Chronic Thromboembolic PH Diagnosis and Management Update: Expert Q&A

Of the 5 different types of pulmonary hypertension (PH), chronic thromboembolic PH (CTEPH) is classified as group 4 PH by the World Health Organization. The other types are pulmonary arterial hypertension (PAH) due to left heart disease, PH due to lung disease, and PH with unclear or multifactorial mechanisms (groups 1, 2, 3, and 5, respectively). CTEPH is a rare disease that has been estimated to affect 1 to 7 per 1 million people each year, and approximately 0.5% to 4% of patients after acute pulmonary embolism (PE).¹ It affects men and women in roughly equal numbers, and median age at diagnosis is 63 years.

The pathogenesis of CTEPH involves both macrovascular and microvascular components. The disease is “secondary to mechanical obstruction from thromboembolism… characterized by arteriopathic changes and remodeling in the pulmonary circulation…,” as explained in a paper published in Cardiology In Review.¹ “The development of CTEPH is associated with traditional thrombotic risk factors like thrombophilias and inflammatory processes, which favor the formation or non-resolution of thrombi/emboli.”

According to previous findings, some of the risk factors for CTEPH are older age (P =.0198), non-O blood groups (P <.0001 in univariate analysis), history of acute venous thromboembolism (P <.0001), and previous large PE (P =.0040 in univariate analysis).² In addition, multiple tissue-level factors have been shown to be increased in patients with CTEPH. 

CTEPH is unique in that it is the only form of PH that can be cured with surgical treatment — pulmonary endarterectomy (PEA) is the current gold standard in CTEPH treatment when possible, although other therapies are available in patients who are not candidates for surgery.³ Without timely treatment, progressive small vessel changes may occur and lead to more progressive PH, right heart failure, and increased morbidy and mortality.

While this underscores the need for timely detection, underdiagnosis of CTEPH is common, and it is often misdiagnosed as idiopathic primary aterial hypertension (PAH). Any patient with unexplained PH or PAH symptoms plus a history of PE (after 6 months of anticoagulation therapy) should be assessed for CTEPH.⁴ Requirements for CTEPH diagnosis include: a clinical suspicion for PH in patients with or without a PE history, echocardiography showing PH or right ventricular dysfunction,  and ventilation/perfusion (V/Q) lung scanning to differentiate between CTEPH and PAH. “Further diagnostic evaluation involves the confirmation of diagnosis with [right heart catheterization], and, in some cases, pulmonary angiography for anatomical localization of the extent of disease, and operability assessment,” the investigatorswrote.¹

For more details on diagnostic and treatment challenges with CTEPH, Cardiology Advisor spoke with Srikanth Yandrapalli, MD, and Wilbert Aronow, MD, of New York Medical College at Westchester Medical Center, 2 co-investigators of the Cardiology In Review paper; and Ivan M. Robbins, MD, professor of medicine in the division of allergy, pulmonary, and critical care medicine at Vanderbilt University Medical Center, and director of the Adult Pulmonary Hypertension Center in Nashville, Tennessee.

Cardiology Advisor: What are some diagnostic challenges pertaining to CTEPH, and how might these be addressed?

Drs Yandrapalli and Aronow: Major diagnostic challenges include the rarity of this entity in clinical practice, as well as  a lack of suspicion of CTEPH in patients presenting with symptoms suggestive of PH. Underutilization of the diagnostic standard radionuclide V/Q scan in the screening evaluation of CTEPH contributes largely to missed or delayed diagnosis of CTEPH

Dr Robbins: Perhaps the biggest challenge is to get clinicians to think about the diagnosis. This is often not on their radar. A second challenge is obtaining a V/Q scan, which is presently the recommended screening test of choice. This is difficult to obtain at many hospitals, and can also be misread. Computed tomography (CT) angiograms are often obtained in patients with acute PE and with CTEPH. However, the findings of CTEPH are different from those seen with acute PE, and often are overlooked by radiologists and interpreted as recurrent acute PE.

We are trying to address these issues by increasing awareness of CTEPH, addressing clinicians at national meetings, and speaking at educational meetings around the country. However, there is still a lot of educating to be done and misunderstanding of this disorder despite the efforts of many experts in the field.

Cardiology Advisor: How is CTEPH typically treated, and what are some of the challenges?

Drs Yandrapalli and Aronow: Treatment depends on the type of disease and operability of the patient. Complete surgical removal of the fibrotic thrombi and obstructive vasculopathy with PEA is the definitive treatment of CTEPH, and results in the most significant and immediate improvement in hemodynamics and clinical status of the patient, if the lesions are operable. This should be done in an expert center with a CTEPH team.