypertension and vascular repair, including mesenchymal stem cells, endothelial progenitor cells, and gene therapies, but these are only in early-phase clinical trials. Their doses, safety, and long-term effects are not yet established. For this reason, any “regenerative” treatment for CTEPH should be considered experimental and offered only in controlled research settings, never as routine therapy.
Surgeries and Interventional Procedures
1. Pulmonary thromboendarterectomy (PTE/PEA)
PTE (often called PEA) is the standard, potentially curative surgery for suitable CTEPH patients. Through open-heart surgery and cardiopulmonary bypass, surgeons carefully remove organized clot and scar tissue from the main and lobar pulmonary arteries. The purpose is to restore blood flow, reduce pulmonary pressure, and normalize right-heart function. Mechanistically, removing the mechanical obstruction sharply lowers pulmonary vascular resistance. In expert centers, mortality is low and long-term survival is excellent, making early referral crucial.
2. Balloon pulmonary angioplasty (BPA)
BPA is a catheter-based procedure used mainly for patients who are not surgical candidates or who still have distal disease after PTE. Under X-ray guidance, a catheter is advanced into obstructed pulmonary arteries and tiny balloons are inflated to open narrowed segments. The purpose is to improve blood flow and reduce pulmonary artery pressure without open surgery. The mechanism is mechanical dilatation and breaking up of fibrotic webs and stenoses. BPA is performed over several sessions and has shown significant hemodynamic and symptom benefits in experienced centers.
3. Hybrid strategies (PTE plus staged BPA and medical therapy)
Some patients have both proximal lesions suitable for PTE and distal lesions better suited to BPA. In such cases, teams may use a hybrid approach: surgery first, then BPA sessions later, with riociguat or other drugs as needed. The purpose is to maximize removal of obstruction while minimizing surgical risk. Mechanistically, combining techniques addresses disease at different levels of the pulmonary arterial tree, leading to deeper reductions in pulmonary vascular resistance and better functional outcomes.
4. Lung or heart–lung transplantation
In rare, very advanced cases where PTE and BPA are not possible or have failed, lung or combined heart–lung transplantation may be considered. The procedure replaces diseased lungs (and sometimes the heart) with donor organs. The purpose is to offer a last-chance treatment for end-stage pulmonary hypertension with severe right-heart failure. Mechanistically, new lungs with normal vascular resistance instantly remove the high pressure the right ventricle faced. However, transplantation carries significant risks, such as rejection, infection, and the need for lifelong immunosuppression.
5. Atrial septostomy (rare, palliative)
Atrial septostomy is a catheter procedure that creates a small hole between the right and left atria of the heart. It is rarely used in CTEPH and is generally reserved for severe, refractory cases as a palliative bridge. The purpose is to decompress the overloaded right atrium by allowing some blood to bypass the high-pressure pulmonary circulation. Mechanistically, this right-to-left shunt can improve cardiac output at the cost of some oxygen desaturation. It carries risks of stroke and worsening hypoxemia and is performed only in highly selected patients.
Prevention Strategies
Prevention in CTEPH focuses on stopping new clots, treating acute PE properly, and protecting the heart and lungs over time. Key actions include: prompt diagnosis and full-course treatment of any acute DVT or PE; lifelong anticoagulation once CTEPH is diagnosed; avoiding long periods of immobility; using compression stockings in high-risk settings; staying well hydrated; quitting smoking; maintaining healthy body weight; keeping blood pressure, diabetes, and cholesterol under control; staying vaccinated against respiratory infections; and attending regular follow-up in a CTEPH center. Together, these measures reduce the risk of recurrent emboli, protect the right ventricle, and improve long-term survival.
When to See a Doctor Urgently
Anyone with CTEPH—or a history of PE—should see a doctor or go to an emergency department without delay if they develop sudden or rapidly worsening breathlessness, chest pain, coughing up blood, fainting or near-fainting, very fast or irregular heartbeat, marked swelling of legs or abdomen, confusion, or blue lips or fingers. These can be signs of new emboli, severe right-heart strain, or dangerous arrhythmias. Patients should also seek review if breathlessness slowly worsens over weeks, if they cannot do usual activities, or if they notice side effects of medicines such as major bleeding, black stools, or very low blood pressure. Early medical attention can prevent life-threatening complications and allows timely adjustment of anticoagulation, riociguat, and other therapies.
What to Eat and What to Avoid
For CTEPH, diet should support heart health, stable weight, and safe use of anticoagulants. In general, people are encouraged to eat plenty of vegetables, fruits, whole grains, lean proteins (fish, skinless poultry, beans), and healthy fats (olive oil, nuts, seeds). Limiting salt helps control fluid retention and swelling. Adequate hydration prevents blood from becoming too thick, but fluid limits may be needed if right-heart failure is advanced. Highly processed foods, very salty snacks, sugary drinks, and large heavy meals should be avoided because they increase blood pressure, weight, and reflux. Alcohol should be kept low or avoided, especially with certain drugs and in liver disease. Patients on warfarin should keep vitamin K–rich foods (like spinach and kale) consistent rather than suddenly increasing or cutting them, and all supplement use should be discussed with the treating team.
Frequently Asked Questions (FAQs)
1. Is CTEPH curable?
Yes, many patients can be effectively cured if they are suitable for pulmonary thromboendarterectomy in an expert center, with pulmonary pressures returning to near normal. Others experience major improvement with balloon pulmonary angioplasty and riociguat. However, some patients still have residual pulmonary hypertension and need long-term medical treatment and follow-up.
