Explore CTEPH in the USA: a progressive form of pulmonary hypertension caused by old blood clots. Discover its signs, advanced diagnosis, and the potentially curative treatments available

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a rare and severe form of pulmonary hypertension (PH) that affects a significant number of individuals in the United States. Unlike other types of pulmonary hypertension, CTEPH has a unique underlying cause and, importantly, is often curable. It arises when blood clots (pulmonary emboli) in the lung's arteries do not dissolve completely over time, instead becoming organized and scar-like.

These chronic, fibrotic obstructions block or narrow the pulmonary arteries, leading to increased blood pressure in the lungs and placing immense strain on the right side of the heart. If left untreated, CTEPH can progress to right heart failure and be fatal.  

Understanding the Pathophysiology of CTEPH

Normally, when a blood clot forms in the lungs (an acute pulmonary embolism, PE), the body's natural clot-dissolving mechanisms and anticoagulant medications usually help the clot resolve within a few weeks or months. However, in a small percentage of individuals (estimated to be around 1-5% of those who experience an acute PE), these clots do not fully disappear. Instead, they organize, fibrose, and adhere to the walls of the pulmonary arteries, creating permanent blockages. This leads to increased resistance to blood flow in the lungs, forcing the right ventricle of the heart to work harder to pump blood through the narrowed vessels. Over time, this sustained strain can cause the right ventricle to enlarge and weaken, eventually leading to right heart failure.  

What makes CTEPH distinct is not just the large, organized clots, but also a secondary remodeling of the smaller, unblocked blood vessels in the lungs, which contributes to the elevated pressures. The exact reasons why some clots become chronic while others resolve are not fully understood, but certain risk factors may increase susceptibility, including larger or recurrent PEs, specific blood clotting disorders, splenectomy, and chronic inflammatory conditions. Importantly, about 25-30% of CTEPH patients have no clear history of a prior acute pulmonary embolism, making diagnosis even more challenging.  

Symptoms of CTEPH in the USA

The symptoms of CTEPH are often non-specific and insidious, mimicking those of more common cardiopulmonary conditions such as asthma, chronic obstructive pulmonary disease (COPD), or heart failure. This can lead to significant diagnostic delays. As the disease progresses, symptoms become more pronounced. Common signs include:  

• Progressive Shortness of Breath (Dyspnea): This is the most common symptom, often worsening with exertion (e.g., climbing stairs, walking uphill).
• Fatigue and Weakness: Generalized tiredness that doesn't improve with rest.  
• Chest Pain or Discomfort: Often related to the strain on the right side of the heart.  
• Dizziness or Lightheadedness: Especially with exertion, and in severe cases, fainting (syncope) can occur.  
• Palpitations: A sensation of a racing or pounding heart.  
• Swelling (Edema): Swelling in the ankles, legs, and abdomen due to fluid retention from right heart failure.  
• Cyanosis: A bluish tint to the lips, fingers, or toes due to low oxygen levels in the blood.  
• Coughing up Blood (Hemoptysis): A less common but serious symptom.

Any individual in the USA experiencing unexplained or worsening shortness of breath and fatigue, especially with a history of blood clots, should be evaluated for CTEPH.

Diagnosis of CTEPH in the USA

Diagnosing CTEPH requires a high index of suspicion and a specialized approach, typically involving a multidisciplinary team at a pulmonary hypertension or CTEPH center of excellence. The diagnostic process usually involves:  

1. Initial Screening for Pulmonary Hypertension:

   • Echocardiogram: A non-invasive ultrasound of the heart that can estimate pressures in the pulmonary arteries and assess the function of the right ventricle. If PH is suspected, further testing is needed.  

2. Screening for CTEPH:

   • Ventilation-Perfusion (V/Q) Scan: This is considered the best initial screening test for CTEPH. It involves inhaling a radioactive gas (ventilation scan) and injecting a radioactive tracer (perfusion scan) to assess airflow and blood flow in the lungs. Mismatches (areas with good airflow but poor blood flow) are highly suggestive of chronic clots.  

