What are the other Names for this Condition? (Also known as/Synonyms)

• CTEPH (Chronic Thromboembolic Pulmonary Hypertension)
• Pulmonary Hypertension due to Chronic Blood Clots in Lungs
• Pulmonary Hypertension due to Embolic Disease

What is Chronic Thromboembolic Pulmonary Hypertension? (Definition/Background Information)

• Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a unique pulmonary vascular condition caused by chronic block of the major lung arteries
• The condition may appear a few months or many years after the sudden blockage in a lung artery by a blood clot (acute pulmonary embolism). However, up to 60% of the individuals may have no history of acute pulmonary embolism
• Pulmonary hypertension (PH) is a disorder characterized by very high blood pressure (above normal) in the lungs due to a variety of causes. It should not be confused with systemic hypertension, otherwise known as ‘high blood pressure’
• An elevated pulmonary blood pressure causes the right side of the heart to work harder, placing an increased burden on the heart. It is often caused by various lung and heart disease but can be associated with many other conditions too
• The World Health Organization (WHO) has clinically classified pulmonary hypertension according to certain groups. Chronic Thromboembolic Pulmonary Hypertension forms part of WHO group 4
• The signs and symptoms of Chronic Thromboembolic Pulmonary Hypertension may include shortness of breath, chest pain, fatigue, and dizziness. The signs and symptoms also depend on any associated conditions
• Following a diagnosis of Chronic Thromboembolic Pulmonary Hypertension, the treatment measures may involve surgery. The prognosis of CTEPH may be improved if the condition is diagnosed promptly and treated appropriately. However, the overall prognosis depends on several factors that may vary from one individual to another

Who gets Chronic Thromboembolic Pulmonary Hypertension? (Age and Sex Distribution)

• Chronic Thromboembolic Pulmonary Hypertension is a rare disorder that occurs at a frequency of 3-30 cases per 1,000,000 individuals
• The presentation of symptoms typically take place in the sixth decade of life i.e., in between ages 50 and 60 years
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Chronic Thromboembolic Pulmonary Hypertension? (Predisposing Factors)

The risk factors Chronic Thromboembolic Pulmonary Hypertension (CTEPH) may include:

• A positive family history may be an important risk factor, since CTEPH can be inherited 
• A prior episode of pulmonary embolism: Studies have demonstrated that approximately 0.5-5% of those who have had a pulmonary embolism may acquire CTEPH
• Older age 
• Previous splenectomy (surgical removal of the spleen)
• Clotting disorders
• Inflammatory diseases such as osteomyelitis
• Cancer

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Chronic Thromboembolic Pulmonary Hypertension? (Etiology)

In individuals with Chronic Thromboembolic Pulmonary Hypertension (CTEPH), the pathogenesis of the condition is thought to be related to the blood vessels in the lungs being obstructed by emboli or old blood clots. This in turn builds up pressure behind the blood clot, contributing to pulmonary hypertension (PH).

• Another working theory is that the small blood vessels in the lungs respond to the alternate blood flow by the similar mechanism seen in pulmonary arterial hypertension, termed vascular remodeling. Small blood vessels narrow and harden which subsequently leads to PH
• Research suggests there may be a genetic predisposition leading to abnormal vascular healing after pulmonary embolism in susceptible individuals. However, no specific gene mutations have been identified in individuals with CTEPH

It is reported that nearly 60% of affected individuals do not have a history of pulmonary embolism, and the cause may be related to clotting problems.

What are the Signs and Symptoms of Chronic Thromboembolic Pulmonary Hypertension?

The signs and symptoms of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) depend on a set of several factors that include the age and overall health status of the individual.

The common signs and symptoms exhibited by individuals with CTEPH are similar to most individuals with pulmonary hypertension. These include:

• Progressive shortness of breath, especially while exercising, is the most common symptom
• Fatigue (frequent tiredness)
• Chest pain
• Dizziness and fainting
• Swelling of the ankles/legs
• Palpitations
• Bluish lips and skin, observed during the later stages
• Irregular heartbeat (arrhythmias)
• Fluid in the abdomen (ascites)

The signs and symptoms related to the associated condition (if any present) may be noted. Often, the detection of the associated condition may help in determining the cause of pulmonary hypertension.

