Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Overview

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a distinct and potentially curable form of pulmonary hypertension that results from unresolved blood clots in the pulmonary arteries. Following an acute pulmonary embolism, most blood clots typically dissolve with time or anticoagulant therapy. However, in some individuals, portions of the clot remain lodged in the arteries, gradually transforming into fibrotic tissue that narrows or obstructs blood flow. This persistent blockage increases pressure within the pulmonary circulation and places a chronic strain on the right side of the heart, eventually leading to progressive heart and respiratory failure if left untreated.

Pathophysiology

CTEPH begins when embolic clots originating usually from deep veins in the legs travel to the lungs and obstruct pulmonary arteries. While the body often reabsorbs such clots with time, in CTEPH they become organized and incorporated into the vessel wall, forming fibrous obstructions. These blockages impair pulmonary blood flow and increase resistance in the pulmonary circulation. In response, the right ventricle must pump harder to move blood through the lungs, leading to right heart hypertrophy and eventual dysfunction.

Additionally, vascular remodeling occurs in smaller adjacent vessels, worsening the elevated pulmonary pressure and contributing further to right heart strain. This progressive cycle of obstruction and vascular remodeling distinguishes CTEPH from transient or fully resolved pulmonary embolisms.

Causes and Risk Factors

The primary trigger of CTEPH is a prior episode of acute pulmonary embolism. However, only a small percentage of patients (less than 5%) who experience a pulmonary embolism go on to develop CTEPH. Risk factors that increase the likelihood of developing the condition include:

History of recurrent or large pulmonary embolisms
Inadequate or prematurely discontinued anticoagulation therapy
Blood clotting disorders (e.g., antiphospholipid syndrome)
Presence of long-term indwelling central venous catheters
Major surgeries or fractures, particularly in the lower limbs
Chronic inflammatory or autoimmune diseases
Splenectomy (removal of the spleen)

Despite these risk factors, CTEPH can also occur in individuals without any identifiable predisposing condition

Symptoms

CTEPH often progresses silently over months or years and may not be diagnosed until symptoms become prominent. The most common symptom is progressive shortness of breath, initially with exertion and eventually at rest.

Other symptoms may include:

Chronic fatigue and reduced exercise tolerance
Chest discomfort or pressure, sometimes accompanied by palpitations
Dizziness or fainting, especially with exertion due to reduced cardiac output
Swelling in the legs or ankles caused by right heart failure
Persistent cough, and occasionally hemoptysis (coughing up blood), particularly in cases with repeated embolic events

These symptoms are often nonspecific and may be misattributed to other respiratory or cardiac conditions, delaying diagnosis.

Diagnosis

A comprehensive diagnostic approach is essential for confirming CTEPH. Evaluation begins with clinical suspicion and proceeds with a series of imaging and functional tests:

Echocardiography helps assess pulmonary artery pressure and evaluate right ventricular function.
CT pulmonary angiography (CTPA) provides detailed visualization of the pulmonary arteries and can reveal chronic thromboembolic changes.
Ventilation-perfusion (V/Q) scan is particularly sensitive for detecting perfusion defects typical of CTEPH.
Right heart catheterization is the gold standard for measuring pulmonary artery pressure and confirming the diagnosis of pulmonary hypertension.
Pulmonary angiography or MRI may also be used in specialized centers to evaluate vascular obstruction and guide treatment planning.

Treatment

The cornerstone of treatment for CTEPH is to relieve the mechanical obstruction in the pulmonary arteries and reduce the pressure overload on the right heart.

The most definitive and potentially curative treatment is:

Pulmonary Endarterectomy (PEA): A complex surgical procedure in which the fibrotic clots and scar tissue are removed from the pulmonary arteries. When performed in specialized centers, PEA offers significant symptom relief and long-term improvement in functional capacity and survival.

For patients who are not candidates for surgery due to inaccessibility of clots or other medical reasons, alternative therapies include:

Balloon Pulmonary Angioplasty (BPA): A minimally invasive procedure where balloon catheters are used to open narrowed vessels. It is increasingly used in inoperable cases or as an adjunct to surgery.
Pulmonary hypertension medications, such as endothelin receptor antagonists or soluble guanylate cyclase stimulators, may be prescribed to manage symptoms and reduce vascular resistance.
Lifelong anticoagulation therapy is mandatory for all patients with CTEPH to prevent new clot formation.

Follow-Up and Prognosis

Long-term follow-up is essential in patients with CTEPH to monitor for recurrence, treatment response, and right heart function. Regular clinical assessments, echocardiograms, and functional tests are necessary to track disease progression.

Patients are encouraged to maintain physical activity within their tolerance limits, avoid smoking, and promptly treat any respiratory infections. In cases where CTEPH is diagnosed early and treated appropriately—especially with PEA surgery—the prognosis is favorable, with many patients experiencing dramatic improvement in symptoms and quality of life. In advanced or inoperable cases, combination therapy and close monitoring can still achieve meaningful symptom control and prolong survival.