3. Confirmation and Characterization:

   • Right Heart Catheterization (RHC): This is the gold standard for confirming a diagnosis of pulmonary hypertension and measuring the exact pressures in the heart and pulmonary arteries. It is crucial for determining the severity of PH and differentiating CTEPH from other forms of PH.  
   • Pulmonary Angiography: A specialized imaging test where a catheter is inserted into the pulmonary arteries and contrast dye is injected, allowing detailed X-ray images of the blood vessels. This test is essential for visualizing the location and extent of the chronic clots and determining if they are surgically accessible.  
   • CT Pulmonary Angiogram (CTPA): A high-resolution CT scan of the chest with contrast dye can also provide detailed images of the pulmonary arteries and surrounding lung tissue, helping to identify chronic clots and assess operability.  

Treatment Options for CTEPH in the USA

The treatment of CTEPH is unique among pulmonary hypertension types because it is potentially curable for many patients. The approach is highly individualized and is best decided by a team at a specialized CTEPH center.  

1. Pulmonary Thromboendarterectomy (PTE) Surgery:

   • The Gold Standard: PTE is a complex, highly specialized surgical procedure that is considered the potentially curative treatment for eligible patients. During the surgery, performed under general anesthesia with cardiopulmonary bypass and deep hypothermia (cooling the body to allow temporary circulatory arrest), surgeons meticulously remove the organized scar tissue and chronic clots from the pulmonary arteries.  
   • Eligibility: PTE is most effective for patients whose clots are located in the more accessible, larger (proximal) pulmonary arteries. Patients' overall health, age, and comorbidities are also considered.
   • Outcomes: For suitable candidates, PTE can dramatically reduce pulmonary artery pressures, improve heart function, alleviate symptoms, and significantly improve long-term survival and quality of life. Recovery involves a period in intensive care and rehabilitation.  

2. Balloon Pulmonary Angioplasty (BPA):

   • Minimally Invasive Option: BPA is a catheter-based procedure performed by interventional cardiologists or pulmonologists. It involves threading a catheter with a small balloon into the blocked pulmonary arteries and inflating the balloon to open the narrowed vessels.  
   • For Inoperable or Residual Disease: BPA is primarily used for patients who are not candidates for PTE surgery (e.g., due to distal clots that are surgically inaccessible, or significant comorbidities) or for those who have residual pulmonary hypertension after PTE. It often requires multiple sessions to achieve optimal results.  

3. Medical Therapy (Pulmonary Hypertension-Targeted Medications):

   • For Inoperable or Residual PH: Medications typically used for pulmonary arterial hypertension (PAH) may be prescribed for patients who are not surgical candidates, or who have persistent PH after PTE or BPA. These drugs work to dilate the pulmonary arteries and reduce pressure. Examples include:  
     • Riociguat (Adempas): An oral soluble guanylate cyclase stimulator, specifically FDA-approved for CTEPH. It's often a first-line medical therapy for inoperable CTEPH or persistent PH after surgery.
     • Endothelin Receptor Antagonists (ERAs) (e.g., macitentan, ambrisentan): Oral medications that block endothelin receptors, causing blood vessel relaxation.  
     • Phosphodiesterase-5 Inhibitors (PDE5i) (e.g., sildenafil, tadalafil): Oral medications that promote vasodilation.  
     • Prostacyclin Pathway Agents (e.g., treprostinil, epoprostenol, selexipag): These can be oral, inhaled, subcutaneous, or intravenous, offering potent vasodilation.  
   • Anticoagulation: Lifelong anticoagulation (blood thinners) is almost always recommended for all CTEPH patients, even after successful surgery, to prevent the formation of new blood clots.  

4. Lung Transplant: In very rare cases, for patients with severe, advanced CTEPH who are not candidates for other treatments and whose condition continues to worsen, lung transplantation may be considered as a last resort.

Early and accurate diagnosis of CTEPH at a specialized center is paramount for optimizing treatment outcomes. With the advanced surgical techniques, interventional procedures, and targeted medications available in the USA, many individuals with CTEPH can experience significant improvements in their health and quality of life.