Complexity of Chronic Thromboembolic Pulmonary Hypertension

A detailed overview of the complex nature of chronic thromboembolic pulmonary hypertension and associated comorbidity.


Charles D. Burger, MD: Group 4 chronic thromboembolic PH [pulmonary hypertension], or CTEPH, is a very challenging area because it’s difficult to understand exactly why a patient goes on to develop chronic thromboembolic pulmonary hypertension. Experience would suggest that the patient probably had a blood clot in the venous circulation in the legs that dislodged and ended up in the pulmonary circulation, what’s referred to as a pulmonary embolus. If that’s diagnosed and treated with blood thinners, 99% of the time or more, the clot in the leg and the clot in the lung completely resolve without any long-term injury to the pulmonary circulation. About 1% of the time, maybe less, that does not happen and the clot in the lung is replaced with a cellular material that adheres to the lining of the inside of the pulmonary arteries, blocks blood flow, and narrows the blood vessels.

That’s referred to as chronic thromboembolism and can be detected with imaging studies. Those patients, because of the blood vessel narrowing, have a high resistance to blood flow. The heart has to generate a higher pressure to overcome that resistance. That is pulmonary hypertension, and it’s in association with chronic thromboembolism, hence the name chronic thromboembolic pulmonary hypertension.

As you work backward from the diagnosis through the patient’s history, there have been efforts to identify patients who might be at more risk for chronic thromboembolic pulmonary hypertension. If they had a large pulmonary embolus and there was an effect on the heart from that large pulmonary embolus at the time of the acute event, that patient might be at higher risk. But the overwhelming majority of those patients have full recovery using only blood thinners.

There may be patients who have blood clots and never know it. Why might that occur? If you’re sedentary for a long period of time—a long car ride or a long plane ride, for example—the circulation in the legs is also sedentary. You might develop a clot in the legs and never really know it. Maybe there was a little swelling, you got up and about later, and you were fine; or a tiny clot broke off and went to the lung, but it wasn’t very symptomatic. There could be patients who have what we call subclinical venous thromboembolism who go on to develop chronic thromboembolic disease.

Why would I even raise that as a possibility? Because 25% to 45% of patients don’t have a previous diagnosis of a venous clot in the legs or pulmonary embolus. Obviously, if the initial cause of CTEPH was a blood clot and the patient never knew it, it was asymptomatic or subclinical. Therefore, you can be surprised at times that patients without this history have CTEPH. That’s why it’s very important to emphasize that all patients who are diagnosed with pulmonary hypertension receive a screening test for CTEPH. The screening test that’s recommended based on the guidelines is a ventilation/perfusion lung scan, a VQ scan. If that’s positive, then you need to perform additional testing because those patients may have a chance for a curative surgery—a pulmonary thromboendarterectomy—or be eligible for specific therapy with riociguat. It’s a very important subgroup to identify.

If all of this overwhelms you as a provider, you need to refer the patient to a pulmonary hypertension center where they have expertise. We have a multidisciplinary group that includes pulmonology, cardiology, critical care doctors, special radiologists who look at these types of imaging studies, and cardiothoracic surgery, etc. We review all these cases to determine the diagnosis and the best treatment. It is very important to have that expertise because it can be very subtle. It’s very important to make a correct diagnosis in order to make the correct treatment recommendations.

Hilary M. DuBrock, MD: There are various comorbidities and risk factors for chronic thromboembolic pulmonary hypertension. These include chronic inflammatory disorders; chronic infections, such as infected pacemaker leads; and patients who have ventricular atrial shunts, a prior splenectomy, or antiphospholipid antibody syndrome or lupus anticoagulant. Additionally, malignancy is a risk factor for chronic thromboembolic pulmonary hypertension and is an important comorbidity in patients with CTEPH. Compared to idiopathic pulmonary arterial hypertension, patients with CTEPH tend to have more comorbidities, and this can impact perioperative risk stratification and eligibility for procedures such as pulmonary thromboendarterectomy.

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