How is Chronic Thromboembolic Pulmonary Hypertension Diagnosed?

To diagnose Chronic Thromboembolic Pulmonary Hypertension (CTEPH), a diagnosis of pulmonary hypertension (PH) must first be established. This involves certain preliminary diagnostic procedures. Depending on the results of these tests, confirmation will be made with a right-heart catheterization.

After a diagnosis is made, the healthcare provider may inquire about a history of blood clotting disorders, a history of blood clots, survey for risk factors associated with blood clots, and/or enquire about a history of pulmonary emboli. This can help in diagnosing and differentiating CTEPH from other types of pulmonary hypertension.

The preliminary procedures may include:

• A complete physical examination of the patient 
• A thorough checking of the patient’s medical history and a detailed checking of the family history of the patient
• Blood tests:
  • Blood tests help rule out other diseases, such as HIV infection, liver disease, rheumatoid or connective tissue disease, and thyroid disease
  • They also help in checking the blood oxygen levels
  • The measurement of brain natriuretic peptide (BNP) can be used to assess the strain on one’s heart
• Chest X-ray: Chest X-rays can reveal structural signs of pulmonary hypertension by identifying changes in the pulmonary arteries or enlargement of the right side of the heart
• Electrocardiogram (ECG): An electrocardiogram checks the electrical impulses of the heart. There are certain identifiable patterns on an ECG that may indicate pulmonary hypertension. However, ECG is not specific enough to diagnose the condition by itself, so a combination of tests may be recommended by the healthcare provider
• Echocardiogram: In this procedure, a sonogram of the heart is taken and used to measure overall functioning as well as measure the pressure within the chambers of the right heart. An echocardiogram is also often times used to monitor a patient’s condition after diagnosis and during treatment
• Pulmonary function tests: These tests help measure the quality of breathing and check the functioning of the lungs (such as how much air is breathed in and out, as well as the quality of oxygen exchange)
• Exercise tolerance test (six-minute walk test): This helps to measure the patient’s ability to exercise
• Nuclear scan (ventilation/perfusion scan or V/Q scan): This tool helps identify any new or chronic blood clots in the vessels of the lungs that could be causing pulmonary hypertension

The gold standard for pulmonary hypertension diagnosis and management is right-heart catheterization and acute vasodilator challenge.

• Right-heart catheterization:
  • If pulmonary hypertension is suspected based off preliminary tests and procedures, a right-heart catheterization test is ordered to help confirm the diagnosis
  • This test can accurately quantify right-heart pressures (measure the pressure within the chambers of the right heart), especially the pressure inside the pulmonary arteries
  • During this procedure, a very small catheter is inserted into a large vein (either within the patient’s groin or neck) and passed into the patient’s heart and vasculature to measure the internal blood pressures 
• Vasodilator study (acute vasodilator challenge):
  • While this test is not used to necessarily “diagnose” pulmonary hypertension, it is used to evaluate the patient for possible therapeutic management
  • Like right-heart catheterization, a catheter is placed within the pulmonary artery to test for vasodilation (or relaxation) in response to a class of medications called calcium channel blockers (CCBs)
  • The response and dosing of CCBs can be evaluated with this procedure

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Chronic Thromboembolic Pulmonary Hypertension?

Following are the possible complications that may arise due to Chronic Thromboembolic Pulmonary Hypertension: 

• Right-sided heart failure with hepatic congestion (due to deposition of stones in the liver)
• Pedal edema: Swelling of the leg or ankle
• Pleural effusions: Building-up of excess fluid around the lungs
• Worsening dyspnea (shortness of breath) upon exertion

How is Chronic Thromboembolic Pulmonary Hypertension Treated?