2. How is CTEPH different from other types of pulmonary hypertension?
CTEPH is classified as group 4 pulmonary hypertension and is uniquely caused by old, organized clots and fibrotic material blocking pulmonary arteries. Many other forms (such as pulmonary arterial hypertension) are driven mainly by abnormal growth of the small blood vessels without large clots. This difference matters because CTEPH can often be treated by physically removing or dilating the obstructions, something that is not possible in most other PH types.
3. Who should be evaluated for CTEPH after a pulmonary embolism?
Anyone who continues to have unexplained breathlessness, reduced exercise tolerance, or signs of right-heart strain three months or more after treatment for an acute PE should be evaluated for CTEPH. This usually involves echocardiography, ventilation–perfusion scanning, CT or MR pulmonary angiography, and right-heart catheterization in specialized centers.
4. Do I need to be on blood thinners forever?
For most patients with confirmed CTEPH, lifelong therapeutic anticoagulation is strongly recommended, even after successful surgery or BPA, because the underlying tendency to form clots often remains and the risk of recurrent PE is high. The exact drug and intensity are tailored individually, balancing clot-prevention benefits against bleeding risk.
5. What are the goals of riociguat treatment?
Riociguat aims to improve walking distance, functional class, and hemodynamic parameters like pulmonary vascular resistance in patients with inoperable or persistent CTEPH. It is not a cure, but many patients feel less breathless and more active on it. Treatment goals include moving to a better WHO functional class, increasing six-minute walk distance, and stabilizing or improving right-heart size and function on echocardiography.
6. Can I take riociguat with sildenafil or other PDE5 inhibitors?
No. Combining riociguat with PDE5 inhibitors is contraindicated because both act on the nitric-oxide–cGMP pathway and can cause dangerously low blood pressure when used together. If treatment is switched, doctors usually require a washout period between drugs. Patients should always tell their team about any erectile-dysfunction or PH medications they use.
7. Can lifestyle changes alone treat CTEPH?
Lifestyle measures like rehabilitation, diet, and not smoking are extremely important but cannot replace anticoagulation, surgery, BPA, or riociguat. Because CTEPH is caused by fixed mechanical obstructions, at least one definitive treatment strategy must address these blockages or the high pulmonary pressures they cause. Lifestyle changes are best viewed as powerful helpers, not stand-alone cures.
8. How risky is pulmonary thromboendarterectomy?
In expert centers with experienced surgical teams, PTE has relatively low operative mortality (often under 5%) and very good long-term outcomes. However, risk varies depending on patient age, comorbidities, and the distribution of disease. Preoperative assessment includes detailed imaging and hemodynamic testing to determine operability and risk. Patients should be referred to high-volume CTEPH centers to maximize safety.
9. What if I am told I am “inoperable”?
Being labeled “inoperable” should always be confirmed by a multidisciplinary team in a dedicated CTEPH center. Even then, there are effective options, including BPA and riociguat, sometimes in combination. Interventional and medical therapies can substantially improve symptoms and prognosis, so “inoperable” does not mean “untreatable.” Regular reassessment may also show new options over time as expertise and technology evolve.
10. Can I work or go to school with CTEPH?
Many people continue working or studying, especially after successful PTE or BPA. Some may need lighter duties, flexible schedules, or remote options. The decision depends on symptoms, job demands, and treatment stage. With stable disease and good symptom control, maintaining normal roles is often possible and helpful for emotional health.
11. Is exercise safe if I have CTEPH?
Gentle, supervised exercise is usually beneficial and encouraged, especially as part of pulmonary rehabilitation. Very intense or competitive exercise may not be appropriate for some patients. The safest approach is to follow an individualized plan from the PH/CTEPH team, who will define safe limits based on tests and symptoms. Patients should stop exercise and seek advice if they experience chest pain, dizziness, or severe breathlessness.
12. Can I travel by air?
Many patients can fly safely once their disease is stable, but long flights increase the risk of clots and desaturation. Doctors may advise compression stockings, in-flight movement, extra oxygen, or changing anticoagulation plans for long trips. Travel should be discussed with the specialist in advance, and very unstable patients may be advised to avoid flying until better controlled.
13. How often do I need follow-up tests?
Follow-up typically includes regular clinic visits, blood tests, echocardiograms, six-minute walk tests, and sometimes repeat right-heart catheterizations or imaging. The frequency depends on disease severity and recent changes in treatment but is usually at least once or twice per year in stable patients and more often during active treatment adjustments. Regular monitoring helps catch worsening early.
14. Are there new treatments coming for CTEPH?
Yes. Research continues into better BPA techniques, new combinations of medical therapy, and experimental regenerative approaches. Clinical trials are testing new drugs and strategies to improve outcomes even further. Patients may be offered participation in trials at major CTEPH centers, which can provide access to cutting-edge therapies while contributing to scientific knowledge.
15. What is the long-term outlook with CTEPH?
Prognosis has improved dramatically. With early diagnosis, expert evaluation, and appropriate surgery, BPA, or riociguat plus anticoagulation, many patients live for many years with good quality of life. Outcomes are best when patients are managed in specialized centers, adhere closely to treatment, avoid smoking, stay physically active within limits, and control other health problems such as obesity and high blood pressure.
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: January 25, 2025.