The treatment of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) depends on a set of several factors that includes the severity of the signs and symptoms, age of the individual, and overall health of the individual. For individuals with CTEPH, treatment of the underlying embolic disease is essential. In general, CTEPH is rare and is best treated at a medical center with appropriate expertise.

For those who are good surgical candidates, there are two main procedures:

• Pulmonary thromboendarterectomy (PTE):
  • In this procedure, large and/or old blood clots are removed from the arteries of the lungs
  • This procedure, in many instances, could completely reverse the condition, thus making it a gold-standard treatment for CTEPH
• Balloon pulmonary angioplasty (BPA):
  • In this procedure, a catheter is placed through the right-side of the heart to the affected vessels containing the clot
  • A balloon is deployed to create a patent opening within the clot
  • This takes place as the clots are pushed to the sides of the vessel walls, thus allowing blood to pass through the blood vessels
  • This treatment often requires multiple (repeat) procedures 

For those who are not appropriate surgical candidates, there are various medical therapies available. Several medical treatments are highlighted below:

• Conventional medical therapies:
  • Calcium channel blockers (CCBs): These are a group of medications that help vasodilate (or relax) the arteries. However, CCBs are only appropriate for patients demonstrating a favorable response to the vasodilator study
  • Inotropic agents: These are medications that assist in the pumping of the heart 
  • Diuretics, salt limitation, and weight monitoring may be recommended, to limit excess strain on the heart
  • Supplemental oxygen may help an individual meet the ‘oxygen needs’ for normal daily activities
  • Blood thinners: These medications help prevent blood clots, especially in the lung blood vessels
• Oral, inhaled, subcutaneous, or intravenous treatment options:
  • Endothelin receptor antagonists (ERAs) help in preventing pulmonary blood vessels from narrowing which helps keep the pressures towards normal levels
  • Phosphodiesterase inhibitors (PDE 5 Inhibitors), prostacyclin analogues, and soluble guanylate cyclase (sGC) stimulators, all aid in allowing vessels of the lungs to vasodilate (or relax)
• Additional treatment options may include:
  • Lifestyle modifications, such as nutrition, exercise, avoiding tobacco, and limiting alcohol consumption, are beneficial
  • Judicious exercising may be effective in limiting deconditioning (by building stamina), improving the quality of life, and exercising capacities. Isometric exercises, such as heavy weightlifting, should be avoided
  • Other treatments, depending on the etiology (cause) of Pulmonary Hypertension, may include various cardiothoracic procedures
  • Lung transplantation may be required with advanced forms of the disorder

How can Chronic Thromboembolic Pulmonary Hypertension be Prevented?

The non-modifiable risk factors for Chronic Thromboembolic Pulmonary Hypertension (CTEPH), such as age, gender, and genetics (family history), cannot be controlled; and therefore, it may not be possible to prevent pulmonary hypertension that develops from these factors. However, an early and effective treatment is critical and imperative.

The most effective method of minimizing one’s risk for CTEPH is to reduce the likelihood of developing the risk factors. This may include:

• Bringing about certain lifestyle changes including:
  • Early ambulation after surgery (if appropriate)
  • Use of compression stockings in case of long periods of immobility
  • Avoiding smoking
  • Maintaining a healthy body weight
  • Ambulation and appropriate exercise during pregnancy, or while taking hormone replacement therapy/birth control pills
• If there is a family history of pulmonary hypertension, then genetic counseling will help assess risks before planning for a child
• For those with a pre-existing condition that is a risk factor for CTEPH, seeking medical attention at the onset of symptoms may help avoid worsening of the condition and complications

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Chronic Thromboembolic Pulmonary Hypertension? (Outcomes/Resolutions)

• The prognosis of Chronic Thromboembolic Pulmonary Hypertension is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications. Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Chronic Thromboembolic Pulmonary Hypertension:

The following DoveMed website link is a useful resource for additional information:

https://www.dovemed.com/diseases-conditions/pulmonary-hypertension-ph/